NEUROSCIENCE PERSPECTIVES
Development of Human Brain Functions
Mark H. Johnson
Aspects of postnatal human brain development are re-
viewed. The development of brain function has commonly
been characterized in terms of the unfolding of a matura-
tional sequence. In contrast, we argue that postnatal func-
tional brain development occurs through a dynamic process
of emerging patterns of interactions between different brain
regions. Some of these processes may also be characteristic
of perceptual and motor skill learning in adults. Possible
implications of these views for our understanding of devel-
opmental disorders are raised. Biol Psychiatry 2003;54:
1312–1316 © 2003 Society of Biological Psychiatry
Key Words: Brain development, cortex, infants, children
Introduction
U nderstanding the functional development of the hu-
man brain is critical for social, educational, and
clinical policies. Given its importance, it is surprising that
until recently very little was known about the topic;
however, with the advent of suitable methods for investi-
gating brain function in infants and children, this area of
neuroscience is now making rapid progress. A critical
focus of current research is the question of how the
development of brain structure (neuroanatomy) relates to
the emerging motor, perceptual, and cognitive functions
during childhood. Another issue central to this topic
concerns the developmental origin of specialized struc-
tures and processing within the brain. One perspective on
this second issue is that functional specialization of re-
gions of the cerebral cortex arises mainly through intrinsic
genetic and molecular mechanisms and that experience
merely plays a role in the final fine-tuning. An alternative
view is that at least some aspects of human functional
brain development involve a prolonged process of func-
tional specialization that is heavily shaped by postnatal
experience. A parallel debate to that among developmental
neuroscientists rages among developmental psychologists.
Some developmental psychologists argue that the human
infant is born with innate modules and core knowledge
relevant to the physical and social world. In contrast,
others propose that many of the changes in behavior
From Birkbeck College, University of London, London, United Kingdom.
Address reprint requests to Mark H. Johnson, Centre for Brain and Cognitive
Development, School of Psychology, Birkbeck College, University of London,
Malet Street, London WC1E 7HX, United Kingdom.
Received October 7, 2002; revised March 3, 2003; accepted April 15, 2003.
© 2003 Society of Biological Psychiatry
observed during infancy are the result of general mecha-
nisms of learning and plasticity. In this article, I will
outline these different viewpoints on typical human func-
tional brain development and briefly discuss implications
for our understanding of certain developmental disorders
and the consequences of perinatal brain damage.
The Structural Development of the Human
Brain
While the developmental neuroanatomy of the mammalian
brain has been researched for decades, at this point
relatively few studies have focused on human postnatal
development. In general, human brain development ap-
pears to follow the same sequence of events observed in
other primates but on a slower time schedule. One model
of genetic control predicts that the more delayed the
general time course of brain development in a species, the
larger the relative volume of the later developing struc-
tures (such as the cerebral cortex and particularly the
frontal cortex) (Clancy et al 2000). In accordance with this
general prediction, the slowed rate of development in
humans is associated with a relatively larger volume of
cortex and an especially large frontal cortex. An additional
important benefit of a slowed time course of brain devel-
opment is that it potentially allows a prolonged postnatal
period during which interaction with the environment can
contribute to the tuning and shaping of circuitry.
There are a number of ways to study postnatal neuro-
anatomical development in humans. Postmortem analyses
have been conducted, albeit usually on small sample sizes.
Developmental positron emission tomography (PET) and
magnetic resonance imaging (MRI) studies are becoming
more common but are sometimes restricted to infants with
suspected clinical symptoms (for detailed review of tech-
niques currently available, see Casey and de Haan 2002).
One conclusion that can be drawn at this point is that
around the time of birth in humans most neurons have
migrated to their appropriate locations within the cortex,
hippocampus, cerebellum, and other structures (although
some neurogenesis continues into adulthood). Also at
birth, subcortical structures are clearly definable and
closely resemble their adult forms. While the major
landmarks (sulci, gyri) of the cerebral cortex are present, it
remains relatively immature at birth in terms of its
interregional and intraregional connectivity.
0006-3223/03/$30.00
doi:10.1016/S0006-3223(03)00426-8
Development of Human Brain Functions
The fourfold increase in the total volume of the brain from
birth to teenage years is not uniform. For example, while
there is a rapid increase in synaptogenesis around the time of
birth for all cortical areas studied, the timing of the most rapid
burst of synapse formation and the final peak density occurs
at different ages in different areas (Huttenlocher and Dab-
holkar 1997). In the visual cortex, there is a rapid burst of
synapse formation at 3 to 4 months, and the maximum
density of around 150% of adult level is reached between
4 and 12 months. Synaptogenesis also starts at the same
time within the prefrontal cortex, but the density increases
much more slowly and does not reach its peak until well
after the first year. This differential time course of devel-
opment of cortical regions is also observable in the living
human brain using PET (Chugani et al 1987). During the
first weeks after birth, glucose uptake is highest in
sensorimotor cortex, thalamus, brainstem, and the cerebel-
lar vermis. By 3 months, there are considerable rises in the
parietal, temporal, and occipital cortices; basal ganglia;
and cerebellar cortex, while such rises are not found in the
frontal and dorsolateral occipital cortex until approxi-
mately 6 to 8 months. There is a continuing rise in overall
resting brain metabolism (glucose uptake) after the first
year of life, with a peak approximately 150% above adult
levels achieved around 4 to 5 years of age for some
cortical areas. As in other mammals, regressive events are
also observed during human brain development. For ex-
ample, PET studies reveal that while the overall level of
glucose uptake reaches a peak during early childhood
which is much higher than that observed in adults, the
rates return to adult levels after about 9 years of age. A
corresponding “rise and fall” in synaptic density (synapses
per neuron) is observed with the density falling to adult
levels at different ages for different cortical regions during
later childhood.
In addition to the formation of dendritic trees and their
associated synapses, most fibers become myelinated dur-
ing postnatal development. Structural MRI images reveal
that the general appearance of brain structures is similar to
that of adults by 2 years of age and that all major fiber
tracts can be observed by 3 years of age (Matsuzawa et al
2001). Increases in white matter extend through adoles-
cence into adulthood, particularly in frontal brain regions
(Giedd et al 1999).
The Functional Development of the Human
Brain
Relating the evidence discussed above on the neuroanatomi-
cal development of the brain to the remarkable changes in
motor, perceptual, and cognitive abilities during the first
decade or so of human life remains a challenging question.
Considerable knowledge about the cognitive and perceptual
BIOL PSYCHIATRY 1313
2003;54:1312–1316
abilities of human infants and children has accrued as a result
of behavioral testing (see Johnson and Mareschal 2001 for
recent review). While controversies remain, one theme
that emerges from these studies is the active role played by
the infant, toddler, or child in attending to novel and
socially relevant stimuli and events. Thus, far from being
a passive learner or blank slate, the developing infant can
be viewed as an active participant in the latter stages of its
own brain development.
To date, much of the research attempting to relate brain
to behavioral development in humans has been from a
maturational viewpoint in which the goal is to relate the
maturation of particular regions of the brain, usually
regions of cerebral cortex, to newly emerging sensory,
motor, and cognitive functions (Figure 1A). Evidence
concerning the differential neuroanatomical development
of cortical regions reviewed earlier is used to determine an
age when a particular region is likely to become func-
tional. Success in a new behavioral task at this age is then
attributed to the maturation of a new brain region. By this
view, functional brain development is the reverse of adult
neuropsychology, with the difference that specific brain
regions are added in instead of being damaged. Despite the
intuitive appeal of the maturational approach, it does not
successfully explain some aspects of human functional
brain development. For example, recent evidence suggests
that some of the regions that are slowest to develop by
neuroanatomical criteria show activity from shortly after
birth (see below). Further, where functional activity has
been assessed by functional magnetic resonance imaging
(fMRI) during a behavioral transition, multiple cortical
and subcortical areas appear to change their response
pattern (Luna et al 2001), rather than one or two previ-
ously silent regions becoming active (mature).
In contrast to the above approach (in which intrar-
egional connectivity matures), an alternative viewpoint,
interactive specialization, assumes that postnatal func-
tional brain development, at least within the cerebral
cortex, involves a process of organizing patterns of inter-
regional interactions (Johnson 2000) (Figure 1B). Accord-
ing to this view, the response properties of a specific
region are partly determined by its patterns of connectivity
to other regions and their patterns of activity. During
postnatal development, changes in the response properties
of cortical regions occur as they interact and compete with
each other to acquire their role in new computational
abilities. By this view, some cortical regions may begin
with poorly defined functions and consequently are par-
tially activated in a wide range of different contexts and
tasks. During development, activity-dependent interac-
tions between regions sharpen up the functions of regions
such that their activity becomes restricted to a narrower set
of circumstances (e.g., a region originally activated by a
1314 BIOL PSYCHIATRY
2003;54:1312–1316
wide variety of visual objects may come to confine its
response to upright human faces). The onset of new
behavioral competencies during infancy will therefore be
associated with changes in activity over several regions
and not just by the onset of activity in one or more
additional region(s). In further contrast to the maturational
approach, this view predicts that during infancy, patterns
of cortical activation during behavioral tasks may be more
extensive than those observed in adults. Additionally,
within broad constraints, successful behavior in the same
tasks can be supported by different patterns of cortical
activation in infants and adults.
Recent evidence does, in fact, indicate that the same
behavior in infants and adults can be mediated by different
M.H. Johnson
Figure 1. A hypothetical illustration of
three accounts of the neural basis of an
advance in behavioral abilities in infants.
(A) Represents a maturational view in
which maturation of one region (in this
case the dorsolateral prefrontal cortex) en-
ables new behavioral abilities to appear.
(B) Illustrates an interactive specialization
view in which the onset of a new behav-
ioral ability is due to changes in the inter-
actions between regions that were already
partially active. By this view, several re-
gions adjust their functionality together to
enable new computations. (C) Shows a
third perspective, skill learning, in which
certain regions become active during the
acquisition of a range of new skills
throughout the life span. The activation of
some of these skill acquisition regions
declines as expertise is developed. Re-
printed with permission from Johnson
(2001) by Nature Reviews Neuroscience.
© 2001 Macmillan Magazines Ltd.
structures and pathways and that there are dynamic
changes in the cortical processing of stimuli during devel-
opment. Experiments with scalp recorded electrical poten-
tials have suggested that there is increasing spatial local-
ization of selective processing with age or experience of a
stimulus class. For example, for word recognition, differ-
ences between known words and control stimuli are initially
found over large areas, but this difference narrows to the
leads over the left temporal lobe only when vocabulary
reaches around 200 words, irrespective of maturational age
(Neville et al 1992). In parallel with changes in the
patterns of regional activation are changes in the “tuning”
of individual regions. For example, when event-related
potentials (ERPs) are recorded during passive exposure to
Development of Human Brain Functions
faces, the resulting component that is sensitive to upright
human faces (the “n170”) in adults is much more broadly
tuned in its response in infants. Specifically, in adults, the
n170 shows a different amplitude and latency to human
upright faces than to animal or inverted faces. In infants,
the equivalent ERP component responds similarly to
upright and inverted human faces (de Haan et al 2002).
This evidence for dynamic changes in cortical processing
during infancy is consistent with a process in which
interregional interactions help to shape intraregional con-
nectivity, such that several regions together come to
support particular perceptual and cognitive functions.
A third perspective on human functional brain develop-
ment (termed skill learning) involves the proposal that the
brain regions active in infants during the onset of new
perceptual or behavioral abilities are similar, or identical
to, those involved in complex skill acquisition in adults
(Figure 1C). With regard to perceptual expertise, Gauthier
et al (1999) have shown that extensive training of adults
with artificial objects (called “greebles”) eventually results
in activation of a cortical region previously associated
with face processing, the fusiform face area. This suggests
that the region is normally activated by faces in adults, not
because it is prespecified for faces, but due to our
extensive expertise with that class of stimulus. Further, it
encourages parallels with the development of face pro-
cessing skills in infants (Gauthier and Nelson 2001). The
extent to which parallels can be drawn between adult
expertise and infant development remains unclear. Future
experiments will need to trace in more detail changes in
the patterns of cortical activation during training in adults
and development in infants.
The differences between the three viewpoints on func-
tional brain development described above can be illus-
trated by consideration of the prefrontal cortex. By neu-
roanatomical criteria, this region of the brain is the slowest
part of the brain to develop, with detectable changes still
occurring into the teenage years (Giedd et al 1999).
According to some, maturation within the frontal lobes is
related to the onset of the ability to successfully reach for
desirable objects toward the end of the first year. Infants
younger than 9 months often fail to accurately retrieve a
hidden object after a short delay period if the object’s
location is changed from one where it was previously
successfully retrieved. Young infants tend to perseverate
by reaching to the hiding location where the object was
found on the immediately preceding trial. This error is
similar to those made by human adults with frontal lesions
and monkeys with lesions to the dorsolateral prefrontal
cortex, leading to the proposal that the maturation of this
region in human infants allows them to retain information
over space and time and to inhibit prepotent responses
(Diamond 2001). In contrast to this maturational view, the
BIOL PSYCHIATRY 1315
2003;54:1312–1316
interactive specialization view would encourage the view
that the onset of a new behavior such as this will entail
changing patterns of interactions between multiple brain
regions (Luna et al 2001). By a skill learning view,
parallels can be drawn with research on adults. Work on
complex motor skill learning tasks in adult primates shows
that parts of prefrontal cortex are often activated during
the early stages of motor skill acquisition, but this activa-
tion recedes to more posterior regions as expertise is
acquired (Miller 2000). Consistent with this latter view,
Csibra et al (2001) examined the cortical activity associ-
ated with the planning of eye movements in 4-month-old
infants. They observed eye movement related potentials
over frontal sites but not over the more posterior (parietal)
sites where they are normally observed in adults. Converg-
ing results are obtained when eye movement tasks are
studied in infants with perinatal focal damage to the
cortex. Infants with damage to the frontal quadrants of the
brain show long-lasting deficits in visual orienting tasks,
but infants with the more posterior damage, which causes
deficits in adults, do not (Craft and Shatz 1994).
Conclusions and Implications for Atypical
Development
The three perspectives on human functional brain devel-
opment discussed above have different implications for
our understanding of developmental disorders and the
effects of brain damage over the first years of life. By the
maturational view, genetic disorders could potentially lead
to focal cortical damage and consequently to selective
cognitive, motor, or perceptual disorders. Symptoms of
these disorders would first become evident at the normal
age of maturation of the regions concerned; however,
recent reviews have concluded that there are few, if any,
human developmental abnormalities of genetic origin that
only affect one or two specific regions of cortex (Johnson
et al 2002). Rather, structural and functional neuroimaging
usually reveal subtle but widespread differences in the
brains of groups with developmental disorders. Relatedly,
claims of domain-specific cognitive deficits in syndromes
such as autism and Williams syndrome have been chal-
lenged and replaced with hypotheses about different styles
or modes of processing (Karmiloff-Smith 1998). Finally, it
is difficult to explain reports of recovery of functions
following early brain damage by the maturational view
without recourse to additional special mechanisms of
plasticity.
According to the interactive specialization view, devel-
opmental disorders of genetic etiology will often involve
disruption of the typical biases and interactions between
regions that give rise to adult patterns of cortical func-
tional specialization. By this view, subtle symptoms
1316 BIOL PSYCHIATRY
2003;54:1312–1316
should be evident from birth, but these will become
compounded through the infant’s abnormal interactions
with its environment. While there are currently few
behavioral studies of developmental disorders during in-
fancy, those that do exist suggest discontinuities in the
patterns of behavioral and cognitive deficits through post-
natal development. For example, in one such disorder,
Williams syndrome, adults present with behavioral deficits
in number tasks but show surprising proficiency in some
aspects of language. A question recently investigated is
whether this pattern of specific deficits is also observed in
Williams syndrome infants, as would be expected if they
have a damaged innate module for numbers. Standard
infant paradigms for assessing number and object naming
skills were used with toddlers with Williams syndrome
(Paterson et al 1999). The toddlers did not show the same
behavioral profile as observed in adults with the syn-
drome, indicating that the profile of behavioral deficits in
developmental disorders can change during ontogeny and
that it is not appropriate to characterize such deficits in
terms of damage to domain-specific modules. From the
interactive specialization perspective, it may also be easier
to understand recovery of function following early damage
since the same mechanisms that ensure specialization
during the typical developmental trajectory could ensure a
different pattern of specialization.
Further assessment of the three perspectives on human
functional brain development presented in this article will
require more improved methods for noninvasive func-
tional imaging methods, such as near infrared spectros-
copy (NIRS)/optical imaging, and more detailed compu-
tational models that generate predictions about both
neuroanatomy and behavior (Casey and de Haan 2002).
Whatever the outcome of these investigations, a better
understanding of functional brain development in human
infants and children may have profound consequences for
educational, clinical, and social policies.
The author acknowledges financial support from the United Kingdom
Medical Research Council (Programme Grant G9715587) and Birkbeck
College.
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