Advanced Review

Music perception and cognition:

development, neural basis, and
rehabilitative use of music
Teppo Särkämö,1,2∗ Mari Tervaniemi1,2,3 and Minna Huotilainen1,2,4

Music is a highly versatile form of art and communication that has been an
essential part of human society since its early days. Neuroimaging studies indicate
that music is a powerful stimulus also for the human brain, engaging not just
the auditory cortex but also a vast, bilateral network of temporal, frontal, parietal,
cerebellar, and limbic brain areas that govern auditory perception, syntactic and
semantic processing, attention and memory, emotion and mood control, and motor
skills. Studies of amusia, a severe form of musical impairment, highlight the right
temporal and frontal cortices as the core neural substrates for adequate perception
and production of music. Many of the basic auditory and musical skills, such
as pitch and timbre perception, start developing already in utero, and babies are
born with a natural preference for music and singing. Music has many important
roles and functions throughout life, ranging from emotional self-regulation, mood
enhancement, and identity formation to promoting the development of verbal,
motor, cognitive, and social skills and maintaining their healthy functioning in
old age. Music is also used clinically as a part of treatment in many illnesses,
which involve affective, attention, memory, communication, or motor deficits.
Although more research is still needed, current evidence suggests that music-
based rehabilitation can be effective in many developmental, psychiatric, and
neurological disorders, such as autism, depression, schizophrenia, and stroke, as
well as in many chronic somatic illnesses that cause pain and anxiety. © 2013 John
Wiley & Sons, Ltd.

How to cite this article:

WIREs Cogn Sci 2013, 4:441–451. doi: 10.1002/wcs.1237

INTRODUCTION Thus far, the oldest concrete evidence regarding the

A s the French poet Victor Hugo (1802–1885) put
it, ‘music expresses that which cannot be said and
on which it is impossible to be silent’. Just like spoken
language, music has been an essential part of every
known human culture and therefore has roots that
reach deep into our very selves and into our brains.
∗
Correspondence to: teppo.sarkamo@helsinki.fi
1 CognitiveBrain Research Unit, Cognitive Science, Institute of
Behavioural Sciences, University of Helsinki, Helsinki, Finland
2 FinnishCentre of Excellence in Interdisciplinary Music Research,
University of Jyväskylä, Jyväskylä, Finland
3 Department of Psychology, University of Jyväskylä, Jyväskylä,
Finland
4
Finnish Institute of Occupational Health, Helsinki, Finland
The authors have declared no conflicts of interest for this article.
early existence of music was obtained a few years
ago from southern Germany, where archaeological
excavations revealed a 40,000-year-old flute made
of bone.1 Some scholars believe that a singing-based
form of communication, a protolanguage, could be
even older, possibly dating back over 200,000 years,
and could have formed a basis for the development
of modern spoken language.2 More recently, various
cultural trends and technological innovations, such
as the karaoke and the choir singing boom, MP3
players, and digital streaming services and players
(e.g., Spotify and iTunes), have made music more
available and easily accessible than ever before. In
its many forms, music has become a popular leisure
activity and hobby through which many of us mediate
our emotional and arousal state, experience creativity

Volume 4, July/August 2013 © 2013 John Wiley & Sons, Ltd. 441
 Advanced Review wires.wiley.com/cogsci

and aesthetic pleasure, and interact with others.
Thanks to modern brain imaging methods, such
as electroencephalography, magnetoencephalography
(MEG), functional magnetic resonance imaging
(fMRI), and positron emission tomography (PET), and
behavioral and clinical studies, we are now starting
to better understand how music affects us and how
it can be used to promote well-being and facilitate
recovery and rehabilitation. In this article, we aim
to provide a brief review of the neural basis of
music in both the healthy and the damaged brain,
the development of musical skills and the meaning of
music in different ages, and the effectiveness of music-
based interventions in various somatic, psychiatric,
and neurological illnesses.
NEURAL BASIS OF MUSIC
Music Processing in the Healthy Brain
Neuroscience of music is a relatively new, fast-
developing field of science, which has during the past
20 years provided a lot of novel information on how
music is processed in the brain, how musical activities
can shape the brain, and what neural mechanisms
underlie the therapeutic effect of music. To date,
converging evidence suggests that music activates an
extremely complex and wide-spread, bilateral network
of cortical and subcortical areas that control many
auditory, cognitive, sensory-motor, and emotional
functions (see Figure 1).
The processing of music begins in the inner ears
where acoustic information is converted to an electric
impulse or signal. The signal then travels along the
auditory nerve to the brain stem (especially to the
inferior colliculus) where certain basic features of
the sound, such as periodicity and intensity, are first
processed. Interestingly, the earliest signs of musical
training can be seen as immediately as 10 milliseconds
after sound onset in the auditory brain stem, which
in musicians can represent the frequency of the sound
with more fidelity than in nonmusicians.3 From the
brain stem, the auditory information is conveyed
to the thalamus and from there primarily to the
auditory cortex (AC), but also directly to limbic areas,
such as the amygdala and the medial orbitofrontal
cortex.4 The primary AC and its neighboring superior
temporal areas analyze the basic acoustic cues of
the sound, including frequency, pitch, sound level,
temporal variation, motion, and spatial location.5 The
left AC has a better temporal resolution and the right
AC has a better spectral resolution, which is thought
to form one crucial premise for the lateralization of

Somatosensory cortex Motor cortex

Insula Thalamus
Inferior parietal lobe Premotor cortex
Precuneus Cingulate gyrus
Angular gyrus
Dorsolateral
prefrontal Medial
cortex prefrontal
cortex

Planum
temporale Hippocampus
Orbitofrontal cortex
Inferior frontal gyrus
Ventral Nucleus accumbens
Cerebellum Superior temporal gyrus tegmental
area Amygdala Striatum
Middle temporal gyrus
Auditory cortex Inferior colliculus

Perceiving the basic acoustic features of music (e.g., frequency, duration, loudness)

Perceiving higher-order musical features (e.g., harmony, intervals, rhythm)

Focusing and keeping track of music in time (attention, working memory)

Recognizing music and recalling associated memories (episodic memory)

Playing, singing and moving to the beat of music (motor functions)

Music-evoked emotions and experiencing pleasure and reward

FIGURE 1 | Schematic illustration of key brain areas associated with music processing-based neuroimaging studies of healthy subjects. Note that
although the image displays the lateral and medial parts of the right hemisphere, many musical subfunctions are actually largely bilateral (with the
exception of pitch and melody processing, which is more lateralized to the right hemisphere).

442 © 2013 John Wiley & Sons, Ltd. Volume 4, July/August 2013
 WIREs Cognitive Science
speech to the left hemisphere and music to the right
hemisphere.6
Music is, however, much more than just the sum
of its basic acoustic features. Upon its initial encoding
and perception, music triggers a sequence of cognitive,
motor, and emotional processes in the brain that are
governed by numerous cortical and subcortical areas.
Next, we outline five such processes.
1. The perception of higher order musical features,
such as chords, harmonies, intervals, and
rhythms, calls for a rule-based syntactic analysis
of complex patterns of spectral and temporal
fluctuations within the sound stream. According
to neuroimaging studies, this takes place in a
network comprising the inferior and medial
prefrontal cortex, the premotor cortex, the
anterior and posterior parts of the superior
temporal gyrus, and the inferior parietal lobe.7,8
2. Continually keeping track of the music,
which always unfolds over time, requires the
engagement of the attention and working
memory system, which is spread over many
prefrontal areas (especially the dorsolateral
prefrontal cortex), the cingulate cortex, and
inferior parietal areas.9,10
3. Hearing music that is familiar to the
listener from past experience triggers processing
especially in the hippocampus as well as in
medial temporal and parietal areas, which are
involved in episodic memory.11,12
4. Hearing music that touches us emotionally
engages a network of many deep limbic and par-
alimbic areas, including various midbrain areas,
striatal areas (especially nucleus accumbens),
the amygdala, the hippocampus, the cingulate
cortex, and the orbitofrontal cortex.13,14 This
dopaminergic network is known as the mesolim-
bic or reward system of the brain and it has
been implicated in the experiencing of emo-
tions, pleasure, and reward and in regulating
the autonomic nervous system (ANS) and the
endocrine (or hormone) system. Recently, the
direct involvement of striatal dopamine in the
emotional reaction to music was demonstrated
in a combined psychophysiological, PET and
fMRI study.15
5. Perceiving the rhythm of music, moving to the
beat of music, or producing music (by singing
or playing an instrument) involves the sensory-
motor networks of the brain, including areas in
the cerebellum, the basal ganglia, and the motor
and somatosensory cortices.16,17
Volume 4, July/August 2013 © 2013 John Wiley & Sons, Ltd.
Music perception and cognition
Music Processing in the Damaged or
Abnormal Brain: Amusia
Our ability to perceive, process, and appreciate
music may become impaired in many neurological
illnesses. The most well-known disorder is amusia,
which can be either innate (congenital amusia) or
result from a brain lesion (acquired amusia). The
term amusia refers to an inability to perceive and/or
produce music, which is not caused by a disorder
in another domain, such as hearing, motor, or
cognitive functions.18,19 Amusia can be observed in
the majority of musical features (perceiving pitch,
timbre, or rhythm or recognizing musical emotions
or musical pieces) or be specific to one or some of
them. The most commonly reported deficit is that
of poor pitch discrimination: amusic individuals are
typically not able to perceive pitch changes smaller
than a semitone.20 As a result, they often have great
difficulties in perceiving sequential notes (or tones)
and, therefore, in recognizing melodies—for some rare
individuals, music may sound more like noise.
It has been estimated that the prevalence of con-
genital amusia is approximately 2–4% in the general
population.21 Genetic studies of congenital amusia
suggest that the disorder is heritable: in amusic fami-
lies, 39% of first-degree relatives have the same deficit,
whereas only 3% have it in the control families.22
Furthermore, dizygotic (identical) twins have more
uniform performance in a musical pitch perception
test than monozygotic (fraternal) twins.23 Compared
to congenital amusia, acquired amusia seems to be
a lot more common deficit, at least after a cere-
brovascular accident such as stroke. In studies of
stroke patients, the reported incidence of amusia
is 60% in the acute stage (about 1 week poston-
set) and around 40% in the subacute/chronic stage
(>3 months postlesion).24,25 On the basis of structural
and functional MRI studies, the crucial neuroanatom-
ical correlate of congenical amusia appears to be the
superior temporal gyrus (AC) and the inferior frontal
gyrus in the right hemisphere as well as the subcorti-
cal white matter tracts (arquate fasciculus) connecting
these areas.26–28 Correspondingly, acquired amusia is
most typically caused by damage to the AC and its
surrounding cortical and subcortical areas (anterior
and posterior superior temporal gyrus and insula) or
to temporoparietal or inferior frontal areas, especially
in the right hemisphere19 (see Figure 2).
Interestingly, amusia can occur independently
of or in parallel with linguistic disorders, thereby
raising an intriguing question of whether the neural
mechanisms of music and speech processing are
separate or shared. In studies of brain-damaged
patients, approximately half of the patients with
443
 Advanced Review
Inferior frontal gyrus
Anterior superior
temporal gyrus
Middle/inferior
temporal gyrus
Insula
Heschl’s gyrus
(auditory cortex)
Planum temporale
Parietal lobe
Spectral processing
Temporal processing
Musical memory
Emotional response to music
FIGURE 2 | Critical brain areas where damage typically leads to an
amusic deficit in spectral processing (perception of pitch intervals or
patterns, tonal structure, and timbre), temporal processing (perception
of time intervals and rhythm), musical memory (recognition of familiar
or novel musical material), or emotional response to music. The size of
each circle is scaled to the proportion of studies of the function
implicating that region. (Reprinted with permission from Ref 19.
Copyright 2006 Oxford University Press)
acquired amusia have been documented to have at
least minor aphasia,19 although there are also cases
of clear double dissociations (amusia without aphasia
and vice versa), suggesting that there may be separate
neural modules for music and speech.29 Recent
studies, however, have found that aphasic patients
also have difficulties in perceiving musical structures30
and, conversely, that individuals with congenital
amusia have difficulties in perceiving the intonation
and prosody of speech,31 thereby supporting the
alternative view that there are commonalities between
speech and music perception at the neural level.
DEVELOPMENT AND UTILITY
OF MUSIC ACROSS LIFE SPAN
Music, especially hearing singing and producing musi-
cal sounds, appears to evoke the natural interest of
infants and children across cultures.32 Indeed, babies
seem to be born with innate musical abilities: even
small infants can detect the pitch, timbre, and dura-
tion of the sounds, recognize familiar melodic and
rhythmic patterns, and prefer consonant over disso-
nant music and singing over speech.32 Infants are also
sensitive to prosody, in other words, to changes in
444 © 2013 John Wiley & Sons, Ltd.
wires.wiley.com/cogsci
the melody, rhythm, stress, and intonation of speech,
which are used to communicate emotions and to
emphasize word meanings in speech. Intuitively, par-
ents tend to speak to their babies in a manner which
utilizes this sensitivity. In fact, infant-directed speech
(or motherese) contains many musical or singing-like
elements, such as strong pitch fluctuations and repet-
itive melodic line, which help the infant to grasp and
acquire the essential structure of natural speech.33
Lullabies and play songs are also globally used to
modulate the arousal level of infants, as reflected, for
example, in salivary cortisol changes.33 At the age of
6 months, babies start to babble and to ‘dance’, i.e.,
to adjust their movements with the tempo of music.34
For a toddler, musical activity is a playground of sorts,
where parents can use reciprocal communication and
rhythmic movements to regulate the emotional and
attentional state of the child. At the same time, the
child him/herself can practice the cognitive, motor,
and social skills needed for speech acquisition and
communication.
At preschool age, children are often enthusiastic
in expressing music with their gestures and movements
and in taking part in musical activities as listeners,
singers, players, and dancers. In many native cul-
tures, music making or dancing is an integral and
natural part of the everyday life of children. For the
developing brain, repeated exposure to music in the
growing environment can be beneficial. In develop-
mental animal studies, an enriched auditory environ-
ment that contains complex sounds or music has been
shown to improve auditory functions, learning, and
memory as well as induce neural plasticity, as indi-
cated by changes in neurotransmitter (e.g., dopamine
and glutamate) and neurotrophin (e.g., brain-derived
neurotrophic factor) levels, synaptic plasticity, and
neurogenesis.35,36 According to studies on children,
musical hobbies can improve auditory and motor
skills as well as high-level cognitive skills such as log-
ical reasoning, executive functioning, attention, and
memory.37–39 Musical skills and music training seem
to be also related to speech perception and pronuncia-
tion of foreign language.40,41 At the neural level, struc-
tural changes in the primary AC, the primary motor
cortex, and the corpus callosum have been observed
already after 15 months of individual piano lessons.37
During adolescence, music serves as a forum
for constructing the developing self-identity, forming
interpersonal relationships, and experiencing agency
and self-control, and in dealing with negative emotions
and stress.42 Furthermore, a key aspect of all musical
activity is emotional expression, which, according
to a recent theory,43 is at least partly mediated
by the mirror neuron system, a set of frontal and
Volume 4, July/August 2013
 WIREs Cognitive Science
parietal cortical structures thought to contribute
to understanding the actions of other people (i.e.,
empathy), learning new skills by imitation, and to
theory of mind and which continue to develop through
adolescence and early adulthood. Musical activity, or
even simple music listening, can thus form a safe
shared and dynamic platform for exploring one’s
emotional processes with respect to others and for
forging relationships through common experiences,
chats, and discussions. Some evolutionary theories
of music postulate that joint musical activities, such
as singing and dancing with others, facilitate the
release of endorphins and the experience of reward
and pleasure, which in turn promote group cohesion
and social bonding.44
Finally, music has a lot to give also in adulthood
and in old age. In most cases, individual musical
preferences are formed during adolescence and early
adulthood—maybe because of this, music also offers
means to refresh and process memories and reflect
on prior experiences later in life. During adulthood,
music is strongly linked to emotional and self-
conceptual processing, mood, and memories.45 Music
continues to play a vital role as well during aging.
Studies suggest that regular musical activities are very
important to seniors in maintaining psychological
well-being and in contributing to positive aging by
providing ways to maintain self-esteem, competence,
and independence and in reducing loneliness and
isolation.46
THERAPEUTIC AND REHABILITATIVE
USE OF MUSIC
Broadly defined, music therapy is an intervention pro-
vided by a trained music therapist where music is used
in a therapeutic interaction with the client to achieve
individually defined goals. The methods utilized in
music therapy include, for example, music listening,
singing, instrument playing, musical improvisation,
and song writing. In contrast, musical interventions
that are provided by other nursing or rehabilitation
staff (typically music listening) are usually referred to
as music medicine. Although both music therapy and
music medicine utilize music as a therapeutic tool,
the key difference between them is the involvement
of a trained music therapist and the therapeutic rela-
tionship between the therapist and the client, which
are important contributors in the efficacy of music
therapy. However, for simplicity, both music therapy
and music medicine are referred to hereafter as music
interventions. The scientific study of the efficacy of dif-
ferent music interventions has increased rapidly during
the past 20 years, and the experimental evidence for
Volume 4, July/August 2013 © 2013 John Wiley & Sons, Ltd.
Music perception and cognition
these interventions is accumulating regarding their
clinical utility and applicability in the treatment and
rehabilitation of many somatic, psychiatric, and neu-
rological illnesses. On the basis of Cochrane Reviews
published so far (www.cochrane.org), there are cur-
rently about 160 published music intervention studies
(involving a total of over 9000 patients) that meet the
strict methodological criteria of a randomized con-
trolled trial (RCT). In the following sections, we will
briefly review what is currently known about the effi-
cacy of music interventions regarding five domains:
emotion, attention and sensory functions, memory,
communication, and motor functions.
Emotion
Perhaps more than any other sensory stimulus, music
is capable of evoking a wide spectrum of deep and
powerful emotions, including, for example, joy, seren-
ity, sadness, and nostalgia. The transient emotional
effect of music is manifested not just as a subjec-
tively experienced feeling or emotional state but also
as a physiological change, for example, in heart rate,
respiration, skin temperature and conductance, and
hormone (e.g., cortisol, oxytocin, and β-endorphin)
secretion,47 indicating an impact on the ANS or
endocrine system as well as the activity of the afore-
mentioned limbic/paralimbic brain areas.13–15 Conse-
quently, music interventions have often been applied
to the rehabilitation of persons suffering from various
affective disorders, such as depression and anxiety,
or from illnesses with more severe neuropsychiatric
symptoms, such as schizophrenia or Alzheimer’s dis-
ease (AD).
In the field of depression, a recent meta-analysis
of five RCTs (n = 237) found that music therapy is an
applicable method that can improve depressed mood,
although more high-quality trials are still needed to
draw more firm clinical conclusions.48 Also, another
meta-analysis, which included RCTs and other con-
trolled studies of patients (n = 319) with various
severe mental disorders, found that music therapy
had a significant positive effect on depression and
anxiety symptoms of the patients.49 One new and
promising therapeutic technique for treating depres-
sion is improvisational psychodynamic music therapy,
which was recently shown to reduce depression and
anxiety symptoms and improve general functioning
in working-age depressed patients.50 In patients diag-
nosed with schizophrenia or schizophrenia-like disor-
der, a recent meta-analysis of eight studies (n = 483)
came to a conclusion that music therapy can help
to improve the global and mental state and the social
functioning of the patients and to reduce their negative
445
 Advanced Review
symptoms, depression, and anxiety, if provided in
sufficient quantity.51
Regarding AD and other forms of dementia, an
updated Cochrane review of 10 studies (n = 396)
reported that music therapy may be effective in
reducing neuropsychiatric and behavioral symptoms,
such as agitation and wandering, as well as
in enhancing social and emotional functioning.52
However, the authors also cautioned that the
methodological variability between the studies
precludes making any robust conclusions about the
clinical utility of music therapy and more high-
quality studies are still called for. Finally, another
line of meta-analytical evidence suggests that music
interventions can be effective in reducing anxiety,
improving mood, and influencing ANS parameters
(heart rate, respiration, and blood pressure) also
in patients suffering from severe chronic somatic
illnesses, including cancer (30 RCTs, n = 1891)53 and
coronary heart disease (23 RCTs, n = 1461).54
Attention and Sensory Functions
One attribute that is also quite unique to music is the
capacity to draw and direct attention and influence
arousal and vigilance. Clinically, this attribute has
been effectively utilized in the alleviation of pain,
which remains as one of the most studied ther-
apeutic applications of music.55 A comprehensive
meta-analysis (51 RCTs, n = 3663), which evaluated
the effect of music interventions compared to controls
on various types of pain (e.g., acute pain, chronic
pain, neuropathic pain, cancer pain, and postsurgi-
cal pain), indicated that music is able to reduce the
level of subjectively experienced pain intensity and
also to reduce the amount of opioids required to
manage the pain, especially in the case of postsur-
gical pain.56 Again, however, the effects were quite
modest according to the authors, and the clinical
importance still remains unclear. In future, the anal-
gesic use of music could be a viable option especially
for children and adolescents with whom there are
less systematic studies of the suitable dosage and
the potential side effects of painkillers.55 In neona-
tal units, music is increasingly used to improve the
behavioral or physiological outcomes of preterm
infants, and currently there is preliminary evidence
that music, especially maternal singing, may reduce
pain and improve sucking and weight gain in preterm
infants.57,58
Another interesting and novel application of
music is the treatment of tinnitus. Tinnitus, the
unpleasant and recurrent perception of a sound, often
a ringing or a buzzing one, in the absence of cor-
responding external sound, is most often caused by
446 © 2013 John Wiley & Sons, Ltd.
wires.wiley.com/cogsci
noise-induced hearing loss or various illnesses, and
ultimately results in maladaptive plastic changes in
the AC. The contemporary view on tinnitus biology
holds that although tinnitus may be triggered by
injury to the inner ear, the neural generators are most
readily found centrally in the brain. On the basis of
an idea of music-induced neuroplasticity and lateral
inhibition in the human AC, Pantev and coworkers
have recently developed a novel treatment strategy
for tonal tinnitus called tailor-made notched music
training (TMNMT). By notching the music energy
spectrum around the individual tinnitus frequency,
the idea of TMNMT is to attract lateral inhibition
to auditory neurons involved in tinnitus perception.
The results of a 12-month controlled follow-up study
(n = 39) found that subjective tinnitus loudness and
annoyance were significantly reduced after TMNMT
but not in a placebo group where the notching
spared the tinnitus frequencies.59 Correspondingly,
MEG results also showed that tinnitus-related audi-
tory evoked fields were significantly reduced after
the TMNMT training.59 Given that tinnitus is highly
prevalent (10–15%) in the adult population, can lead
to severe depression and even suicide, and currently
lacks effective drug treatment, these results are highly
important and promising.
A third example of the attention-influencing
effect of music is attention-deficit/hyperactivity dis-
order (ADHD). Abikoff et al.60 performed a study
where 20 ADHD children and 20 healthy control
children worked on an arithmetic task while being
exposed to their favorite music, to background speech
(news report), and to silence. The performance of
the control children did not differ between the three
conditions, whereas the ADHD children performed
significantly better in the music condition than in
the speech and silence conditions, especially if the
music condition was the first.60 In addition to ADHD,
music may have an attention-stimulating effect also
on stroke patients suffering from unilateral spatial
neglect (USN), a deficit in awareness for information
presented on the side of space that is contralateral to
the site of the brain lesion (e.g., impaired awareness
of the left side following a right hemisphere lesions).
In one study, 14 USN patients were given tactile,
auditory verbal, or auditory nonverbal (white noise
or classical music) stimulation or no stimulation while
performing a visuospatial copying task.61 Only non-
verbal auditory stimuli were found to decrease neglect
on the task.61 In another study of three USN patients,
especially music that was emotionally pleasant to the
patient was found to ameliorate neglect in a visual
awareness task and also induce functional coupling
between the emotional and visual attentional brain
Volume 4, July/August 2013
 WIREs Cognitive Science
areas in the right hemisphere.62 In summary, music
seems to be effective, at least temporarily, in modi-
fying the orientation and maintenance of attention in
persons suffering from a neurological disorder, sug-
gesting that it could potentially be utilized in their
education and rehabilitation.
Memory
Hearing and perceiving music naturally entail keeping
track of the incoming auditory information as the
music unfolds in time, analyzing the structure and
meaning of the music, and identifying the music
and retrieving the experiences and memories that
are associated with it. In the brain, all this recruits
areas associated with auditory sensory memory,
working memory, and episodic and semantic memory.
By affecting our mood and arousal state, music
can also temporarily improve cognitive performance,
including memory performance,63 although this effect
is still somewhat controversial.64 However, there is
some evidence suggesting that this may also occur
in persons with dementia. Irish et al.65 tested the
autobiographical recall of 10 AD individuals and
10 control subjects under two conditions, music
(exposure to Vivaldi’s ‘Spring’) and silence, and found
that the performance of the AD individuals improved
considerably in the music condition. Similarly,
in another study, 29 elderly persons with mild
or moderate dementia answered autobiographical
memory questions from three life eras (remote,
medium-remote, and recent) while being exposed
to familiar music, novel music, cafeteria noise, or
quiet.66 Recall was significantly better in music
than in noise or quiet, especially regarding remote
experiences.66 Interestingly, music may also function
as a mnemonic aid in AD. In a recent study, 13
AD individuals and 14 healthy older controls were
presented with printed lyrics of unfamiliar children’s
songs accompanied by either spoken or sung versions
of the songs.67 AD individuals had better recognition
accuracy for the sung lyrics than the spoken lyrics,
whereas the healthy controls showed no significant
differences.67
Taken together, these results suggest that music
may have a small short-term facilitating effect on
memory performance in dementia, but currently the
data are still insufficient to draw firm conclusions
about the clinical efficacy of music in dementia, espe-
cially regarding its long-term cognitive effect.68,69 In
contrast, studies of healthy seniors have found that
regular musical activities, such as playing an instru-
ment, can improve cognitive functioning, for example,
in tasks of attention and executive functioning.70
In a longitudinal study of 469 subjects older than
Volume 4, July/August 2013 © 2013 John Wiley & Sons, Ltd.
Music perception and cognition
75 years, frequent reading, playing board games,
playing musical instruments, and dancing were found
to be the leisure activities that were most associated
with a lower risk of developing dementia later.71
Also, in a recent randomized longitudinal study of
elderly stroke patients (n = 55), daily music listen-
ing was found to have a positive effect on the
recovery of verbal memory and focused attention
compared with patients who listened daily to audio
books or received only standard care.72 The positive
effects on memory were also coupled with reduced
depression and confusion during the early recov-
ery stage,73 suggesting that the positive effect of
music on cognition is at least partly mediated by
enhanced mood.
Communication
Both music and speech are forms of communication
that make use of the acoustic properties of sound,
such as pitch, timbre, and rhythm. This link is
evident also in studies of musical training, which
have shown that musical training can enhance the
processing of the acoustic features of speech and
also facilitate language skills, such as reading, speech
segmentation, and perceiving speech in noise.3,41
According to the recent OPERA hypothesis,74 these
beneficial effects may be related to the fact that the
brain networks processing the acoustic features of
music and speech overlap anatomically; that music
places higher demands on the precision of processing
in these shared networks than speech; and that
the musical activities, which engage this network,
typically elicit strong positive emotions, are frequently
repeated, and require focused attention. Clinically,
music has been utilized in training communication
skills in various patient groups.
One clinical population who often lacks proper
communication skills but in many cases has enhanced
auditory and musical abilities, such as superior pitch
processing, are children with an autistic spectrum dis-
order (ASD). Currently, some meta-analytical (three
RCTs, n = 24) evidence exists that music therapy may
help ASD children to improve their communicative
skills.75 Music may be an especially important thera-
peutic tool for those ASD children who are nonverbal.
Recently, a novel intervention called auditory-motor
mapping training (AMMT) has been developed, which
aims to promote speech production by training the
association between sounds and articulatory actions
using intonation and bimanual motor activities. In a
small pilot study, six ASD children who had no intel-
ligible speech were given frequent sessions of AMMT
and were all found to improve in their ability to
447
 Advanced Review
articulate words and phrases, with generalization also
to nonpracticed items.76
Another example of a music-based rehabilitation
method that emphasizes the melodic and rhythmic
elements of speech is melodic intonation therapy
(MIT), which has been developed to train speech
production in aphasic patients. The core idea of MIT
is to lead nonfluent aphasic patients from singing
simple, 2-3 syllable phrases to speaking longer phrases
by utilizing melodic intonation (intoning syllables on
different pitches), inner rehearsal (covert production
of the phrase), and rhythmic motor sequencing
(tapping with the functioning left hand once per
syllable). Although the efficacy of MIT has yet to
be substantiated in an RCT, evidence from small case
series suggests that an intense course of MIT can lead
to improvement in spontaneous language skills.77 Pilot
fMRI and diffusion tensor imaging data indicate that
the verbal improvement may be related to functional
and structural neuroplastic changes in the spared right
frontotemporal network.77
Motor Functions
Rhythm and movement are intimately connected to
music. In fact, some cultures do not even differentiate
‘music’ and ‘dance’ in their vocabulary. Also in
the human brain, almost all musical activity, even
the passive listening of music, automatically recruits
motor areas, and there is rich connectivity between
auditory and motor brain areas.17 Clinically, our
innate tendency to sequence and entrain movements to
the beat of music has been utilized in the rehabilitation
of walking in many neurological illnesses, including
stroke, traumatic brain injury, and Parkinson’s disease
(PD). One method has proved to be especially useful
in this respect: rhythmic auditory stimulation (RAS).
In RAS, an external auditory rhythm is provided by
a metronome or by specifically prepared music tapes
and adapted to the gait cadence of the patient—the
idea is that auditory rhythms entrain motor rhythms
via the close neural connections between the auditory
and motor areas. A recent meta-analysis of studies
of music therapy in acquired brain injury patients
(seven RCTs, n = 184) concluded that RAS may be
beneficial for improving gait parameters in stroke
patients, including gait velocity, cadence, stride length,
and gait symmetry.78 Also in PD, there is evidence that
patients are able to stabilize and synchronize their
disturbed gait with the help of an external auditory
rhythm79,80 and that their motor coordination may
be temporarily improved by familiar and stimulating
music.81
Another way to use music in motor rehabilita-
tion is to utilize active music making in the form of
448 © 2013 John Wiley & Sons, Ltd.
wires.wiley.com/cogsci
instrument playing. Recently, a method called music-
supported therapy (MST) has been developed where
fine and gross motor movements of the affected upper
extremity are trained by playing progressively more
difficult series of tones or simple melodies with a
simplified MIDI-piano keyboard or electronic drum
set. Studies of both subacute (n = 77) and chronic
(n = 20) stroke patients found MST to be effective
in improving both fine and gross motor skills with
respect to the speed, precision, and smoothness of
movements.82,83 The fMRI results also suggest that
MST may have a facilitating impact on the activity
and functional connectivity of the auditory-motor net-
works in the temporal and frontal lobes that support
musical perception and learning.83
CONCLUSION
In this article, we have reviewed a number of stud-
ies, which together shed light on the neural basis,
development, and rehabilitative use of music. Modern
neuroimaging has shown that musical activities, rang-
ing from simple music listening to singing and playing
a musical instrument, have diverse positive effects
on the structure and function of the brain. Musical
activities have different roles and meanings in different
phases of life: during infancy and early childhood, they
can support speech development; during school years,
they can develop cognitive and attentional skills; dur-
ing adolescence, they help to build self-identity and
enhance emotional self-regulation; and during adult-
hood and old age, they help maintain cognitive perfor-
mance and memory and improve mood. Clinically, the
use of music therapy and other music interventions as
a form of treatment and rehabilitation has received sci-
entific support especially in somatic, psychiatric, and
neurological illnesses involving deficits in emotions,
attention and sensory functions, memory, communi-
cation, and motor functions. Currently, research in
the fields of music therapy, psychology, and cognitive
and affective neuroscience is beginning to merge, and
now there are ongoing multidisciplinary studies in
many countries aimed toward determining the clinical
impact of music and uncovering its underlying neural
mechanisms. In the future, especially large-scale and
high-quality RCTs that combine both reliable and
valid behavioral outcome measures and modern psy-
chophysiological and neuroimaging measures would
be optimal and highly valuable in this regard. Another
topic, which is becoming more and more important
with the recent development of portable music players
and the increasing popularity of communal musical
hobbies, is the long-term impact of self-directed musi-
cal leisure activities (such as music listening and choir
Volume 4, July/August 2013
 WIREs Cognitive Science
singing) on health and well-being, especially in elderly
persons. In summary, although the research field is
still relatively young and more studies are still needed,
music can be considered as a viable and promising
REFERENCES
1. Conard NJ, Malina M, Münzel SC. New flutes doc-
ument the earliest musical tradition in southwestern
Germany. Nature 2009, 460:737–740.
2. Mithen S. The Singing Neanderthals: The Origins of
Music, Language, Mind and Body. London: Weidenfeld
& Nicolson; 2005.
3. Kraus N, Chandrasekaran B. Music training for the
development of auditory skills. Nat Rev Neurosci 2010,
11:599–605.
4. LeDoux J. Emotion circuits in the brain. Annu Rev
Neurosci 2000, 23:155–184.
5. Hall DA, Hart HC, Johnsrude IS. Relationships between
human auditory cortical structure and function. Audiol
Neurootol 2003, 8:1–18.
6. Zatorre RJ, Belin P, Penhune VB. Structure and func-
tion of auditory cortex: music and speech. Trends Cogn
Sci 2002, 6:37–46.
7. Janata P, Birk JL, Van Horn JD, Leman M, Till-
mann B, Bharucha JJ. The cortical topography of tonal
structures underlying Western music. Science 2002,
298:2167–2170.
8. Patel AD. Language, music, syntax and the brain. Nat
Neurosci 2003, 6:674–681.
9. Zatorre RJ, Evans AC, Meyer E. Neural mechanisms
underlying melodic perception and memory for pitch.
J Neurosci 1994, 14:1908–1919.
10. Janata P, Tillmann B, Bharucha JJ. Listening to poly-
phonic music recruits domain-general attention and
working memory circuits. Cogn Affect Behav Neurosci
2002, 2:121–140.
11. Janata P. The neural architecture of music-evoked
autobiographical memories. Cereb Cortex 2009,
19:2579–2594.
12. Platel H, Baron JC, Desgranges B, Bernard F, Eustache
F. Semantic and episodic memory of music are sub-
served by distinct neural networks. Neuroimage 2003,
20:244–256.
13. Blood AJ, Zatorre RJ. Intensely pleasurable responses
to music correlate with activity in brain regions impli-
cated in reward and emotion. Proc Natl Acad Sci U S
A 2001, 98:11818–11823.
14. Koelsch S. Towards a neural basis of music-evoked
emotions. Trends Cogn Sci 2010, 14:131–137.
15. Salimpoor VN, Benovoy M, Larcher K, Dagher A,
Zatorre RJ. Anatomically distinct dopamine release
Volume 4, July/August 2013 © 2013 John Wiley & Sons, Ltd.
Music perception and cognition
nonpharmacological form of treatment and rehabili-
tation and, more generally, as an enriching and useful
hobby that can shape the development and maintain
the healthy functioning of the brain across life.
during anticipation and experience of peak emotion
to music. Nat Neurosci 2011, 14:257–262.
16. Grahn JA, Rowe JB. Feeling the beat: premotor and stri-
atal interactions in musicians and nonmusicians during
beat perception. J Neurosci 2009, 29:7540–7548.
17. Zatorre RJ, Chen JL, Penhune VP. When the brain plays
music: auditory-motor interactions in music perception
and production. Nat Rev Neurosci 2007, 8:547–558.
18. Peretz I. The nature of music from a biological perspec-
tive. Cognition 2006, 100:1–32.
19. Stewart L, von Kriegstein K, Warren JD, Griffiths TD.
Music and the brain: disorders of musical listening.
Brain 2006, 129:2533–2553.
20. Foxton JM, Dean JL, Gee R, Peretz I, Griffiths TD.
Characterization of deficits in pitch perception underly-
ing ‘tone deafness’. Brain 2004, 127:801–810.
21. Henry MJ, McAuley JD. On the prevalence of congeni-
tal amusia. Music Percept 2010, 27:413–418.
22. Peretz I, Cummings S, Dubé MP. The genetics of con-
genital amusia (tone deafness): a family-aggregation
study. Am J Hum Genet 2007, 81:582–588.
23. Drayna D, Manichaikul A, de Lange M, Snieder H,
Spector T. Genetic correlates of musical pitch recogni-
tion in humans. Science 2001, 291:1969–1972.
24. Särkämö T, Tervaniemi M, Soinila S, Autti T, Silven-
noinen HM, Laine M, Hietanen M. Cognitive deficits
associated with acquired amusia after stroke: a neu-
ropsychological follow-up study. Neuropsychologia
2009, 47:2642–2651.
25. Ayotte J, Peretz I, Rousseau I, Bard C, Bojanowski M.
Patterns of music agnosia associated with middle cere-
bral artery infarcts. Brain 2000, 123:1926–1938.
26. Hyde KL, Lerch JP, Zatorre RJ, Griffiths TD, Evans
AC, Peretz I. Cortical thickness in congenital amu-
sia: when less is better than more. J Neurosci 2007,
27:13028–13032.
27. Hyde KL, Zatorre RJ, Peretz I. Functional MRI evidence
of an abnormal neural network for pitch processing in
congenital amusia. Cereb Cortex 2011, 21:292–299.
28. Loui P, Alsop D, Schlaug G. Tone deafness: a
new disconnection syndrome? J Neurosci 2009, 29:
10215–10220.
29. Peretz I, Coltheart M. Modularity of music processing.
Nat Neurosci 2003, 6:688–691.
449
 Advanced Review
30. Patel AD, Iversen JR, Wassenaar M, Hagoort P. Musi-
cal syntactic processing in agrammatic Broca’s aphasia.
Aphasiology 2008, 22:776–789.
31. Liu F, Patel AD, Fourcin A, Stewart L. Intonation
processing in congenital amusia: discrimination, identi-
fication and imitation. Brain 2010, 133:1682–1693.
32. Trehub SE. The developmental origins of musicality.
Nat Neurosci 2003, 6:669–673.
33. Nakata T, Trehub S. Infants’ responsiveness to mater-
nal speech and singing. Infant Behav Dev 2004,
27:455–464.
34. Zentner M, Eerola T. Rhythmic engagement with music
in infancy. Proc Natl Acad Sci U S A 2010, 107:
5768–5773.
35. Angelucci F, Fiore M, Ricci E, Padua L, Sabino A,
Tonali PA. Investigating the neurobiology of music:
brain-derived neurotrophic factor modulation in the
hippocampus of young adult mice. Behav Pharmacol
2007, 18:491–496.
36. Bose M, Muñoz-Llancao P, Roychowdhury S, Nichols
JA, Jakkamsetti V, Porter B, Byrapureddy R, Salgado
H, Kilgard MP, Aboitiz F, et al. Effect of the environ-
ment on the dendritic morphology of the rat auditory
cortex. Synapse 2010, 64:97–110.
37. Hyde KL, Lerch J, Norton A, Forgeard M, Winner E,
Evans AC, Schlaug G. Musical training shapes structural
brain development. J Neurosci 2009, 29:3019–3025.
38. Schellenberg EG. Music lessons enhance IQ. Psychol Sci
2004, 15:511–514.
39. Moreno S, Bialystok E, Barac R, Schellenberg EG,
Cepeda NJ, Chau T. Short-term music training enhances
verbal intelligence and executive function. Psychol Sci
2011, 22:1425–1433.
40. Milovanov R, Tervaniemi M. The interplay between
musical and linguistic aptitudes: a review. Front Psychol
2011, 2:321.
41. Besson M, Chobert J, Marie C. Transfer of training
between music and speech: common processing, atten-
tion, and memory. Front Psychol 2011, 2:94.
42. Saarikallio S, Erkkilä J. The role of music in adolescents’
mood regulation. Psychol Music 2007, 35:88–109.
43. Molnar-Szakacs I, Overy K. Music and mirror neurons:
from motion to ’e’motion. Soc Cogn Affect Neurosci
2006, 1:235–241.
44. Dunbar RI. The origin and subsequent evolution of lan-
guage. In: Christiansen MH, Kirby S, eds. Language
Evolution. Oxford: Oxford University Press; 2003,
219–234.
45. Saarikallio S. Music as emotional self-regulation
throughout adulthood. Psychol Music 2010, 39:
307–327.
46. Cohen A, Bailey B, Nilsson T. The importance of music
to seniors. Psychomusicology 2002, 18:89–102.
450 © 2013 John Wiley & Sons, Ltd.
wires.wiley.com/cogsci
47. Lundqvist LO, Carlsson F, Hilmersson P, Juslin PN.
Emotional responses to music: experience, expression,
and physiology. Psychol Music 2009, 37:61–90.
48. Maratos AS, Gold C, Wang X, Crawford MJ. Music
therapy for depression. Cochrane Database Syst Rev
2008, 1:CD004517.
49. Gold C, Solli HP, Krüger V, Lie SA. Dose-response
relationship in music therapy for people with serious
mental disorders: systematic review and meta-analysis.
Clin Psychol Rev 2009, 29:193–207.
50. Erkkilä J, Punkanen M, Fachner J, Ala-Ruona E, Pöntiö
I, Tervaniemi M, Vanhala M, Gold C. Individual music
therapy for depression: randomised controlled trial. Br
J Psychiatry 2011, 199:132–139.
51. Mössler K, Chen X, Heldal TO, Gold C. Music ther-
apy for people with schizophrenia and schizophrenia-
like disorders. Cochrane Database Syst Rev 2011,
12:CD004025.
52. Vink AC, Bruinsma MS, Scholten RJ. Music therapy
for people with dementia. Cochrane Database Syst Rev
2011, 3:CD003477.
53. Bradt J, Dileo C. Music for stress and anxiety reduction
in coronary heart disease patients. Cochrane Database
Syst Rev 2009, 2:CD006577.
54. Bradt J, Dileo C, Grocke D, Magill L. Music inter-
ventions for improving psychological and physical out-
comes in cancer patients. Cochrane Database Syst Rev
2011, 8:CD006911.
55. Bernatzky G, Presch M, Anderson M, Panksepp J. Emo-
tional foundations of music as a non-pharmacological
pain management tool in modern medicine. Neurosci
Biobehav Rev 2011, 35:1989–1999.
56. Cepeda MS, Carr DB, Lau J, Alvarez H. Music for pain
relief. Cochrane Database Syst Rev 2006, 2:CD004843.
57. McMahon E, Wintermark P, Lahav A. Auditory brain
development in premature infants: the importance of
early experience. Ann N Y Acad Sci 2012, 1252:17–24.
58. Hartling L, Shaik MS, Tjosvold L, Leicht R, Liang
Y, Kumar M. Music for medical indications in the
neonatal period: a systematic review of randomised
controlled trials. Arch Dis Child Fetal Neonatal Ed
2009, 94:F349–F354.
59. Okamoto H, Stracke H, Stoll W, Pantev C. Listening
to tailor-made notched music reduces tinnitus loudness
and tinnitus-related auditory cortex activity. Proc Natl
Acad Sci USA 2010, 107:1207–1210.
60. Abikoff H, Courtney ME, Szeibel PJ, Koplewicz HS.
The effects of auditory stimulation on the arithmetic
performance of children with ADHD and nondisabled
children. J Learn Disabil 1996, 29:238–246.
61. Hommel M, Peres B, Pollak P, Memin B, Besson G,
Gaio JM, Perret J. Effects of passive tactile and auditory
stimuli on left visual neglect. Arch Neurol 1990, 47:
573–576.
Volume 4, July/August 2013
 WIREs Cognitive Science
62. Soto D, Funes MJ, Guzmán-García A, Warbrick
T, Rotshtein P, Humphreys GW. Pleasant music over-
comes the loss of awareness in patients with visual
neglect. Proc Natl Acad Sci U S A 2009, 106:
6011–6016.
63. Greene CM, Bahri P, Soto D. Interplay between affect
and arousal in recognition memory. PLoS One 2010,
5:e11739.
64. Jäncke L, Sandmann P. Music listening while you learn:
no influence of background music on verbal learning.
Behav Brain Funct 2010, 6:3.
65. Irish M, Cunningham CJ, Walsh JB, Coakley D, Lawlor
BA, Robertson IH, Coen RF. Investigating the enhanc-
ing effect of music on autobiographical memory in
mild Alzheimer’s disease. Dement Geriatr Cogn Disord
2006, 22:108–120.
66. Foster NA, Valentine ER. The effect of auditory stim-
ulation on autobiographical recall in dementia. Exp
Aging Res 2001, 27:215–228.
67. Simmons-Stern NR, Budson AE, Ally BA. Music as a
memory enhancer in patients with Alzheimer’s disease.
Neuropsychologia 2010, 48:3164–3167.
68. Baird A, Samson S. Memory for music in Alzheimer’s
disease: unforgettable? Neuropsychol Rev 2009, 19:
85–101.
69. Bruer RA, Spitznagel E, Cloninger CR. The tempo-
ral limits of cognitive change from music therapy in
elderly persons with dementia or dementia-like cogni-
tive impairment: a randomized controlled trial. J Music
Ther 2007, 44:308–328.
70. Bugos JA, Perlstein WM, McCrae CS, Brophy TS,
Bedenbaugh PH. Individualized piano instruction
enhances executive functioning and working memory
in older adults. Aging Ment Health 2007, 11:464–471.
71. Verghese J, Lipton RB, Katz MJ, Hall CB, Derby CA,
Kuslansky G, Ambrose AF, Sliwinski M, Buschke H.
Leisure activities and the risk of dementia in the elderly.
N Engl J Med 2003, 348:2508–2516.
72. Särkämö T, Tervaniemi M, Laitinen S, Forsblom
A, Soinila S, Mikkonen M, Autti T, Silvennoinen
HM, Erkkilä J, Laine M, et al. Music listening enhances
cognitive recovery and mood after middle cerebral
artery stroke. Brain 2008, 131:866–876.
FURTHER READING
Deutsch D, ed. The Psychology of Music. 3rd Edition. San Diego: Academic Press; 2013.
Hallam S, Cross I, Thaut M, eds. The Oxford Handbook of Music Psychology. Oxford: Oxford University Press; 2009.
Hannon EE, Trainor LJ. Music acquisition: effects of enculturation and formal training on development. Trends Cogn Sci
2007, 11:466–472.
Juslin PN, Sloboda J, eds. Handbook of Music and Emotion: Theory, Research, Applications. Oxford: Oxford University
Press; 2011.
Levitin DJ, Tirovolas AK. Current advances in the cognitive neuroscience of music. Ann N Y Acad Sci 2009, 1156:211–231.
Volume 4, July/August 2013 © 2013 John Wiley & Sons, Ltd.
Music perception and cognition
73. Särkämö T, Soto D. Music listening after stroke: bene-
ficial effects and potential neural mechanisms. Ann N Y
Acad Sci 2012, 1252:266–281.
74. Patel AD. Why would musical training benefit the neu-
ral encoding of speech? The OPERA hypothesis. Front
Psychol 2011, 2:142.
75. Gold C, Wigram T, Elefant C. Music therapy for autistic
spectrum disorder. Cochrane Database Syst Rev 2006,
2:CD004381.
76. Wan CY, Bazen L, Baars R, Libenson A, Zipse L,
Zuk J, Norton A, Schlaug G. Auditory-motor mapping
training as an intervention to facilitate speech output
in non-verbal children with autism: a proof of concept
study. PLoS One 2011, 6:e25505.
77. Schlaug G, Norton A, Marchina S, Zipse L, Wan CY.
From singing to speaking: facilitating recovery from
nonfluent aphasia. Future Neurol 2010, 5:657–665.
78. Bradt J, Magee WL, Dileo C, Wheeler BL, McGilloway
E. Music therapy for acquired brain injury. Cochrane
Database Syst Rev 2010, 7:CD006787.
79. McIntosh GC, Brown SH, Rice RR, Thaut MH. Rhyth-
mic auditory-motor facilitation of gait patterns in
patients with Parkinson’s disease. J Neurol Neurosurg
Psychiatry 1997, 62:22–26.
80. Hove MJ, Suzuki K, Uchitomi H, Orimo S, Miyake
Y. Interactive rhythmic auditory stimulation reinstates
natural 1/f timing in gait of Parkinson’s patients. PLoS
One 2012, 7:e32600.
81. Bernatzky G, Bernatzky P, Hesse HP, Staffen W,
Ladurner G. Stimulating music increases motor coor-
dination in patients afflicted with Morbus Parkinson.
Neurosci Lett 2004, 361:4–8.
82. Schneider S, Münte T, Rodriguez-Fornells A, Sailer
M, Altenmüller E. Music-supported training is more
efficient than functional motor training for recovery of
fine motor skills in stroke patients. Music Percept 2010,
27:271–280.
83. Rodriguez-Fornells A, Rojo N, Amengual JL, Ripollés
P, Altenmüller E, Münte TF. The involvement of audio-
motor coupling in the music-supported therapy applied
to stroke patients. Ann N Y Acad Sci 2012, 1252:
282–293.
451
 REVIEW ARTICLE
published: 18 February 2015
doi: 10.3389/fpsyg.2014.01185

Neurobiological foundations of neurologic music therapy:

rhythmic entrainment and the motor system
Michael H. Thaut1 *, Gerald C. McIntosh 2 and Volker Hoemberg 3
1
Center for Biomedical Research in Music, Colorado State University, Fort Collins, CO, USA
2
Department of Neurology, University of Colorado Health, Fort Collins, CO, USA
3
SRH Neurorehabilitation Hospital Bad Wimpfen, Bad Wimpfen, Germany

Edited by:
Fabien Gouyon, Instituto de
Engenharia de Sistemas e
Computadores – Tecnologia e Ciência,
Portugal
Reviewed by:
Robert J. Ellis, Beth Israel Deaconess
Medical Center, USA
Jaakko Erkkilä, University of
Jyväskylä, Finland
*Correspondence:
Michael H. Thaut, Center for
Biomedical Research in Music,
Colorado State University, Fort
Collins, CO, USA
e-mail: michael.thaut@colostate.edu
Entrainment is defined by a temporal locking process in which one system’s motion or
signal frequency entrains the frequency of another system. This process is a universal
phenomenon that can be observed in physical (e.g., pendulum clocks) and biological
systems (e.g., fire flies). However, entrainment can also be observed between human
sensory and motor systems. The function of rhythmic entrainment in rehabilitative training
and learning was established for the first time by Thaut and colleagues in several research
studies in the early 1990s. It was shown that the inherent periodicity of auditory rhythmic
patterns could entrain movement patterns in patients with movement disorders (see for
a review: Thaut et al., 1999). Physiological, kinematic, and behavioral movement analysis
showed very quickly that entrainment cues not only changed the timing of movement
but also improved spatial and force parameters. Mathematical models have shown that
anticipatory rhythmic templates as critical time constraints can result in the complete
specification of the dynamics of a movement over the entire movement cycle, thereby
optimizing motor planning and execution. Furthermore, temporal rhythmic entrainment
has been successfully extended into applications in cognitive rehabilitation and speech
and language rehabilitation, and thus become one of the major neurological mechanisms
linking music and rhythm to brain rehabilitation. These findings provided a scientific basis
for the development of neurologic music therapy.
Keywords: auditory rhythm, entrainment, music, neurologic music therapy, rehabilitation

PRINCIPLES OF ENTRAINMENT or movement periods when moving independently, but when

In 1666, the Dutch physicist Christian Huygens discovered that
the pendulum frequencies of two clocks mounted on the same
wall or board became synchronized to each other. He surmised
that the vibrations of air molecules would transmit small amounts
of energy from one pendulum to the other and synchronize
them to a common frequency. However, when set on different
surfaces the effect disappeared. The transmitting medium was
actually the vibrating board or wall. For air molecule vibrations
there would have been too much dampening in the process of
energy transmission, as was later discovered. The effect was sub-
sequently confirmed by many other experiments and was called
entrainment. In entrainment the different amounts of energy
transferred between the moving bodies due to the asynchronous
movement periods cause negative feedback. This feedback drives
an adjustment process in which the different energy amounts
are gradually eliminated to zero until both moving bodies move
in resonant frequency or synchrony. The stronger “oscillator”
locks the weaker into its frequency. When both oscillating bod-
ies have equally strong energy, both systems move toward each
other: the faster system slows down and the slower system
speeds up until they lock into a common movement period
(Pantaleone, 2002).
Technically, entrainment in physics refers to the frequency
locking of two oscillating bodies, i.e., bodies that can move in sta-
ble periodic or rhythmic cycles. They have different frequencies
interacting they assume a common period. Incidentally, Huy-
gens’ pendulums actually assumed a common period 180◦ out
of phase, which he called “odd sympathy.” It is now known
that entrainment can occur in various phase relationships of
the movement onsets of the oscillating bodies. A stable phase
relationship is achieved when both bodies start and stop their
movement period at the same time. However, this is not a nec-
essary prerequisite for entrainment to occur. The deciding factor
for entrainment is the common period of the oscillating move-
ments of the two bodies. The common period entrainment is of
critical importance for clinical applications of rhythmic entrain-
ment as a temporal cue in motor rehabilitation (Kugler and
Turvey, 1987; Thaut et al., 1998a). Common period entrainment
establishes that the rhythmic cue provides a continuous time
reference during the complete duration of the movement to be
regulated.
AUDITORY SYSTEM AND TIME PERCEPTION
The importance of the auditory system in the control of move-
ment was traditionally given much lesser attention in motor
control theory and research than the visual or propriocep-
tive system. Therefore, auditory rhythm and more complex
auditory time structures associated with musical patterns were
not give much functional value in motor learning or motor
rehabilitation. Consequently, application to motor therapies

www.frontiersin.org February 2015 | Volume 5 | Article 1185 | 1

Thaut et al.
played no role in traditional music therapy. Music was assigned
mostly a motivational role for movement performance (Thaut,
2005).
However, basic neurophysiology and biophysics of sensori-
motor connectivity have always shown intriguing interactions
between the auditory and the motor system. The ability of
the auditory system to rapidly construct stable temporal tem-
plates is well known (see for a review: Thaut and Kenyon,
2003). The auditory system is superbly constructed to detect
temporal patterns in auditory signals with extreme precision
and speed, as required by the nature of sound as only exist-
ing in temporal vibration patterns (Moore, 2003). In those
tasks, the auditory system is faster and more precise than the
visual and tactile systems (Shelton and Kumar, 2010). Since
sound waves that are most important for speech and music
and other perceptual tasks are based on periodic motions that
repeat themselves in regularly recurring cycles, the auditory
system is also perceptually geared toward detecting and con-
structing rhythmic sound patterns. Finally, many studies have
now shown that auditory rhythmic cues can entrain motor
responses. For example, Thaut et al. (1998b) demonstrated that
finger and arm movements instantaneously entrain to the period
of a rhythmic stimulus (e.g., metronome beat) and stay locked
to the metronome frequency even when subtle tempo changes
are induced into the metronome that are consciously not per-
ceived. These findings have been confirmed by other studies (cf,
Large et al., 2002).
NEURAL ENTRAINMENT
The neural basis for auditory-motor entrainment is lesser under-
stood. Two early electrophysiological studies (Paltsev and Elner,
1967; Rossignol and Melvill Jones, 1976) showed how sound
signals and rhythmic music can prime and time muscle acti-
vation via reticulospinal pathways. It is now well-established
that the auditory system has richly distributed fiber connec-
tions to motor centers from the spinal cord upward on brain
stem, subcortical, and cortical levels (Koziol and Budding, 2009;
Schmahmann and Pandya, 2009; Felix et al., 2011). Although the
specific basis of neural entrainment mechanisms remains not fully
explored, several studies have at least been able to link neu-
ral oscillation patterns in the auditory system to the time and
frequency dynamics of rhythmic sound stimuli. Fujioka et al.
(2012) showed modulations in neuromagnetic beta oscillations
related to the rhythmic stimulus frequency in auditory areas,
motor areas (sensorimotor cortex, supplementary motor area)
as well as the inferior frontal gyrus and the cerebellum. Tier-
ney and Kraus (2013) demonstrated consistent neural responses
in the inferior colliculus (IC) synchronized to a rhythmic audi-
tory stimulus (the syllable “da”). The IC is an early auditory
pathway nucleus in the brain stem with rich projections to the
cerebellum via the dorsolateral pontine nuclei. Since the cere-
bellum is activated in sensorimotor synchronization tasks (cf.
Stephan et al., 2002; Grahn et al., 2011) and activations in dis-
tinct cerebellar regions correspond to different aspects of the
temporal dynamics of rhythmic synchronization (Thaut et al.,
2009b; Konoike et al., 2012) – such as pattern detection or track-
ing changes in rhythmic interval duration – the representation
Frontiers in Psychology | Auditory Cognitive Neuroscience
Rhythmic entrainment in neurorehabilitation
of timing information in the IC may be an important function
in auditory-to-motor transformations during rhythmic entrain-
ment. Finally, an MEG study by Tecchio et al. (2000) showed
amplitude changes in the M100 component of auditory evoked
field potential linearly entrained by changes in the rhythmic inter-
val durations, i.e., longer intervals were associated with higher
M100 intensities and vice versa. This entrainment pattern was
also observable during subliminal duration changes at 2% of the
absolute interval duration. However, the exact neural transmis-
sion mechanisms from auditory to motor centers have not been
fully explored.
Of greatest importance in the context of motor rehabilitation
was the finding that the injured brain can indeed access rhythmic
entrainment mechanisms. Early studies of gait training in hemi-
paretic stroke rehabilitation (Thaut et al., 1993, 1997), Parkinson’s
disease (Thaut et al., 1996; McIntosh et al., 1997), traumatic brain
injury (Hurt et al., 1998), and cerebral palsy (Thaut et al., 1998)
confirmed behaviorally the existence of rhythmic entrainment
processes in clinical populations. Studies extending entrainment
to hemiparetic arm rehabilitation followed closely (Whitall et al.,
2000; Thaut et al., 2002).
Rhythmic entrainment established the first testable motor the-
ory for the role of auditory rhythm and music in therapy. The
subsequent studies led to the need to codify and standardize
rhythmic-musical application for motor rehabilitation (Thaut,
2005; Thaut and Hoemberg, 2014). Theses techniques became the
initial foundation of the clinical repertoire of neurologic music
therapy.
TIMING BASED MOVEMENT OPTIMIZATION
The comprehensive effect of rhythmic entrainment on motor
control raises some important theoretical questions as to the
mechanisms modulating these changes. We know that firing rates
of auditory neurons, triggered by auditory rhythm and music,
entrain the firing patterns of motor neurons, thus driving the
motor system into different frequency levels. There are two addi-
tional mechanisms are of great clinical importance in regard to
entrainment. The first is that auditory stimulation primes the
motor system in a state of readiness to move. Priming increases
subsequent response quality.
The second, more specific aspect of entrainment refers to
the changes in motor planning and motor execution it cre-
ates. Rhythmic stimuli create stable anticipatory time scales or
templates. Anticipation is a critical element in improving move-
ment quality. Rhythm provides precise anticipatory time cues
for the brain to plan ahead and be ready. Furthermore, suc-
cessful movement anticipation is based on foreknowledge of the
duration of the cue period. During entrainment two movement
oscillators – in our case neurally based – of different peri-
ods entrain to a common period. In auditory entrainment the
motor period entrains to the period of the auditory rhythm.
Entrainment is always driven by frequency or period entrain-
ment – that is, the common periods may or may not be in
perfect phase lock (i.e., the onset of the motor response would
be perfectly synchronized to the auditory beat). Beat entrain-
ment is a commonly misunderstood concept. Entrainment is
not defined by beat or phase entrainment – it is defined by
February 2015 | Volume 5 | Article 1185 | 2
Thaut et al.
period entrainment (Large et al., 2002; Thaut and Kenyon, 2003;
Nozaradan et al., 2011).
Period entrainment offers the solution to why auditory rhythm
also changes the spatial kinematic and dynamic force measures
of muscle activation, e.g., as evidenced by smoothing of velocity
and acceleration profiles. Foreknowledge of the duration of the
movement period changes computationally everything in motor
planning for the brain. Velocity and acceleration are mathematical
time derivatives of movement position. Consider that a move-
ment cycle, e.g., of the wrist joint in reaching movements, consists
of a finite number of position coordinates (x,y,z) each associated
with a particular time (t) value during the movement period. If we
consider, for simplification, the position coordinate x (t) to be con-
tinuous rather than a discrete function of the following statements
can describe mathematically the relationship between position,
velocity, and acceleration without going into the mathematical
equation detail:
• The velocity v(t) at any time t is the first time derivative of
position x(t) and is equal to the numerical value of the slope of
the position curve at the time t.
• The acceleration a(t) at any time t is the second time derivative
of position x(t), the first time derivative of velocity v(t), and is
equal to the numerical value of the slope of the velocity curve
at time t.
• The position x at any time t is numerically equal to the area
under the velocity-time curve between zero and t.
• The velocity v at any time t is numerically equal to the area
under the acceleration-time curve between zero and t.
Given this background information and using an optimiza-
tion criterion, e.g., such as minimization of peak acceleration,
we can now show that the movement trajectory as a function of
time in three-dimensional space is completely determined as a
consequence of the optimization condition, i.e., the entire move-
ment cycle is fixed in time due to period entrainment. The fact
that an anticipatory temporal constraint on the movement period
(given by the stimulus period) results in a kinematically well-
defined optimization problem allows for a mathematical analysis
showing a complete specification of the three-dimensional coordi-
nates of a limb trajectory. In other words, reduction in trajectory
variability of the arm during a reaching movement or the knee
during a step cycle is a natural outcome of the rhythmic time
constraint.
In clinical language, by fixating movement time through a
rhythmic interval the brain’s internal timekeeper now has an
additional externally triggered timekeeper with a precise refer-
ence interval, a continuous time reference (CTR). This time
period presents time information to the brain at any stage of
the movement. The brain knows at any point of the move-
ment how much time has elapsed and how much time is
left, enabling enhanced anticipatory mapping and scaling of
optimal velocity and acceleration parameters across the move-
ment interval. The brain tries to optimize the movement
now by matching it to the given template. This process will
result not only in changes in movement speed but also in
smoother and less variable movement trajectories and mus-
cle recruitment. One can conclude that auditory rhythm, via
www.frontiersin.org
Rhythmic entrainment in neurorehabilitation
physiological period entrainment of the motor system, acts as
a forcing function to optimize all aspects of motor control.
Rhythm not only influences movement timing – time as the
central coordinative unit of motor control – but also modu-
lates patterns of muscle activation and control of movement in
space (Thaut et al., 1999). Rhythmic cues provide comprehen-
sive optimization information to the brain for re-programming
movement.
With this understanding of the underlying mechanisms of
entrainment it is clinically less important if the patients synchro-
nize their motor response exactly to the beat – it is important
that they entrain to the rhythmic period because the period tem-
plate contains the critical information to optimize motor planning
and motor execution. Research has indeed shown that the timing
of the motor response relative to the beat can fluctuate whereas
the movement period entrains very quickly and precisely to the
rhythmic period and the period entrainment is maintained dur-
ing frequency changes in the rhythmic stimulus interval (Thaut
et al., 1998b).
CLINICAL APPLICATIONS OF ENTRAINMENT
The insights from rhythmic auditory-motor studies led to a
complete re-conceptualization of the role of complex auditory
stimuli such as music for therapy and rehabilitation. Tradition-
ally, the role of music in therapy had been considered from
social science models as a stimulus for personal interpretation
in regard to well-being, emotional response, and social relation-
ship. Although these properties of music are also important for
therapeutic functions the new discoveries re-focused the role of
music as therapeutic stimulus on its structural properties shap-
ing sensory perception linked to motor function (de l’Etoile, 2010;
Altenmueller and Schlaug, 2013).
The early clinical findings have been replicated and extended
by a number of other research groups substantiating the existence
of rhythmic auditory-motor circuitry for entrainment in hemi-
paretic gait rehabilitation (Ford et al., 2007; Roerdink et al., 2007,
2011; Thaut et al., 2007; Spaulding et al., 2013). A large num-
ber of RAS-Studies have replicated and extended the beneficial
use of RAS for mobility in Parkinson’s disease (see for review:
deDreu et al., 2012).
After successful experiments entraining endogenous biologi-
cal rhythms of neural gait oscillators a new question emerged.
Can rhythmic entrainment also be applied to entrain whole body
movements, especially arm and hand movements that are not
driven by underlying biological rhythms? The answer was found
by turning functional upper extremity movements, which are usu-
ally discrete and non-rhythmic, into repetitive cyclical movement
units which now could be matched to rhythmic time cues. Several
clinical research studies have successfully investigated rhythmic
cuing for upper extremity for full body coordination, especially
in hemiparetic stroke rehabilitation (Luft et al., 2004; McCombe-
Waller et al., 2006; Schneider et al., 2007; Altenmueller et al., 2009;
Malcolm et al., 2009; Grau-Sanchez et al., 2013) and in children
with cerebral palsy (Peng et al., 2010; Wang et al., 2013).
The improvements in stroke arm rehabilitation were compa-
rable in size to data from research in constraint induced therapy
(CIT; Massie et al., 2009).
February 2015 | Volume 5 | Article 1185 | 3
Thaut et al.
MORE CLINICAL APPLICATIONS OF ENTRAINMENT
Rhythmic entrainment extends beyond motor control. Emerg-
ing research shows that speech rate control affecting intelli-
gibility, oral motor control, articulation, voice quality, and
respiratory strength may greatly benefit from rhythmic entrain-
ment using rhythm and music (Pilon et al., 1998; Wambaugh
and Martinez, 2000; Thaut et al., 2001; Natke et al., 2003;
Lim et al., 2013). Recent findings in aphasia rehabilitation
suggest that the rhythmic component in melodic intona-
tion therapy may be equally as important as the activation
of intact right hemispheric speech circuitry through singing
(Stahl et al., 2011).
Lastly, the potential of temporal entrainment of cognitive
function has only recently emerged as an important driver of
therapeutic change. The recognition that timing and sequenc-
ing also have a critical function in cognitive abilities (Conway
et al., 2009) has led to research investigating the potential role of
music and rhythm as cognitive rehabilitation technique. Sound
in music is inherently temporal and sequential and may serve as
a “scaffold” to bootstrap the representation of temporal sequen-
tial patterns in cognitive functions such as memory (Conway
et al., 2009). Bootstrapping non-musical information to the
rhythmic-melodic patterns of a musical “scaffold” may offer sev-
eral advantages to enhance deep encoding during acquisition
and retrieval in memory training. Music may cue the tempo-
ral order and sequencing of information. The rhythmic-melodic
contour may create a pattern structure unto which information
units can be mapped. The phrase structure of music patterns
may segment the total information units into a smaller set of
large chunks or overarching units thus reducing memory load
(Wallace, 1994). This last point may constitute a particular
advantage in music since musical mnemonics, such as short
songs, are usually composed by a small alphabet of pitches and
rhythmic motifs (Snyder, 2000). Large information units con-
structed of large alphabets (e.g., word lists, number tables) can
be mapped on a small pitch and rhythm alphabet which is
organized into redundant, repetitive, and anticipatory “mem-
ory units” reducing memory load and increasing deep encoding
(Thaut et al., 2009a).
FROM ENTRAINMENT TO COMPLEXITY
Neurologic music therapy techniques in cognitive and
speech/language rehabilitation are relying to a large extent on
the role of timing in music and rhythm. However, the dis-
covery that a musical element such as rhythm can be a very
effective driver of therapeutic learning and training, has led to
a new look to consider the therapeutic potential of all musical
elements within a framework of music perception and music
playing. In other words, rhythmic entrainment opened the
doors to shifting from predominantly interpretative models of
music in therapy to perceptual based models. Interpretative
applications of music in therapy remain important, especially
when psychosocial, affective/expressive, or associative long-term
memory goals become a functional focus of therapy. However,
research has now shown how the whole complexity of musi-
cal elements can be shaped into functional therapy. Perceptual
exercises built on melodic and harmonic patterns in music may
Frontiers in Psychology | Auditory Cognitive Neuroscience
Rhythmic entrainment in neurorehabilitation
be applied to train sustained, selective, divided, focused, and
alternating attention in clinical settings (Gardiner and Thaut,
2014). Music as a complex auditory language has been applied
to re-training auditory perception deficits and enhance speech
perception (Tierney and Kraus, 2013; Mertel, 2014). Special appli-
cations of music-based auditory perception training have been
used with cochlear-implant users (Mertel, 2014). In patients
with hemi-spatial visual neglect therapeutic exercises using music
listening and instrument playing that emphasize auditory and
visual focus on the neglect side have been shown to be success-
ful in reducing neglect (Hommel et al., 1990; Abiru et al., 2007;
Soto et al., 2009; Bodak et al., 2014). Finally, guided elementary
composition and improvisation exercises in music emphasizing
complexity thinking, decision making, problem solving, reason-
ing, affective evaluation, self-organization, comprehension, etc.
have been shown to be successful in improving executive func-
tion in persons with traumatic brain injury (Thaut et al., 2009b;
Hegde, 2014).
FRONTIERS FOR NEUROLOGIC MUSIC THERAPY
The discovery of entrainment for therapeutic purposes in the
early 1990s has led to a strong body of research evidence that
the periodicity of auditory rhythmic patterns could improve
movement patterns in patients with movement disorders. Motor
control theory and motor neurophysiology propose that changes
in motor patterns are due to priming of the motor system
and anticipatory rhythmic templates in the brain that allow for
optimal anticipation, motor planning, and execution with an
external rhythmic cue. The ability for the brain to use entrain-
ment to re-program the execution of a motor pattern has made
rhythmic entrainment an important tool in motor rehabilita-
tion (Thaut and Abiru, 2010; Thaut and McIntosh, 2014). More
recently, temporal rhythmic entrainment has been extended
into applications in cognitive rehabilitation and speech and lan-
guage rehabilitation, with emerging evidence that mechanisms
of rhythmic entrainment may be an essential tool for reha-
bilitation in all domains of neurologic music therapy (Thaut,
2010; Thaut and Hoemberg, 2014). The temporal structure
of music remains a central element in therapy and rehabilita-
tion. However, the discovery of rhythmic entrainment has also
opened the door to exploring the therapeutic mechanisms in
other elements of music such as melody and harmony, and
finally in the pattern structure of music as a complex audi-
tory language to stimulate and (re)-train complex cognitive
functions. Neurologic music therapy as a codified and stan-
dardized treatment model, currently comprising 20 techniques
in motor, speech/language, and cognitive rehabilitation, has
emerged and has been medically been accepted quite rapidly
over the past 15 years. However, since NMT was built on exist-
ing research data, the future shape of NMT will be dynamically
driven by continued research. One of the largest areas of ther-
apeutic need is in psychiatric rehabilitation. Emerging views
on the nature of mental illness, driven by new insights from
neuropsychiatric research, may allow a more focused exten-
sion of NMT techniques in the areas executive and psychosocial
function, attention, and memory to contribute to psychiatric
treatment.
February 2015 | Volume 5 | Article 1185 | 4
Thaut et al.
REFERENCES
Abiru, M., Mihara, Y., and Kikuchi, Y. (2007). The effects of neurologic music therapy
on hemispatial neglect in a hemiparetic stroke patient: a case study. Neurol. Med.
67, 88–94.
Altenmueller, E., Marco-Pallares, J., Muente, T. F., and Schneider, S. (2009).
Neural reorganization underlies improvement in stroke-induced motor dysfunc-
tion by music-supported therapy. Ann. N. Y. Acad. Sci. 1169, 395–405. doi:
10.1111/j.1749-6632.2009.04580.x
Altenmueller, E., and Schlaug, G. (2013). Neurobiological aspects of neurologic
music therapy. Music Med. 5, 210–216. doi: 10.1177/1943862113505328
Bodak, R., Malhotra, P., Bernardi, N. F., Cocchini, G., and Stewart, L. (2014).
Reducing chronic visuo-spatial neglect following right hemisphere stroke through
instrument playing. Front. Hum. Neurosci. 8:413. doi: 10.3389/fnhum.2014.00413
Conway, C. M., Pisoni, D. B., and Kronenberger, W. G. (2009). The importance of
sound for cognitive sequending abilities. Curr. Dir. Psychol. Sci. 18, 275–279. doi:
10.1111/j.1467-8721.2009.01651.x
deDreu, M. J., van der Wilk, A. S., Poppe, E., Kwakkel, G., and van Wegen, E. E.
(2012). Rehabilitation, exercise therapy and music in patients with Parkinson’s
disease: a meta-analysis of the effects of music-based movement therapy on walk-
ing ability, balance, and quality of life. Parkinsonism Relat. Disord. 18, 114–119.
doi: 10.1016/S1353-8020(11)70036-0
de l’Etoile, S. (2010). Neurologic music therapy: a scientific paradigm for clinical
practice. Music Med. 2, 78–84. doi: 10.1177/1943862110364232
Felix, R. A., Fridberger, A., Leijon, S., Berrebi, A. S., and Magnusson, A.
K. (2011). Sound rhythms are encoded by postinhibitory rebound spik-
ing in the superior paraolivary nucleus. J. Neurosci. 31, 12566–12578. doi:
10.1523/JNEUROSCI.2450-11.2011
Ford, M., Wagenaar, R., and Newell, K. (2007). The effects of auditory rhythms
and instruction on walking patterns in individuals post stroke. Gait Posture 26,
150–155. doi: 10.1016/j.gaitpost.2006.08.007
Fujioka, T., Trainor, L. J., Large, E. W., and Ross, B. (2012). Internalized timing of
isochronous sounds is represented in neuromagnetic beta oscillations. J. Neurosci.
32, 1791–1802. doi: 10.1523/JNEUROSCI.4107-11.2012
Gardiner, J. C., and Thaut, M. H. (2014). “Musical executive function training,” in
Oxford Handbook of Neurologic Music Therapy, eds M. H. Thaut and V. Hoemberg
(Oxford: Oxford University Press), 279–293.
Grahn, J. A., Henry, M. J., and McAuley, J. G. (2011). FMRI investigation of cross-
modal interactions in beat perception: audition primes vision but not vice versa.
Neuroimage 54, 1231–1243. doi: 10.1016/j.neuroimage.2010.09.033
Grau-Sanchez, J., Armengual, J. L., Rojo, N., Vecian de Las heras, M., Rubio, F.,
Altenmueller, E., et al. (2013). Plasticity in the sensorimotor cortex induced by
music-supported therapy in stroke patients: a TMS-study. Front. Hum. Neurosci.
7:494. doi: 10.3389/fnhum.2013.00494
Hegde, S. (2014). Music-based cognitive remediation therapy for patients with
traumatic brain injury. Front. Neurol. 5:34. doi: 10.3389/fneur.2014.00034
Hommel, M., Peres, B., Pollak, P., Memin, B., Besson, G., Gaio, J. M., et al. (1990).
Effects of passive tactile and auditory stimuli on left visual neglect. Arch. Neurol.
47, 573–576. doi: 10.1001/archneur.1990.00530050097018
Hurt, C. P., Rice, R. R., McIntosh, G. C., and Thaut, M. H. (1998). Rhythmic
auditory stimulation in gait training for patients with traumatic brain injury. J.
Music Ther. 35, 228–241. doi: 10.1093/jmt/35.4.228
Konoike, N., Kotozaki, Y., Miyachi, S., Miyauchi, C. M., Yomogida, Y., Akimoto, Y.,
et al. (2012). Rhythm information represented in the fronto-parieto-cerebellar
motor system. Neuroimage 63, 328–338. doi: 10.1016/j.neuroimage.2012.07.002
Koziol, L. F., and Budding, D. E. (2009). Suncortical Structures and Cogni-
tion: Implications for Neuropsychological Assessment. New York: Springer. doi:
10.1007/978-0-387-84868-6
Kugler, P. N., and Turvey, M. T. (1987). Information, Natural Law, and the Self-
Assembly of Rhythmic Movement. Hillside, NJ: Lawrence Erlbaum Assoc. Inc.
Large, E. W., Jones, M. R., and Kelso, J. A. S. (2002). Tracking simple and complex
sequences. Psychol. Res. 66, 3–17. doi: 10.1007/s004260100069
Lim, K., Kim, Y., Lee, H., Yoo, J., Hwang, J., Kim, J., et al. (2013). The therapeutic
effect of neurologic music therapy and speech language therapy in post-stroke
aphasic patients. Ann. Rehabil. Med. 37, 556–562. doi: 10.5535/arm.2013.
37.4.556
Luft, A. R., McCombe-Waller, S., and Whitall, J. (2004). Repetitive bilateral arm
training and motor cortex activation in chronic stroke: a randomized controlled
trial. JAMA 292, 1853–1861. doi: 10.1001/jama.292.15.1853
www.frontiersin.org
Rhythmic entrainment in neurorehabilitation
Malcolm, M. P., Massie, C., and Thaut, M. H. (2009). Rhythmic auditory-motor
entrainment improves hemiparetic arm kinematics during reaching movements.
Top. Stroke Rehabil. 16, 69–79. doi: 10.1310/tsr1601-69
Massie, C., Malcolm, M., Greene, D., and Thaut, M. H. (2009). Effects of
constraint-induced therapy on kinematic outcomes and compensatory move-
ment patterns: an exploratory study. Arch. Phys. Med. Rehabil. 90, 571–579. doi:
10.1016/j.apmr.2008.09.574
McCombe-Waller, S., Harris-Love, M., Liu, W., and Whitall, J. (2006). Temporal
coordination of the arms during bilateral simultaneous and sequential move-
ments in patients with chronic hemiparesis. Exp. Brain Res. 168, 450–454. doi:
10.1007/s00221-005-0235-3
McIntosh, G. C., Brown, S. H., Rice, R. R., and Thaut, M. H. (1997). Rhythmic
auditory-motor facilitation of gait patterns in patients with Parkinson’s disease.
J. Neurol. Neurosurg. Psychiatry 62, 122–126. doi: 10.1136/jnnp.62.1.22
Mertel, K. (2014). “Auditory perception training,” in Oxford Handbook of Neurologic
Music Therapy, eds M. H. Thaut and V. Hoemberg (Oxford: Oxford University
Press), 227–256.
Moore, B. C. J. (2003). Psychology of Hearing. New York: Elsevier.
Natke, U., Donath, T. M., and Kalveram, K. T. (2003). Control of voice fundamental
frequency in speaking versus singing. J. Acoust. Soc. Am. 113, 1587–1593. doi:
10.1121/1.1543928
Nozaradan, S., Peretz, I., Missal, M., and Mouraux, A. (2011). Tagging the
neuronal entrainment to beat and meter. J. Neurosci. 31, 10234–10240. doi:
10.1523/JNEUROSCI.0411-11.2011
Paltsev, Y. I., and Elner, A. M. (1967). Change in functional state of the segmental
apparatus of the spinal cord under the influence of sound stimuli and its role in
voluntary movement. Biophysics 12, 1219–1226.
Pantaleone, J. (2002). Synchronization of metronomes. Am. J. Phys. 70, 992–1000.
doi: 10.1119/1.1501118
Peng, Y., Lu, T., Wang, T., Chen, Y., Liao, H., Lin, K., et al. (2010). Immediate effects
of therapeutic music on loaded sit-to-stand movement in children with spastic
diplegia. Gait Posture 33, 274–278. doi: 10.1016/j.gaitpost.2010.11.020
Pilon, M., McIntosh, K. W., and Thaut, M. H. (1998). Auditory versus visual
timing cues as external rate control to enhance verbal intelligibility in mixed
spastic-ataxia dysarthric speakers: a pilot study. Brain Inj. 12, 793–803. doi:
10.1080/026990598122188
Roerdink, M., Bank, P. J. M., Peper, C., and Beek, P. J. (2011). Walking to the beat
of different drums: practical implications for the use of acoustic rhythms in gait
rehabilitation. Gait Posture 33, 690–694. doi: 10.1016/j.gaitpost.2011.03.001
Roerdink, M., Lamoth, C. J. C., Kwakkel, G., van Wieringen, P. C. W., and Beek, P.
J. (2007). Gait coordination after stroke: benefits of acoustically paced treadmill
walking. Phys. Ther. 87, 1009–1022. doi: 10.2522/ptj.20050394
Rossignol, S., and Melvill Jones, G. (1976). Audiospinal influences in man studied
by the H-reflex and its possible role in rhythmic movement synchronized to
sound. Electroencephalogr. Clin. Neurophysiol. 41, 83–92. doi: 10.1016/0013-
4694(76)90217-0
Schmahmann, J. D., and Pandya, D. N. (2009). Fiber Pathways of the Brain. Oxford:
Oxford University Press.
Schneider, S., Schoenle, P. W., Altenmueller, E., and Muente, T. (2007). Using
musical instruments to improve motor skill recovery following stroke. J. Neurol.
254, 1339–1346. doi: 10.1007/s00415-006-0523-2
Shelton, J., and Kumar, G. P. (2010). Comparison between auditory and visual single
reaction time. Neurosci. Med. 1, 30–32. doi: 10.4236/nm.2010.11004
Snyder, B. (2000). Music and Memory. Cambridge, MA: MIT Press.
Soto, D., Funes, M. J., Guzmán-García, A., Warbrick, T., Rotshtein, P., and
Humphreys, G. W. (2009). Pleasant music overcomes the loss of awareness in
patients with visual neglect. Proc. Natl. Acad. Sci. U.S.A. 106, 6011–6016. doi:
10.1073/pnas.0811681106
Spaulding, J., Barber, B., Colby, M., Cormack, B., Mick, T., and Jenkins, M. E. (2013).
Cueing and gait improvement among people with Parkinson’s disease: a meta-
analysis. Arch. Phys. Med. Rehabil. 94, 562–570. doi: 10.1016/j.apmr.2012.10.026
Stahl, B., Kotz, S. A., Henseler, I., Turner, R., and Geyer, S. (2011). Rhythm in
disguise: why singing may not hold the key to recovery from aphasia. Brain 134,
3083–3093. doi: 10.1093/brain/awr240
Stephan, K. M., Thaut, M. H., Wunderlich, G., Schicks, W., Tian, B., Tellmann, L.,
et al. (2002). Conscious and subconscious sensorimotor synchronization: pre-
frontal cortex and the influence of awareness. Neuroimage 15, 345–352. doi:
10.1006/nimg.2001.0929
February 2015 | Volume 5 | Article 1185 | 5
Thaut et al.
Tecchio, F., Salustri, C., Thaut, M. H., Pasqualetti, P., and Rossini, P. M. (2000).
Conscious vs unconscious adaptation: a MEG study of cerebral responses to
rhythmic auditory stimuli. Exp. Brain Res. 135, 222–220. doi: 10.1007/s0022100
00507
Thaut, M. H. (2005). Rhythm, Music, and the Brain: Scientific Foundations and
Clinical Applications. New York: Routledge.
Thaut, M. H. (2010). Neurologic music therapy in cognitive rehabilitation. Music
Percept. 27, 281–285. doi: 10.1525/mp.2010.27.4.281
Thaut, M. H., and Abiru, M. (2010). Rhythmic auditory stimulation in rehabilitation
of movement disorders: a review of current research. Music Percept. 27, 263–269.
doi: 10.1525/mp.2010.27.4.263
Thaut, M. H., Bin, T., and Azimi-Sadjadi, M. (1998a). Rhythmic finger-tapping
sequences to cosine-wave modulated metronome sequences. Hum. Mov. Sci. 17,
839–863. doi: 10.1016/S0167-9457(98)00031-1
Thaut, M. H., Miller, R. A., and Schauer, L. M. (1998b). Multiple synchronization
strategies in rhythmic sensorimotor tasks: phase vs. period adaptation. Biol.
Cybern. 79, 241–250. doi: 10.1007/s004220050474
Thaut, M. H., Gardiner, J. C., Holmberg, D., Horwitz, J., Kent, L., Andrews, G., et al.
(2009a). Neurologic music therapy improves executive function and emotional
adjustment in traumatic brain injury rehabilitation. Ann. N. Y. Acad. Sci. 1169,
406–416. doi: 10.1111/j.1749-6632.2009.04585.x
Thaut, M. H., Stephan, K. M., Wunderlich, G., Schicks, W., Tellmann, L., Herzog, H.,
et al. (2009b). Distinct cortico-cerebellar activations in rhythmic auditory motor
synchronization. Cortex 45, 44–53. doi: 10.1016/j.cortex.2007.09.009
Thaut, M. H., and Hoemberg, V. (2014). Oxford Handbook of Neurologic Music
Therapy. Oxford: Oxford University Press.
Thaut, M. H., Hurt, C. P., Dragan, D., and McIntosh, G. C. (1998). Rhythmic
entrainment of gait patterns in children with cerebral palsy. Dev. Med. Child
Neurol 40, 15.
Thaut, M. H., and Kenyon, G. P. (2003). Rapid motor adaptations to subliminal
frequency shifts in syncopated rhythmic sensorimotor synchronization. Hum.
Mov. Sci. 22, 321–338. doi: 10.1016/S0167-9457(03)00048-4
Thaut, M. H., Kenyon, G. P., Hurt, C. P., McIntosh, G. C., and Hoem-
berg, V. (2002). Kinematic optimization of spatiotemporal patterns in paretic
arm training with stroke patients. Neuropsychologia 40, 1073–1081. doi:
10.1016/S0028-3932(01)00141-5
Thaut, M. H., Kenyon, G. P., Schauer, M. L., and McIntosh, G. C. (1999). The
connection between rhythmicity and brain function. IEEE Eng. Med. Biol. 18,
101–108. doi: 10.1109/51.752991
Thaut, M. H., Leins, A., Rice, R. R., Kenyon, G. P., Argstatter, H., Fetter,
M., et al. (2007). Rhythmic auditory stimulation improves gait more than
NDT/Bobath training in near ambulatory patients early post stroke: a single-
blind randomized control trial. Neurorehabil. Neural Repair 21, 455–459. doi:
10.1177/1545968307300523
Thaut, M. H., and McIntosh, G. C. (2014). Neurologic music therapy in stroke
rehabilitation. Curr. Phys. Med. Rehabil. Rep. 2, 106–113. doi: 10.1007/s40141-
014-0049-y
Frontiers in Psychology | Auditory Cognitive Neuroscience
Rhythmic entrainment in neurorehabilitation
Thaut, M. H., McIntosh, G. C., McIntosh, K. W., and Hoemberg, V. (2001). Audi-
tory rhythmicity enhances movement and speech motor control in patients with
Parkinson’s disease. Funct. Neurol. 16, 163–172.
Thaut, M. H., McIntosh, G. C., Prassas, S. G., and Rice, R. R. (1993). The
effect of auditory rhythmic cuing on temporal stride and EMG patterns in
hemiparetic gait of stroke patients. Neurorehabil. Neural Repair 7, 9–16. doi:
10.1177/136140969300700103
Thaut, M. H., McIntosh, G. C., and Rice, R. R. (1997). Rhythmic facilitation of gait
training in hemiparetic stroke rehabilitation. J. Neurol. Sci. 151, 207–212. doi:
10.1016/S0022-510X(97)00146-9
Thaut, M. H., McIntosh, G. C., Rice, R. R., Miller, R. A., Rathbun, J., and Brault, J. M.
(1996). Rhythmic auditory stimulation in gait training with Parkinson’s disease
patients. Mov. Disord. 11, 193–200. doi: 10.1002/mds.870110213
Tierney, A., and Kraus, N. (2013). The ability to move to a beat is linked to the
consistency of neural responses to sound. J. Neurosci. 33, 14981–14988. doi:
10.1523/JNEUROSCI.0612-13.2013
Wallace, W. T. (1994). Memory for music – effect of melody on recall of text. J. Exp.
Psychol. Learn. Mem. Cogn. 20, 1471–1485. doi: 10.1037/0278-7393.20.6.1471
Wambaugh, J. L., and Martinez, A. L. (2000). Effects of rate and rhythm control
treatment on consonant production accuracy in apraxia of speech. Aphasiology
14, 851–871. doi: 10.1080/026870300412232
Wang, T. H., Peng, Y. C., Chen, Y. L., Lu, T. W., Liao, H. F., Tang, P. F., et al. (2013). A
home-based program using patterned sensory enhancement improves resistance
exercise effects for children with cerebral palsy: a randomized controlled trial.
Neurorehabil. Neural Repair doi: 10.1177/11545968313491001
Whitall, J., McCombe Waller, S., Silver, K. H., and Macko, R. F. (2000).
Repetitive bilateral arm training with rhythmic auditory cuing improves
motor function in chronic hemiparetic stroke. Stroke 31, 2390–2395. doi:
10.1161/01.STR.31.10.2390
Conflict of Interest Statement: The authors declare that the research was conducted
in the absence of any commercial or financial relationships that could be construed
as a potential conflict of interest.
Received: 04 June 2014; accepted: 29 September 2014; published online: 18 February
2015.
Citation: Thaut MH, McIntosh GC and Hoemberg V (2015) Neurobiological founda-
tions of neurologic music therapy: rhythmic entrainment and the motor system. Front.
Psychol. 5:1185. doi: 10.3389/fpsyg.2014.01185
This article was submitted to Auditory Cognitive Neuroscience, a section of the journal
Frontiers in Psychology.
Copyright © 2015 Thaut, McIntosh and Hoemberg. This is an open-access article
distributed under the terms of the Creative Commons Attribution License (CC BY).
The use, distribution or reproduction in other forums is permitted, provided the original
author(s) or licensor are credited and that the original publication in this journal is cited,
in accordance with accepted academic practice. No use, distribution or reproduction is
permitted which does not comply with these terms.
February 2015 | Volume 5 | Article 1185 | 6

Edited by:
Marta Bienkiewicz,
Aix-Marseille University, France
Reviewed by:
Yi-Huang Su,
Technical University of Munich,
Germany
Madeleine Hackney,
Atlanta VA Medical Center, USA;
Emory University, USA
*Correspondence:
Alfredo Raglio
alfredo.raglio@unipv.it
Specialty section:
This article was submitted to
Movement Disorders, a section of the
journal Frontiers in Neurology
Received: 07 June 2015
Accepted: 10 August 2015
Published: 31 August 2015
Citation:
Raglio A (2015) Music therapy
interventions in Parkinson’s disease:
the state-of-the-art.
Front. Neurol. 6:185.
doi: 10.3389/fneur.2015.00185
Frontiers in Neurology | www.frontiersin.org
OPINION
published: 31 August 2015
doi: 10.3389/fneur.2015.00185
Music therapy interventions
in Parkinson’s disease: the
state-of-the-art
Alfredo Raglio *
Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy
Keywords: relational music therapy, neurological music therapy, rehabilitation, rhythm, motor symptoms, non-
motor symptoms
Parkinson’s disease (PD) is a neurological disorder involving the progressive degeneration of the
dopaminergic system, which gives rise to movement-related dysfunctions (such as bradykinesia,
tremor, and rigidity) as well as other symptoms, mainly of cognitive and psychological nature. In
the latter case, mood disorders prevails frequently causing anxiety and depression in all phases of
the disease, sometimes even before the motor symptoms occur.
Aarsland and colleagues (1) report that 35% of the patients affected by PD present depression,
whereas Richard (2) states that anxiety is to be found in 40% of the cases.
The literature shows that playing and listening to music may modulate emotions, behaviors,
movements, communication, and cognitive factors, modifying the activity of the brain areas involved
in the perception and regulation of these aspects (3, 4).
Music can produce substantial effects on movement-related symptoms as well as psychological
ones in PD treatment. Concerning the first aspect, rhythm has a crucial role in rehabilitation,
enhancing connections between the motor and auditory systems (5).
Literature showed how a rhythmic auditory cues-based training can produce a compensation of
the cerebello-thalamo-cortical network leading to beneficial effects, for example, improving not only
speed and step length but also perceptual and motor timing abilities (6, 7).
Areas involving rhythm perception are closely related to those that regulate movement (such as
the premotor cortex, supplementary motor area, cerebellum, and basal ganglia – especially putamen)
(8–18). A study conducted with fMRI (19) shows that whereas a regular pulse (in contrast to an
irregular one) generally activates basal ganglia in a significant way, this is not the case in PD. Other
studies (7, 20) support the idea that external cues (in particular rhythmical cues) can modulate the
activity within the impaired timing system. This may mean that a regular rhythmic pulse stimulates
the putamen activity, facilitating movement and providing an input for sequential movements and
impaired automatized processes. Moreover, this could compensate for the lack of dopaminergic
stimulation.
Rhythm can be also perceived visually and through the tactile sense, but the reaction time of
the human auditory system is shorter by 20–50 ms, when compared to visual and tactile stimuli;
moreover, it has a stronger capacity of perceiving rhythm periodicity and structure (6). Therefore,
rhythm influences the kinetic system (through synchronization and adjustment of muscles to
auditory stimuli), facilitates movement synchronization, coordination, and regularization, and may
even produce an internal rhythm that persists in the absence of stimuli (21–23).
Many studies report that musical rhythm in PD treatment can improve gait (speed, frequency,
and step length), limbs coordination, postural control, and balance (7, 18, 24–36). In view of the
above, Neurologic Music Therapy (NMT) – especially Rhythmic Auditory Stimulation, one of its
techniques – characterizes this approach to the disease: NMT aims at enhancing sensory, cognitive,
and motor functions (as in PD treatment, in which specific rhythmic techniques can strengthen and
improve the rehabilitative process).
1 August 2015 | Volume 6 | Article 185
Raglio Music therapy in Parkinson’s rehabilitation

Studies pertaining to non-motor symptoms (e.g., psychological
aspects, such as anxiety or depression) are fewer in number, and
therefore results are less certain (24, 36–41). From this point
of view, music therapy approaches focused on the relationship
between music therapist and patient serve as interventions that
can produce substantial psychological improvements, creating
moments of empathetic relationship and emotional connection.
Sound is indeed an important means of communication, espe-
cially in a non-verbal context, promoting emotional expression
and regulation. In PD treatment, the music therapeutic approach
described above, based on free improvisation, is most assuredly
less used, or maybe less documented. Sound/music improvisation
can be considered as the main technique in the active music ther-
apy approaches (42). During the improvisation, music therapist
and patient interact freely using musical instruments, generally
without musical rules or themes.
Moreover, making, and listening to, music can be considered as
strong stimuli from the emotional point of view, playing an impor-
tant role in the activation of the limbic system and neuro-chemical
circuits (i.e., of the reward system) (43, 44).
A distinction between the relational and rehabilitative approach
is extremely important, not only to determine the type of inter-
vention but also to define the specific identity of the music
therapy approach. In the former, the music therapist aims at
building a relationship with the patient by means of inter-
action with melodic and rhythmical instruments and singing
(improvisation). This facilitates the expression and modulation
of patients’ emotions and promotes communication and empa-
thetic relationships. In the latter, the music therapist proposes
music-based exercises (in particular using rhythmical patterns)
to improve motor, cognitive, and sensory functions, generally
impaired by neurological damage. Although the two methods
are often mutually influenced, there is a substantial difference
in terms of goals, intervention models, techniques, and music
therapy training. From this perspective, I believe that research
should take these aspects into account, in order to focus on goals
more accurately, while maintaining the possibility of overlapping
the two approaches – making them complementary rather than
antithetical. Often literature does not consider the distinction
among these different music therapy approaches, defining every
experience as “music therapy.” In contrast to this, I believe that
the achievement of an adequate definition regarding different
types of intervention is necessary; it should also highlight different
theoretical and methodological bases and their different areas
of application. To this end, a recent article by Raglio and Oasi
(45) reports the main characteristics of music-based interventions,
deriving from an in-depth analysis of their related contents and of
literature.
Table 1 shows how clinical studies characterized by strong sci-
entific implications (Randomized Controlled Trials and Clinical
Controlled Trials) and based on rehabilitative treatments (not
on evaluating tasks in the presence of a musical stimulus) are
lacking in literature. The table summarizes the main effects pro-
duced on motor and non-motor symptoms and distinguishes the
various interventions in terms of different musical contents and
techniques.
In PD treatment based on NMT, it is important to understand
what specifically acts on the disease: it is unclear, for example,
whether the beat produces an effect by itself in neuromotor
rehabilitation or, in contrast, the effects are produced by music

TABLE 1 | Randomized Controlled Trials and Controlled Clinical Trials from PubMed database regarding Parkinson’s disease, including clinical studies
(based on rehabilitative treatments) in English.

Reference Motor outcomes Non-motor outcomes Subjects Interventions/duration Follow-up

n experimental
group + n
control group

(7) Improving in perceptual and
motor timing
(24) Improving over time in motor
function, cognitive function
(verbal memory, language, and
executive function and attention)
(25) Improving in functional gait,
balance, and freezing
(40) Slight improvement over time in
tremor
(41) Significant improvement in
bradykinesia
(34) Improving in gait parameters
(velocity, stride length and step
cadence)
Not evaluated
Slight improvement over time
quality of life
Not evaluated
Improving over time in mood
and anxiety; modest
improvement on quality of life
Improving over time in
emotional functions, activities
of daily living and quality of life
Not evaluated
15 + 20 Rhythmic auditory cueing (beat + superimposed Yes
familiar songs)/4 weeks (30 min/session,
3 sessions/week)
12 + 6 Ronnie Gardiner rhythm and music (music None
method uses music, rhythm, movements and
speech)/6 weeks (1 h/session, 2 sessions/week)
8+8 Rhythmic auditory stimulation (RAS)/6 weeks Yes
(45–60 min/session, 3 sessions/week)
18 + 18 Music relaxation/4 weeks (45 min/session, Yes
2 sessions/week)
16 + 16 Music therapy sessions (choral singing, voice Yes
exercise, rhythmic and free body movements, and
improvisational music therapy techniques)/
3 months (2 h/session, weekly sessions)
15 + 11 Rhythmic auditory stimulation (RAS) None
(beat + superimposed music)/3 weeks
(30 min/session, daily)

Search criteria: (“music” OR “music therapy” OR “rhythmic auditory stimulation”) AND “Parkinson.”

Frontiers in Neurology | www.frontiersin.org 2 August 2015 | Volume 6 | Article 185

Raglio
(that we can consider the sum and combination of rhythm,
melody, harmony, and other parameters) with a marked pulse (6).
In fact, if music is excluded from interventions as described in
many studies, we have to ask ourselves what then is the role of
music therapists; furthermore, should such rhythm-based inter-
ventions be considered as part of music therapy programs, or
rather simply as rehabilitative methods supported by rhythm,
given that music does not assume a crucial role.
Additional weak points of NMT studies are given by the small
sample size, the short duration of treatments and by the frequent
lack of medium and long-term assessment (follow-up).
Another consideration is connected with the possibility to
prove whether an effect produced during rehabilitation can persist
also in the absence of stimuli. In this sense, the aforementioned
studies conducted by Benjamin (21), Jackendoff (22), and Palmer
and Krumhansl (23) offer various starting points that should be
discussed in-depth, concerning the potential of the retrieval of
imagined rhythm/music components, even after the stimuli have
ceased or are absent (46).
A limited number of studies take the psychological outcome
into account; these studies propose techniques based on a rela-
tional approach, which aims to develop an empathetic communi-
cation with the patient through the medium of sound. In music
therapy, the active relational approach is based mainly on impro-
visation (42), and, from a practical standpoint, emphasizes the
chances of enhancing and synchronizing the patient’s movements.
When reviewing videotapes of the therapeutic sessions based on
this approach, it becomes clear that there are significant changes
in regularity and fluency of movement of the upper limbs that also
References
1. Aarsland D, Påhlhagen S, Ballard CG, Ehrt U, Svenningsson P. Depression
in Parkinson disease: epidemiology, mechanisms and management. Nat Rev
Neurol (2011) 8(1):35–47. doi:10.1038/nrneurol.2011.189
2. Richard IH. Anxiety disorders in Parkinson’s disease. Adv Neurol (2005)
96:42–55.
3. Hillecke T, Nickel A, Bolay HV. Scientific perspectives on music therapy. Ann
N Y Acad Sci (2005) 1060:271–82. doi:10.1196/annals.1360.020
4. Koelsch S. A neuroscientific perspective on music therapy. Ann N Y Acad Sci
(2009) 1169:374–84. doi:10.1111/j.1749-6632.2009.04592.x
5. Thaut MH. Rhythm, Music and the Brain: Scientific Foundations and Clinical
Applications. New York, NY: Taylor & Francis Group (2005).
6. Nombela C, Hughes LE, Owen AM, Grahn JA. Into the groove: can rhythm
influence Parkinson’s disease? Neurosci Biobehav Rev (2013) 37:2564–70. doi:
10.1016/j.neubiorev.2013.08.003
7. Benoit CE, Dalla Bella S, Farrugia N, Obrig H, Mainka S, Kotz SA. Musically
cued gait-training improves both perceptual and motor timing in Parkinson’s
disease. Front Hum Neurosci (2014) 8:494. doi:10.3389/fnhum.2014.00494
8. Bijsterbosch JD, Lee KH, Hunter MD, Tsoi DT, Lankappa S, Wilkinson ID, et al.
The role of the cerebellum in sub- and supraliminal error correction during
sensorimotor synchronization: evidence from fMRI and TMS. J Cogn Neurosci
(2011) 23(5):1100–12. doi:10.1162/jocn.2010.21506
9. Thaut MH, Stephan KM, Wunderlich G, Schicks W, Tellmann L, Her-
zog H, et al. Distinct cortico-cerebellar activations in rhythmic auditory
motor synchronization. Cortex (2009) 45(1):44–53. doi:10.1016/j.cortex.2007.
09.009
10. Grahn JA, Rowe JB. Feeling the beat: premotor and striatal interactions
in musicians and nonmusicians during beat perception. J Neurosci (2009)
29(23):7540–8. doi:10.1523/JNEUROSCI.2018-08.2009
11. Bengtsson SL, Ullén F, Ehrsson HH, Hashimoto T, Kito T, Naito E, et al.
Listening to rhythms activates motor and premotor cortices. Cortex (2009)
45(1):62–71. doi:10.1016/j.cortex.2008.07.002
Frontiers in Neurology | www.frontiersin.org
Music therapy in Parkinson’s rehabilitation
positively influence the patient’s sound/music production. The
music therapy relational approach in PD treatment is, therefore,
less usual but equally as important; it is, in fact, less performance-
centered and takes the patient’s personal expression into account,
thus allowing a dynamic calibration of the stimulus, through a
process of continuous regulation, combining and integrating the
physical and psychological components. Considerations emerg-
ing from the relational music therapeutic experience in PD treat-
ment emphasize the rhythmic component of improvisation, lead-
ing the patient into synchronization, at the same time maintaining
freedom of expression and a non-prescriptive approach based
on the free sonorous-music improvisation. This facilitates the
integration of psychological aspects (the empathetic relationship,
the regulation, and modulation of emotional expressions) with
motor functions (speed and fluency of movement, in particular
of the upper limbs).
Therefore, interventions that involve music can offer important
starting points in PD rehabilitation, effectively acting on motor,
as well as non-motor symptoms. In this sense, research should
increase the number of studies based on strong methodological
criteria, also including a clear description of the intervention –
whether it be relational or rehabilitating – a consistent and numer-
ically significant sample, in addition to more sensitive tools to
evaluate motor and psychological outcomes. In conclusion, a
stronger research methodology and a clearer definition of the
exact medium or parameter in music related to specific output
of rehabilitation are needed. This will allow the development of
adequate, and increasingly specific and effective music therapy
approaches.
12. Chen JL, Penhune VB, Zatorre RJ. Listening to musical rhythms recruits motor
regions of the brain. Cereb Cortex (2008) 18(12):2844–54. doi:10.1093/cercor/
bhn042
13. Grahn JA, Brett M. Rhythm and beat perception in motor areas of the brain.
J Cogn Neurosci (2007) 19(5):893–906. doi:10.1162/jocn.2007.19.5.893
14. Lewis PA, Miall RC. Distinct systems for automatic and cognitively controlled
time measurement: evidence from neuroimaging. Curr Opin Neurobiol (2003)
13(2):250–5. doi:10.1016/S0959-4388(03)00036-9
15. Mayville JM, Fuchs A, Ding M, Cheyne D, Deecke L, Kelso JA. Event-
related changes in neuromagnetic activity associated with syncopation and
synchronization timing tasks. Hum Brain Mapp (2001) 14(2):65–80. doi:10.
1002/hbm.1042
16. Schubotz RI, von Cramon DY. Interval and ordinal properties of sequences
are associated with distinct premotor areas. Cereb Cortex (2001) 11(3):210–22.
doi:10.1093/cercor/11.3.210
17. Ullén F, Bengtsson SL. Independent processing of the temporal and ordinal
structure of movement sequences. J Neurophysiol (2003) 90(6):3725–35. doi:10.
1152/jn.00458.2003
18. McIntosh GC, Brown SH, Rice RR, Thaut MH. Rhythmic auditory-motor facil-
itation of gait patterns in patients with Parkinson’s disease. J Neurol Neurosurg
Psychiatry (1997) 62(1):22–6. doi:10.1136/jnnp.62.1.22
19. Grahn JA. The role of the basal ganglia in beat perception: neuroimaging
and neuropsychological investigations. Ann N Y Acad Sci (2009) 1169:35–45.
doi:10.1111/j.1749-6632.2009.04553.x
20. Jahanshahi M, Jenkins IH, Brown RG, Marsden CD, Passingham RE, Brooks DJ.
Self-initiated versus externally triggered movements. I. An investigation using
measurement of regional cerebral blood flow with PET and movement-related
potentials in normal and Parkinson’s disease subjects. Brain (1995) 118:913–33.
doi:10.1093/brain/118.4.913
21. Benjamin WE. A theory of musical meter. Music Percept (1984) 1:355–413.
doi:10.2307/40285269
22. Jackendoff RS. A Generative Theory of Tonal Music. Cambridge, IN: MIT Press
(1983).
3 August 2015 | Volume 6 | Article 185
Raglio
23. Palmer C, Krumhansl CL. Mental representations for musical meter. J Exp Psy-
chol Hum Percept Perform (1990) 16:728–41. doi:10.1037/0096-1523.16.4.728
24. Pohl P, Dizdar N, Hallert E. The Ronnie Gardiner rhythm and music method – a
feasibility study in Parkinson’s disease. Disabil Rehabil (2013) 35(26):2197–204.
doi:10.3109/09638288.2013.774060
25. Kadivar Z, Corcos DM, Foto J, Hondzinski JM. Effect of step training
and rhythmic auditory stimulation on functional performance in Parkin-
son patients. Neurorehabil Neural Repair (2011) 25(7):626–35. doi:10.1177/
1545968311401627
26. Thaut MH, Abiru M. Rhythmic auditory stimulation in rehabilitation of move-
ment disorders: a review of current research. Music Percept (2010) 27:263–9.
doi:10.1525/MP.2010.27.4.263
27. Rochester L, Burn DJ, Woods G, Godwin J, Nieuwboer A. Does auditory
rhythmical cueing improve gait in people with Parkinson’s disease and cognitive
impairment? A feasibility study. Mov Disord (2009) 24(6):839–45. doi:10.1002/
mds.22400
28. Arias P, Cudeiro J. Effects of rhythmic sensory stimulation (auditory, visual)
on gait in Parkinson’s disease patients. Exp Brain Res (2008) 186(4):589–601.
doi:10.1007/s00221-007-1263-y
29. Satoh M, Kuzuhara S. Training in mental singing while walking improves gait
disturbance in Parkinson’s disease patients. Eur Neurol (2008) 60(5):237–43.
doi:10.1159/000151699
30. del Olmo MF, Cudeiro J. Temporal variability of gait in Parkinson disease:
effects of a rehabilitation programme based on rhythmic sound cues. Parkin-
sonism Relat Disord (2005) 11(1):25–33. doi:10.1016/j.parkreldis.2004.09.002
31. Lim I, van Wegen E, de Goede C, Deutekom M, Nieuwboer A, Willems A,
et al. Effects of external rhythmical cueing on gait in patients with Parkinson’s
disease: a systematic review. Clin Rehabil (2005) 19(7):695–713. doi:10.1191/
0269215505cr906oa
32. Bernatzky G, Bernatzky P, Hesse HP, Staffen W, Ladurner G. Stimulating music
increases motor coordination in patients afflicted with Morbus Parkinson.
Neurosci Lett (2004) 361(1–3):4–8. doi:10.1016/j.neulet.2003.12.022
33. Thaut MH, McIntosh KW, McIntosh GC, Hoemberg V. Auditory rhythmicity
enhances movement and speech motor control in patients with Parkinson’s
disease. Funct Neurol (2001) 16(2):163–72.
34. Thaut MH, McIntosh GC, Rice RR, Miller RA, Rathbun J, Brault JM. Rhythmic
auditory stimulation in gait training for Parkinson’s disease patients. Mov
Disord (1996) 11(2):193–200. doi:10.1002/mds.870110213
35. Hurt CP, Rice RR, McIntosh GC, Thaut MH. Rhythmic auditory stimulation
in gait training for patients with traumatic brain injury. J Music Ther (1998)
35(4):228–41. doi:10.1093/jmt/35.4.228
36. Miller RA, Thaut MH, McIntosh GC, Rice RR. Components of EMG symmetry
and variability in parkinsonian and healthy elderly gait. Electroencephalogr Clin
Neurophysiol (1996) 101(1):1–7. doi:10.1016/0013-4694(95)00209-X
Frontiers in Neurology | www.frontiersin.org
Music therapy in Parkinson’s rehabilitation
37. De Dreu MJ, van der Wilk AS, Poppe E, Kwakkel G, van Wegen EE. Reha-
bilitation, exercise therapy and music in patients with Parkinson’s disease: a
meta-analysis of the effects of music-based movement therapy on walking
ability, balance and quality of life. Parkinsonism Relat Disord (2012) 18:S114–9.
doi:10.1016/S13538020(11)700360
38. Elefant C, Baker FA, Lotan M, Lagesen SK, Skeie GO. The effect of group
music therapy on mood, speech, and singing in individuals with Parkinson’s
disease – a feasibility study. J Music Ther (2012) 49(3):278–302. doi:10.1093/
jmt/49.3.278
39. Hayashi A, Nagaoka M, Mizunu Y. Music therapy in Parkinson’s disease:
improvement of parkinsonian gait and depression with rhythmic auditory
stimulation. Parkinsonism Relat Disord (2006) 12(Suppl 2):S76. doi:10.1016/j.
parkreldis.2006.05.026
40. Craig LH, Svircev A, Haber M, Juncos JL. Controlled pilot study of the effects of
neuromuscular therapy in patients with Parkinson’s disease. Mov Disord (2006)
21(12):2127–33. doi:10.1002/mds.21132
41. Pacchetti C, Mancini F, Aglieri R, Fundarò C, Martignoni E, Nappi G. Active
music therapy in Parkinson’s disease: an integrative method for motor and emo-
tional rehabilitation. Psychosom Med (2000) 62:386–93. doi:10.1097/00006842-
200005000-00012
42. Gold C, Solli HP, Krüger V, Lie SA. Dose-response relationship in music
therapy for people with serious mental disorders: systematic review and
meta-analysis. Clin Psychol Rev (2009) 29(3):193–207. doi:10.1016/j.cpr.2009.
01.001
43. Koelsch S. Brain correlates of music-evoked emotions. Nat Rev Neurosci (2014)
15(3):170–80. doi:10.1038/nrn3666
44. Chanda ML, Levitin DJ. The neurochemistry of music. Trends Cogn Sci (2013)
17(4):179–93. doi:10.1016/j.tics.2013.02.007
45. Raglio A, Oasi O. Music and health: what interventions for what results? Front
Psychol (2015) 6:230. doi:10.3389/fpsyg.2015.00230
46. Schaefer RS, Morcom AM, Roberts N, Overy K. Moving to music: effects of
heard and imagined musical cues on movement-related brain activity. Front
Hum Neurosci (2014) 8:774. doi:10.3389/fnhum.2014.00774
Conflict of Interest Statement: The author declares that the research was con-
ducted in the absence of any commercial or financial relationships that could be
construed as a potential conflict of interest.
Copyright © 2015 Raglio. This is an open-access article distributed under the terms
of the Creative Commons Attribution License (CC BY). The use, distribution or
reproduction in other forums is permitted, provided the original author(s) or licensor
are credited and that the original publication in this journal is cited, in accordance with
accepted academic practice. No use, distribution or reproduction is permitted which
does not comply with these terms.
4 August 2015 | Volume 6 | Article 185

Edited and reviewed by:
Hauke R. Heekeren,
Freie Universität Berlin, Germany
*Correspondence:
Teppo Särkämö
teppo.sarkamo@helsinki.fi
Received: 17 December 2015
Accepted: 25 February 2016
Published: 09 March 2016
Citation:
Särkämö T, Altenmüller E,
Rodríguez-Fornells A and Peretz I
(2016) Editorial: Music, Brain, and
Rehabilitation: Emerging Therapeutic
Applications and Potential Neural
Mechanisms.
Front. Hum. Neurosci. 10:103.
doi: 10.3389/fnhum.2016.00103
Frontiers in Human Neuroscience | www.frontiersin.org
EDITORIAL
published: 09 March 2016
doi: 10.3389/fnhum.2016.00103
Editorial: Music, Brain, and
Rehabilitation: Emerging Therapeutic
Applications and Potential Neural
Mechanisms
Teppo Särkämö 1*, Eckart Altenmüller 2 , Antoni Rodríguez-Fornells 3, 4, 5 and
Isabelle Peretz 6, 7
1
Cognitive Brain Research Unit, Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland, 2 Institute of Music
Physiology and Musicians’ Medicine, University of Music, Drama and Media Hanover, Hanover, Germany, 3 Cognition and
Brain Plasticity Unit, Bellvitge Research Biomedical Institute, Barcelona, Spain, 4 Department of Basic Psychology, University
of Barcelona, Barcelona, Spain, 5 Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain, 6 International
Laboratory for Brain, Music, and Sound Research and Centre for Research on Brain, Language and Music, Montréal, QC,
Canada, 7 Department of Psychology, Université de Montréal, Montréal, QC, Canada
Keywords: music, cognition, movement, brain, neurological disorders, rehabilitation, neuroimaging
The Editorial on the research topic
Music, Brain, and Rehabilitation: Emerging Therapeutic Applications and Potential Neural
Mechanisms
Music is an important source of enjoyment, learning, and well-being in life as well as a rich,
powerful, and versatile stimulus for the brain. With the advance of modern neuroimaging
techniques during the past decades, we are now beginning to understand better what goes on in the
healthy brain when we listen, play, think, and feel music and how the structure and function of the
brain can change as a result of musical training and expertise. In the healthy brain, there is already
mounting evidence that a large-scale bilateral network of temporal, frontal, parietal, cerebellar,
and limbic/paralimbic brain areas associated with auditory perception, language, syntactic and
semantic processing, attention and working memory, semantic and episodic memory, rhythmic
and motor functions, and emotions and reward underlies the processing of music (Koelsch, 2011,
2014; Zatorre and Salimpoor, 2013; Janata, 2015) and to which extent this neural network could
be shaped by musical training (Kraus and Chandrasekaran, 2010; Herholz and Zatorre, 2012;
Brown et al., 2015). In the field of neurology, music has traditionally been studied in the context
of musical deficits (e.g., amusia; Peretz et al., 2003), music-related symptoms (e.g., musicogenic
epilepsy; Maguire, 2015), cases of exceptional or preserved musical functions (e.g., singing in
aphasia; Johnson and Graziano, 2015), and neurological disorders of professional musicians (e.g.,
musician’s dystonia; Altenmüller et al., 2015).
During the last decade, there has been increasing interest and progress in adopting music as
a therapeutic tool in neurological rehabilitation, and many novel music-based methods have been
developed to improve motor, cognitive, language, emotional, and social deficits in persons suffering
from a debilitating neurological illness, ranging from childhood and adolescence [e.g., autism
(Geretsegger et al., 2014), dyslexia (Flaugnacco et al., 2015)] to adulthood and old age [e.g., stroke
(Särkämö et al., 2008; Bradt et al., 2010; Rodríguez-Fornells et al., 2012; Altenmüller and Schlaug,
2015), Parkinson’s disease (Nombela et al., 2013; Bloem et al., 2015), and dementia (Vink et al.,
2011; Baird and Samson, 2015)]. Traditionally, the fields of music neuroscience and music therapy
1 March 2016 | Volume 10 | Article 103
Särkämö et al.
have progressed independently, providing separate lines of
evidence for how music is processed in the healthy brain and
how it can be used therapeutically. We are now finally reaching
a point where these fields are starting to merge and integrate,
providing novel and important information about how music is
processed in the damaged or abnormal brain, how structural and
functional recovery of the brain can be enhanced by music-based
rehabilitation methods, and what neural mechanisms underlie
the therapeutic effects of music (for a related discussion, see
Magee and Stewart). In the future, this information is pivotal
for increasing our understanding of how and why music works
in rehabilitation and for developing more effective music-based
applications that are better targeted at specific brain processes
and better tailored toward the individual rehabilitation needs of
patients.
With these goals in mind, we launched the current Research
Topic, jointly hosted by Frontiers in Human Neuroscience and
Frontiers in Auditory Cognitive Neuroscience, which aimed
to bring together research across multiple disciplines with a
special focus on music, brain, and neurological rehabilitation.
We invited researchers to present research addressing either
how musical skills and attributes, such as music perception,
experiencing music emotionally, or playing or singing, are
affected by a developmental or acquired neurological disorder
or what is the applicability, effectiveness, and mechanisms of
music-based rehabilitation methods in neurological patients.
We were delighted that our call was met with enthusiasm
and was answered by many research groups across the world,
resulting in altogether 27 papers published in Frontiers in
Human Neuroscience (21 papers) and Frontiers in Auditory
Cognitive Neuroscience (six papers). Twenty-three papers were
Original Research Articles, three were Reviews, and one was
a General Commentary. There were altogether 132 authors
from 14 countries (Australia, Canada, China, Cuba, Denmark,
Finland, France, Germany, Italy, Netherlands, Poland, Spain,
UK, and USA), providing an interesting cross-section to the
global state-of-the-art on research currently done in the field of
music, neuroscience, and neurorehabilitation. Broadly classified,
the papers focused on six core topics: (i) music and hearing
impairment; (ii) music, rhythm, and language; (iii) music,
rhythm, and movement; (iv) music, learning, and memory; (v)
responsiveness to music in severe neurological disorders; and (vi)
novel sound-based technological advances. Next, we will provide
a brief overview of these studies.
MUSIC AND HEARING IMPAIRMENT
Four papers presented novel research related to deafness and
cochlear implants (CIs), auditory prostheses that restore hearing
ability via electrical stimulation of the auditory nerve. Due to the
spectrotemporally degraded nature of the sound transmission, CI
users typically face many challenges in more complex listening
tasks, such as when perceiving music. Petersen et al. report an
EEG study where they compared adolescent, prelingually deaf CI
users and normal-hearing controls for their mismatch negativity
(MMN) responses to different auditory changes (pitch, timbre,
Frontiers in Human Neuroscience | www.frontiersin.org
Editorial: Music, Brain, and Rehabilitation
intensity, and rhythm) in a musical melodic context. Compared
to the healthy controls, the MMN responses were smaller in CI
users. Especially the MMN to pitch changes was diminished in CI
users, whereas they showed significant MMNs to timbre, rhythm,
and intensity changes. Using the same musical multi-feature
paradigm and EEG, Timm et al. compared adult CI users, who
were postlingually deafened and late-implanted, with normal-
hearing controls. The adult CI users showed abolished MMNs to
complex rhythmic changes as well as smaller and later MMNs
to pitch changes, whereas they elicited MMNs comparable
to controls for timbre and intensity changes. Together, these
findings indicate that although both pre- and postlingually
deaf CI users have clear pitch discrimination difficulties, their
brains are nevertheless able to extract more musically relevant
information from sound than previously thought, making music-
based interventions a viable tool for CI users.
The impact of musical training on auditory perceptual and
cognitive performance in deaf children (with CIs or hearing aids)
was studied by Rochette et al. Utilizing an innovative interactive
game, they compared auditory discrimination, identification,
scene analysis, and working memory as well as phonetic
discrimination between deaf children who had previously
received music lessons for 1.5–4 years and control deaf children
who had not received music lessons. The musically trained
children showed better performance in auditory scene analysis,
auditory working memory, and phonetic discrimination tasks
than the non-trained children, suggesting that musical training
in deaf children contributes to the development of auditory
attention and perception, which, in turn, can facilitate auditory-
related cognitive and linguistic skills. The link between musical
training and perception of degraded pitch was also studied by
Fuller et al. They compared normal hearing musicians and non-
musicians on tasks involving speech, vocal emotion, and melodic
contour identification under normal and CI simulation listening
conditions. Better performance in musicians was observed for
vocal emotion and melodic contour identification in both
conditions and for word identification only in the CI condition.
Overall, this musician effect was stronger as the importance of
pitch in the task increased, suggesting that musical training can
be beneficial especially for challenging pitch perception, as in the
case of the CI.
MUSIC, RHYTHM, AND LANGUAGE
The close linkage between music, rhythm, and language,
especially in the context of reading and speech production
impairments, was explored in four papers. Flaugnacco et al.
evaluated a group of dyslexic children with an extensive
battery of neuropsychological tests, phonological tasks, and
psychoacoustic and musical tasks. Results indicated a strong link
between several temporal skills, such as meter perception and
rhythm reproduction, and phonological and reading abilities,
encouraging the use of music training, especially focused on
rhythm, as rehabilitative tool in dyslexic children. Zumbansen
et al. performed a cross-over study in three stroke patients with
Broca’s aphasia aimed at evaluating the relative contribution
2 March 2016 | Volume 10 | Article 103
Särkämö et al.
of rhythm and pitch on the effectiveness of melodic intonation
therapy (MIT), a structured singing-based rehabilitation protocol
for aphasia. They assessed connected speech, speech accuracy
of trained and non-trained sentences, motor-speech agility, and
mood before and after receiving melodic therapy (with pitch
and rhythm), rhythmic therapy (with rhythm only), and normal
spoken therapy. The results showed that whereas all treatments
improved speech accuracy in trained sentences, the melodic
therapy elicited the strongest generalization effect both to non-
trained stimuli and to connected speech, underscoring the
importance of both rhythm and pitch components in MIT.
The roles of the different components of MIT and its
underlying mechanisms were also discussed by Merrett et al. In
their comprehensive review of MIT literature, they identified
four mechanisms potentially underlying the efficacy of MIT:
neuroplastic reorganization of language function, activation
of the mirror neuron system and multimodal integration,
utilization of shared or specific features of music and language,
and motivation and mood. These mechanisms are not mutually
exclusive, but reflect the neurobiological, cognitive, and
emotional effects of MIT, and together contribute to the efficacy
of the therapy. Fujii and Wan reviewed studies about the role
of rhythm in music and in speech perception and production
and their rehabilitation. With an aim of explaining how and why
musical rhythm can benefit speech and language rehabilitation,
they propose a novel SEP hypothesis postulating that “sound
envelope processing” and “synchronization and entrainment to
pulse” may help stimulate different brain networks, including
auditory afferent, subcortical-prefrontal, striato-thalamo-
cortical, and cortical motor efferent circuits, which underlie
human communication.
MUSIC, RHYTHM, AND MOVEMENT
Five papers discussed the links between music, rhythm, and
movement in the healthy brain and in Parkinson’s disease (PD)
and stroke patients. Using fMRI in healthy subjects, Schaefer et al.
studied how imagined or musical cueing changes the way the
motor system is activated during simple movements. Moving to
real music increased the activation in specific cerebellar areas
whereas moving to imagined music activated especially pre-
supplementary and basal ganglia motor areas, indicating that
these two types of cueing have a different neural basis. Leow
et al. explored the impact of different auditory cues, varying
in their beat salience and musical nature, on the ability to
synchronize one’s movements to the auditory rhythm. In a
behavioral experiment, they showed that high-groove music
was superior to low-groove music in synchronizing gait and
in eliciting longer and faster steps and that low-groove music
was particularly detrimental to gait in weak beat-perceivers,
indicating that both beat salience and beat perception skills are
important mediators in movement cueing.
Auditory cueing can improve gait in PD patients (Nombela
et al., 2013; Bloem et al., 2015). Benoit et al. extended this finding
by determining whether auditory-cued gait training with music
can facilitate both motor and perceptual timing in PD patients.
Frontiers in Human Neuroscience | www.frontiersin.org
Editorial: Music, Brain, and Rehabilitation
Indeed, the training was shown to enhance patients’ performance
in both motor timing (movement synchronization, tapping) and
in perceptual timing (duration discrimination, beat detection in
music) tasks, supporting the idea that coupling gait to rhythmic
auditory cues in PD relies on a neuronal network engaged in both
perceptual and motor timing. In their Commentary, Mattei et al.
also discuss the role of motor, cognitive, and speech networks on
emotion recognition through music in PD.
Music-supported training (MST) using musical instruments
can improve motor recovery of arm movements after stroke
(Rodríguez-Fornells et al., 2012; Altenmüller and Schlaug, 2015).
Van Vugt et al. extended the application of MST to the social
domain by comparing stroke patients who played synchronously
(together group) and who played one after the other (in-turn
group). Both groups showed improvements in fine motor control
and tapping and reductions in depression and fatigue, but
the in-turn group showed greater improvement in fine motor
skills, suggesting that stroke patients may benefit from learning
through observation in MST. In two stroke patients with chronic
unilateral spatial neglect, Bodak et al. assessed the impact of a
music intervention that involved making sequential goal-directed
actions in the neglected space by playing scales and melodies
on chime bars from right to left. The patients demonstrated
short- and long-term improvement on visual cancelation tasks,
indicating that active music-making with a horizontally aligned
instrument may help neglect patients attend more to their
affected side.
MUSIC, LEARNING, AND MEMORY
The interactions between music and learning and memory were
explored in older adults and in patients with medial temporal
lobe damage, multiple sclerosis (MS), stroke, and Alzheimer’s
disease (AD) in six papers. Using fNIRS, Ferreri et al. investigated
whether music listening can improve episodic memory and
modulate prefrontal cortex (PFC) activity during memory
encoding in older adults. Compared to a silent background,
upbeat music facilitated source-memory performance, and
decreased dorsolateral PFC activity bilaterally, suggesting music
can help older adults in memory encoding by modulating
prefrontal activity in a non-demanding fashion. The long-
term neural impact of music listening on stroke recovery was
studied by Särkämö et al. Using voxel-based morphometry, they
showed that compared to verbal stimuli (audio books) and
standard rehabilitation, listening to music daily after an acute left
hemisphere stroke increased gray matter volume in a network of
prefrontal (superior frontal gyrus) and limbic (anterior cingulate
cortex, ventral striatum) areas linked to better cognitive and
emotional recovery. The results suggest that a musically enriched
recovery environment can induce fine-grained neuroanatomical
changes in the recovering brain.
The use of music as a mnemonic aid in MS and AD patients
was investigated by two groups. In a behavioral and EEG study,
Thaut et al. compared the learning of spoken and musical (sung)
word lists in MS patients. Compared to the spoken condition,
patients in the music condition showed overall better verbal
3 March 2016 | Volume 10 | Article 103
Särkämö et al.
recall and better word order memory coupled with stronger
bilateral learning-related frontal synchronization, suggesting
that a musical mnemonic recruits stronger oscillatory network
synchronization in prefrontal areas in MS patients during word
learning. Moussard et al. explored the potential of music to
facilitate motor learning in healthy older adults and AD patients.
The participants learned sequences of meaningless gestures
accompanied either by music or metronome and done either
in synchrony with the experimenter or after the experimenter.
In healthy controls, musical accompaniment had no impact but
synchronization helped learning. In contrast, in AD patients,
musical accompaniment improved learning but synchronization
interfered with retention, indicating that music may act as a
mnemonic for motor sequence learning in AD.
Music-related learning in patients with medial temporal
lobe damage and memory impairments was also studied by
two groups. Using fMRI, Alonso et al. tested the modulatory
influence of the hippocampus on neural adaptation to song
melodies and lyrics. Compared to healthy controls, patients
with left hippocampal sclerosis showed reduced adaptation
effects to repeated lyrics and melodies in lateral temporal lobe
regions, indicating that the integrated representation of lyrics and
melodies is likely tied to the integrity of the left medial temporal
lobe. Valtonen et al. present a case study of learning novel
musical pieces by patient LSJ who was a skilled amateur violist
before becoming profoundly amnesic after extensive bilateral
hippocampal and medial temporal lobe damage caused by
encephalitis. Three novel pieces of viola music were introduced,
two of which LJS practiced playing and one which LJS did not
train. Relative to the control piece, LSJ showed significant pre-
to post-training improvement in the practiced pieces, which was
retained in a longitudinal follow-up. These findings demonstrate
that non-hippocampal structures can support complex musical
learning.
RESPONSIVENESS TO MUSIC IN
NEUROLOGICAL DISORDERS
The emotional and cognitive responsiveness to music in children
with severe neurological illness, adults with autism spectrum
disorder (ASD), and patients with a disorder of consciousness
(DOC) were explored in four papers. Using behavioral measures
and EEG, Bringas et al. studied the effects of a music
therapy program focusing on attention and communication
training through music in children with severe neurological
illness (e.g., cerebral palsy). Compared to a control group
receiving standard rehabilitation, the music therapy group
improved on neuropsychological status, especially on attention
and communication, coupled with neuroplasticity indexed by
an enhanced MMN response to phonemic changes in frontal
and cingulate regions. Using fMRI, Gebauer et al. investigated
the neural correlates of emotion recognition in music in high-
functioning adults with ASD and healthy controls. Although
both groups engaged similar neural networks during processing
of emotional music, ASD individuals showed increased activity
to happy vs. sad music in dorsolateral PFC and in rolandic
Frontiers in Human Neuroscience | www.frontiersin.org
Editorial: Music, Brain, and Rehabilitation
operculum/insula, indicating increased cognitive processing and
physiological arousal to emotional music in ASD.
O’Kelly et al. compared EEG, heart rate variability, respiration,
and behavioral responses of healthy subjects with brain injured
DOC individuals in vegetative (VS) or minimally conscious
(MCS) states to different types of music (live preferred music,
improvised music entrained to respiration, disliked music),
white noise, and silence. Part of the VS and MCS patients
were clearly responsive to preferred music as shown by both
blink responses and increased EEG amplitude in frontal alpha
or theta bands, indicating that music-based approaches are
potentially useful as prognostic indicators and rehabilitation
methods in the DOC patients. Rollnik and Altenmüller provide
a comprehensive overview of the use of music therapy in
neurological rehabilitation of patients with coma and DOC. They
conclude that although DOC patients seem to show emotional
processing of auditory information and a musically enriched
environment setting may have therapeutic value, more research
with clearly defined patient cohorts, standardized intervention
protocols, valid clinical outcome measures, and longer and more
extensive monitoring is still needed in the DOC population.
NOVEL SOUND-BASED TECHNOLOGICAL
ADVANCES
Recent technological developments were introduced in three
papers. Niu et al. studied the feasibility of a new speech
synthesizer that utilizes the myocontrol of limb muscles recorded
with EMG to drive the synthesis of intelligible speech. Using
this device, both healthy subjects and dyskinetic CP patients
were able to learn to generate English vowels, some of which
were correctly identifiable by naive listeners. In the future, this
approach may provide a “virtual voice” with both intellectual
and social-emotional content to individuals with severe speech-
motor disorders. Loui et al. presented a novel method for
diagnosing seizures in epilepsy, based on the sonification of
EEG data. They found that after a short training period
subjects could successfully distinguish seizures from non-
seizures using the auditory modality alone. Eventually, EEG
sonification may help in managing, predicting, and ultimately
controlling seizures using biofeedback. Another method focusing
on sonification was introduced by Scholz et al. They presented
a novel portable sonification device suitable for real-time 3D
sonification of arm movements and explored optimal spatial
mapping parameters of tone pitch and brightness. A learning
experiment in healthy older persons showed that mapping pitch
on the vertical axis and brightness on the horizontal axis seems
an optimal constellation for motor sonification. Ultimately,
movement sonification may provide an efficient and motivating
way to rehabilitate gross-motor arm skills in hemiparetic stroke
patients.
AUTHOR CONTRIBUTIONS
All authors listed, have made substantial, direct and intellectual
contribution to the work, and approved it for publication.
4 March 2016 | Volume 10 | Article 103
Särkämö et al.
REFERENCES
Altenmüller, E., Ioannou, C. I., and Lee, A. (2015). Apollo’s curse: neurological
causes of motor impairments in musicians. Prog. Brain Res. 217, 89–106. doi:
10.1016/bs.pbr.2014.11.022
Altenmüller, E., and Schlaug, G. (2015). Apollo’s gift: new aspects of neurologic
music therapy. Prog. Brain Res. 217, 237–252. doi: 10.1016/bs.pbr.2014.11.029
Baird, A., and Samson, S. (2015). Music and dementia. Prog. Brain Res. 217,
207–235. doi: 10.1016/bs.pbr.2014.11.028
Bloem, B. R., de Vries, N. M., and Ebersbach, G. (2015). Nonpharmacological
treatments for patients with Parkinson’s disease. Mov. Disord. 30, 1504–1520.
doi: 10.1002/mds.26363
Bradt, J., Magee, W. L., Dileo, C., Wheeler, B. L., and McGilloway, E. (2010). Music
therapy for acquired brain injury. Cochrane Database Syst. Rev. 7:CD006787.
doi: 10.1002/14651858.cd006787.pub2
Brown, R. M., Zatorre, R. J., and Penhune, V. B. (2015). Expert music performance:
cognitive, neural, and developmental bases. Prog. Brain Res. 217, 57–86. doi:
10.1016/bs.pbr.2014.11.021
Flaugnacco, E., Lopez, L., Terribili, C., Montico, M., Zoia, S., and Schön, D.
(2015). Music training increases phonological awareness and reading skills in
developmental dyslexia: a randomized control trial. PLoS ONE 10:e0138715.
doi: 10.1371/journal.pone.0138715
Geretsegger, M., Elefant, C., Mössler, K. A., and Gold, C. (2014). Music therapy
for people with autism spectrum disorder. Cochrane Database Syst. Rev.
6:CD004381. doi: 10.1002/14651858.cd004381.pub3
Herholz, S. C., and Zatorre, R. J. (2012). Musical training as a framework for
brain plasticity: behavior, function, and structure. Neuron 76, 486–502. doi:
10.1016/j.neuron.2012.10.011
Janata, P. (2015). Neural basis of music perception. Handb. Clin. Neurol. 129,
187–205. doi: 10.1016/B978-0-444-62630-1.00011-1
Johnson, J. K., and Graziano, A. B. (2015). Some early cases of aphasia and the
capacity to sing. Prog. Brain Res. 216, 73–89. doi: 10.1016/bs.pbr.2014.11.004
Koelsch, S. (2011). Towards a neural basis of processing musical semantics. Phys.
Life Rev. 8, 89–105. doi: 10.1016/j.plrev.2011.04.004
Koelsch, S. (2014). Brain correlates of music-evoked emotions. Nat. Rev. Neurosci.
15, 170–180. doi: 10.1038/nrn3666
Frontiers in Human Neuroscience | www.frontiersin.org
Editorial: Music, Brain, and Rehabilitation
Kraus, N., and Chandrasekaran, B. (2010). Music training for the development of
auditory skills. Nat. Rev. Neurosci. 11, 599–605. doi: 10.1038/nrn2882
Maguire, M. (2015). Music and its association with epileptic disorders. Prog. Brain
Res. 217, 107–127. doi: 10.1016/bs.pbr.2014.11.023
Nombela, C., Hughes, L. E., Owen, A. M., and Grahn, J. A. (2013). Into the groove:
can rhythm influence Parkinson’s disease? Neurosci. Biobehav. Rev. 37(10 Pt 2),
2564–2570. doi: 10.1016/j.neubiorev.2013.08.003
Peretz, I., Champod, A. S., and Hyde, K. (2003). Varieties of musical disorders. The
Montreal Battery of Evaluation of Amusia. Ann. N.Y. Acad. Sci. 999, 58–75. doi:
10.1196/annals.1284.006
Rodríguez-Fornells, A., Rojo, N., Amengual, J. L., Ripollés, P., Altenmüller, E.,
and Münte, T. F. (2012). The involvement of audio-motor coupling in the
music-supported therapy applied to stroke patients. Ann. N.Y. Acad. Sci. 1252,
282–293. doi: 10.1111/j.1749-6632.2011.06425.x
Särkämö, T., Tervaniemi, M., Laitinen, S., Forsblom, A., Soinila, S., Mikkonen,
M., et al. (2008). Music listening enhances cognitive recovery and
mood after middle cerebral artery stroke. Brain 131(Pt 3), 866–876. doi:
10.1093/brain/awn013
Vink, A. C., Bruinsma, M. S., and Scolten, R. J. (2011). Music therapy
for people with dementia. Cochrane Database Syst. Rev. 3:CD003477. doi:
10.1002/14651858.CD003477.pub2
Zatorre, R. J., and Salimpoor, V. N. (2013). From perception to pleasure: music
and its neural substrates. Proc. Natl. Acad. Sci. U.S.A. 110, 10430–10437. doi:
10.1073/pnas.1301228110
Conflict of Interest Statement: The authors declare that the research was
conducted in the absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.
Copyright © 2016 Särkämö, Altenmüller, Rodríguez-Fornells and Peretz. This is an
open-access article distributed under the terms of the Creative Commons Attribution
License (CC BY). The use, distribution or reproduction in other forums is permitted,
provided the original author(s) or licensor are credited and that the original
publication in this journal is cited, in accordance with accepted academic practice.
No use, distribution or reproduction is permitted which does not comply with these
terms.
5 March 2016 | Volume 10 | Article 103
doi:10.1093/brain/awl171 Brain (2006), 129, 2533–2553

REVIEW ARTICLE
Music and the brain: disorders of musical listening
Lauren Stewart,1,2,3 Katharina von Kriegstein,1,3 Jason D. Warren4 and Timothy D. Griffiths1,3
1
Auditory Group, Newcastle University, Newcastle upon Tyne, 2Institute of Cognitive Neuroscience,
3
Wellcome Department of Imaging Neuroscience, and 4Dementia Research Centre, Institute of Neurology, University
College London, London, UK
Correspondence to: Tim Griffiths, Cognitive Neurology Clinic, Newcastle General Hospital, Westgate Road,
Newcastle upon Tyne NE4 6BE, UK
E-mail: t.d.griffiths@ncl.ac.uk

The study of the brain bases for normal musical listening has advanced greatly in the last 30 years. The evidence
from basic and clinical neuroscience suggests that listening to music involves many cognitive components with
distinct brain substrates. Using patient cases reported in the literature, we develop an approach for under-
standing disordered musical listening that is based on the systematic assessment of the perceptual and cognitive
analysis of music and its emotional effect. This approach can be applied both to acquired and congenital
deficits of musical listening, and to aberrant listening in patients with musical hallucinations. Both the bases
for normal musical listening and the clinical assessment of disorders now have a solid grounding in systems

Downloaded from by guest on January 16, 2015

neuroscience.

Keywords: brain disorders; lesions; listening; music

Abbreviations: HG = Heschl’s gyrus; MBEA = Montreal battery for the evaluation of amusia; MEG = magnetoencephalography;
PAC = primary auditory cortex; PT = planum temporale; SPET = single photon emission tomography
Received February 14, 2006. Revised May 8, 2006. Accepted May 31, 2006. Advance Access publication July 15, 2006.

Introduction
It is now 30 years since the publication of the volume Music
and the Brain edited by Critchley and Henson (1977). That
work still has a place on the bookshelves of many neurologists,
as a vade mecum of the neurology of the musical brain. Dur-
ing the last 30 years, however, there have been a considerable
number of advances in the field, which we consider here.
First, our understanding of the normal musical brain has
increased enormously, providing us with a much better
understanding of the brain bases for normal musical listen-
ing. Many of these advances have been made possible by the
application of techniques that demonstrate the functional
organization of the musical brain, especially haemodynamic
(PET and fMRI) and electrophysiological (EEG and MEG)
imaging techniques. Our understanding based on these tech-
niques is evolving all the time, and critically underpins the
characterization of musical disorders.
The data from functional imaging can ever be only as good
as the theoretical constructs on which the experiments are
based: the second major advance in the understanding of
musical disorders has been the evolution of the constructs
themselves. Based on these, we now have theoretically moti-
vated instruments for the systematic evaluation of musical
disorders: in effect, these instruments are musical equivalents
of the better-known aphasia batteries, such as the Aachen
Aphasia Test (Huber et al., 1984). Modular schemes
for musical perception [e.g. Peretz and Coltheart (2003),
see Fig. 1] are both informed by the study of patients (espe-
cially the demonstration of dissociated deficits), and allow
the development of research tools that can be used in
the clinic. These tools have allowed reports of musical dis-
orders to evolve from historical anecdotes to systematic
accounts. The development of tools for evaluating different
aspects of musical disorders is by no means complete, and
clinical evaluation remains a challenge in view of both
evolving theoretical accounts and the wide variation in musi-
cal experience and training in the general population.
The third major advance is that we can now examine with
greater precision the changes in the brain that accompany
musical disorders. Thirty years ago detailed anatomical
information about lesion patients was only available in

# The Author (2006). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
2534 Brain (2006), 129, 2533–2553
Fig. 1 Cognitive model of musical processing. Musical analysis is
divided into distinct neuropsychological components. The current
review considers the neural instantiation of such components, and
considers musical listening disorders in terms of deficient or
aberrant operation of the components. Based on Peretz I,
Coltheart M, ‘Modularity of music processing’, 2003. Reprinted by
permission from Macmillan Publishers Ltd: Nature Neuroscience
6(7): 688–91, copyright 2003.
the rare cases where there was accompanying pathological
data. In terms of structural anatomy, lesions can now be
defined precisely using structural MRI, whilst the evolution
of structural MRI analyses, such as voxel-based morphome-
try (Ashburner and Friston, 2000) allows the identification of
subtle anatomical changes in disorders where the anatomical
brain basis is not immediately obvious. This precise char-
acterization of lesions allows us to visualize which parts of
the normal cortical network, as identified using functional
imaging, have been damaged.
Here, we will describe some of the recent advances in our
understanding of normal musical listening that allow a better
understanding of disorders, before a systematic review of the
disorders themselves. Musical listening is used here to refer
not only to the perception of music, but also to what might
be referred to as ‘musical cognition’: the ordering of incom-
ing musical information according to rule-based structures
and musical recognition. Apart from musical cognition,
another important aspect of musical listening is the trigger-
ing of an emotional response, an effect which we will also
discuss. We therefore consider a range of deficits in musical
listening that includes but is not restricted to the condition
of amusia, which is typically defined as a music-specific
agnosia.
Normal musical listening and normal
musical brains: some recent advances
Components of normal musical listening have been investi-
gated in a number of studies in which the brain substrates for
these are defined by changes in the haemodynamic response
L. Stewart et al.
to the mean synaptic firing rate (PET and fMRI) (Logothetis
et al., 2001) or the effect of summed graded post-synaptic
potentials in dendrites (EEG and MEG) (Wood, 1987). Here
we consider these components in order to establish a con-
ceptual framework within which to consider the effect of
brain disorders. In addition to these studies, there have
been a number of recent advances in our understanding
of the structural and functional organization of the brains
of musicians, which need to be borne in mind when
considering the effects of brain disorders.
The auditory pathway and cortices
Music, like any sound, music is processed in the ascending
auditory pathway to the auditory cortex. That processing
includes active analysis of the spectro-temporal structure
of the stimulus rather than the simple passive relay of infor-
mation (Harms et al., 1998; Griffiths et al., 2001). The
human auditory cortex is situated in the superior-temporal
plane within the Sylvian fissure, which can be best visualized
on a tilted axial section, such as those shown in Fig. 2.
Cytoarchitechtonically defined primary auditory cortex
(PAC) is located in the medial part of Heschl’s gyrus,
Downloaded from by guest on January 16, 2015
(HG) (or the anterior HG in individuals in whom the
gyrus is duplicated) running anterolaterally in the plane.
There is considerable variation of the relationship between
the cytoarchitechtonically defined area and the macroscopic
boundaries (Rademacher et al., 2001), which needs to be
taken into account when considering the effects of lesions
defined by macroscopic markings. Lateral to the PAC in HG
are secondary auditory cortical areas that may correspond to
the human homologues of macaque areas R and RT [see
Patterson et al., (2002) for Discussion]. Behind HG lies
the planum temporale (PT), which can be described as an
auditory association area based on the involvement of this
area in the processing of both auditory stimuli and stimuli in
other modalities (Griffiths and Warren, 2002).
Pitch
Pitch has been argued to be a fundamental component of
music in every known human culture (McDermott and
Hauser, 2005). A critical point about pitch is that it is a
percept, rather than a physical attribute of the sound stimu-
lus, and the exact relationship between the stimulus
attributes and the percept is still debated (Plack et al.,
2006). Studies where the strength of perceived pitch has
been varied by varying the fine temporal structure of
sound have demonstrated prominent responses that reflect
activity in secondary cortex in lateral HG rather than pri-
mary cortex (Gutschalk et al., 2002; Patterson et al., 2002).
Another study (Penagos et al., 2004), where the pitch
strength was altered by varying the spectrum, demonstrated
a similar mapping of pitch strength to secondary cortex,
suggesting the possibility of a ‘pitch centre’ in lateral HG
where there is encoding of the percept as opposed to the
stimulus properties. Interestingly, recent recording work on
Disorders of musical listening
Fig. 2 Pitch processing in superior-temporal cortex. The lower
centre panels show an axial structural MRI for nine subjects tilted
by 34.4 to show the superior-temporal plane. HG shown in white
runs anterolaterally within the superior-temporal plane. Changes in
brain activity as assessed by blood-oxygen-level-dependent
response are shown in colour. Noise stimuli, compared to rest,
activate large regions of the superior-temporal plane (shown in
blue) including medial HG containing primary cortex, lateral HG
containing secondary cortex, PT posterior to HG and planum
polare anterior to it. Pitch stimuli, compared to noise stimuli with
a similar spectrum, produce peak activation in secondary cortex in
lateral HG (shown in red). Sequences of variable pitch (tonal
melody in green or random-pitch sequence in cyan), compared to a
monotonous sequence, produce right-lateralized activation in
lateral HG, posterior superior-temporal gyrus, and planum polare.
The data are consistent with hierarchical mechanisms for pitch
analysis with a ‘pitch centre’ that represents the pitch of individual
notes in lateral HG and more distributed representation of pitch
sequences in superior-temporal lobe. Reprinted from Patterson
RD, Uppenkamp S, Johnsrude IS, Griffiths TD. The processing of
temporal pitch and melody information in auditory cortex. Neuron
2002; 36: 767–76, copyright 2002, with permission from Elsevier.
the primates can also be interpreted in terms of the existence
of a ‘pitch centre’ in secondary auditory cortex (Bendor and
Wang, 2005)
In music, pitch is used to construct melodies (patterns of
pitch over time), chords (the simultaneous presentation of
more than one pitch) and harmonies (the simultaneous
presentation of more than one melody). Bilateral brain
activation during the analysis of pitch sequences occurs in
the anterior and posterior superior-temporal lobes with a
degree of right lateralization (Griffiths et al., 1998;
Patterson et al., 2002) (see Fig. 2). In these passive
listening experiments, no difference was demonstrated
between random-pitch sequences and tonal melodies. In
experiments where subjects were required to follow a
melody and compare the pitch at different points,
additional activation was demonstrated in the right frontal
operculum (Zatorre et al., 1994). In Western tonal
music, melodies are constructed using keys where only
certain notes are allowed within the octave. Activity
has been demonstrated in the mesiofrontal cortex that
Brain (2006), 129, 2533–2553 2535
depends on both the key and the history of keys visited
in a piece (Janata et al., 2002). Other studies [reviewed in
Koelsch and Siebel (2005)] have demonstrated responses in
the lateral frontal lobes in the region of Broca’s area and its
right homologue to deviation from an expected chord (based
on tonal context). A study that examined the activation in
the comparison between orchestral music and temporally
‘scrambled’ music (Levitin and Menon, 2003) also showed
frontal activation bilaterally in the pars orbitalis area.
The picture that emerges from these studies of pitch is that
the normal perception of pitch and simple pitch sequences
involves networks that include the auditory cortices and
adjacent areas in the superior-temporal lobes. These percep-
tual features of music are shared with other sounds,
such as speech, and there is considerable overlap in the
activation in temporal lobe areas produced by speech and
music (Price et al., 2005). In the future, differences between
speech and musical processing in these areas may emerge
based on patterns of connectivity that can be demonstrated
by techniques, such as dynamic causal modelling in fMRI
(Friston et al., 2003) and coherence analysis in EEG and
MEG (Patel and Balaban, 2000). In contrast to perceptual
analysis, active rule-based analysis of simultaneous and
Downloaded from by guest on January 16, 2015
sequential pitch structures (harmony and melody) that
depends upon exposure requires much more distributed
processing involving the frontal lobes. The data seem to
favour the existence of music-specific cortical networks
for such cognitive analysis and MEG experiments (Patel
and Balaban, 2000) have demonstrated that the coherence
between widely spaced elements of these networks is
greatest during the processing of pitch sequences with a
pitch contour that is similar to music. However, our under-
standing of the brain basis for more cognitive aspects of pitch
analysis, such as tonal analysis, is still at a very early stage.
Timbre
A further fundamental aspect of musical structure is timbre,
a perceptual property that allows us to distinguish between
different instruments. In German, timbre translates to
‘Klangfarbe’ (literally ‘sound-colour’), emphasizing the
extent to which this property of sound can be used to express
different parts of the musical ‘palette’. Timbre is important
in the separation of musical ‘streams’ (Bregman, 1990) and
has been used as a musical device in the work of Schönberg
and Webern who composed Klangfarbenmelodien (literally,
‘sound-colour melodies’) based on timbral sequences. Tim-
bre has been shown, using the technique of multidimen-
sional scaling (McAdams and Cunible, 1992; Caclin et al.,
2005), to have a number of dimensions that can be associated
with different physical properties of the stimulus, related to
aspects of the spectral or temporal structure. In a study
where several dimensions of timbre were altered simulta-
neously, bilateral changes in activity were observed in the
posterior superior-temporal lobes (Menon et al., 2002).
Studies focusing on the analysis of the spectral dimension
2536 Brain (2006), 129, 2533–2553
of timbre also demonstrated involvement of the posterior
superior-temporal lobes, in addition to right-lateralized
activity in the superior-temporal sulcus (Warren et al.,
2005). Analysis of the voice, the prototypical musical instru-
ment, has also been shown to be associated with activity in
the right superior-temporal sulcus (Belin et al., 2000).
Temporal structure
The brain substrates underlying analysis of the temporal
organization of music (rhythm and metre) have been less
thoroughly investigated compared with those that underlie
pitch perception. Several studies have used simple patterns of
beats without a particular musical context. A PET study
(Penhune et al., 1998) demonstrated activity in the lateral
cerebellum and basal ganglia during the reproduction of a
rhythm. A functional MRI (fMRI) study (Sakai et al., 1999)
based on the comparison of sequences without motor repro-
duction suggested a different representation of sequences
with time intervals that were in integer ratios compared
with non-integer ratios. The former type of ratio is more
common in music, and produced increased activity in the
anterior lobe of the cerebellum. A recent study (Xu et al.,
2006) showed activation of cerebellar areas during
both perception and performance of temporal sequences.
These studies, showing activation in motor structures,
suggest the possibility of a motor theory of rhythm percep-
tion, as a parallel to the motor theory of speech perception
(Liberman and Mattingly, 1985) whereby our perception
of rhythm might depend on the motor mechanisms
required for its production. Behavioural work in infants
(Phillips-Silver and Trainor, 2005) suggests an interaction
between information about body movement and perceived
rhythm, where there is an alteration of perceived rhythm due
to imposed body movement (bouncing). The functional
imaging studies above emphasise differences between
the perceptual bases of temporal and melodic structure.
However, a study in which both dimensions were present,
but subjects performed either a melodic or a temporal task
showed a very similar network of activation in the posterior
superior-temporal lobes, cerebellum and basal ganglia
(Griffiths et al., 1999).
Emotion
The above studies of the normal brain have considered dif-
ferent aspects of music by looking at its component parts,
but it can be reasonably argued that the musical listening
experience is an emergent property that is greater than the
sum of its parts. One example would be the emotional trans-
formation (the ‘shiver down the spine’) that many people
experience while listening to certain pieces of music. This
is an intense, involuntary physiological response, which is
triggered by the emotional response to different music in
different individuals. An elegant experiment using PET
(Blood and Zatorre, 2001) examined the brain basis for
this and showed activation for the contrast between sounds
that produced ‘shivers’ and those that did not. The contrast
L. Stewart et al.
demonstrated activity, not in the superior-temporal lobe
areas activated during melody analysis, but in areas pre-
viously implicated in other intensely pleasurable activities,
including the ventral striatum, amygdala, and orbitofrontal
cortex. An fMRI study contrasting unpleasantly transformed
music with pleasant music (Koelsch et al., 2006) also demon-
strated activity in mesiolimbic areas including the amygdala,
in addition to activity in auditory cortex that was not shown
in the study by Blood and Zatorre (2001). The study by
Koelsch et al., (2006) used pitch shifts of melodies to achieve
a dissonant sound with control over the long-term spectrum
and temporal envelope of the stimulus. An earlier PET study
(Blood et al., 1999) that examined the effect of manipulating
consonance and dissonance on brain activity, also showed
activation in mesiolombic areas, as did an fMRI study in
which non-musicians listened passively to unfamiliar music,
which they later rated as pleasant (Brown et al., 2004). The
difference in activity in auditory cortex in these studies may
reflect details of the paradigms or techniques, but the com-
mon variation in mesiolimbic activity associated with emo-
tion in music is fundamentally different to the activation
during manipulations of other musical components.
Downloaded from by guest on January 16, 2015
Specialization of the musical brain
One problem with the assessment of musical disorders is the
difficulty in defining a ‘normal musical brain’. Whilst apha-
sia schedules can reasonably assume a degree of uniformity
in education, where most people are trained to a certain
level, that assumption cannot be made with respect to
music. An early study based on differences in melody dis-
crimination depending on whether they were presented to
the left or the right ear (Bever and Chiarello, 1974) suggested
differences in brain lateralization between musicians and
non-musicians. A number of neuro-imaging studies have
demonstrated structural differences in the brains of musi-
cians in auditory (Schneider et al., 2002), motor (Amunts
et al., 1997), somatosensory (Gaser and Schlaug, 2003),
superior parietal (Gaser and Schlaug, 2003), callosal (Schlaug
et al., 1995a) and cerebellar (Hutchinson et al., 2003) areas.
Longitudinal studies have demonstrated functional brain
reorganization after even short periods of musical training
(Gaab et al., 2006; Stewart et al., 2003), although the extent
to which these changes endure after training is unknown.
Studies of the subpopulation of musicians who possess abso-
lute pitch (AP) suggest differences in brain organization
from those without the ability. Structural studies using
both region-of-interest approaches (Schlaug et al., 1995b)
and interrogation of the whole brain with voxel-based mor-
phometry (Luders et al., 2004) both suggest increases in
leftward asymmetry in the PT associated with AP. Functional
imaging (Zatorre et al., 1998) demonstrates different net-
works of activity during pitch interval judgement in AP:
subjects without AP show activity in right inferior frontal
areas, which can be plausibly argued to reflect a form of
working memory for pitch, whilst AP possessors engage
Disorders of musical listening
left dorsolateral frontal areas that may reflect associative ana-
lysis. Critical to the interpretation of structural and functional
differences in skilled performers is the question of whether
such differences are the result of musical training or whether
whether such differences may contribute to an individual’s
decision to learn music, or to persist in learning music when
others may give up. In partial favour of the argument that
these differences arise from, rather than enable, skill devel-
opment is the demonstration that the extent of the structural
difference often correlates with the age of onset of musical
training (Amunts et al., 1997) or intensity of practice
(Bengtsson et al., 2005; Gaser and Schlaug, 2003). However,
only longitudinal studies in which differences in brain struc-
ture can be measured in the same individuals as learning
proceeds will be able to unequivocally demonstrate the
differential influence of nature versus nurture.
A framework for consideration of
disorders of musical listening
The above discussion is intended to suggest some general
principles regarding the neural bases of musical analysis by
the brain: for a more detailed account the reader is referred
to Peretz and Zatorre (2005). What emerges from such a
consideration is the principle that different components of
music (pitch, melody, rhythm, timbre and emotion) are
underpinned by different psychological mechanisms and
neural substrates. This principle is most clearly evident in
the case of pitch and melody: the evidence suggests a scheme
in which the perception of pitch and simple patterns of pitch
is supported by mechanisms in the auditory cortices, whilst
cognitive analysis of patterns within the pitch and time-
domains requires more distributed networks including the
frontal cortex.
In view of the discussion above, any attempt to produce a
systematic framework within which to consider disorders of
musical processing may seem doomed. It can be reasonably
argued that no universal and robust assessment could ever be
applied to all patients, taking account of the many diverse
components of musical listening and emotional response,
and the large variation in musical experience and training
between subjects. However, clinical disorders can be
approached systematically even if assessment is necessarily
limited to particular domains of musical processing. In the
next section, ‘Acquired deficits in musical listening’, we
apply the systematic perspective developed above to pub-
lished cases of acquired disorders of musical listening. In pre-
senting the data, we recognize that these studies differ widely
in the premorbid musical expertise of the patients described,
the musical domains studied and the methods of assessment
used. We then consider cases of developmental amusia and
musical hallucinations within a similar framework.
Acquired deficits in musical listening
The clinical neurologist is generally concerned with under-
standing and characterizing deficits as they present in the
Brain (2006), 129, 2533–2553 2537
individual patient with an acquired brain lesion. The study of
patients with musical deficits is over a century old (see
Critchley and Henson, 1977) and the clinical case study
remains central to understanding the musical brain. Only
by studying the behavioural correlates of focal brain damage
is it possible to identify critical anatomical substrates for
particular musical functions within the distributed brain net-
works identified by functional imaging of the normal brain.
Here we present a comprehensive overview of case studies of
acquired disorders of musical listening, with the aim of
establishing general patterns that hold across the literature
on these disorders. Our primary objective is to characterize
the brain basis for the clinical symptomatology of musical
listening disorders. However, this is a challenging enterprise
with a number of limitations.
The first set of limitations applies to any cognitive neu-
ropsychological study. Naturally occurring brain lesions are
rarely circumscribed, with locations dictated by pathological
processes, especially vascular anatomy. The pattern of deficits
frequently changes over time, and premorbid behavioural
measures are generally lacking. Assessment and interpreta-
tion of particular functions may also be confounded by
co-existing deficits (e.g. aphasia). Focal brain lesions occur
Downloaded from by guest on January 16, 2015
within functional networks. Although neuropsychological
evidence can be used to infer that a particular region is
critical for a function, it should be noted that the affected
region may not be sufficient, in and of itself, to support the
function, which may depend equally on other regions within
a broader network. Accordingly, maps of the effects of
lesions (such as those in Figs 3 and 4) should not be equated
with maps of the whole network required for a particular
function. Rather, they represent the critical components of
normal networks. We have already suggested by studies
described in the section ‘Normal musical listening and nor-
mal musical brains: some recent advances’. We suggested in
the same section that early musical perceptual analysis might
be a product, not only of analysis within particular cortical
areas, but of patterns of connectivity between cortical areas
that are commonly engaged during the analysis of different
types of sound. With respect to lesions, it is worth bearing in
mind that these might disconnect areas involved in different
processes, as well as damaging the areas themselves.
Further limitations are specific to music. The effect of the
lesion depends on the premorbid level of musical compe-
tence and awareness, which varies widely in the general
population. The level of musical training influences the
kinds of assessment that can be performed, and musical
training may be associated with structural differences and
functional brain organization. The assessment of musical
functions is intrinsically difficult: while tools exist for mea-
suring and calibrating for premorbid musical ability and
experience [e.g. Grison’s Levels of Musical Culture
(Grison, 1972)], the Barbizet scale of Premorbid Musical
Ability [cited in Prior et al. (1990) and the battery
of Wertheim and Botez (1961)], these tools have not
been used systematically. Music perceptual abilities are not
2538 Brain (2006), 129, 2533–2553 L. Stewart et al.

Downloaded from by guest on January 16, 2015

Fig. 3 Sites of brain lesions in individual cases of musical listening disorders. Eleven cartoons are shown, each depicting the brain
in a schematic axial view that includes all key anatomical areas involved in music listening (identified on the top cartoon); the corpus
callosum (black), superior-temporal plane (light grey) and middle/inferior temporal gyri (dark grey areas, in exploded view) are coloured
for ease of identification. The ten musical functions analysed in Supplementary Table 1 are each assigned to a separate cartoon. The number
of cases in which a deficit in that function is identified are shown on the figure, and the total number of cases in which that function
was assessed is shown in parentheses below each figure. amyg = amygdala; aSTG = anterior superior-temporal gyrus; bg = basal
ganglia; cc = corpus callosum; fr = frontal; hc = hippocampal; HG = Heschl’s gyrus; ic = inferior colliculi; i = inferior; ins = insula; l = lateral;
m = medial; thal = thalamus; PT = planum temporale; TG = temporal gyrus.
Disorders of musical listening Brain (2006), 129, 2533–2553 2539

Downloaded from by guest on January 16, 2015

Fig. 4 Critical brain substrates for musical listening disorders across studies. Five cartoons are shown, each depicting the brain in a
schematic axial section that includes all key anatomical areas involved in music listening (identified on the top cartoon); the corpus callosum
(black), superior-temporal plane (light grey) and middle/inferior temporal gyri (dark grey areas, in exploded view) are coloured for ease of
identification. Musical functions analysed in Supplementary Table 1 have been grouped as follows: pitch processing (pitch interval, pitch
pattern, tonal structure, timbre); temporal processing (time interval, rhythm); musical memory (familiar and novel material); and emotional
response to music. Each group of functions is assigned to a separate cartoon; individual functions are identified to the right of the
corresponding cartoon. Raw data from Supplementary Table 1 have been thresholded; the presence of a coloured circle corresponding to a
particular function in a region indicates that at least 50% of studies of the function implicate that region. The size of each circle is scaled
according to the proportion of studies of the function implicating that region (see text). Metre is not represented as no brain area was
implicated in 50% or more of cases. amyg = amygdala; aSTG = anterior superior-temporal gyrus; bg = basal ganglia; cc = corpus callosum;
fr = frontal; hc = hippocampal; HG = Heschl’s gyrus; ic = inferior colliculi; i = inferior; ins = insula; l = lateral; m = medial; thal = thalamus; PT
= planum temporale; TG = temporal gyrus.
2540 Brain (2006), 129, 2533–2553 L. Stewart et al.

routinely assessed in a neuropsychological examination, and
require at least some level of musical sophistication to
administer and interpret. In research settings, the Montreal
Battery for the Evaluation of Amusia [MBEA (Peretz et al.,
2003)] offers the advantages of simplicity, comprehensiveness
and the availability of normative data, but many other batteries
have been used to assess individual clinical cases (see Appendix).
While the format of many tests is broadly similar (e.g. same/
different tasks with pairs of melodies) the details may differ in
ways that are important for interpretation.
The identification of cases of acquired disorders of musical
listening based on symptom profiles in individual patients
constitutes the traditional ‘symptom-led’ approach of the
clinical neurologist. This approach is, however, subject to
several fundamental criticisms (Zatorre, 1985). The method
of ascertainment is intrinsically biased, since cases may be
identified due to a particular pattern of deficits, or because
the patient was previously a professional musician and there-
fore highly aware of the deficit. Individual cases are anato-
mically and clinically heterogeneous making it difficult to
draw more general conclusions about the necessary brain
substrates that are common to all individuals.
For these reasons, an alternative approach to the clinical
deficit by a process of systematic search is of quite different
significance to the same deficit volunteered as a clinical
symptom. Comparisons between the two literatures in
order to draw conclusions about the role of particular
brain regions in particular musical functions must therefore
be made with care. The information about musical listening
deficits obtained from the symptom-led and lesion-led lit-
erature is complementary, both anatomically and function-
ally. In this review, lesion-led studies are therefore
considered as an adjunct to our primary focus on sympto-
matic disorders of musical listening.
Selection and analysis of clinical cases in
this review
Table 1 lists published clinical case studies selected for ana-
lysis on the basis of the following criteria: presentation with a
symptomatic musical deficit (of musical listening or produc-
tion) or a general auditory agnosia including a musical def-
icit; documentation of a systematic and objective evaluation
of musical listening; and an adequate anatomical description
of the lesion based on brain imaging (MRI, CT or angio-
graphy), or neuropathology. Table 2 lists published series of

Downloaded from by guest on January 16, 2015

study of musical deficits has been advocated, based on the patients with lesions that meet all criteria except the presence
study of cases selected on the basis of a particular brain of a symptomatic deficit. Supplementary Tables 1 and 2
lesion, rather than clinical symptoms: the ‘lesion-led’ appro- characterize these cases in greater systematic detail. All
ach. Using this approach, groups of patients in whom the cases meeting our criteria were analysed in terms of lesion
locus and extent of brain damage are relatively homogeneous location, and the components of musical listening based on
are assessed systematically on tests of musical perception. contemporary models.
This approach has been used most widely in patients who In the symptom-led literature (Table 1 and Supplementary
have undergone temporal lobectomy for the relief of intract- Table 1), lesions have been analysed according to aetiology,
able epilepsy. By classifying patients according to the side side and specific brain regions affected, based on the brain
and extent of the resection, it is possible to assess the role of images supplied or the description of the imaging or
each cerebral hemisphere and particular cortical areas within neuropathology in the original reports. The analysis by
each hemisphere in particular musical functions. It is also
possible to test patients before and after surgery (Milner, Table 1 Acquired symptom-led reports
1962; Shankweiler, 1966; Kester et al., 1991) so that indivi-
duals serve as their own controls, thereby minimising the Brust (Case 2) (1980) Mazzucchi et al. (1982)
Confavreux et al. (1992) Mendez and Geehan (MS) (1988)
effects of inter-individual variability inherent to group com- Di Pietro et al. (2004) Patel et al. (CN) (1998)
parisons. Eustache et al. (Cases 1 and 2) Patel et al. (IR) (1998)
However, the lesion-led approach itself has significant (1990)
limitations. Resections for epilepsy sample only a restricted Fries and Swihart (1990) Peretz et al. (CN) (1994)
fraction of the brain (chiefly the anterior temporal lobe), Fujii et al. (1990) Peretz (CN) (1996)
Griffiths et al. (1997) Peretz et al. (IR) (1997)
because of the nature of the disease process and the need Griffiths et al. (2004) Peretz et al. (IR) (1998)
to protect eloquent brain areas. This anatomical emphasis Griffiths et al. (2006) Peretz and Gagnon (IR) (1999)
also occurs in naturally occurring (chiefly, vascular) lesions, Habib et al. (1995) Peretz et al. (IR) (2001)
but these predominantly affect different areas in the poster- Hattiangadi et al. (2005) Piccirilli et al. (2000)
ior temporal lobe and beyond. Moreover, patients with Hofman et al. (1993) Satoh et al. (2005)
Johannes et al. (1998) Spreen et al. (1965)
intractable epilepsy are likely to have longstanding altera- Johkura et al. (1998) Tanaka et al. (1987)
tions of cortical organization, and the relevance of such Kohlmetz et al. (2003) Terao et al. (2005)
changes to the organization of the healthy brain is difficult Lechevalier et al. (1984) Tramo et al. (MS) (1990)
to determine. The assessments are biased toward easily Levin and Rose (1979) Tramo et al. (MS) (2002)
measured perceptual deficits, whilst the principal complaint Mavlov (1980) Uvstedt (Case 9) (1937)
Mazzoni et al. (1993) Wilson et al. (2002)
of symptomatic patients is often emotional: they no
longer enjoy music. The issue of behavioural relevance is See Supplementary Table 1 for comprehensive description of
fundamental to lesion-led studies: the identification of a reports.
Disorders of musical listening Brain (2006), 129, 2533–2553 2541

Table 2 Acquired lesion-led reports
Resection cases
Gosselin et al. (2005)
Johnsrude et al. (2000)
Kester et al. (1991)
Liegeois-Chauvel et al. (1998)
Milner (1962)
Samson and Zatorre (1988)
Samson and Zatorre (1991)
Samson and Zatorre (1992)
Samson and Zatorre (1994)
Samson et al. (2001)
Samson et al. (2002)
Shankweiler (1966)
Warrier and Zatorre (2004)
Zatorre (1985)
Zatorre (1988)
Zatorre and Halpern (1993)
Zatorre and Samson (1991)
See Supplementary Table 2 for comprehensive description of
reports.
Stroke/other type
of lesion
Ayotte et al. (2000)
Grossman et al. (1981)
Peretz (1990)
Prior et al. (1990)
Robin et al. (1990)
Samson et al. (2001)
Schuppert et al. (2000)
Shapiro et al. (1981)
Sidtis and Volpe
(1988)
Tramo and Bharucha (1991)
Although the emotional response to music is rarely tested,
it is often part of the presentation and we have therefore
included subjective report as a measure of emotional proces-
sing.
Aside from the data obtained via musical testing, several
other abilities are relevant to interpretation of the clinical
literature. The patient’s premorbid level of musical compe-
tence is included where described. The interval between the
cerebral event and the time of musical assessment is indi-
cated, since substantial recovery can occur during this inter-
val. Musical listening deficits may associate with or dissociate
from linguistic ability and the ability to perceive other types
of complex sounds, (such as environmental sounds): we
therefore also include measures of language and environ-
mental sound perception where available. Though data are
available for only a proportion of cases, pure tone audio-
metry is of relevance in order to demonstrate that musical
perceptual problems are not the result of peripheral hearing
loss, and audiometric findings are therefore included where
provided.
Our analysis of the symptom-led literature on acquired
disorders is presented graphically in Figs 3 and 4. The dis-
tribution of deficits across case studies has been rendered on

Downloaded from by guest on January 16, 2015

region includes a detailed subdivision of the temporal lobe
including auditory cortical areas implicated in normal musi-
cal listening: the temporal lobe is divided into medial HG
(containing PAC), lateral HG (secondary auditory cortex),
PT, anterior STG/temporal pole, insula, middle and inferior
temporal gyri, and mesial temporal lobe and amygdala.
Regions outside the temporal lobe including areas implicated
in normal musical listening in the section ‘Normal musical
listening and normal musical brains: some recent advances’
are divided into the ascending auditory pathways (inferior
colliculi, auditory thalamus and auditory radiation), inferior
parietal lobe, frontal operculum, other frontal lobe areas,
basal ganglia, occipital lobe, cerebellum and corpus callosum.
Most studies included in the lesion-led literature summary
(Table 2 and Supplementary Table 2) describe temporal
lobectomy series; the right hand section of that table includes
studies where patients with other patterns of brain damage
(chiefly, stroke) are tested for musical perception. The latter
studies lack the anatomical precision of the temporal lobect-
omy studies, because patients are assigned to rather broadly
defined anatomical groups (e.g. right or left stroke). How-
ever, we include them because of their utility in addressing
questions of laterality.
In Supplementary Tables 1 and 2, pitch analysis (pitch
interval, pitch pattern and tonal structure) and temporal
analysis (time interval, metre and rhythm) are arranged
hierarchically. Timbre is separated as a perceptual property
distinct from pitch and the timing of notes. Recognition
memory for novel melodies or familiar music is included
as a separate category. In some cases, a patient’s performance
is judged by the authors to be impaired even in the absence
of formal comparison with control subjects: in such cases,
we classified patients’ performance as ‘below expected’.
template brain schematics representing each of the key ana-
tomical regions involved in musical listening. In Fig. 3, the
distribution of deficits is shown separately for each musical
function. In Fig. 4, the data have been grouped according to
the broad functional hierarchies outlined above: pitch, tim-
bre, temporal information, musical memory and emotion. In
addition, a transformation procedure has been applied to
generate a visual analogue of the relative importance of
each region for particular musical functions. The data
were first thresholded so that a given function is only
ascribed to a particular brain region if at least 50% of studies
of that function implicate that region. Data meeting this
threshold criterion are represented as coloured circles. In
each brain region, the size of each circle is scaled according
to the proportion of studies that implicate that region for
a particular function. The distribution of coloured circles in
Fig. 4 therefore indicates the anatomical emphasis of lesions
producing different types of musical listening deficits, while
the size of the circles indicates the relative extent to which
particular brain areas contribute to each deficit.
General principles
Taken together, the case reports analysed here (Supplemen-
tary Tables 1 and 2 and Figs 3 and 4) suggest that the break-
down of musical listening in the lesioned brain follows
certain basic principles. It is clear that a deficit in musical
listening does arise as a consequence of a central disturbance
of auditory processing: of all the cases in Supplementary
Table 1 that included audiometry, none had a musical
listening deficit that could be attributed to a peripheral
hearing deficit. The brain lesions that produce deficits in
musical listening are widely distributed (Fig. 3), but with
2542 Brain (2006), 129, 2533–2553
a preponderance of locations in the right hemisphere (Fig. 4).
The results from functional imaging studies of musical lis-
tening reviewed above implicate a bilateral network of areas
involved in musical listening, but the results from acquired
cases of amusia suggest that right hemispheric structures,
including superior-temporal cortex (principally non-PAC),
and other areas including the insula and frontal lobe are the
necessary components of this network. However, even
though right-sided lesions are more commonly associated
with deficits in pitch and other domains (Fig. 4), left
sided lesions can also, though less commonly, produce def-
icits in these aspects of musical listening (Fig. 3). It should be
borne in mind that the preponderance of right hemispheric
lesions associated with musical listening deficits may, at least
partially, reflect a sampling bias: individuals with left hemi-
sphere damage are often aphasic and testing of non-linguistic
skills is often difficult and rarely a priority.
The majority of cases are attributable to cerebrovascular
events, though other pathologies, such as focal cerebral
degeneration (‘progressive amusia’) are represented
(Confavreux et al., 1992). Because of the nature of these
lesions, musical listening disorders are rarely ‘pure’ (Supple-
mentary Table 1): over half the cases are associated with
disorders of speech perception, and approximately a third
of the cases with disorders of environmental sound percep-
tion. In most cases available data on speech processing are
limited, preventing clear comment about the general asso-
ciation of directly related speech deficits (e.g. perceptual
dysprosody) or other deficits in the speech domain. There
is some evidence from Supplementary Table 1 to suggest that
the earlier stages of an acquired deficit in musical listening
(e.g. less than one year after onset) tend to be accompanied
by more deficits in listening to other classes of sounds: this in
turn suggests that a disorder in musical listening can emerge
as an isolated deficit following the recovery phase of a more
generalized auditory agnosia.
Within the domain of music, it is rare that the effects of
lesions are functionally specific. Figs 3 and 4 show that many
areas are implicated in more than one function. However, it
is clear that the necessary bases for music processing are
separable: relatively isolated deficits of pitch (Peretz et al.,
1994), temporal (Mavlov, 1980), timbral (Kohlmetz et al.,
2003), mnemonic (Peretz, 1996) and emotional (Griffiths
et al., 2004) processing have all been described. More
fine-grained dissociations also occur: for instance, between
pitch interval and pitch contour (Liegeois-Chauvel et al.,
1998; Peretz, 1990) and between rhythm and metre (Di
Pietro et al., 2004; Wilson et al., 2002). The data suggest
a general scheme in which any brain substrate identified as
critical for a particular musical function will have relative
rather than absolute specificity for that function. With this in
mind, the following sections consider candidate brain sub-
strates for each of these musical functions, based on the
symptom-led and lesion-led evidence amassed in Supple-
mentary Tables 1 and 2 and summarized in Figs 3 and
4. Where possible, this evidence is related to organizational
L. Stewart et al.
schemes emerging from functional imaging studies in nor-
mal subjects, in order to show how lesion anatomy fits
within the distributed functional networks that normally
mediate music perception.
Pitch: interval
The components of pitch perception have been widely stu-
died in both the symptom-led and lesion-led literature that
concerns disorders of musical listening. Deficits in the ana-
lysis of pitch intervals (the detection of a pitch change and/or
the discrimination of the direction of a pitch change) are
most strongly associated with lesions involving lateral HG
and non-primary auditory cortical areas in PT and the
parieto-temporal junction (Fig. 4). The detection of pitch
differences and the discrimination of pitch direction are
functionally separable, but have been distinguished only
infrequently in symptom-led studies. Where it has been spe-
cifically assessed, impaired pitch-difference detection is gen-
erally associated with involvement of subcortical structures
and ascending auditory pathways or PAC in medial HG
(Habib et al., 1995; Tramo et al., 2002; Hattiangadi et al.,
2005; Terao et al., 2005) while impaired pitch-direction
Downloaded from by guest on January 16, 2015
discrimination is generally associated with involvement of
lateral HG (Lechevalier et al., 1984; Tanaka et al., 1987;
Tramo et al., 2002; Terao et al., 2005).
These data are congruent with evidence from temporal
lobectomy series (Supplementary Table 2). Right-lateral
HG resection leads to deficits in the detection of pitch
change direction in pure tones (Johnsrude et al., 2000)
and complex tones (Zatorre, 1988) These findings, especially
the latter, suggest that aspects of pitch perception, as
opposed to the sensory representation of frequency- and
time-domain properties of the stimulus, depend on the
integrity of cortical areas beyond PAC. This is consistent
with the concept of a ‘pitch centre’ in lateral HG that
emerges from functional imaging of the normal musical
brain.
Pitch: pattern
Deficits in the analysis of pitch patterns, like melodies, com-
prising multiple notes, are common in acquired disorders of
musical listening (Supplementary Table 1). The deficits are
most often associated with lesions posterior to HG, in PT
and the parieto-temporal junction, and anterior to HG in
anterior STG (Figs 3 and 4). The occurrence of such a deficit
is more common following right-sided rather than left sided
lesions. Melody discrimination has also been widely assessed
in the lesion-led literature (Supplementary Table 2): right
but not left temporal lobectomy impairs discrimination of
pitch pattern, even where HG is not included (Milner, 1962).
However, inclusion of HG produces deficits in melody per-
ception over and above those due to the resection of the
temporal lobe anterior to it (Zatorre, 1985; Samson and
Zatorre, 1988). In a study comparing resections involving
posterior versus anterior STG (Liegeois-Chauvel et al.,
Disorders of musical listening
1998), posterior resection was associated with more severe
impairment of pitch pattern perception; this effect could
not be attributed to involvement of HG. Right anterior tem-
poral lobe resections have also been associated with impaired
working memory for pitch (Zatorre and Samson, 1991),
which is likely to affect perception of long-term structure
in melodies, and more specifically, discrimination tasks
requiring comparisons between sequential stimuli.
Pitch contour (the pattern of ‘ups’ and ‘downs’ in a mel-
ody) and the actual pitch values can be considered as corre-
sponding to psychologically distinct ‘global’ and ‘local’ levels
of pitch processing, respectively (Dowling and Harwood,
1985). These levels can be probed by tasks which require
discrimination of melodies with different pitch contour
(‘global’ tasks) or different actual pitch values with the
same contour (‘local’ tasks), respectively. The local tasks
are often also referred to as interval tasks, as both the abso-
lute value of notes and the intervals before and after them are
changed. A ‘pure’ global task would require transposition
between the melodies compared (like a shift in key) to pre-
vent the use of any local information. However, this renders
the task much harder for non-musicians and the MBEA does
not employ it. That different sites of brain damage may
differentially affect the use of local and global information
in melodies was first demonstrated by Peretz (1990) who
showed that patients with right cerebral hemisphere strokes
could assess neither global nor local information in melodies,
while patients with strokes involving the left hemisphere
could use global but not local information. Isolated impair-
ments of local processing were observed, but isolated impair-
ments of global processing were not, leading Peretz to
propose an influential hierarchical model of co-operation
between the hemispheres. According to this model, the
right hemisphere derives pitch contour, which is then ela-
borated upon by the left hemisphere which fills in the
detailed pitch structure. In the model, prior contour proces-
sing is necessary for actual pitch values to be processed:
lesions involving the right hemisphere therefore compromise
the processing of both contour and the actual pitch values
whereas lesions involving the left hemisphere prevent actual
pitch values being added to the contour provided by the
right hemisphere. This model was supported by the findings
of a temporal lobectomy series (Liegeois-Chauvel et al.,
1998). In this series, isolated deficits of pitch interval proces-
sing were observed with resections of right or left anterior
temporal cortex, whereas deficits of both contour and inter-
val processing were associated with resections of right tem-
poral cortex, and no isolated deficits of contour processing
were found. However, other evidence suggests that the hier-
archical co-operativity model should be qualified. Schuppert
et al. (2000) found that patients with left hemisphere damage
were impaired in the use of both local and global informa-
tion, although isolated deficits in the use of contour infor-
mation were not observed.
Taken together, these studies build on evidence from
functional imaging and suggest that a critical substrate for
Brain (2006), 129, 2533–2553 2543
analysis of the direction of pitch change is located in right-
lateral HG. The analysis of pitch direction in adjacent notes
can be considered as a building block for contour in
sequences of notes, which in turn may be a necessary step
in the analysis of local-pitch information. In the symptom-
led studies shown in Fig. 4 the analysis of pitch pattern
involves right temporal areas beyond HG, whilst the lesion-
led work suggests co-operativity between the hemispheres to
process local and global aspects of that pattern. The data are
broadly congruent with functional imaging studies of normal
subjects showing distributed activation beyond HG when
subjects are presented with pitch sequences as opposed to
monotonous pitch (Patterson et al., 2002). The functional
imaging literature has not yet systematically addressed local
and global analysis.
Pitch: tonal structure
Few clinical studies have addressed the analysis of tonal
structure as a specific component of musical listening.
Tonal structure refers to rule-based patterns of pitch deter-
mined by key. While both tonal and atonal pitch patterns
exhibit global and local structure, tonal structure is specific to
Downloaded from by guest on January 16, 2015
tonal music (i.e. most Western music composed before the
twentieth century). The most widely used test of this type of
processing is the scale task in the MBEA, which assesses the
ability of subjects to detect notes that are out of key. Deficits
in tonal analysis have been associated with damage involving
a predominantly right-sided network of non-primary audi-
tory cortical areas including lateral HG, PT, parieto-temporal
junction, insula, anterior STG and frontal operculum (Fig. 4).
The frontal opercular involvement is proportionately greater
than other aspects of pitch processing, but the number of
studies is small. Functional imaging of neurologically normal
individuals suggests a particular involvement of the frontal
lobes in tonal analysis, but the studies are based on different
techniques and show different loci for frontal lobe involve-
ment (Janata et al., 2002; Koelsch and Siebel, 2005).
Timbre
Timbral perception has a number of dimensions that can be
related to different acoustic properties of the incoming
sound, and lesions affecting any or all of these dimensions
could in principle lead to a deficit of timbre perception.
Many clinical studies include reports of perceptual altera-
tions in the perceived quality of music (often described as
unpleasant, ‘flat’ or ‘mechanical’ in nature) or inability
to recognize musical instruments, which might represent
specific defects of timbre perception. However, timbre as
a distinct functional component of music has only been
assessed infrequently in the clinical literature (Supplemen-
tary Tables 1 and 2). This evidence suggests that a network of
areas in the right superior-temporal lobe that overlaps closely
with areas implicated in pitch pattern analysis is critical for
normal timbre perception (Fig. 4). Timbral deficits have
generally been observed in conjunction with pitch pattern
2544 Brain (2006), 129, 2533–2553
deficits (Supplementary Table 1); however, timbral deficits
with spared pitch pattern perception have also been
described after strokes involving right STG (Kohlmetz
et al., 2003; Mazzucchi et al., 1982). The deficits may extend
to the discrimination of timbre in voices and environmental
sounds (Mazzucchi et al., 1982).
These findings from the symptom-led literature are mir-
rored by studies of temporal lobectomy series (Supplemen-
tary Table 2). Right temporal lobectomy leads to deficits in
the perception of timbral change when this is in the spectral
dimension (Milner, 1962; Samson and Zatorre, 1994), tem-
poral dimension (Samson and Zatorre, 1994), or both
(Samson et al., 2002). This last study also suggested a subtle
effect of left temporal lobectomy deficit on the processing of
timbre associated with melodies but not single notes.
The pre-eminence of non-primary auditory cortical areas
in timbre processing and the close relation between timbre
and pitch perception is supported by emerging evidence
from normal functional imaging studies (Menon et al.,
2002; Warren et al., 2005). The analysis of particular dimen-
sions of timbre is a clear direction for future studies of
individual patients (Kohlmetz et al., 2003).
Temporal structure: time interval, rhythm
and metre
Like pitch perception, the perception of timing information
in music can be analysed hierarchically: the lowest level of
temporal processing that we consider here corresponds to
the detection of simple durational differences in a tone or
detection of a silent interval between two tones. These basic
timing elements can be built into more complex structures
embedded in metre and rhythm. Schuppert et al. (2000)
propose a hierarchal scheme where metre and rhythm can
be considered as global and local properties in the
time-domain. The symptom-led evidence implicates predo-
minantly right-sided non-primary auditory cortical areas
posterior to HG in the perception of time interval differ-
ences, and bilateral areas widely distributed beyond HG in
the perception of rhythm (Fig. 4). Evidence from lesion-led
studies broadly supports a bilateral organization: impaired
durational processing has been described following right
temporal lobectomy (Milner, 1962) and impaired gap detec-
tion following left temporo-parietal strokes (Robin et al.,
1990). Impaired detection of rhythmic violations has been
described in left temporo-parietal stroke (Robin et al., 1990)
and left hippocampal sclerosis (Samson et al., 2001), while
other studies have not demonstrated laterality differences
(Shapiro et al., 1981; Peretz, 1990; Schuppert et al., 2000).
At least some of these apparent discrepancies in lateralization
may reflect task effects: for example, the detection of rhyth-
mic errors in familiar tunes (Prior et al., 1990; Samson et al.,
2001) may require musical processing that is not required for
the discrimination of simple rhythmic patterns.
Comparatively few studies of metrical processing have
been conducted and evidence for a critical brain substrate
L. Stewart et al.
remains inconclusive. This is likely to be due at least in part
to the difficulty of assessing metre reliably, particularly in
subjects without formal musical training. In the small
symptom-led literature, impairments of metre perception
have been associated with individual lesions widely distrib-
uted in both cerebral hemispheres (Fig. 3). This pattern has
been echoed in lesion-led studies. In temporal lobectomy
series, Liegeois-Chauvel et al. (1998) found metrical impair-
ments following left and right anterior temporal lobe resec-
tions, while Kester et al. (1991) found a specific decrement in
performance following right but not left anterior temporal
resection. Neither Ayotte et al. (2000) nor Peretz (1990)
found stroke patients with heterogeneous left and right
hemisphere strokes to be impaired relative to neurologically
normal control subjects, while Schuppert et al., (2000) found
that both left and right hemispheric stroke patients were
impaired relative to controls.
Though still tentative, the clinical evidence suggests a con-
vergence with functional imaging data in healthy subjects, at
least in terms of the overlap between the processing mechan-
isms within the domains of pitch and temporal structure
(Griffiths et al., 1999). It is striking that no lesion studies
included in our review have implicated the cerebellum in
Downloaded from by guest on January 16, 2015
disorders of rhythm, since functional imaging studies
(Mathiak et al., 2004) and work in cerebellar patients
(Mangels et al., 1998; Harrington et al., 2004) suggest a
role for the cerebellum in temporal processing. This may
reflect selection bias, since all cases included in our review
were required to incorporate a ‘systematic and objective
evaluation of musical listening’ and patients presenting
with a timing deficit may be less likely to be tested
for other aspects of musical listening, compared with
patients presenting with deficts in the pitch domain.
Memory: familiar and novel material
Impaired recognition of familiar tunes is described in a
number of studies (Lechevalier et al., 1984; Peretz et al.,
1994, 1998; Griffiths et al., 1997; Johannes et al., 1998;
Peretz and Gagnon, 1999; Ayotte et al., 2000; Piccirilli
et al., 2000; Wilson et al., 2002; Satoh et al., 2005). In all
these cases, recognition problems were accompanied by
impaired pitch-pattern perception. However, perception
and recognition can sometimes dissociate. Patients may
have intact perception but impaired recognition (Eustache
et al., 1990 (case 1); Peretz, 1996) or the converse (Eustache
et al., 1990 (case 2); Schuppert et al., 2000). The presence of
intact perception with impaired recognition also occurs in
visual disorders, where that dissociation has been termed
associative (as opposed to apperceptive) agnosia (Lissauer,
1890). By analogy with models for vision, apperceptive
amusia could arise from abnormal perception of incoming
musical material, whereas associative amusia could arise
from abnormal association of normally perceived music
with stored representations. Cases of abnormal perception
of music in the presence of normal recognition of familiar
Disorders of musical listening
tunes are not predicted by hierarchal models of normal func-
tion, where perception precedes association. The dissociation
may be explained by the presence of multiple cues that can
lead to recognition of familiar tunes that allow deficits in
particular domains to be overcome.
Figs 3 and 4 demonstrate that deficits in the perception
and recognition of familiar tunes may occur with damage in
either cerebral hemisphere involving the anterior STG and
insula (Lechevalier et al., 1984; Peretz et al., 1994, 1998;
Peretz and Gagnon, 1999; Satoh et al., 2005). In the lesion-
led literature, familiar-tune recognition was found to be
deficient specifically in association with damage involving
the right insula (Ayotte et al., 2000).
Impaired recognition of novel material is tested in the
incidental memory test from the MBEA, which assesses
implicit encoding and retrieval of novel musical material.
Clinical impairments of musical incidental memory are asso-
ciated with damage involving a bilateral network of areas that
closely overlaps the network implicated in the recognition of
familiar tunes (Fig. 4), and extends into left middle and
inferior temporal cortex. In temporal lobectomy series, inci-
dental memory deficits have been described following both
right and left anterior resections (Zatorre, 1985; Samson and
Zatorre, 1992).
Emotion
Most people listen to music purely for the aesthetic pleasure
it brings. A loss of enjoyment in musical listening is a com-
mon presenting complaint in clinical disorders of musical
listening (Supplementary Table 1). In many cases, this loss of
pleasure is accompanied by a perceptual derangement: ‘like
an out of tune child’s dulcimer’ (Griffiths et al., 1997),
‘mechanical’ (Griffiths et al., 2006) or ‘instruments [may
lose] their distinctive features of timbre and sound dull’
(Piccirilli et al., 2000). Associated impairments of pitch pat-
tern perception (Habib et al., 1995) and generalized auditory
agnosia (Mazzucchi et al., 1982) have been documented. The
most consistent association of altered emotional response to
music across studies is damage involving the right posterior
temporal lobe and insula (Fig. 4). However, few clinical
studies have specifically assessed musical emotion.
Just as perception and recognition for musical material
may dissociate, so too may perception and emotional
response to music. Isolated deficits of musical emotional
response have been described: the patient of Griffiths et al.
(2004) had been used to experiencing an emotional trans-
formation while listening to Rachmaninov preludes (the ‘shi-
ver down the spine’ phenomenon) but this was lost following
an infarction involving left amygdala and insula. In a tem-
poral lobectomy series (Gosselin et al., 2005), patients who
had undergone resections of the left or right medial temporal
lobe, including the amygdala but sparing the STG, found
fearful music less scary than a group of matched controls.
Conversely, intact emotional response despite impaired
music perception has also been observed (Lechevalier et al.,
1984; Peretz et al., 1998; Peretz and Gagnon, 1999). The
Brain (2006), 129, 2533–2553 2545
patient of Peretz et al. (1998) still derived pleasure from
music, and was able to classify tunes as happy or sad and
to discriminate tunes based on emotional tone despite severe
perceptual and recognition impairments.
These findings are consistent with the emerging functional
imaging evidence in neurologically normal individuals impli-
cating the insula and amygdala as crucial mediators of the
emotional response to music as for other kinds of affective
stimuli (Blood et al., 1999; Blood and Zatorre, 2001). How-
ever, the complex nature of the emotional dimension in
music makes it necessary for clinical studies to adopt
more sophisticated methodologies derived from basic neu-
roscience in order to dissect apart the critical brain substrates
for musical emotion. There may be a hierarchy of emotional
responses analogous to those identified for pitch and tem-
poral information: the perception of sounds as consonant
and dissonant is universal in Western culture, whilst the
subject-specific associative phenomenon of ‘shiver’ may be
considered to be an aspect of emotion which is context
dependent.
Developmental disorders of musical
Downloaded from by guest on January 16, 2015
listening
Case reports of lifelong tone-deafness go back more than a
century, but it has only been in the last five years that the
condition has undergone systematic investigation using the
same tools that have been applied to acquired disorders of
musical listening. The disorder was first characterized in this
way by Peretz and colleagues using the MBEA and given the
label ‘congenital amusia’ (Ayotte et al., 2002). This term
emphasises the disorder as a true perceptual agnosia, in
which the perception of music is abnormal in the presence
of normal hearing and otherwise preserved cognition. Inter-
estingly, the symptom that leads to the initial identification
of such subjects is often an inability to sing (usually picked
up by their friends and relatives rather than the subjects
themselves). However, the systematic studies below consis-
tently demonstrate musical perceptual abnormalities. It
remains unclear whether the disorder is homogeneous or
whether it has more than one underlying basis. Deficits in
the pitch domain are most striking, but variable, whilst the
presence of abnormality in other domains is not a consistent
finding.
Pitch
Formal characterization of musical perception using the
MBEA (Ayotte et al., 2002) demonstrates consistent deficits
in the domain of pitch-pattern perception (pitch contour,
actual pitch value and key structure). Our group (Foxton
et al., 2004) has carried out tests in which processing of basic
pitch patterns are assessed. The group of subjects identified
as having amusia using the MBEA and criteria of Peretz were
found to have abnormal perception of pitch change and
pitch direction, the most striking changes being demon-
strated for pitch direction. Most subjects in the amusic
2546 Brain (2006), 129, 2533–2553
group had thresholds for the identification of pitch direction
that were well above a semitone (the normal threshold is a
fraction of a semitone) and likely relevant to the perception
of Western music. Given that pitch direction can be thought
of as a ‘building block’ for contour (the pattern of ‘ups’ and
‘downs’ in a melody), this work suggests a fundamental
deficit in pitch processing that is below the level of melody
processing. However, the presence of such a causative deficit
would predict that the deficit could be overcome by creating
melodic sequences with large intervals. The fact that this is
not the case (Foxton et al., 2004) argues against a simple low-
level deficit in pitch direction as a single causal mechanism
for melodic deficits in amusia. However, it remains possible
that an inability to analyse pitch direction leads to a failure to
develop normal pitch pattern perception even in the pre-
sence of large intervals (i.e. a two-stage mechanism).
A question that arises immediately is whether deficits in
pitch contour analysis extend to the ‘melody of speech’
(Monrad-Krohn, 1947), which is one aspect of prosody.
In normal speech, pitch contour allows us to understand
the difference between phrases that are statements and
phrases that are questions. It also conveys emotional empha-
sis and the characteristics of regional accents. Although, a
number of cases of disordered perception of pitch contour in
speech have been found in association with acquired amusia,
developmental amusia subjects have not been found to have
such deficits. When required to discriminate sentences that
differed in their intonation, amusics were found to perform
as well as controls. However, when the phrases were replaced
by sequences of discrete notes that matched the mean pitch
of each syllables (Ayotte et al., 2002) or a continuous pitch
‘track’ matched to the speech (Patel et al., 2005), amusic
subjects could not perceive the difference. Peretz and
Hyde (2003) originally suggested that the preservation of
this aspect of prosody in speech was due to the larger
pitch changes in speech compared to Western music. The
data based on ‘extracted’ pitch contour (Ayotte et al., 2002
and Patel et al., 2005) do not allow such a straightforward
interpretation. One possibility is that the amusic subjects can
achieve normal performance on the intonation task by rely-
ing on cues other than pitch contour, such as intensity dif-
ferences.
Temporal structure
Aside from the problem with singing, subjects with amusia
can have problems with ‘following the beat’ and with dan-
cing, consistent with a deficit in the processing of metre and
rhythm. In ‘The Motorcycle Diaries’, Che Guevara (a noted
amusic) dances a tango while those around him dance a
lively mambo (Guevara, 2003). Hyde and Peretz (2003)
found that although subjects with congenital amusia had
a deficit in detection of pitch changes in an otherwise mono-
tonic sequence, their detection of a change in the timing
of a note in an otherwise regular sequence was normal. A
subsequent study in a different group of amusics (Foxton
et al., 2006) replicated the finding of normal detection of
L. Stewart et al.
timing deviation within simple rhythms, but showed that
when subjects were required to detect the same deviation
in a melodic, as opposed to monotonic context, their per-
formance was impaired. The results support a model in
which the abnormal perception of pitch pattern in amusia
also affects the perception of the temporal structure of music.
The result is interesting in view of studies of acquired amusia
(Peretz and Kolinsky, 1993) suggesting that the brain
mechanisms for melodic and rhythmic analysis are separable
up to a certain point, after which they interact.
Emotion
The emotional processing of music in subjects with devel-
opmental amusia is an issue which is ripe for investigation.
Our experience is that this group of individuals exhibits
considerable individual variation with respect to this. Sub-
jects demonstrated to have the same perceptual deficits with
the MBEA can either enjoy music or find it unpleasant: one
subject described Rachmaninov’s second piano concerto as
‘like a banging or noise’. The dissociation between the per-
ception of music and its emotional effect is consistent with
evidence from normal functional imaging and clinical studies
Downloaded from by guest on January 16, 2015
of acquired lesions (Supplementary Table 1) that strongly
suggest distinct substrates. However, the basis for such indi-
vidual variation is unknown.
Neural substrate
The brain basis for congenital amusia has not been exten-
sively investigated. In general these individuals do not have a
history of neurological damage, and structural brain imaging
using MRI reveals no gross structural differences. The
technique of voxel-based morphometry allows structural
MRI data from two or more groups of individuals
(e.g. amusic versus non-amusic individuals) to be interro-
gated with regard to potential regional differences in grey
and white matter density. A recent study demonstrated
changes in white matter density in the inferior right
frontal lobe (Hyde et al., 2006) and EEG studies of responses
to pitch changes (Peretz et al., 2005) have demonstrated
normal N1 responses to tones but abnormal N2-P3
responses at longer latency. The N1 response arises from
the PT whilst the longer latency responses have a number
of more distributed generators. Congruent with the work
based on structural MRI, this work suggests brain abnorm-
alities in amusia that may occur in areas distinct from audi-
tory cortex.
Further studies will be required to ascertain the locus and
nature of the abnormality in these developmental cases. A
straightforward prediction regarding this disorder would be
that one or more of the key nodes of the musical listening
network have failed to develop normally (Fig. 4 would
suggest superior-temporal cortex and areas including
the insula and frontal lobe as candidate regions) but an
alternative prediction, which can be tested with MRI tech-
niques, such as diffusion tensor imaging and dynamic causal
Disorders of musical listening Brain (2006), 129, 2533–2553 2547

modelling, would be that the abnormality lies in the con-
nections between these critical nodes.
Prevalence and genetics
Using a screening test called the Distorted Tunes Test, which
tests the perception of key violation, the prevalence of con-
genital amusia has been estimated to be 5% (Kalmus and
Fry, 1980). A recent study of undergraduates by Cuddy et al.,
(2005) showed that those students who declared themselves
to be tone-deaf scored similarly on the MBEA to a group of
students who did not. This is perhaps unsurprising: the label
tone-deaf is colloquially used to describe those who cannot
sing in tune. Although up to 15% of the population report
difficulties in singing in tune, the majority of these people
can perceive music normally. People with amusia form a
subgroup of out-of-tune singers. Because of their perceptual
difficulties, they are not necessarily aware that they sing out-
of-tune and would be less likely to self-label as tone deaf
compared with people who have singing difficulties but are
perceptually normal. This is congruent with our observation
that subjects are often referred by their relatives, without
being aware of the problem themselves.
Other forms of aberrant musical listening
The preceding sections considered disorders that can be
characterized as deficits in musical listening. This section
considers what might be thought of as exuberant musical
listening: musical perception occurring inappropriately as a
result of sound input or in the absence of sound input.
An example of the former phenomenon is musical
palinacousis: the continued perception of music after the
music has stopped. The latter description defines musical
hallucinations.
General comments
Musical hallucinations have been reported from a number of
perspectives (including those of audiology, neurology and
psychiatry) and the perspective adopted will bias the case
description and interpretation. No studies of unbiased popu-
lations are available, and few studies have carried out a
systematic and thorough assessment of auditory function,
neurological and psychiatric status. The studies that have
been carried out to examine brain substrate, mainly in the
population with deafness, suggest a neural correlate of the
hallucinations in brain networks including the superior-

Downloaded from by guest on January 16, 2015

Studies of concordance rates in twins suggest that musical
listening has a high degree of heritabilty. Drayna et al. (2001)
studied performance on the Distorted Tunes Test in mono-
zygotic and dizygotic twins and estimated that between 70
and 80% of performance variance could be accounted for by
genetic differences. However, it is currently not known
whether congenital amusia captures those individuals at
the low end of the musical listening ability spectrum or
whether it is a categorically distinct condition. Familial
cases are common and autosomal dominant inheritance
with incomplete penetrance has been suggested (Kalmus
and Fry, 1980).
temporal lobes. Aetiological theories often focus on single
factors, but the case reports reveal a number of patients with
co-existent factors that might be relevant.
Musical hallucinations associated with
deafness
Table 3 lists published cases of musical hallucinations and
Supplementary Table 3 characterises the features of the
patients described. The most common associated factor is
acquired deafness, usually in subjects in middle to later life
and more commonly in women. We have now assessed

Table 3 Musical hallucination reports

Agrawal and Sherman (2004) Fisman (1991) Nagaratnam et al. (1996)
Aizenberg et al. (1986) Fukunishi et al. (1998a) Nevins (1991)
Aizenberg et al. (1991) Fukunishi et al. (1998b) Paquier et al. (1992)
Ali (2002) Fukunishi et al. (1999) Patel et al. (1987)
Allen (1985) Gertz et al. (1996) Raghuram et al. (1980)
Baba et al. (2003) Glbert (1993) Roberts et al. (2001)
Berrios (1990) Gilchrist and Kalucy (1983) Ross et al. (1975)
Cascino and Adams (1986) Griffiths (2000) Rozanski and Rosen (1952)
Cerrato et al. (2001) Hammeke et al. (1983) Saba and Keshavan (1997)
Clark (1998) Hecaen and Ropert (1959) Schielke et al. (2000)
Cole et al. (2002) Hermesh et al. (2004) Schiffter and Straschill (1977)
Couper (1994) Inzelberg et al. (1993) Steinberg et al. (1998)
Curtin and Redmund (2002) Izumi et al. (2002) Stricker and Winger (2003)
Douen and Bourque (1997) Kasai et al. (1999) Tanriverdi et al. (2001)
Erkwoh et al. (1993) Keshavan et al. (1988) Terao (1995)
Evers et al. (2002) Lennox (1988) Terao and Tani (1998)
Fenelon et al. (1993) Miller and Crosby (1979) Vallada and Gentil (1991)
Fenton and McRae (1989) Moore (2003) Warner and Aziz (2005)
Fernandez et al. (1998) Mori et al. (2006) Warren and Schott (2006)
Fischer et al. (2004) Murata et al. (1994)

See Supplementary Table 3 for comprehensive description of reports.

2548 Brain (2006), 129, 2533–2553
>20 subjects in this category. Where the audiology data are
specified, subjects usually have moderate to severe deafness,
but the onset of this can be acute or gradual. Prevalence has
been estimated at 2.5% in the deaf elderly attending an
audiology clinic (Cole et al., 2002). Subjects usually complain
of hearing familiar tunes, such as popular songs and hymns
(Griffiths, 2000; Warner and Aziz, 2005). The musical
experience is usually a ‘coherent whole’ in that a formed
percept with melody and rhythm, with or without lyrics,
is experienced. When the subjects are profoundly deaf
and unable to hear music normally the hallucinations are
often experienced in the same way as normal music before
the onset of acquired deafness. The percept can evolve
from tinnitus, and one of our subjects described an inter-
mediate type of percept based on a succession of ‘buzzy’
pitches that formed a melody. More commonly, however,
subjects experience normal musical instruments and voices.
Associated palinacousis is common. The most striking
feature of the phenomenon is its salience: the majority of
subjects that we have seen describe a percept that is so vivid
that they initially feel there is actual music playing in
the room. With time, however, subjects generally come to
attribute the problem to the ears or the brain, and there
is generally no associated delusional system. A number
of treatment strategies have been employed, but in our
experience the only way to help is to improve hearing via
amplification.
The basis for musical hallucinosis in the deaf is not fully
established. Cases with evolution from tinnitus suggest a
possible basis in the cochlea, which has been proposed by
Gordon (1997) as a universal explanation for musical hallu-
cinations. The phenomenology of musical hallucinations,
especially the perception of complex-patterned sequences
and the consistency with previous listening experience,
strongly suggest the involvement of central mechanisms.
Griffiths (2000) suggested a mechanism based on amplified
musical imagery, where the decreased signal-to-noise ratio in
auditory transmission in the deaf leads to the inappropriate
activation of cortical networks usually involved in perception
and imagery. This model can be characterized as an ampli-
fication of normal imagery that is usually suppressed by
auditory input. However, a model based on deafness and
normal central processing cannot account for the fact that
only a small proportion of subjects with moderate or severe
deafness develop the disorder. In our experience, vascular
risk factors other than old age are over-represented, whilst a
number of the patients in Supplementary Table 3 have co-
morbid psychiatric disease.
Studies that examine brain activity during hallucinations
have shown increased activity within the network of areas
demonstrated to be active during normal musical perception.
Griffiths (2000) showed bilateral perfusion increases in ante-
rior and posterior temporal lobes, frontal opercula and cer-
ebellum in a group PET study of four subjects. Kasai et al.
(1999) showed increased perfusion in right anterior
superior-temporal lobe and right frontal operculum using
L. Stewart et al.
SPET (single positron emission tomography) in one subject,
in addition to bilateral alteration in the N100m neuromag-
netic responses that arise from the posterior superior-
temporal lobes. These studies support the idea that the
phenomenon in the deaf is associated with activity in
the normal brain networks that are active during musical
perception and imagery.
Musical hallucinations associated with
neurological disorder
Cases of musical hallucinations where a single neurological
mechanism is likely to be causative are rarer than the cases in
association with deafness. Supplementary Table 3 describes
hallucinations associated with lesions in the brainstem or
right or left cerebral hemispheres. Berrios (1990) has empha-
sized abnormality of the right hemisphere, which, in the
reported cases, is more commonly affected than the left. If
the cases are associated with epileptic foci, the phenomen-
ology of the hallucinations may include experiential features
that are not a feature of cases associated with deafness.
Cases of musical hallucinations in association with degen-
erative disorders are rare, although they have been described
Downloaded from by guest on January 16, 2015
in association with dementia. In one such case, Mori et al.
(2006) reported increased perfusion measured with SPET
in the left temporal lobe and angular gyrus of a patient
with Alzheimer’s disease. A number of other reports
have described musical hallucinations associated with the
acute use of centrally acting drugs (see Supplementary
Table 3).
Musical hallucinations associated with
psychiatric disorder
Auditory musical hallucinations in psychiatric populations
are rarer than auditory verbal hallucinations. The phenom-
enon has been described in association with depression,
schizophrenia, obsessive-compulsive disorder and alcohol-
ism. Berrios (1991) argued that psychosis and personality
traits are not important predisposing factors, and Fukunishi
et al. (1998a) found a prevalence rate of only 0.2%
(six patients) in a population of 3578 general psychiatry
inpatients (three of these patients were deaf). In contrast,
Hermesh et al. (2004) reported a lifetime prevalence of
musical hallucinations of 20% in a population of 190 psy-
chiatric outpatients. A particularly high rate (40%) was
found in obsessive-compulsive disorder.
Robert Schumann suffered musical hallucinations as part
of a psychotic illness. In 1854, he initially experienced a
simple pitch (the note ‘A’), which evolved into ‘magnificent
music, with instrument of splendid resonance, the like of
which has never been heard on earth before’ and which was
incorporated in his violin concerto. The grandiose nature of
this description suggests bipolar disorder, but there is debate
about whether he had neurosyphilis [although there was no
clear evidence for this at autopsy (Janisch and Nauhaus,
1986)].
Disorders of musical listening
Conclusion
The aim of this review has been to produce a practical over-
view of disorders that might be seen in the clinic, rather than
to impose a particular theoretical system. However the dis-
orders described above can be understood in terms of the
broad principles of normal musical listening that were devel-
oped at the start of the review. Normal musical listening
involves the rule based analysis of patterns of sound in dis-
tributed cortical systems extending well beyond the auditory
cortices. Many disorders of musical listening can be under-
stood in terms of altered processing (either deficient or
aberrant processing) within these cortical systems.
Considering the variety of pathological processes, lesion
locations, assessment tools and premorbid abilities that
interact in the disorders of musical listening, the degree
of consensus already achieved between clinical and experi-
mental literatures since Critchley and Henson produced
their landmark work is remarkable. Nevertheless, many indi-
vidual patients do not fit the preliminary consensus, and
only systematic evaluation of further cases will determine
where that consensus should be refined or overturned.
This enterprise will be facilitated by the advent of readily
available techniques for manipulating and presenting musi-
cal stimuli, and analytical methods with which to image the
functioning brain and to delineate functional as well as ana-
tomical connections between brain regions. Such techniques
provide the opportunity to advance beyond brain mapping
and the identification of processing ‘centres’ to more sophis-
ticated and physiologically realistic models based on critical
‘nodes’ in distributed networks with selectivity (rather than
exclusivity) for processing particular perceptual and cogni-
tive components of music. The neuroscience of music will
benefit from current trends in cognitive neuroscience as a
whole: these include improved generic models of complex
cognitive functions, a greater appreciation of the role of
plasticity and learning in human cognition, and a broader
emphasis on the cognitive, affective and social context of
music perception alongside the traditional focus on the ele-
mentary building blocks of music. The emerging apprecia-
tion and understanding of developmental deficits of music
perception is likely to become a key theme in the field,
complementary to the analysis of acute deficits induced
by acquired lesions in previously normal brains. Group stu-
dies of developmental amusia should be supplemented by
more carefully controlled group studies of acquired musical
deficits, by studies that focus specifically on special groups,
such as trained musicians, and by prospective studies of
phenomena, such as musical training that remain poorly
understood.
The clinical neurologist will continue to have a central role
in explaining the many remaining discrepancies, and in elu-
cidating the critical roles played by particular brain regions
within the distributed networks outlined by functional ima-
ging and other techniques in the healthy brain. We look
forward to the further insights that the next thirty years
will surely bring.
Brain (2006), 129, 2533–2553 2549
Supplementary data
Supplementary data are available at Brain Online.
Acknowledgements
Our work is supported by the Wellcome Trust (L.S., J.D.W.
and T.D.G.) and VW Foundation (K.v.K.). J.D.W. received
support from an EC grant to the APOPIS Consortium.
References
Agrawal AK, Sherman LK. Voriconazole-induced musical hallucinations.
Infection 2004; 32: 293–5.
Aizenberg D, Schwartz B, Modai I. Musical hallucinations, acquired deafness,
and depression. J Nerv Ment Dis 1986; 174: 309–11.
Aizenberg D, Dorfman-Etrog P, Zemishlany Z, Hermesh H. Musical
hallucinations and hearing deficit in a young non-psychotic female.
Psychopathology 1991; 24: 45–8.
Ali JA. Musical hallucinations and deafness: a case report and review of
the literature. Neuropsychiatry Neuropsychol Behav Neurol 2002; 15:
66–70.
Allen JR. Salicylate-induced musical perceptions. N Engl J Med 1985;
313: 642–3.
Amunts K, Schlaug G, Jancke L, Steinmetz H, Schleicher A, Dabringhaus A,
et al. Motor cortex and hand motor skills: structural compliance in the
human brain. Hum Brain Mapp 1997; 5: 206–15.
Ashburner J, Friston KJ. Voxel-based morphometry—the methods. Neuro-
Downloaded from by guest on January 16, 2015
image 2000; 11: 805–21.
Ayotte J, Peretz I, Rousseau I, Bard C, Bojanowski M. Patterns of music
agnosia associated with middle cerebral artery infarcts. Brain 2000;
123: 1926–38.
Ayotte J, Peretz I, Hyde K. Congenital amusia. A group study of adults
afflicted with a music-specific disorder. Brain 2002; 125: 238–51.
Baba A, Hamada H, Kocha H. Musical hallucinations in schizophrenia. 2.
Relations with verbal hallucinations. Psychopathology 2003; 36: 104–10.
Belin P, Zatorre RJ, Lafaille P, Ahad P, Pike B. Voice-selective areas in human
auditory cortex. Nature 2000; 403: 309–12.
Bendor D, Wang X. The neuronal representation of pitch in primate auditory
cortex. Nature. 2005; 436: 1161–5.
Bengtsson SL, Nagy Z, Skare S, Forsman L, Forssberg H, Ullen F. Extensive
piano practicing has regionally specific effects on white matter develop-
ment. Nat Neurosci 2005; 8: 1148–50.
Bentley A. Measures of musical abilities. London: NEFR-Nelson; 1985.
Berrios GE. Musical hallucinations. A historical and clinical study. Br J
Psychiatry 1990; 156: 188–94.
Berrios GE. Musical hallucinations: a statistical analysis of 46 cases.
Psychopathology 1991; 24: 356–60.
Bever TG, Chiarello RJ. Cerebral dominance in musicians and nonmusicians.
Science 1974; 185: 537–9.
Blood AJ, Zatorre R. Intensely pleasurable responses to music correlate with
activity in brain regions implicated in reward and emotion. Proc Natl Acad
Sci USA 2001; 98: 11818–23.
Blood AJ, Zatorre RJ, Bermudez P, Evans AC. Emotional responses to pleasant
and unpleasant music correlate with activity in paralimbic brain regions.
Nat Neurosci 1999; 2: 382–7.
Bregman AS. Auditory scene analysis. Cambridge, MA: MIT Press; 1990.
Brown S, Martinez MJ, Parsons LM. Passive music listening spontaneously
engages limbic and paralimbic systems. Neuroreport 2004; 15: 2033–7.
Brust JC. Music and language: musical alexia and agraphia. Brain 1980;
103: 367–92.
Caclin A, McAdams S, Smith BK, Winsberg S. Acoustic correlates of timbre
space dimensions: a confirmatory study using synthetic tones. J Acoust Soc
Am 2005; 118: 471–82.
Cascino GD, Adams RD. Brainstem auditory hallucinosis. Neurology 1986;
36: 1042–7.
Cerrato P, Imperiale D, Giraudo M, Baima C, Grasso M, Lopiano L, et al.
Complex musical hallucinosis in a professional musician with a left
2550 Brain (2006), 129, 2533–2553
subcortical haemorrhage. J Neurol Neurosurg Psychiatry 2001; 71:
280–1.
Clark J. Case history of a patient with musical hallucinations and Parkinson’s
disease. Int J Geriatr Psychiatry 1998; 13: 886–7.
Cole MG, Dowson L, Dendukuri N, Belzile E. The prevalence and
phenomenology of auditory hallucinations among elderly subjects
attending an audiology clinic. Int J Geriatr Psychiatry 2002; 17: 444–52.
Confavreux C, Croisile B, Garassus P, Aimard G, Trillet M. Progressive
amusia and aprosody. Arch Neurol 1992; 49: 971–6.
Couper J. Unilateral musical hallucinations and all that jazz. Aust NZ J
Psychiatry 1994; 28: 516–9.
Critchley M, Henson RA, editors. Music and the brain. Studies in the
neurology of music. London: Heinemann; 1977.
Cuddy LL, Balkwill L-L, Peretz I, Holden RR. Musical difficulties: a study of
‘tone deafness’ among university students. Ann NY Acad Sci 2005;
1060: 311–24.
Curtin F, Redmund C. Musical hallucinations during a treatment with
benzodiazepine. Can J Psychiatry 2002; 47: 789–90.
Di Pietro M, Laganaro M, Leemann B, Schnider A. Receptive amusia:
temporal auditory processing deficit in a professional musician following a
left temporo-parietal lesion. Neuropsychologia 2004; 42: 868–77.
Douen AG, Bourque PR. Musical auditory hallucinosis from Listeria
rhombencephalitis. Can J Neurol Sci 1997; 24: 70–2.
Dowling WJ, Harwood DL. Music and cognition. London: Academic Press;
1985.
Drayna D, Manichaikul A, de Lange M, Snieder H, Spector T. Genetic
correlates of musical pitch recognition in humans. Science 2001;
291: 1969–72.
Erkwoh R, Ebel H, Kachel F, Reiche W, Ringelstein EB, Bull U, et al. 18FDG-
PET and electroencephalographic findings in a patient suffering from
musical hallucinations. Nuklear Medizin 1993; 32: 159–63.
Eustache F, Lechevalier B, Viader F, Lambert J. Identification and
discrimination disorders in auditory perception: a report on two cases.
Neuropsychologia 1990; 28: 257–70.
Evers S, Ellger T, Ringelstein EB, Knecht S. Is hemispheric language
dominance relevant in musical hallucinations? Two case reports. Eur Arch
Psychiatry Clin Neurosci 2002; 252: 299–302.
Fenelon G, Marie S, Ferroir JP, Guillard A. Musical hallucinations: 7 cases.
Rev Neurol (Paris) 1993; 149: 462–7.
Fenton GW, McRae DA. Musical hallucinations in a deaf elderly woman.
Br J Psychiatry 1989; 155: 401–3.
Fernandez A, Crowther TR, Vieweg WV. Musical hallucinations induced by
propranolol. J Nerv Ment Dis 1998; 186: 192–4.
Fischer CE, Marchie A, Norris M. Musical and auditory hallucinations: a
spectrum. Psychiatry Clin Neurosci 2004; 58: 96–8.
Fisman M. Musical hallucinations: report of two unusual cases. Can J
Psychiatry 1991; 36: 609–11.
Foxton JM, Dean JL, Gee R, Peretz I, Griffiths TD. Characterization of deficits
in pitch perception underlying ‘tone deafness’. Brain 2004; 127: 801–10.
Foxton JM, Nandy RK, Griffiths TD. Rhythm deficits in ‘tone deafness’. Brain
Cogn , 2006; Epub May 7, 2006.
Fries W, Swihart AA. Disturbance of rhythm sense following right hemisphere
damage. Neuropsychologia 1990; 28: 1317–23.
Friston KJ, Harrison L, Penny W. Dynamic causal modelling. Neuroimage
2003; 19: 1273–1302.
Fujii T, Fukatsu R, Watabe S, Ohnuma A, Teramura K, Kimura I, et al.
Auditory sound agnosia without aphasia following a right temporal lobe
lesion. Cortex 1990; 26: 263–8.
Fukunishi I, Horikawa N, Onai H. Prevalence rate of musical hallucinations in
a general hospital setting. Psychosomatics 1998a; 39: 175.
Fukunishi I, Kitaoka T, Shirai T, Watanabe S. Musical hallucinations after
childbirth in a female patient on hemodialysis. Nephron 1998b; 79: 105.
Fukunishi I, Kita Y, Harihara Y, Kubota K, Takayama T, Kawarasaki H, et al.
Musical hallucinations after living-donor liver transplantation. Psychoso-
matics 1999; 40: 530–1.
Gaab N, Gaser C, Schlaug G. Improvement-related functional plasticity
following pitch memory training. Neuroimage 2006; 31: 255–63.
L. Stewart et al.
Gaser C, Schlaug G. Brain structures differ between musicians and non-
musicians. J Neurosci 2003; 23: 9240–5.
Gertz HJ, Gohringer K, Schimmelpfennig C. Successful carbamazepine
therapy of 2 cases of music hallucinations. Nervenarzt 1996; 67:
387–9.
Gilbert GJ. Pentoxifylline-induced musical hallucinations. Neurology 1993;
43: 1621–2.
Gilchrist PN, Kalucy RS. Musical hallucinations in the elderly: a variation on
the theme. Aust NZ J Psychiatry 1983; 17: 286–7.
Gordon AG. Do musical hallucinations always arise from the inner ear? Med
Hypotheses 1997; 49: 111–22.
Gordon E. Musical aptitude profile. Boston: Houghton-Mifflin; 1965.
Gosselin N, Peretz I, Noulhiane M, Hasboun D, Beckett C, Baulac M, et al.
Impaired recognition of scary music following unilateral temporal lobe
excision. Brain 2005; 128: 628–40.
Griffiths TD. Musical hallucinosis in acquired deafness. Phenomenology and
brain substrate. Brain 2000; 123: 2065–76.
Griffiths TD, Warren JD. The planum temporale as a computational hub.
Trends Neurosci 2002; 25: 348–53.
Griffiths TD, Rees A, Witton C, Cross PM, Shakir RA, Green GG. Spatial and
temporal auditory processing deficits following right hemisphere infarc-
tion. A psychophysical study. Brain 1997; 120: 785–94.
Griffiths TD, Buchel C, Frackowiak RSJ, Patterson RD. Analysis of temporal
structure in sound by the human brain. Nat Neurosci 1998; 1: 422–7.
Griffiths TD, Johnsrude I, Dean JL, Green GG. A common neural substrate for
the analysis of pitch and duration pattern in segmented sound?
Neuroreport 1999; 10: 3825–30.
Downloaded from by guest on January 16, 2015
Griffiths TD, Uppenkamp S, Johnsrude I, Josephs O, Patterson RD. Encoding
of the temporal regularity of sound in the human brainstem. Nat Neurosci
2001; 4: 633–7.
Griffiths TD, Warren JD, Dean JL, Howard D. ‘When the feeling’s gone’: a
selective loss of musical emotion. J Neurol Neurosurg Psychiatry 2004;
75: 344–5.
Griffiths TD, Warren JD, Jennings AR. Dystimbria: a distinct musical
syndome? In: Proceedings of the Ninth International Conference for
Musical Perception and Cognition, Bologna, Italy, 2006.
Grison B. Une etude sur les alterations musicales au cours des lesions
hemispheriques. [Thesis]. Paris: University of Paris; 1972.
Grossman M, Shapiro BE, Gardner H. Dissociable musical processing
strategies after localized brain damage. Neuropsychologia 1981; 19:
425–33.
Guevara E. The motorcycle diaries: notes on a Latin American journey. New
York: Ocean Press; 2003.
Gutschalk A, Patterson RD, Rupp A, Uppenkamp S, Scherg M. Sustained
magnetic fields reveal separate sites for sound level and temporal regularity
in human auditory cortex. Neuroimage 2002; 15: 207–16.
Habib M, Daquin G, Milandre L, Royere ML, Rey M, Lanteri A, et al. Mutism
and auditory agnosia due to bilateral insular damage - role of the insula in
human communication. Neuropsychologia 1995; 33: 327–39.
Hammeke TA, McQuillen MP, Cohen BA. Musical hallucinations associated
with acquired deafness. J Neurol Neurosurg Psychiatry 1983; 46: 570–2.
Harms MP, Melcher JR, Weisskoff R. Time courses of fMRI signals in the
inferior colliculus, medial geniculate body, and auditory cortex show
different dependencies on noise burst rate. Neuroimage 1998; 7: S365.
Harrington DL, Lee RR, Boyd LA, Rapcsak SZ, Knight RT. Does the
representation of time depend on the cerebellum? Brain 2004; 127: 561–74.
Hattiangadi N, Pillion JP, Slomine B, Christensen J, Trovato MK, Speedie LJ.
Characteristics of auditory agnosia in a child with severe traumatic brain
injury: a case report. Brain Lang 2005; 92: 12–25.
Hecaen H, Ropert R. Ann Med Psychol (Paris) 1959; 117: 257–306.
Hermesh H, Konas S, Shiloh R, Dar R, Marom S, Weizman A, et al. Musical
hallucinations: prevalence in psychotic and nonpsychotic outpatients. J Clin
Psychiatry 2004; 65: 191–7.
Hofman S, Klein C, Arlazoroff A. Common hemisphericity of language and
music in a musician. A case report. J Commun Disord 1993; 26: 73–82.
Huber W, Weniger D, Poeck K, Willmes K. The Aachen aphasia test. Adv
Neurol 1984; 42: 291–303.
Disorders of musical listening
Hutchinson S, Lee LH, Gaab N, Schlaug G. Cerebellar volume of musicians.
Cereb Cortex 2003; 13: 943–9.
Hyde KL, Peretz I. ‘Out-of-pitch’ but still ‘in-time’. An auditory
psychophysical study in congenital amusic adults. Ann NY Acad Sci
2003; 999: 173–6.
Hyde KL, Zatorre RJ, Griffiths TD, Lerch JP, Peretz I. The brain morphometry
of congenital amusic individuals. Brain 2006. In press.
Inzelberg R, Vishnievskaya S, Korczyn AD. Transient musical hallucinosis.
J Neurol Neurosurg Psychiatry 1993; 56: 833.
Izumi Y, Terao T, Ishino Y, Nakamura J. Differences in regional cerebral
blood flow during musical and verbal hallucinations. Psychiatry Res 2002;
116: 119–23.
Janata P, Birk JL, Van Horn JD, Leman M, Tillmann B, Bharucha JJ. The
cortical topography of tonal structures underlying Western music. Science
2002; 298: 2167–70.
Janisch W, Nauhaus G. Autopsy report of the corpse of the composer Robert
Schumann - publication and interpretation of a rediscovered document.
Zentralbl Allg Pathol 1986; 132: 129–36.
Johannes S, Jobges ME, Dengler R, Munte TF. Cortical auditory disorders: a
case of non-verbal disturbances assessed with event-related brain
potentials. Behav Neurol 1998; 11: 55–73.
Johkura K, Matsumoto S, Hasegawa O, Kuroiwa Y. Defective auditory
recognition after small hemorrhage in the inferior colliculi. J Neurol Sci
1998; 161: 91–6.
Johnsrude IS, Penhune VB, Zatorre RJ. Functional specificity in right
human auditory cortex for perceiving pitch direction. Brain 2000;
123: 155–63.
Kalmus H, Fry DB. On tune deafness (dysmelodia): frequency, development,
genetics and musical background. Ann Hum Genet 1980; 43: 369–82.
Kasai K, Asada T, Yumoto M, Takeya J, Matsuda H. Evidence for functional
abnormality in the right auditory cortex during musical hallucinations.
Lancet 1999; 354: 1703–4.
Keshavan MS, Kahn EM, Brar JS. Musical hallucinations following removal of
a right frontal meningioma. J Neurol Neurosurg Psychiatry 1988;
51: 1235–6.
Kester DB, Saykin AJ, Sperling MR, O’Connor MJ, Robinson LJ, Gur RC.
Acute effect of anterior temporal lobectomy on musical processing.
Neuropsychologia 1991; 29: 703–8.
Koelsch S, Siebel WA. Towards a neural basis of music perception. Trends
Cogn Sci 2005; 9: 578–84.
Koelsch S, Fritz T, V Cramon DY, Muller K, Friederici AD. Investigating
emotion with music: an fMRI study. Hum Brain Mapp 2006; 27:
239–50.
Kohlmetz C, Muller SV, Nager W, Munte TF, Altenmuller E. Selective loss of
timbre perception for keyboard and percussion instruments following a
right temporal lesion. Neurocase 2003; 9: 86–93.
Lechevalier B, Rossa Y, Eustache F, Schupp C, Boner L, Bazin C. Un cas de
surdit, corticale, pargnant en partie la musique. Rev Neurol 1984;
140: 190–201.
Lennox G. Auditory hallucinations due to ear disease. Br J Psychiatry 1988;
153: 713–4.
Levin HS, Rose JE. Alexia without agraphia in a musician after transcallosal
removal of a left intraventricular meningioma. Neurosurgery 1979;
4: 168–174.
Levitin DJ, Menon V. Musical structure is processed in ‘language’ areas of the
brain: a possible role for Brodmann area 47 in temporal coherence.
Neuroimage 2003; 20: 2142–52.
Liberman AM, Mattingly IG. The motor theory of speech perception revised.
Cognition 1985; 21: 1–36.
Liegeois-Chauvel C, Peretz I, Babai M, Laguittin V, Chauvel P. Contribution
of different cortical areas in the temporal lobes to music processing. Brain
1998; 121: 1853–67.
Lissauer H. Ein Fall von Seelenblindheit nebst einem Beitrage zur Theorie
derselben. Arch Psychiatr Nervenkr 1890; 21: 222–70.
Logothetis NK, Pauls J, Augath M, Triniath T, Oeltermann A. Neurophy-
siological investigation of the basis of the fMRI signal. Nature 2001;
412: 150–7.
Brain (2006), 129, 2533–2553 2551
Luders E, Gaser C, Jancke L, Schlaug G. A voxel-based approach to gray
matter asymmetries. Neuroimage 2004; 22: 656–64.
Mangels AR, Ivry RB, Shimizu N. Dissociable contributions of the prefrontal
and neocerebellar cortex to time perception. Brain Res Cogn Brain Res
1998; 7: 15–39.
Mathiak K, Hertrich I, Grodd W, Ackermann H. Discrimination of temporal
information at the cerebellum: functional magnetic resonance imaging of
nonverbal auditory memory. Neuroimage 2004; 21: 154–62.
Mavlov L. Amusia due to rhythm agnosia in a musician with left hemisphere
damage: a non-auditory supramodal defect. Cortex 1980; 16: 331–8.
Mazzoni M, Moretti P, Pardossi L, Vista M, Muratorio A, Puglioli M.
A case of music imperception. J Neurol Neurosurg Psychiatry 1993;
56: 322.
Mazzucchi A, Marchini C, Budai R, Parma M. A case of receptive amusia with
prominent timbre perception defect. J Neurol Neurosurg Psychiatry 1982;
45: 644–7.
McAdams S, Cunible JC. Perception of timbral analogies. Philos Trans R Soc
Lond B Biol Sci 1992; 336: 383–9.
McDermott J, Hauser M. The origins of music: innateness, development, and
evolution. Music Percept 2005; 23: 29–59.
Mendez MF, Geehan GR. Cortical auditory disorders:clinical and psychoa-
coustic features. J Neurol Neurosurg Psychiatry 1988; 51: 1–9.
Menon V, Levitin DJ, Smith BK, Lembke A, Krasnow BD, Glazer D, et al.
Neural correlates of timbre change in harmonic sounds. Neuroimage 2002;
17: 1742–54.
Miller TC, Crosby TW. Musical hallucinations in a deaf elderly patient. Ann
Neurol 1979; 5: 301–2.
Downloaded from by guest on January 16, 2015
Milner B. Laterality effects in audition. In: Mountcastle VB, editor.
Interhemispheric relations and cerebral dominance. Baltimore: Johns
Hopkins University Press; 1962. p. 177–95.
Monrad-Krohn GH. Dysprosody or altered ‘melody of language’. Brain 1947;
70: 405–15.
Moore TA. Musical hallucinations induced by oxycodone. Am J Geriatr
Psychiatry 2003; 11: 470.
Mori T, Ikeda M, Fukuhara R, Sugawara Y, Nakata S, Matsumoto N, et al.
Regional cerebral blood flow change in a case of Alzheimer’s disease with
musical hallucinations. Eur Arch Psychiatry Clin Neurosci 2006; 256:
236-9.
Murata S, Naritomi H, Sawada T. Musical auditory hallucinations caused by a
brainstem lesion. Neurology 1994; 44: 156–8.
Nagaratnam N, Virk S, Brdarevic O. Musical hallucinations associated with
recurrence of a right occipital meningioma. Br J Clin Pract 1996; 50:
56–7.
Nevins MA. Musical hallucinations and triazolam use. N J Med 1991;
88: 907–8.
Paquier P, van Vugt P, Bal P, Cras P, Parizel PM, van Haesendonck J, et al.
Transient musical hallucinosis of central origin:a review and clinical study.
J Neurol Neurosurg Psychiatry 1992; 55: 1069–73.
Patel AD, Balaban E. Temporal patterns of human cortical activity reflect tone
sequence structure. Nature 2000; 404: 80–84.
Patel AD, Peretz I, Tramo M, Labreque R. Processing prosodic and musical
patterns: a neuropsychological investigation. Brain Lang 1998; 61:
123–44.
Patel AD, Foxton JM, Griffiths TD. Musically tone-deaf individuals have
difficulty discriminating intonation contours extracted from speech. Brain
Cogn 2005; 59: 310–3.
Patel HC, Keshavan MS, Martin S. A case of Charles Bonnet syndrome with
musical hallucinations. Can J Psychiatry 1987; 32: 303–4.
Patterson RD, Uppenkamp S, Johnsrude IS, Griffiths TD. The processing of
temporal pitch and melody information in auditory cortex. Neuron 2002;
36: 767–76.
Penagos H, Melcher JR, Oxenham AJ. A neural representation of pitch
salience in nonprimary human auditory cortex revealed with functional
magnetic resonance imaging. J Neurosci 2004; 24: 6810–15.
Penhune VB, Zatorre RJ, Evans AC. Cerebellar contributions to motor timing:
a PET study of auditory and visual rhythm reproduction. J Cogn Neurosci
1998; 10: 752–65.
2552 Brain (2006), 129, 2533–2553
Peretz I. Processing of local and global musical information by unilateral
brain-damaged patients. Brain 1990; 113: 1185–205.
Peretz I. Can we lose memory for music? A case of music agnosia in a non-
musician J Cogn Neurosci 1996; 8: 481–96.
Peretz I, Kolinsky R. Boundaries of separability between melody and rhythm
in music discrimination: a neuropsychological perspective. Q J Exp Psychol
A 1993; 46: 301–25.
Peretz I, Gagnon L. Dissociation between recognition and emotion for
melodies. Neurocase 1999; 5: 21–30.
Peretz I, Coltheart M. Modularity of music processing. Nat Neurosci 2003;
6: 688–91.
Peretz I, Hyde KL. What is specific to music processing? Insights from
congenital amusia. Trends Cogn Sci 2003; 7: 362–7.
Peretz I, Zatorre RJ. Brain organization for music processing. Annu Rev
Psychol 2005; 56: 89–114.
Peretz I, Kolinsky R, Tramo M, Labrecque R, Hublet C, Demeurise G, et al.
Functional dissociations following bilateral lesions of auditory cortex.
Brain 1994; 117: 1283–1301.
Peretz I, Belleville S, Fontaine F. Dissociations entre musique et langage apres
atteine cerebrale; un nouveau cas d’amusie sans aphasie. Can J Exp Psychol
1997; 51: 354–68.
Peretz I, Cagnon L, Bouchard B. Music and emotion: perceptual
determinants, immediacy, and isolation after brain damage. Cognition
1998; 68: 111–41.
Peretz I, Blood AJ, Penhune V, Zatorre R. Cortical deafness to dissonance.
Brain 2001; 124: 928–40.
Peretz I, Champod A-S, Hyde KL. Varieties of musical disorders. The
Montreal battery of evaluation of amusia. Ann NY Acad Sci 2003; 999: 58.
Peretz I, Brattico E, Tervaniemi M. Abnormal electrical brain responses to
pitch in congenital amusia. Ann Neurol 2005; 58: 478–82.
Phillips-Silver J, Trainor LJ. Feeling the beat: movement influences infant
rhythm perception. Science 2005; 308: 1430.
Piccirilli M, Sciarma T, Luzzi S. Modularity of music: evidence from a case of
pure amusia. J Neurol Neurosurg Psychiatry 2000; 69: 541–5.
Plack CJ, Oxenham AJ, Fay RR, Popper AN, editors. Pitch: neural coding and
perception. New York: Springer Verlag; 2006 In press.
Price C, Thierry G, Griffiths T. Speech-specific auditory processing: where is
it? Trends Cogn Sci 2005; 9: 271–6.
Prior M, Kinsella G, Giese J. Assessment of musical processing in brain-
damaged patients: implications for laterality of music. J Clin Exp
Neuropsychol 1990; 12: 301–12.
Rademacher J, Morosan P, Schormann T, Schleicher A, Werner C, Freund H-
J, et al. Probabalistic mapping and volume measurement of human primary
auditory cortex. Neuroimage 2001; 13: 669–83.
Raghuram R, Keshavan MD, Channabasavanna SM. Musical hallucinations in
a deaf middle-aged patient. J Clin Psychiatry 1980; 41: 357.
Roberts DL, Tatini U, Zimmerman RS, Bortz JJ, Sirven JI. Musical
hallucinations associated with seizures originating from an intracranial
aneurysm. Mayo Clinic Proc 2001; 76: 423–6.
Robin DA, Tranel D, Damasio H. Auditory perception of temporal and
spectral events in patients with focal left and right cerebral lesions. Brain
Lang 1990; 39: 539–55.
Ross ED, Jossman PB, Bell B, Sabin T, Geschwind N. Musical hallucinations in
deafness. JAMA 1975; 231: 620–2.
Rozanski J, Rosen H. Musical hallucinosis in otosclerosis. Confin Neurol
1952; 12: 49–54.
Saba PR, Keshavan MS. Musical hallucinations and musical imagery:
prevalence and phenomenology in schizophrenic inpatients. Psycho-
pathology 1997; 30: 185–90.
Sakai K, Hikosaka O, Miyauchi S, Takino R, Tamada T, Iwata NK, et al.
Neural representation of a rhythm depends on its interval ratio. J Neurosci
1999; 19: 10074–81.
Samson S, Zatorre RJ. Melodic and harmonic discrimination following
unilateral cerebral excision. Brain Cogn 1988; 7: 348–60.
Samson S, Zatorre RJ. Recognition memory for text and melody of songs after
unilateral temporal lobe lesion: evidence for dual encoding. J Exp Psychol
Learn Mem Cogn 1991; 17: 793–804.
L. Stewart et al.
Samson S, Zatorre RJ. Learning and retention of melodic and verbal
information after unilateral temporal lobectomy. Neuropsychologia 1992;
30: 815–26.
Samson S, Zatorre RJ. Contribution of the right temporal lobe to musical
timbre discrimination. Neuropsychologia 1994; 32: 231–40.
Samson S, Ehrle N, Baulac M. Cerebral substrates for musical temporal
processes. Ann NY Acad Sci 2001; 930: 166–78.
Samson S, Zatorre RJ, Ramsay JO. Deficits of musical timbre perception after
unilateral temporal lobe lesion revealed with multidimensional scaling.
Brain 2002; 125: 511–23.
Satoh M, Takeda K, Murakami Y, Onouchi K, Inoue K, Kuzuhara S. A case of
amusia caused by the infarction of anterior portion of bilateral temporal
lobes. Cortex 2005; 41: 77–83.
Schielke E, Reuter U, Hoffmann O, Weber JR. Musical hallucinations with
dorsal pontine lesions. Neurology 2000; 55: 454–5.
Schlaug G, Jancke L, Huang Y, Staiger JF, Steinmetz H. Increased corpus
callosum size in musicians. Neuropsychologia 1995a; 33: 1047–55.
Schlaug G, Jancke L, Huang Y, Steinmetz H. In vivo evidence of structural
brain asymmetry in musicians. Science 1995b; 267: 699–701.
Schneider P, Scherg M, Dosch HG, Specht HJ, Gutschalk A, Rupp A.
Morphology of Heschl’s gyrus reflects enhanced activation in the auditory
cortex of musicians. Nat Neurosci 2002; 5: 688–94.
Schuppert M, Munte TF, Wieringa BM, Altenmuller E. Receptive amusia:
evidence for cross-hemispheric neural networks underlying music
processing strategies. Brain 2000; 123: 546–59.
Seashore CE. The psychology of musical talent. Boston: Silver, Burdett and
Company; 1919.
Downloaded from by guest on January 16, 2015
Shankweiler D. Effects of temporal lobe damage on the perception
of dichotically presented melodies. J Comp Physiol Psychol 1966; 62:
115–9.
Shapiro BE, Grossman M, Gardner H. Selective musical processing deficits in
brain damaged populations. Neuropsychologia 1981; 19: 161–9.
Shiffter R, Straschill M. Aura continua musicalis - bericht uber einen
Krankheitsfall mit sensorishem Status epilepticus. Nervenarzt 1977;
48: 321–5.
Sidtis JJ, Volpe BT. Selective loss of complex-pitch or speech discrimination
after unilateral lesion. Brain Lang 1988; 34: 235–45.
Spreen O, Benton AL, Fincham RW. Auditory agnosia without aphasia. Arch
Neurol 1965; 13: 84–92.
Steinberg R, Flesch M, Gunther W. Schizophrenic symptoms and the
perception of sound. In: Nielzen S, Olsson O, editors. Clinical
psychoacoustics - schizophrenia. Lund: Lund University Press; 1998.
Stewart L, Henson R, Kampe K, Walsh V, Turner R, Frith U. Brain changes
after learning to read and play music. Neuroimage 2003; 20: 71–83.
Stricker RB, Winger EE. Musical hallucinations in patients with Lyme disease.
South Med J 2003; 96: 711–5.
Tanaka Y, Yamadori A, Mori E. Pure word deafness following bilateral lesions.
Brain 1987; 110: 381–403.
Tanriverdi N, Sayilgan MA, Ozcurumez G. Musical hallucinations associated
with abruptly developed bilateral loss of hearing. Acta Psychiatr Scand
2001; 103: 153–5.
Terao T. Tricyclic-induced musical hallucinations and states of relative
sensory deprivation. Biol Psychiatry 1995; 38: 192–3.
Terao T, Tani Y. Carbamazepine treatment in a case of musical
hallucinations with temporal lobe abnormalities. Aust NZ J Psychiatry
1998; 32: 454–6.
Terao Y, Mizuno T, Shindoh M, Sakurai Y, Ugawa Y, Kobayashi S, et al. Vocal
amusia in a professional tango singer due to a right superior-temporal
cortex infarction. Neuropsychologia 2005; 44: 479–88.
Tramo MJ, Bharucha JJ. Musical priming by the right hemisphere post-
callosotomy. Neuropsychologia 1991; 29: 313–25.
Tramo MJ, Bharucha JJ, Musiek FE. Music perception and cognition
following bilateral lesions of auditory cortex. J Cogn Neurosci 1990;
2: 195–212.
Tramo MJ, Shah GD, Braida LD. Functional role of auditory cortex in
frequency processing and pitch perception. J Neurophysiol 2002;
87: 122–39.
Disorders of musical listening
Ustvedt HI. Ueber die Untersuchung der musikalischen Funktionen bei
Patienten mit Gehirnleiden besonders bei Patienten mit Aphasie. Acta Med
Scand 1937; 86: 1–186.
Vallada HP, Gentil V. Musical hallucinations triggered by clomipramine? Br J
Psychiatry 1991; 159: 888–9.
Warner N, Aziz V. Hymns and arias: musical hallucinations in older people in
Wales. Int J Geriatr Psychiatry 2005; 20: 658–60.
Warren JD, Jennings AR, Griffiths TD. Analysis of the spectral envelope of
sounds by the human brain. Neuroimage 2005; 24: 1052–7.
Warren JD, Schott G. Musical hallucinations in a musician. J Neurol 2006.
In press.
Warrier CM, Zatorre RJ. Right temporal cortex is critical for utilization of
melodic contextual cues in a pitch constancy task. Brain 2004; 127: 1616–25.
Wertheim N, Botez MI. Receptive amusia: a clinical analysis. Brain 1961;
84: 19–30.
Wilson SJ, Pressing JL, Wales RJ. Modelling rhythmic function in a musician
post-stroke. Neuropsychologia 2002; 40: 1494–505.
Brain (2006), 129, 2533–2553 2553
Wood CC. Generators of event-related potentials. In: Halliday VB, Butler SR,
Paul R, editors. A textbook of clinical neurophysiology. New Yoek: Wiley:
1987. p. 535–67.
Xu D, Liu T, Ashe J, Bushara KO. Role of the Olivo-Cerebellar System in
Timing. J Neurosci 2006; 26: 5990–5.
Zatorre RJ. Pitch perception of complex tones and human temporal lobe
function. J Acoust Soc Am 1988; 84: 566–72.
Zatorre RJ, Samson S. Role of the right temporal neocortex in retention of
pitch in auditory short-term memory. Brain 1991; 114: 2403–17.
Zatorre RJ, Halpern AR. Effect of unilateral temporal lobe excision on
perception and imagery of songs. Neuropsychologia 1993; 31: 221–32.
Zatorre RJ, Evans AC, Meyer E. Neural mechanisms underlying
melodic perception and memory for pitch. J Neurosci 1994; 14:
1908–19.
Zatorre RJ, Perry DW, Beckett CA, Westbury CF, Evans AC. Functional
anatomy of musical processing in listeners with absolute pitch and relative
pitch. Proc Natl Acad Sci USA 1998; 95: 3172–7.
Downloaded from by guest on January 16, 2015
From perception to pleasure: Music and its
neural substrates
Robert J. Zatorrea,1 and Valorie N. Salimpoora,b
a
Montreal Neurological Institute, McGill University, Montreal, QC, Canada H3A 2B4; and bRotman Research Institute, Baycrest Centre, University of Toronto,
Toronto, ON, Canada M6A 2E1
Edited by John C. Avise, University of California, Irvine, CA, and approved April 9, 2013 (received for review February 15, 2013)
Music has existed in human societies since prehistory, perhaps
because it allows expression and regulation of emotion and
evokes pleasure. In this review, we present findings from cogni-
tive neuroscience that bear on the question of how we get from
perception of sound patterns to pleasurable responses. First, we
identify some of the auditory cortical circuits that are responsible
for encoding and storing tonal patterns and discuss evidence that
cortical loops between auditory and frontal cortices are important
for maintaining musical information in working memory and for
the recognition of structural regularities in musical patterns, which
then lead to expectancies. Second, we review evidence concerning
the mesolimbic striatal system and its involvement in reward,
motivation, and pleasure in other domains. Recent data indicate
that this dopaminergic system mediates pleasure associated with
music; specifically, reward value for music can be coded by activity
levels in the nucleus accumbens, whose functional connectivity
with auditory and frontal areas increases as a function of in-
creasing musical reward. We propose that pleasure in music arises
from interactions between cortical loops that enable predictions
and expectancies to emerge from sound patterns and subcortical
systems responsible for reward and valuation.
cognition | functional imaging | auditory cortex
S ome 40,000 years ago, a person—a musician—picked up a
vulture bone that had delicately and precisely incised holes
along its length and blew upon it to play a tune. We know this
thanks to recent remarkable archeological finds (Fig. 1) near the
Danube, where several such flutes were uncovered (1). What
bears reflection here is that, for an instrument to exist in the
upper Paleolithic, music must have already existed in an ad-
vanced form for many thousands of years already; else it would
have been impossible to construct something as technologically
advanced as a flute that plays a particular scale. We may safely
infer therefore that music is among the most ancient of human
cognitive traits.
Musical Origins
Knowing that music has ancient origins is important in estab-
lishing it as part of our original “human mental machinery,” but
it does not tell us why it may have developed. The answer to this
question may always remain unknown, but for insight we may
turn to Darwin. One of his most well-known comments about
music, from The Descent of Man, is this one: “As neither the
enjoyment nor the capacity of producing musical notes are fac-
ulties of the least direct use to man in reference to his ordinary
habits of life, they must be ranked among the most mysterious
with which he is endowed” (2). Ten years later, in his autobi-
ography, he reflected on and lamented his own musical anhe-
donia with these words: “...if I had to live my life again, I would
have made a rule to read some poetry and listen to some music at
least once every week; for perhaps the parts of my brain now
atrophied would thus have been kept active through use. The
loss of these tastes is a loss of happiness, and may possibly be
injurious to the intellect, and more probably to the moral char-
acter, by enfeebling the emotional part of our nature” (3). This
10430–10437 | PNAS | June 18, 2013 | vol. 110 | suppl. 2
insightful remark contains a possible answer to the mystery al-
luded to in the earlier quote, for here Darwin articulates
a thought that most people would intuitively agree with: that
music can generate and enhance emotions, and that its loss
results in reduced happiness. He even goes so far as to suggest
that music might serve to prevent atrophy of neural circuits as-
sociated with emotion, an intriguing concept.
Enhancement, communication, and regulation of emotion no
doubt constitute powerful reasons for the existence, and possibly
for the evolution, of music, a topic that others have addressed
more specifically than we will here (4–6). Such lines of inquiry
will not tell us why music might have such properties, however.
Music is the most abstract of arts: its aesthetic appeal has little to
do with relating events or depicting people, places, or things,
which are the province of the verbal and visual arts. A sequence
of pitches—such as might have been produced by an ancient
flute—concatenated in a certain way, cannot specifically denote
anything, but can certainly result in emotions. Psychological
models suggest a number of distinct mechanisms associated with
the many different emotional responses that music can elicit (7).
However, in the present contribution, we focus specifically on
a particular aspect of musically elicited affective response: pleasure.
Because pleasure and reward are linked, and there is a vast liter-
ature concerning the neural basis for reward, studying musical
pleasure gives us a set of hypotheses that serve as a framework for
studying what might otherwise appear as an intractable question.
To understand how we get from perception to pleasure, we
therefore start with an overview of the perceptual analysis of mu-
sical sounds, and then move to the neurobiology of reward, before
attempting a synthesis of the two.
Neurobiology of Musical Cognition
In thinking of how evolution may have specifically shaped the
human auditory system, we should consider what is most char-
acteristic of the way we use sound. One obvious feature that
stands out is that humans use sound to communicate cognitive
representations and internal states, including emotion. Both
speech and music can be thought of in this way (8), and one
could go so far as to say they constitute species-specific signals.
However, unlike the call systems of other species, ours is gen-
erative and highly recursive; that is, complex structures are cre-
ated out of a limited set of primitives in a combinatorial manner
by the application of syntactic rules. An important property of
both speech and music that is relevant to their innate nature is
that they appear in the vast majority of members of the species
fairly early in development, following a relatively fixed sequence,
This paper results from the Arthur M. Sackler Colloquium of the National Academy of
Sciences, “In the Light of Evolution VII: The Human Mental Machinery,” held January 10–
12, 2013, at the Arnold and Mabel Beckman Center of the National Academies of Sciences
and Engineering in Irvine, CA. The complete program and audio files of most presenta-
tions are available on the NAS Web site at www.nasonline.org/evolution_vii.
Author contributions: R.J.Z. and V.N.S. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
1
To whom correspondence should be addressed. E-mail: robert.zatorre@mcgill.ca.
www.pnas.org/cgi/doi/10.1073/pnas.1301228110
 or tone-deafness (16), may be caused by a disruption of this sys-
tem (17, 18).
The organization of frequency maps, which are similarly to-
pographic across both monkeys (19, 20) and humans (21, 22),
presents another relevant homology. However, a more relevant
feature for our discussion is sensitivity to the perceptual quality
of pitch. Pitch results from periodicity; such sounds have bi-
ological significance because in nature they are almost exclusively
Fig. 1. Ancient bone flute. The flute, made from the radius bone of a vul- produced by vocal tracts of other animals, compared with aperi-
ture, has five finger holes and a notch at the end where it was to be blown; odic natural sounds (wind, water). The ability to track pitch would
fine lines are precisely incised near the finger holes, probably reflecting thus be a useful trait for an organism to develop in navigating an
measurements used to indicate where the finger holes were to be carved. acoustic environment. Neurophysiological studies have identified
Radiocarbon dating indicates it comes from the Upper Paleolithic period, pitch-sensitive neurons in marmosets that respond in an invariant
more than 35,000 y ago. Adapted by permission from Macmillan Publishers,
manner to sounds that have the same pitch but vary in their
ref. 1, copyright 2009.
harmonic composition (23), thus allowing for pitch information to
be processed despite irrelevant acoustical variation. Several lines
and taking as their input sounds from the immediate environment. of evidence converge to suggest that a similar neural specializa-
A neural architecture must therefore exist such that it allows for tion for pitch may exist in the human auditory cortex, in one or
these capacities to emerge. more regions located lateral to core areas (24–26).
Such neural organization necessarily had to emerge from However, in humans, pitch also serves an important information-
precursors, and it is therefore useful to consider some of the bearing function because it serves as a medium for encoding and
features of nonhuman primate auditory cortex to identify both transmitting information. Both speech and music make use of
homologies and unique properties (9, 10). Primate auditory pitch variation; but its use in music seems to have some particular
properties that distinguish it from its use in speech (27). Notably,
cortex, like visual and somatosensory systems, can be thought of
pitch as used in music across many cultures tends to be organized
as organized in a hierarchical manner, such that core areas are
as discrete elements, or scales (as opposed to in speech where
surrounded by belt and parabelt regions within the superior
pitch changes tend to be continuous), and these elements gen-
portion of the temporal lobe, with corresponding patterns of
erally have fixed, specific frequency ratios associated with them.
feedforward and feedback projections (9) (Fig. 2); both the
These properties are precisely what would be produced by an
cytoarchitecture and connectivity of the different subfields sup-
instrument such as our ancient flute, with its fixed finger holes
port this organization (11). Another organizational feature producing discrete tones at specific pitches. Thus, music requires
present across species are the distinct pathways starting in the a nervous system able to encode and produce pitch variation with
core areas and proceeding in two directions: one dorsally and a great degree of accuracy. Substantial evidence implicates mech-
posteriorly toward parietal areas, the other ventrally and anteri- anisms in the right cerebral hemisphere, including pitch-special-
orly within the temporal lobe (9); both pathways have eventual ized cortical areas, in this fine-grained, accurate pitch mechanism
targets in separate areas of the frontal cortices and are best both in perception (28–30) and production (31), as contrasted
thought of as bidirectional. This architecture creates a series of
functional loops that allow for integration of auditory information
with other modalities; they also permit interactions between au-
ditory and motor systems related to action, and to planning or
organization of action, and to memory systems. These inter-
actions with planning and memory functions result in the ability to
make predictions based on past events, a topic we shall return
to below.
Functional loops between frontal and temporal cortices also
play a particularly important part in working memory. Unlike
visual events, which can often be static (a scene, an object),
auditory events are by their very nature evanescent, leaving no
traces other than those that the nervous system can create. To be
able to concatenate discrete auditory events such that meaning
can be encoded or decoded thus requires a working memory
system that can maintain information dynamically for further
processing. Here may lie one important species difference:
monkeys seem to have a very limited capacity to retain auditory
events in working memory (12, 13) compared with their excellent
visual working memory; this limitation may help explain their
relative paucity of complex, combinatorial auditory communica-
tion ability. In contrast, humans have excellent ability to maintain
auditory information as it comes in, which accounts for our ability
to relate one sound to another that came many seconds or Fig. 2. Schematic of putative functional pathways for auditory information
minutes earlier (consider a long spoken sentence whose meaning processing in the human brain. Pathways originating in core auditory areas
is not clear until the last word; or a long melody that only comes to project outward in a parallel but hierarchical fashion toward belt and par-
abelt cortices (colored areas). Subsequently, several distinct bidirectional
a resolution at the end). Several neuroimaging studies have
functional streams may be identified: Ventrally, processing streams progress
pointed to interactions between auditory cortices and inferior toward targets in superior and inferior temporal sulcus and gyrus, eventually
frontal regions, especially in the right hemisphere, in the pro- terminating in the inferior frontal cortex. Dorsally, projections lead toward
cessing of tonal information, in part due to working memory distinct targets in parietal, premotor, and dorsolateral frontal cortices.
requirements for tonal tasks (14, 15). Indeed, congenital amusia, Adapted from ref. 6.

Zatorre and Salimpoor PNAS | June 18, 2013 | vol. 110 | suppl. 2 | 10431
with the left auditory cortical system, which instead seems to be
specialized for speech sounds that do not require as great accu-
racy in pitch tracking.
Melodies consist of combinations of individual pitches; so
once separate tones are encoded by this early cortical system,
combinations of pitches need to be processed. Tonal melodies
can be structured in terms of the scales that they are constructed
from, and the pitch contours. Both lesion (32, 33) and neuro-
imaging studies (26, 34) demonstrate that cortical areas beyond
the pitch-related regions come into play as one goes from single
sounds to patterns, and that these involve both the anteroventral
and posterodorsal pathways, following a hierarchical organiza-
tion. The global picture that emerges is that areas more distal
from core and belt regions are likely involved in performing
computations beyond pitch extraction, involving combinations of
tonal elements: for example related to analysis of musical in-
terval size (35) and/or melodic contour (36). However, perhaps
because of the feedback connectivity from distal regions back to
core and belt areas, there is also evidence that auditory category
information may sometimes be encoded in a more distributed
fashion (37).
The perceptual processing steps just described only allude to
the mechanisms involved in passively listening to a sequence of
sounds. However, perception of something like a melody does
not proceed in a simple sequential manner. It also involves an
active component, such that expectancies are generated based
upon a listener’s implicit knowledge about musical rules that
have been acquired by previous exposure to music of that cul-
ture. Thus, hearing a particular set of tones leads one to expect
certain specific continuations with greater probability than others
(38, 39). This phenomenon is significant because it points to our
highly adaptive ability to predict future events based on past
regularities. There is good evidence that the relevant sequential
contingencies are encoded based on a process of statistical
learning (40), which emerges early in life for both speech and
music (41) and is also operative in adulthood (42). This de-
pendency on environmental exposure also means that different
individuals will have different sets of perceptual templates to the
extent that they have been exposed to different musical systems
or cultures, a point we return to below.
The neural substrates associated with musical expectancies
and their violation have been measured using electrophysiolog-
ical markers. These studies show that there is sensitivity to pre-
dictions based on a variety of features including contour (43) and
interval size (44), as well as harmonies (45, 46). The localization
of these processes is complex and not fully deciphered, but most
likely involves interactions between belt/parabelt auditory corti-
ces and inferior frontal cortices, using the anteroventral pathway
described above (47, 48). In keeping with the concept of hier-
archical organization, violations of more abstract features are
associated with changes coming from frontal areas: for example,
if a chord is introduced that is itself consonant but is unexpected
in terms of the harmonic relationships established by earlier
chords, there will be a response in the inferior frontal cortex,
typically stronger on the right side (49, 50).
Melodies of course contain temporal patterns as well as pitch
patterns. Cognitive science has identified some relevant hierar-
chical organization in the way rhythms are processed (8, 51) such
that there are more local and more global levels. Meter, defined
as repeating accents that structure temporal events, would be
a key level of global organization; it gains importance in our
context because it can be thought of as providing a temporal
framework for expected events. That is, in metrically organized
music, a listener develops predictions about when to expect
sounds to occur (a parallel to how tonality provides the listener
with a structure to make predictions about what pitches to ex-
pect). Neuroimaging studies have suggested that this metrical
mechanism may depend on interactions between auditory
10432 | www.pnas.org/cgi/doi/10.1073/pnas.1301228110
cortices and the more dorsal pathways of the system, particularly
with the premotor cortex and dorsolateral frontal regions (for
a review, see ref. 52) although subcortical basal ganglia struc-
tures also play an important role (53, 54). The interaction with
motor-related areas provides a possible explanation for the close
link between temporal structure in music and movement. It is not
far-fetched to suppose that the people listening to that ancient
flute were also dancing.
The findings of these various lines of research point toward the
conclusion that interactions between auditory and frontal corti-
ces along both the ventral and dorsal streams generate repre-
sentations of structural regularities of music, which are essential
for creating expectancies of events as they unfold in time. This
system no doubt plays a critical role in many aspects of perception.
In fact, similar phenomena have been described for linguistic
expectancies (55, 56). However, as we shall see below, these same
systems may also hold part of the key to understanding why music
can induce pleasure.
A final important phenomenon in considering the role of au-
ditory cortex in complex perceptual processes is that it is also
involved in imagery, that is, the phenomenological experience
of perception in the absence of a stimulus. Musical imagery is
a particularly salient form of this experience, as almost anyone
can imagine a musical piece “in the mind’s ear.” Cognitive psy-
chology has shown that imaginal experiences are psychologically
real in so far as they can be quantified, and because they share
features of real perception, including temporal accuracy and
pitch acuity (57, 58). Several neuroimaging studies have shown
the neural reality of this phenomenon because, even in the ab-
sence of sound, portions of belt or parabelt auditory cortex are
consistently recruited when people perform specific imagery
tasks (59, 60). This imagery ability is relevant here because it
shows that auditory cortex must contain memory traces of past
perceptual events, and that these traces are not merely semantic
in nature, but rather reflect perceptual attributes of the originally
experienced sound. In the case of music, we may say that these
traces, accumulated over time, can also be thought of as tem-
plates, containing information about sound patterns that recur in
musical structures. One might also ask how this information, if
it’s stored in these cortical areas, is accessed or retrieved. Al-
though the mechanism is far from being understood, it appears
that the frontotemporal loops mentioned above are also relevant
for retrieval; this conclusion is supported by evidence that
functional interactions between temporal and frontal cortices are
enhanced during musical imagery (61). Moreover, the degree of
activity in this network is predictive of individual differences in
subjective vividness of imagery, supporting a direct link between
engagement of this frontotemporal system and ability to imagine
music. This network, as we shall see, may also play an important
role in musically mediated pleasure, and recruitment of the re-
ward network, the topic to which we now turn.
Neurobiology of Reward
A reward can be thought of as something that produces a he-
donic sense of pleasure. Because this is a positive state, we tend
to be reinforced to repeat the behavior that leads to this desir-
able outcome (62). A biological substrate for reinforcement was
discovered in Montreal over half a century ago, when Olds and
Milner (63) reported that electrical stimulation of a specific part
of a rat’s brain caused the animal to continuously return to the
location where this stimulation had occurred. Subsequent studies
demonstrated that, if rats are given a chance to stimulate these
areas, they would forgo all other routine behaviors, such as
grooming, eating, and sleeping (64, 65). The electrical stimula-
tion was targeting pathways leading to the mesolimbic striatum,
and it has now been widely demonstrated that dopamine release
in these regions can lead to reinforcement of behaviors (66–68).
Zatorre and Salimpoor
 In the animal kingdom, the phylogenetically ancient meso-
limbic reward system serves to reinforce biologically significant
behaviors, such as eating (69), sex (70), or caring for offspring
(71). In humans, dopamine release and hemodynamic activity in
the mesolimbic areas has also been demonstrated to reinforce
biologically adaptive behaviors, such as eating (72) and behaviors
related to love and sex (73, 74). However, as animals become
more complex, additional factors become important for suc-
cessful survival. For example, among human societies, having
a certain amount of money can predict successful survival. Not
surprisingly, obtaining money is highly reinforcing, and has also
been demonstrated to involve the mesolimbic striatal areas (75).
The reinforcing qualities of such secondary rewards suggest that
humans are able to understand the conceptual value of an ab-
stract item that does not contain inherent reward value. In line
with this, many people obtain pleasure from other stimuli that
are conceptually meaningful, with little direct relevance for
survival, and listening to music is one example. As Darwin ob-
served, music has no readily apparent functional consequence
and no clear-cut adaptive function (4). However, listening to
music is ubiquitous throughout human societies since at least
Paleolithic times. How does a seemingly abstract sequence of
sounds produce such potent and reinforcing effects?
How Does Music Cause Pleasure?
It is widely believed that the pleasure people experience in music
is related to emotions induced by the music, as individuals often Fig. 3. Neural correlates of processing highly rewarding music. (A) Spatial
report that they listen to music to change or enhance their conjunction analysis between [11C]raclopride positron emission tomography
emotions (7). To examine this link, we performed an experiment and fMRI while listeners heard their selected pleasurable music revealed
in which we asked listeners to select highly pleasurable music increased hemodynamic activity in the ventral striatum (VS) during peak
and, while listening to it, rate their experience of pleasure con- emotional moments (marked by “chills”), and the dorsal striatum (DS) pre-
tinuously as we assessed any changes in emotional arousal (76). ceding chills, in the same regions that showed dopamine release. Adapted
from ref. 74. (B) fMRI scanning showing that the best predictor of reward
Increased sympathetic nervous system activity is implicated in
value of new music (as marked by monetary bids in an auction paradigm)
“fight or flight” responses (77) and thought to be automated; was activity in the striatum, particularly the NAcc; the NAcc also showed
therefore it serves as a reliable measure of emotional arousal. We increased functional connectivity with the superior temporal gyri (STG) and
measured heart rate, respiration rate, skin conductance, body the right inferior frontal gyrus (IFG) as musical stimuli gained reward value.
temperature, and blood volume pulse amplitude to track changes Adapted from ref. 94.
that correspond to increasing levels of self-reported pleasure.
The results revealed a robust positive correlation between online
ratings of pleasure and simultaneously measured increases in rewarding, and links music directly to the other, biologically re-
sympathetic nervous system activity, thus showing a link between warding stimuli outlined above.
objective indices of arousal and subjective feelings of pleasure. If the pleasures associated with music are at least in part related
Next we turn to the mechanisms through which emotional to the dopaminergic systems that we share with numerous other
arousal can become rewarding. If emotional responses to music vertebrates, why do they seem to be uniquely a part of human
target dopaminergic activity in the reinforcement circuits of the behavior? Can animals tell the difference between ancient flutes,
brain, there should be a mechanism through which these responses Mahler, and Britney Spears? And if so, do they care? The closest
could be considered rewarding. To examine this question, our phenomena to music in the animal kingdom are biologically sig-
laboratory has performed two studies in which participants se- nificant vocalizations. However, these musical sounds are thought
lected music that they find highly emotional and pleasurable (78, to be limited to an adaptive role toward territory defense and
79). To have an objective measure of peak emotional arousal, mate attraction, rather than for abstract enjoyment (84, 85).
people brought in music that gives them “chills,” which are be- When given a choice between listening to music versus silence,
lieved to be physical manifestations of peak emotional responses our close evolutionary relatives (tamarins and marmosets) gen-
(78, 80, 81), and related to increased sympathetic nervous
erally prefer silence (86). Some animals may be capable of pro-
system arousal (76). In the first study, we demonstrated that the
cessing basic aspects of sound with relevance for music. For
ventral striatum and other brain regions associated with emotion
were recruited as a function of increasing intensity of the chills example, rhesus monkeys do demonstrate an ability to judge that
response (78). This finding thus importantly identified that the two melodies are the same when they are transposed by one or
mesolimbic reward system could be recruited by an abstract aes- two octaves (87). However, this ability is limited: the monkeys
thetic stimulus. Several other studies have shown consistent findings failed to perform this task if melodies were transposed by 0.5 or
(82, 83); however, because all these studies measured hemodynamic 1.5 octaves. There is also some evidence (88, 89) that monkeys
responses, they did not address whether the dopaminergic system can distinguish between consonance and dissonance. However,
was involved. Therefore, we performed another study (Fig. 3A) they do not seem to consider consonant sounds more pleasurable,
with ligand-based positron emission tomography (PET) (79), us- based on the finding (90) that cotton-top tamarins showed a clear
ing raclopride, a radioligand that binds competitively with dopa- preference for species-specific feeding chirps over distress calls,
mine receptors. We compared dopamine release in response to but no preference for consonant versus dissonant intervals. Al-
pleasurable vs. neutral music and confirmed that strong emotional though certain individuals of some species do demonstrate motor
responses to music lead to dopamine release in the mesolimbic entrainment to externally generated rhythmic stimuli (91, 92),
striatum, which can help explain why music is considered there is no evidence that primates do so; moreover, such

Zatorre and Salimpoor PNAS | June 18, 2013 | vol. 110 | suppl. 2 | 10433
behaviors have been observed in interactions with humans, and
not in natural settings. Thus, overall, there is scant evidence that
other species possess the mental machinery to decode music in
the way humans do, or to derive enjoyment from it.
Why do certain combinations of sounds seem aesthetically
pleasant to humans, but not to other animals, even primates? To
better understand how we can obtain pleasure from musical
sounds, it is important to realize that the mesolimbic systems do
not work in isolation, and their influence will be largely dependent
on their interaction with other regions of the brain. Mesolimbic
striatal regions are found in many organisms, including early
vertebrates (93); however, the anatomical connectivity of these
regions with the rest of the brain varies across species depending
on the complexity of the brain (94). For example, the mesolimbic
reward system becomes highly interconnected with the prefrontal
cortices in mammals (95). Furthermore, as animals become more
complex, the concept of reward can take on different forms. For
example, we humans enjoy activities as diverse as attending con-
certs, reading fiction, visiting museums, or taking photographs, as
well as less “high-brow” but still aesthetic pursuits such as deco-
rating our vehicles, matching our wardrobes, or planting flowers.
Aesthetic rewards are often highly abstract in nature and gener-
ally involve important cognitive components. In particular, they
are highly culture-dependent and therefore imply a critical role
for learning and social influences. These features suggest that
they may involve the “higher-order” and more complex regions of
the brain that are more evolved in humans. Brain imaging studies
of aesthetic reward processing lend support to this idea by dem-
onstrating activity in the cerebral cortex, particularly the pre-
frontal cortex (96–98), which is most evolved in humans (99).
The cerebral cortex contains stores of information accumulated
throughout an organism’s existence. As such, cortical contributions
to aesthetic stimulus processing are consistent with the idea that
previous experiences may play a critical role the way an individual
may experience certain sounds as pleasurable or rewarding. Al-
though evidence exists for some basic similarities in how people
across cultures respond to certain cues (100), the rewarding na-
ture of aesthetic stimuli is not entirely universal, differing signif-
icantly across cultures, and between individuals within cultures.
These responses are related to subjective interpretation of the
stimulus, which is likely to be related to previous experiences with
a particular stimulus or other similar stimuli. It has been proposed
that all individuals have a “musical lexicon” (101), which repre-
sents a storage system for musical information that they have been
exposed to throughout their lives, including information about
the relationships between sounds and syntactic rules of music
structure specific to their prior experiences. This storage system
may contain templates that can be applied to incoming sound
information to help the individual better categorize and un-
derstand what he or she is hearing. As such, each time a sequence
of sounds is heard, several templates may be activated to fit the
incoming auditory information. This process will inevitably lead
to a series of predictions that may be confirmed or violated, and
ultimately determine its reward value to the individual.
To examine the neural substrates of predictions and reward
associated with music, and how these may contribute to plea-
surable responses, in a new study, we scanned people with func-
tional MRI (fMRI) as they listened to music that they had not
heard before and examined the neural activity associated with the
reward value of music (102). We assessed the reward value of
each piece of music by giving individuals a chance to purchase it in
an auction paradigm (103), such that higher monetary bids served
as indicators of higher reward value. We were interested in ex-
amining the neural activity associated with hearing musical
sequences for the first time, and examining the neural activity that
can distinguish between musical sequences that become “re-
warding” to an individual compared with those that they do not
care to hear again. The results (Fig. 3B) revealed that activity in
10434 | www.pnas.org/cgi/doi/10.1073/pnas.1301228110
the mesolimbic striatal areas, especially the nucleus accumbens
(NAcc), was most associated with reward value of musical stimuli,
as measured by the amount bid. The NAcc has been implicated in
making predictions, anticipating, and reward prediction errors—
that is, the calculated difference between what was expected and
the actual outcome (104–106). A prediction may result in a posi-
tive, zero, or negative prediction error, depending on the organ-
ism’s expectations and the outcome (107–109), and a number of
studies have demonstrated that prediction errors are related to
dopamine neurons in the midbrain (110, 111) and may be mea-
sured in the NAcc (104, 105). This result therefore provides evi-
dence that temporal predictions play an important role in the way
in which individuals obtain pleasure from musical stimuli. A
second and perhaps more important finding was that auditory
cortices in the superior temporal gyrus (STG), which were highly
and equally active during processing of all musical stimuli, showed
robustly increased functional interactions with the NAcc during
processing of musical sequences with high, compared with low,
reward value. As discussed above, auditory cortices are the site of
processing not only of incoming auditory information, but also of
more abstract computations related to perception, imagery, and
temporal prediction. Increased functional connectivity between
the NAcc and STG as reward value increases suggests that pre-
dictions were linked with information contained in the STG,
which we think is related to templates of sound information
gathered through an individual’s prior experiences with musical
sounds (likely based in part on implicit knowledge, such as might
arise via statistical learning). This functional interaction between
subcortical reward circuits involved in prediction and highly in-
dividualized regions of the cerebral cortex can explain why dif-
ferent people like different music, and how this may be a function
of their previous experiences with musical sounds. Moreover,
consistent with the studies reviewed above linking the STG with
the inferior frontal cortex and implicating this region with hier-
archical expectations during music processing, we found in-
creased connectivity also of frontal cortex with the NAcc during
highly rewarding music processing. These corticostriatal inter-
actions exemplify the cognitive nature of rewarding responses to
music and help to explain why the complexities of the highly
evolved human brain allow for the experience of pleasure to an
abstract sequence of sound patterns.
In the experiment described, we used new music to rule out
veridical expectations (112), or explicit expectations of how
musical passages may unfold based on familiarity with the mu-
sical selections. However, explicit expectations can also lead to
activity in the mesolimbic striatal regions. In the earlier study
(79), we found activity in the dorsal striatum (caudate nucleus)
during the period immediately preceding the chills, that is,
during a phase of anticipation (Fig. 3A). Indeed, this dorsal
component of the mesolimbic striatum has previously been
associated with anticipation (113). The dorsal striatum has in-
tricate anatomical connections with various parts of the pre-
frontal cortex (114, 115). The frontal lobes, particularly the
prefrontal cortices, are involved in executive functions, such as
temporal maintenance of information in working memory and
relating information back to earlier events, temporal sequencing,
planning ahead, creating expectations, anticipating outcomes,
and planning actions to obtain rewards (116, 117). These cog-
nitive processes are highly significant during musical processing,
and it would be consistent that striatal circuits would provide
a mechanism for the temporal nuances that give rise to feelings
of anticipation and craving. Therefore, it is likely that the cere-
bral cortex and striatum work together to make predictions
about potentially rewarding future events and assess the out-
come of these predictions. Additional support implicating the
caudate in anticipation comes from other studies that implicate
the dorsal striatum in anticipating desirable stimuli, when the
behavior is habitual and expected (113, 118). In this way, the
Zatorre and Salimpoor
signals that predict the onset of a desirable event can become
reinforcing per se. In the case of music, this prediction may in-
clude sound sequences that signal the onset of the highly desir-
able part of the music. Previously neutral stimuli may thus
become conditioned to serve as cues signaling the onset of the
rewarding sequence. Frontal cortices (119, 120), and their
interactions with the basal ganglia (121), have also been impli-
cated in processing syntactically unexpected events during music,
suggesting that they might be involved in keeping track of tem-
poral unfolding of sound patterns and their structural relation-
ships, further supporting the role of striatal connectivity with the
most evolved regions of the human brain during music process-
ing. It is important to note that the NAcc has also been dem-
onstrated to play a role in anticipation with other types of
stimuli, such as monetary rewards (122). The functional roles of
these structures are therefore not simply attributable to any one
dimension, but are dynamically altered as a function of a variety
of factors, not all of which have yet been identified.
The NAcc played an important role with both familiar and
novel music. In the case of familiar music, hemodynamic activity
in the NAcc was associated with increasing pleasure, and maxi-
mally expressed during the experience of chills, which represent
the peak emotional response; these were the same regions that
showed dopamine release. The NAcc is tightly connected with
subcortical limbic areas of the brain, implicated in processing,
detecting, and expressing emotions, including the amygdala and
hippocampus. It is also connected to the hypothalamus, insula,
and anterior cingulate cortex (99), all of which are implicated
in controlling the autonomic nervous system, and may be re-
sponsible for the psychophysiological phenomena associated
with listening to music and emotional arousal. Finally, the
NAcc is tightly integrated with cortical areas implicated in
“high-level” processing of emotions that integrate information
from various sources, including the orbital and ventromedial
frontal lobe. These areas are largely implicated in assigning and
maintaining reward value to stimuli (104, 123) and may be
critical in evaluating the significance of abstract stimuli that we
consider pleasurable.
Putting It All Together
The studies we have reviewed begin to point the way to a neurobi-
ological understanding of how patterns of otherwise meaningless
sounds can result in highly rewarding, pleasurable experiences. The
key concepts revolve around the idea of temporal expectancies,
their associated predictions, and the reward value generated by
these predictions. As we have seen, auditory cortical regions
contain specializations for analysis and encoding of elementary
sound attributes that are found in music, particularly pitch values
and durations. These elements are processed in a hierarchical
1. Conard NJ, Malina M, Münzel SC (2009) New flutes document the earliest musical
tradition in southwestern Germany. Nature 460(7256):737–740.
2. Darwin C (1871) The Descent of Man, and Selection in Relation to Sex (John Murray,
London).
3. Darwin C (1887) The Life and Letters of Charles Darwin (John Murray, London).
4. Hauser MD, McDermott J (2003) The evolution of the music faculty: A comparative
perspective. Nat Neurosci 6(7):663–668.
5. Wallin N, Merker B, Brown S (2000) The Origins of Music (MIT Press, Cambridge, MA).
6. Mithen S (2005) The Singing Neanderthals: The Origins of Music, Language, Mind
and Body (Weidenfeld & Nicolson, London).
7. Juslin PN, Sloboda JA (2001) Music and Emotion: Theory and Research (Oxford Univ
Press, Oxford).
8. Patel AD (2008) Music, Language, and the Brain (Oxford Univ Press, New York).
9. Rauschecker JP, Scott SK (2009) Maps and streams in the auditory cortex: nonhuman
primates illuminate human speech processing. Nat Neurosci 12(6):718–724.
10. Zatorre RJ, Schönwiesner M (2011) Cortical speech and music processes revealed by
functional neuroimaging. The Auditory Cortex, eds Winer JA, Schreiner CE (Springer,
New York), pp 657–677.
11. Kaas JH, Hackett TA, Tramo MJ (1999) Auditory processing in primate cerebral cor-
tex. Curr Opin Neurobiol 9(2):164–170.
Zatorre and Salimpoor
manner within auditory areas to represent patterns of sounds as
opposed to individual sounds. The interactions between auditory
areas and frontal cortices via the ventral and dorsal routes are
critical in allowing working memory to knit together the separate
sounds into more abstract representations, and in turn, in gen-
erating tonal and temporal expectancies based on structural reg-
ularities found in music. These expectancies are rooted in templates
derived from an individual’s history of listening, which are likely
stored in auditory cortices.
The reward system, phylogenetically old, may be most par-
simoniously explained as a mechanism to promote certain
adaptive behaviors, with dopaminergic circuits playing a critical
role in establishing salience and reward value of relevant
stimuli and the sensations generated by them. An important
part of this system seems to be devoted to reward prediction; as
indicated above, fulfillment of prediction leads to dopamine
release in the striatum, with a greater response associated with
better-than-expected reward. The findings of enhanced func-
tional interactions between the auditory cortices, valuation-
related cortices, and the striatum as a function of how much
a new piece of music is liked provide a link between these two
major lines of research. We suggest that the interactions that
we observed represent greater informational cross-talk between
the systems responsible for pattern analysis and prediction
(cortical) with the systems responsible for assigning reward
value itself (subcortical). Thus, the highly evolved cortical sys-
tem is able to decode tonal or rhythmic relationships, at both
local and more global levels of organization, that are found in
music, such that it can generate expectations about upcoming
events based on past events. However, the emotional arousal
associated with these predictions, we think, is generated by the
interactions with the striatal dopaminergic system. This frame-
work, and others like it (124), could also be thought of more
broadly as applicable to other types of aesthetic rewards: for
example, some authors have suggested that visual aesthetic
experiences may arise from interactions across cortical regions
involved in perception and memory (125); also, Cela-Conde
et al. (126) emphasize synchronization across cortical fields as
important for visual aesthetics.
Our ability to enjoy music can perhaps now be seen as a little
less mysterious than Darwin thought, when viewed as the out-
come of our human mental machinery, both its phylogenetically
ancient, survival-oriented circuits and its more recently evolved
cortical loops that allow us to represent information, imagine
outcomes, make predictions, and act upon our stored knowledge.
We have little doubt that the ancient musicians, armed with the
same machinery as us, and able to coax patterns of tones from
a vulture bone, experienced and communicated pleasure, beauty,
and wonder, just as much as we do today.
12. Fritz J, Mishkin M, Saunders RC (2005) In search of an auditory engram. Proc Natl
Acad Sci USA 102(26):9359–9364.
13. Scott BH, Mishkin M, Yin P (2012) Monkeys have a limited form of short-term
memory in audition. Proc Natl Acad Sci USA 109(30):12237–12241.
14. Zatorre RJ, Evans AC, Meyer E (1994) Neural mechanisms underlying melodic per-
ception and memory for pitch. J Neurosci 14(4):1908–1919.
15. Gaab N, Gaser C, Zaehle T, Jancke L, Schlaug G (2003) Functional anatomy of pitch
memory—an fMRI study with sparse temporal sampling. Neuroimage 19(4):1417–1426.
16. Ayotte J, Peretz I, Hyde K (2002) Congenital amusia: A group study of adults afflicted
with a music-specific disorder. Brain 125(Pt 2):238–251.
17. Hyde KL, et al. (2007) Cortical thickness in congenital amusia: When less is better
than more. J Neurosci 27(47):13028–13032.
18. Loui P, Alsop D, Schlaug G (2009) Tone deafness: A new disconnection syndrome?
J Neurosci 29(33):10215–10220.
19. Kaas JH, Hackett TA (2000) Subdivisions of auditory cortex and processing streams in
primates. Proc Natl Acad Sci USA 97(22):11793–11799.
20. Petkov CI, Kayser C, Augath M, Logothetis NK (2006) Functional imaging reveals
numerous fields in the monkey auditory cortex. PLoS Biol 4(7):e215.
21. Formisano E, et al. (2003) Mirror-symmetric tonotopic maps in human primary au-
ditory cortex. Neuron 40(4):859–869.
PNAS | June 18, 2013 | vol. 110 | suppl. 2 | 10435
22. Schönwiesner M, von Cramon DY, Rübsamen R (2002) Is it tonotopy after all?
Neuroimage 17(3):1144–1161.
23. Bendor D, Wang X (2005) The neuronal representation of pitch in primate auditory
cortex. Nature 436(7054):1161–1165.
24. Penagos H, Melcher JR, Oxenham AJ (2004) A neural representation of pitch salience
in nonprimary human auditory cortex revealed with functional magnetic resonance
imaging. J Neurosci 24(30):6810–6815.
25. Zatorre RJ (1988) Pitch perception of complex tones and human temporal-lobe
function. J Acoust Soc Am 84(2):566–572.
26. Patterson RD, Uppenkamp S, Johnsrude IS, Griffiths TD (2002) The processing of
temporal pitch and melody information in auditory cortex. Neuron 36(4):767–776.
27. Zatorre RJ, Baum SR (2012) Musical melody and speech intonation: Singing a dif-
ferent tune. PLoS Biol 10(7):e1001372.
28. Zatorre RJ, Gandour JT (2008) Neural specializations for speech and pitch: Moving
beyond the dichotomies. Philos Trans R Soc Lond B Biol Sci 363(1493):1087–1104.
29. Zatorre RJ, Belin P, Penhune VB (2002) Structure and function of auditory cortex:
Music and speech. Trends Cogn Sci 6(1):37–46.
30. Hyde KL, Peretz I, Zatorre RJ (2008) Evidence for the role of the right auditory cortex
in fine pitch resolution. Neuropsychologia 46(2):632–639.
31. Ozdemir E, Norton A, Schlaug G (2006) Shared and distinct neural correlates of
singing and speaking. Neuroimage 33(2):628–635.
32. Stewart L, von Kriegstein K, Warren JD, Griffiths TD (2006) Music and the brain:
Disorders of musical listening. Brain 129(Pt 10):2533–2553.
33. Zatorre RJ (1985) Discrimination and recognition of tonal melodies after unilateral
cerebral excisions. Neuropsychologia 23(1):31–41.
34. Griffiths TD, Büchel C, Frackowiak RSJ, Patterson RD (1998) Analysis of temporal
structure in sound by the human brain. Nat Neurosci 1(5):422–427.
35. Klein ME, Zatorre RJ (2011) A role for the right superior temporal sulcus in cate-
gorical perception of musical chords. Neuropsychologia 49(5):878–887.
36. Lee Y-S, Janata P, Frost C, Hanke M, Granger R (2011) Investigation of melodic
contour processing in the brain using multivariate pattern-based fMRI. Neuroimage
57(1):293–300.
37. Ley A, et al. (2012) Learning of new sound categories shapes neural response pat-
terns in human auditory cortex. J Neurosci 32(38):13273–13280.
38. Krumhansl CL (1990) Cognitive Foundations of Musical Pitch (Oxford Univ Press, New
York).
39. Huron D (2006) Sweet Anticipation: Music and the Psychology of Expectaction (MIT
Press, Cambridge, MA).
40. Schön D, Francois C (2011) Musical expertise and statistical learning of musical and
linguistic structures. Front Psychol 2:167.
41. Saffran JR (2003) Mechanisms of musical memory in infancy. The Cognitive Neuro-
science of Music, eds Peretz I, Zatorre RJ (Oxford Univ Press, New York), pp 32–41.
42. Loui P, Wu EH, Wessel DL, Knight RT (2009) A generalized mechanism for perception
of pitch patterns. J Neurosci 29(2):454–459.
43. Tervaniemi M, Rytkönen M, Schröger E, Ilmoniemi RJ, Näätänen R (2001) Superior
formation of cortical memory traces for melodic patterns in musicians. Learn Mem
8(5):295–300.
44. Trainor LJ, McDonald KL, Alain C (2002) Automatic and controlled processing of
melodic contour and interval information measured by electrical brain activity. J
Cogn Neurosci 14(3):430–442.
45. Koelsch S, Gunter TC, Friederici AD, Schröger E (2000) Brain indices of music pro-
cessing: “Nonmusicians” are musical. J Cogn Neurosci 12(3):520–541.
46. Leino S, Brattico E, Tervaniemi M, Vuust P (2007) Representation of harmony rules in
the human brain: Further evidence from event-related potentials. Brain Res 1142:
169–177.
47. Opitz B, Rinne T, Mecklinger A, von Cramon DY, Schröger E (2002) Differential
contribution of frontal and temporal cortices to auditory change detection: fMRI
and ERP results. Neuroimage 15(1):167–174.
48. Schönwiesner M, et al. (2007) Heschl’s gyrus, posterior superior temporal gyrus, and
mid-ventrolateral prefrontal cortex have different roles in the detection of acoustic
changes. J Neurophysiol 97(3):2075–2082.
49. Maess B, Koelsch S, Gunter TC, Friederici AD (2001) Musical syntax is processed in
Broca’s area: An MEG study. Nat Neurosci 4(5):540–545.
50. Tillmann B, et al. (2006) Cognitive priming in sung and instrumental music: Activa-
tion of inferior frontal cortex. Neuroimage 31(4):1771–1782.
51. Large EW, Palmer C (2002) Perceiving temporal regularity in music. Cogn Sci 26:1–37.
52. Zatorre RJ, Chen JL, Penhune VB (2007) When the brain plays music: Auditory-motor
interactions in music perception and production. Nat Rev Neurosci 8(7):547–558.
53. Grahn JA, Rowe JB (2009) Feeling the beat: Premotor and striatal interactions in
musicians and nonmusicians during beat perception. J Neurosci 29(23):7540–7548.
54. Kung S-J, Chen JL, Zatorre RJ, Penhune VB (2013) Interacting cortical and basal
ganglia networks underlying finding and tapping to the musical beat. J Cogn
Neurosci 25(3):401–420.
55. Friederici AD, Rüschemeyer S-A, Hahne A, Fiebach CJ (2003) The role of left inferior
frontal and superior temporal cortex in sentence comprehension: Localizing syn-
tactic and semantic processes. Cereb Cortex 13(2):170–177.
56. Patel AD (2003) Language, music, syntax and the brain. Nat Neurosci 6(7):674–681.
57. Halpern AR (1988) Mental scanning in auditory imagery for songs. J Exp Psychol
Learn Mem Cogn 14(3):434–443.
58. Janata P (2012) Acuity of mental representations of pitch. Ann N Y Acad Sci 1252(1):
214–221.
59. Zatorre RJ, Halpern AR (2005) Mental concerts: Musical imagery and auditory cortex.
Neuron 47(1):9–12.
60. Herholz SC, Lappe C, Knief A, Pantev C (2008) Neural basis of music imagery and the
effect of musical expertise. Eur J Neurosci 28(11):2352–2360.
10436 | www.pnas.org/cgi/doi/10.1073/pnas.1301228110
61. Herholz SC, Halpern AR, Zatorre RJ (2012) Neuronal correlates of perception, im-
agery, and memory for familiar tunes. J Cogn Neurosci 24(6):1382–1397.
62. Thorndike EL (1911) Animal Intelligence (Macmillan, New York).
63. Olds J, Milner P (1954) Positive reinforcement produced by electrical stimulation of
septal area and other regions of rat brain. J Comp Physiol Psychol 47(6):419–427.
64. Wise RA (1978) Catecholamine theories of reward: A critical review. Brain Res 152(2):
215–247.
65. Routtenberg A, Lindy J (1965) Effects of the availability of rewarding septal and
hypothalamic stimulation on bar pressing for food under conditions of deprivation.
Journal of Comparative and Psychophysiological Psychology 60:158–161.
66. Schultz W (2007) Behavioral dopamine signals. Trends Neurosci 30(5):203–210.
67. Leyton M (2010) The neurobiology of desire: Dopamine and the regulation of mood
and motivational states in humans. Pleasures of the Brain, eds Kringelbach ML,
Berridge KC (Oxford Univ Press, New York).
68. Glimcher PW (2011) Understanding dopamine and reinforcement learning: The
dopamine reward prediction error hypothesis. Proc Natl Acad Sci USA 108(Suppl 3):
15647–15654.
69. Hernandez L, Hoebel BG (1988) Food reward and cocaine increase extracellular
dopamine in the nucleus accumbens as measured by microdialysis. Life Sci 42(18):
1705–1712.
70. Pfaus JG, Damsma G, Wenkstern D, Fibiger HC (1995) Sexual activity increases do-
pamine transmission in the nucleus accumbens and striatum of female rats. Brain Res
693(1-2):21–30.
71. Hansen S, Bergvall AH, Nyiredi S (1993) Interaction with pups enhances dopamine
release in the ventral striatum of maternal rats: A microdialysis study. Pharmacol
Biochem Behav 45(3):673–676.
72. Small DM, Jones-Gotman M, Dagher A (2003) Feeding-induced dopamine release in
dorsal striatum correlates with meal pleasantness ratings in healthy human volun-
teers. Neuroimage 19(4):1709–1715.
73. Aron A, et al. (2005) Reward, motivation, and emotion systems associated with early-
stage intense romantic love. J Neurophysiol 94(1):327–337.
74. Komisaruk BR, Whipple B (2005) Functional MRI of the brain during orgasm in
women. Annu Rev Sex Res 16:62–86.
75. Knutson B, Adams CM, Fong GW, Hommer D (2001) Anticipation of increasing
monetary reward selectively recruits nucleus accumbens. J Neurosci 21(16):RC159.
76. Salimpoor VN, Benovoy M, Longo G, Cooperstock JR, Zatorre RJ (2009) The re-
warding aspects of music listening are related to degree of emotional arousal. PLoS
ONE 4(10):e7487.
77. Cacioppo JT, Tassinary LG, Berntson GG (2007) Handbook of Psychophysiology
(Cambridge Univ Press, New York).
78. Blood AJ, Zatorre RJ (2001) Intensely pleasurable responses to music correlate with
activity in brain regions implicated in reward and emotion. Proc Natl Acad Sci USA
98(20):11818–11823.
79. Salimpoor VN, Benovoy M, Larcher K, Dagher A, Zatorre RJ (2011) Anatomically
distinct dopamine release during anticipation and experience of peak emotion to
music. Nat Neurosci 14(2):257–262.
80. Panksepp J (1995) The emotional source of “chills” induced by music. Music Percept
13:171–207.
81. Rickard NS (2004) Intense emotional responses to music: A test of the physiological
arousal hypothesis. Psychol Music 32(4):371–388.
82. Koelsch S, Fritz T, V Cramon DY, Müller K, Friederici AD (2006) Investigating emotion
with music: An fMRI study. Hum Brain Mapp 27(3):239–250.
83. Menon V, Levitin DJ (2005) The rewards of music listening: Response and physio-
logical connectivity of the mesolimbic system. Neuroimage 28(1):175–184.
84. Catchpole CK, Slater PJB (1995) Bird Song: Biological Themes and Variations (Cam-
bridge Univ Press, Cambridge).
85. Marler P (1999) Origins of music and speech: Insights from animals. The Origins of
Music, eds Wallin NL, Merker B, Brown S (MIT Press, Cambridge, MA).
86. McDermott J, Hauser MD (2007) Nonhuman primates prefer slow tempos but dislike
music overall. Cognition 104(3):654–668.
87. Wright AA, Rivera JJ, Hulse SH, Shyan M, Neiworth JJ (2000) Music perception and
octave generalization in rhesus monkeys. J Exp Psychol Gen 129(3):291–307.
88. Fishman YI, et al. (2001) Consonance and dissonance of musical chords: Neural
correlates in auditory cortex of monkeys and humans. J Neurophysiol 86(6):
2761–2788.
89. Izumi A (2000) Japanese monkeys perceive sensory consonance of chords. J Acoust
Soc Am 108(6):3073–3078.
90. McDermott J, Hauser M (2004) Are consonant intervals music to their ears? Spon-
taneous acoustic preferences in a nonhuman primate. Cognition 94(2):B11–B21.
91. Schachner A, Brady TF, Pepperberg IM, Hauser MD (2009) Spontaneous motor en-
trainment to music in multiple vocal mimicking species. Curr Biol 19(10):831–836.
92. Patel AD, Iversen JR, Bregman MR, Schulz I (2009) Experimental evidence for syn-
chronization to a musical beat in a nonhuman animal. Curr Biol 19(10):827–830.
93. O’Connell LA, Hofmann HA (2011) The vertebrate mesolimbic reward system and
social behavior network: A comparative synthesis. J Comp Neurol 519(18):
3599–3639.
94. Northcutt RG, Kaas JH (1995) The emergence and evolution of mammalian neo-
cortex. Trends Neurosci 18(9):373–379.
95. Cardinal RN, Parkinson JA, Hall J, Everitt BJ (2002) Emotion and motivation: The role
of the amygdala, ventral striatum, and prefrontal cortex. Neurosci Biobehav Rev
26(3):321–352.
96. Vartanian O, Goel V (2004) Neuroanatomical correlates of aesthetic preference for
paintings. Neuroreport 15(5):893–897.
97. Kawabata H, Zeki S (2004) Neural correlates of beauty. J Neurophysiol 91(4):
1699–1705.
Zatorre and Salimpoor
 98. Cela-Conde CJ, et al. (2004) Activation of the prefrontal cortex in the human visual
aesthetic perception. Proc Natl Acad Sci USA 101(16):6321–6325.
99. Haber SN, Knutson B (2010) The reward circuit: Linking primate anatomy and human
imaging. Neuropsychopharmacology 35(1):4–26.
100. Fritz T, et al. (2009) Universal recognition of three basic emotions in music. Curr Biol
19(7):573–576.
101. Peretz I, Coltheart M (2003) Modularity of music processing. Nat Neurosci 6(7):
688–691.
102. Salimpoor VN, et al. (2013) Interactions between the nucleus accumbens and audi-
tory cortices predict music reward value. Science 340(6129):216–219.
103. Becker GM, DeGroot MH, Marschak J (1964) Measuring utility by a single-response
sequential method. Behav Sci 9(3):226–232.
104. O’Doherty JP (2004) Reward representations and reward-related learning in the
human brain: Insights from neuroimaging. Curr Opin Neurobiol 14(6):769–776.
105. Pessiglione M, Seymour B, Flandin G, Dolan RJ, Frith CD (2006) Dopamine-dependent
prediction errors underpin reward-seeking behaviour in humans. Nature 442(7106):
1042–1045.
106. McClure SM, Berns GS, Montague PR (2003) Temporal prediction errors in a passive
learning task activate human striatum. Neuron 38(2):339–346.
107. Sutton RS, Barto AG (1998) Reinforcement Learning: An Introduction (MIT Press,
Cambridge, MA).
108. Schultz W (1998) Predictive reward signal of dopamine neurons. J Neurophysiol
80(1):1–27.
109. Montague PR, Dayan P, Sejnowski TJ (1996) A framework for mesencephalic dopa-
mine systems based on predictive Hebbian learning. J Neurosci 16(5):1936–1947.
110. Bayer HM, Glimcher PW (2005) Midbrain dopamine neurons encode a quantitative
reward prediction error signal. Neuron 47(1):129–141.
111. Morris G, Arkadir D, Nevet A, Vaadia E, Bergman H (2004) Coincident but distinct
messages of midbrain dopamine and striatal tonically active neurons. Neuron 43(1):
133–143.
112. Bharucha J (1994) Tonality and expectation. Musical Perceptions, ed Aiello R (Oxford
Univ Press, Oxford), pp 213-239.
Zatorre and Salimpoor
113. Boileau I, et al. (2006) Modeling sensitization to stimulants in humans: An
[11C]raclopride/positron emission tomography study in healthy men. Arch Gen
Psychiatry 63(12):1386–1395.
114. Postuma RB, Dagher A (2006) Basal ganglia functional connectivity based on
a meta-analysis of 126 positron emission tomography and functional magnetic
resonance imaging publications. Cereb Cortex 16(10):1508–1521.
115. Monchi O, Petrides M, Strafella AP, Worsley KJ, Doyon J (2006) Functional role of the
basal ganglia in the planning and execution of actions. Ann Neurol 59(2):257–264.
116. Petrides M, Pandya DN (2004) The frontal cortex. The Human Nervous System, eds
Paxinos G, Mai JK (Elsevier, New York), 2nd Ed.
117. Stuss DT, Knight RT (2002) Principles of Frontal Lobe Function (Oxford Univ Press,
New York).
118. Belin D, Everitt BJ (2008) Cocaine seeking habits depend upon dopamine-dependent
serial connectivity linking the ventral with the dorsal striatum. Neuron 57(3):
432–441.
119. Tillmann B, Janata P, Bharucha JJ (2003) Activation of the inferior frontal cortex in
musical priming. Brain Res Cogn Brain Res 16(2):145–161.
120. Koelsch S, Kilches S, Steinbeis N, Schelinski S (2008) Effects of unexpected chords and
of performer’s expression on brain responses and electrodermal activity. PLoS ONE
3(7):e2631.
121. Seger CA, et al. (2013) Corticostriatal contributions to musical expectancy percep-
tion. J Cogn Neurosci, 10.1162/jocn_a_00371.
122. Knutson B, Cooper JC (2005) Functional magnetic resonance imaging of reward
prediction. Curr Opin Neurol 18(4):411–417.
123. Chib VS, Rangel A, Shimojo S, O’Doherty JP (2009) Evidence for a common repre-
sentation of decision values for dissimilar goods in human ventromedial prefrontal
cortex. J Neurosci 29(39):12315–12320.
124. Kringelbach M, Vuust P (2009) The pleasure of music. Pleasures of the Brain, eds
Kringelbach M, Berridge K (Oxford Univ Press, New York), pp 255–269.
125. Biederman I, Vessel E (2006) Perceptual pleasure and the brain. Am Sci 94:249–255.
126. Cela-Conde CJ, et al. (2013) Dynamics of brain networks in the aesthetic appreciation.
Proc Natl Acad Sci USA 110:10454–10461.
PNAS | June 18, 2013 | vol. 110 | suppl. 2 | 10437