Trends in

Neurosciences
Special Issue: The Neuroscience of Interoception
Review

Functions of Interoception: From Energy

Regulation to Experience of the Self
Karen S. Quigley ,1,2,* Scott Kanoski,3 Warren M. Grill,4 Lisa Feldman Barrett,5,6 and Manos Tsakiris7,8

We review recent work on the functions of interoceptive processing, by which the Highlights
nervous system anticipates, senses, and integrates signals originating from the A key function of interoception is signal-
body. We focus on several exemplar functions of interoception, including energy ing about the body’s energy status,
which then drives the behaviors needed
regulation (ingestion and excretion), memory, affective and emotional experience,
to renew energy resources.
and the psychological sense of self. We emphasize two themes across these
functions. First, the anatomy of interoceptive afferents makes it difficult to manip- Methodologies to manipulate and mea-
ulate or directly measure interoceptive signaling in humans. Second, recent evi- sure interoceptive signaling in humans
are currently limited, which presents a
dence shows that multimodal integration occurs across interoceptive modalities challenge for the full understanding of
and between interoceptive and exteroceptive modalities. Whereas exteroceptive some of the functions of interoceptive
multimodal integration has been studied relatively extensively, fundamental processing.
questions remain regarding multimodal integration that involves interoceptive
Recent work suggests that the accessi-
modalities. Future empirical work is required to better understand how and bility of C-tactile afferent nerve endings
where multimodal interoceptive integration occurs. and their fibers in mammalian hairy skin,
a pathway that mediates affective touch
and shares anatomical features with
The Multiple Functions of Interoception classical interoceptive afferents, may
The past two decades have seen rapid growth in research activity devoted to interoception and provide an externally accessible experi-
interoceptive processing [1]. Some of the functions of interoception have a long scientific history mental channel for the manipulation
(e.g., heartbeat perception), whereas others have more recently coalesced into a robust and of interoceptive signaling in healthy
humans.
substantial literature (e.g., the psychological sense of self). In this review we focus on a set of ex-
emplar functions of interoceptive processing. In particular, we examine functions that support the In real-world situations, sensations
regulation of energy intake and outflow, as well as mental phenomena such as memory, affective (e.g., touch) are usually multimodal,
and emotional experience, and the ‘sense of self’. Arguably, even these relatively high-level men- with the co-location of sense data com-
ing from activity in both interoceptive
tal processes have their origins in what is every organism’s ultimate concern; namely, the efficient (affective touch) and exteroceptive
regulation of energy to support life [2–4]. (tactile) afferents.

In this review, we use the term interoception to refer to ‘the overall process of how the nervous sys-
tem (central and autonomic) senses, interprets, and integrates signals originating from within the
body, providing a moment-by-moment mapping of the body’s internal landscape across con-
scious and unconscious levels’ [5]. Throughout, we emphasize two themes. First, viscerosensory
1
signaling is difficult to directly measure and experimentally manipulate in humans because intero- Department of Psychology,
Northeastern University, Boston, MA,
ceptive afferents are thin, typically unmyelinated, and diffusely arrayed, making it difficult to use tra- USA
ditional peripheral nerve stimulation approaches. Although findings from animal models face 2
Edith Nourse Rogers Memorial VA
questions regarding their generalizability to humans, such studies are instrumental in motivating re- Hospital, Bedford, MA, USA
3
Department of Biological Sciences,
searchers to develop new experimental methods, some of which might ultimately be applicable in University of Southern California, Los
humans as well. Second, using distinctions drawn by anatomists and neurophysiologists between Angeles, CA, USA
4
interoceptive and exteroceptive sensory systems, it is now clear that multisensory integration Department of Biomedical Engineering,
Duke University, Durham, NC, USA
(see Glossary) can occur not only across two exteroceptive modalities, but also across diverse in- 5
Department of Psychology,
teroceptive inputs as well as across combinations of interoceptive and exteroceptive modalities. Northeastern University, Boston, MA,
Accordingly, in this review we use the term multisensory integration in a broader way than the USA
6
Massachusetts General Hospital,
more traditional sense of integration across exteroceptive modalities [6]. We provide illustrative ex- Harvard Medical School, Boston, MA,
amples of this broader view of multisensory integration. We conclude with the example of affective USA

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© 2020 Elsevier Ltd. All rights reserved.
 Trends in Neurosciences

7
touch, which illustrates the idea of interoceptive and exteroceptive multisensory integration, and Department of Psychology, Royal
Holloway, University of London,
the feasibility of manipulating interoceptive sensory signaling in humans. London, UK
8
Department of Behavioural and Cognitive
Interoception and Energy Regulation Sciences, Faculty of Humanities,
Education and Social Sciences, University
Allostasis and Homeostasis of Luxembourg, Luxembourg
Evolutionary considerations have led neuroscientists to suggest that mammalian brains evolved
to control the motor functions of their bodies in the context of their current array of exteroceptive
*Correspondence:
and interoceptive sensory signals [4,7,8]. Some have even suggested that a key function, if not k.quigley@northeastern.edu
the key function of exteroceptive sensory processing, is the support of motor control [7–9]. (K.S. Quigley).
Anatomically, the interoceptive system has an organization similar to that of skeletomotor control,
with viscerosensory inputs directly linked to visceromotor outputs [5,10]. Finally, all sensory
systems are subject to evolutionary selection pressures that drive the need to minimize neural en-
ergetic costs [11]. In this way, energy regulation is a key concern for a brain, and the optimization
of energy efficiency is a key constraint for both brain and body [2,12]. We suggest that a key func-
tion of interoception is to support the efficient mobilization of crucial resources to where they are
needed most, as well as the efficient removal of waste. In this perspective, the body can be seen
as the brain’s effector and sensor, enabling a delicate balance of resource intake and outflow and
efficiently controlling movements that support resource intake, including foraging, ingestion,
breathing, and circulation [4,13]. The body must also remove waste products via movements
that include breathing, circulation, elimination, and defecation.

To optimally support these major bodily functions, the brain also maximizes overall energy
efficiency by anticipating imminent resource needs, a process referred to as allostasis [2,14].
The body is also supported by ‘in-the-moment’ local regulatory processes or homeostasis.
Homeostasis can operate independent of predictive or anticipatory regulation by the brain, but
can also be modulated by the brain when necessary. Homeostasis provides local regulation
that fine-tunes peripheral functions or makes adjustments in cases where error correction is
needed, when predictive regulation fails to precisely match local needs. Together, allostasis
and homeostasis enable the body’s most metabolically expensive organ, the brain, to operate
at near-peak efficiency [2].

Energetic regulation occurs via both neural and humoral means, with many of the chemical ener-
getic mediators functioning in both the peripheral body and the brain where they modulate both
short- and longer-term shifts in energy mobilization and utilization (e.g., ghrelin, leptin, lactate
[15–21]). For example, plasma ghrelin is high before feeding and low after it [15], and ghrelin re-
ceptors are found in all major tissues of the body [22]. Leptin, by contrast, is released predomi-
nantly by white adipose tissue stores and its serum levels change with the cycle of the
circadian rhythm and are lower before feeding [18,23]. Together these two mediators provide in-
teroceptive signals of the peripheral energetic state. Lactate also serves as a hormonal energetic
signal [21]. Mediators such as ghrelin and leptin appear to have not only direct endocrine effects in
the CNS, but also indirect effects via vagal and spinal visceral afferent signaling [23–25] (see also
‘Interoception and Feeding’). Recent evidence in animal models also suggests that interoceptive
signaling by cytokine release [e.g., interleukin (IL)-1β, IL-6] can occur via the carotid body, a crit-
ical peripheral chemosensor for energetically relevant mediators such as oxygen, carbon dioxide,
and potentially even glucose [26,27]. This suggests an emerging and important role for the
immune system in interoceptive signaling to the brain about energetic status (e.g., [28]). These
newer lines of evidence parallel classical findings [29] showing that proinflammatory cytokines
in the immune system can convey, via the vagus nerve, interoceptive signals required to generate
fever and sickness behaviors. An ongoing challenge, however, is the difficulty of assessing such
interoceptive mechanisms in humans, where one typically cannot safely manipulate these

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important, life-sustaining energy regulation signals. Finally, the multiplicity of energetic mediators Glossary
also reveals considerable multisensory integration both across different interoceptive modalities Affective feelings: the lower-
(e.g., glucose and proinflammatory cytokines [28]) and across interoceptive and exteroceptive dimensional qualia of experience that are
modalities (e.g., vision and ghrelin in feeding [30]). most commonly described as having
features of valence (pleasant vs
unpleasant) and arousal (activated vs
Interoception and Feeding deactivated). Many theories of emotion
Food procurement and consumption are important energy regulation functions that are strongly suggest that affective feelings arise from
influenced by the detection and interpretation of interoceptive signals of energy need, appetite, interoceptive processes.
Affective touch: touch that
satiation, and satiety. These signals fluctuate dynamically based on energy status and can affect
preferentially activates CT afferent fibers
the hedonic aspects of food intake control independent of actual energetic need [31]. The most and is reported by humans to be
prominent biological pathways by which energy-status-related interoceptive states concerning affectively pleasant. Sensations
food intake are communicated from the periphery to the brain are: (i) the vagus nerve, which com- associated with affective touch most
often occur when hairy skin is stroked at
municates gut-derived within-meal signals directly to the caudal brainstem [24]; and (ii) endocrine-
a moderate force and velocity, with
mediated signaling from the periphery to the CNS [32]. Interoceptive energy status cues do not, stimuli at body temperature. These
however, reflexively or obligatorily orchestrate feeding behavior. Rather, the capacity for energy sensations mimic those used in
need, appetite, satiation, or satiety to initiate, terminate, or delay feeding behavior requires: common interactions among primates
such as grooming or caressing.
(i) appropriate interpretation of and attention to these signals; (ii) the integration of these signals Allostasis: physiological regulatory
with previous learned experiences; and (iii) integration with exteroceptive sensory information [30]. processes that enhance an organism’s
The latter is particularly relevant to foraging behavior, as the interoceptive signals of energetic deficit efficiency by anticipating future needs
and preparing to meet them before they
needed to initiate foraging must be integrated with visuospatial, olfactory, and other environmental
arise.
sensory stimuli to successfully locate a food source. Thus, a key feature of energy regulation is the Cystometry: a technique for measuring
requirement for multisensory integration of interoceptive and exteroceptive cues. Moreover, brain re- the contractile force exerted by the
gions that process both interoceptive and exteroceptive energy-status signals, including the bladder during the retention or voiding of
urine.
orbitofrontal cortex, nucleus accumbens, and lateral hypothalamus, are also critical in regulating re-
Emotion: emotions constitute events
ward and affective behavior (see ‘Affective and Emotional Experiences’), suggesting that such mul- that arise from the brain’s efforts to give
tisensory integration can simultaneously influence multiple, interrelated behavioral outcomes [33]. meaning to sense data, including
interoceptive data, which are categorized
in a given situation using an emotion
The hippocampus is a brain region classically studied in the context of visuospatial and episodic concept such as ‘anger’ or ‘happiness’.
memory processing. The hippocampus appears also to be important for the interpretation of Emotion concepts are used to categorize
energy-status signals and their integration with previous learned experiences and with exterocep- when affective feelings are strong but also
based on current external, situational
tive sensory signals. A growing body of literature has implicated the hippocampus in the learned
cues. Emotional events always include
control of feeding behavior [30,34]. For example, rats with selective hippocampal lesions are unable experience (e.g., the experience of the
to use interoceptive energy-status cues (e.g., 0- vs 24-h food restriction) as discriminative stimuli world as threatening or novel) but only
for reinforcement [35,36]. Relatedly, human amnesic patients with nonselective bilateral damage sometimes include the conscious
experience of emotion (e.g., an
to the hippocampus and adjacent medial temporal lobe structures do not seem to appropriately
awareness that one is fearful).
use hunger, satiation, and satiety cues, as exemplified by their failure to adjust hunger ratings External urethral sphincter (EUS):
after eating as well as their consumption of multiple consecutive meals [37,38]. Endocrine signaling, the external urinary sphincter,
in addition to input via the vagus nerve [39] (see ‘Interoception and Memory’), also communicates comprising skeletal muscle, is controlled
by motor fibers of the pudendal nerve.
energy status to the hippocampus, with the hippocampus containing receptors for many feeding-
When activated, the external urinary
related endocrine and neuropeptide mediators (reviewed in [30]), including ghrelin, which was sphincter inhibits voiding of the bladder.
shown to act in the hippocampus as an interoceptive signal of energy need in otherwise food- Ghrelin: a peptide released in
sated rats [40]. These recent findings of multiple neural and humoral mechanisms of interoceptive substantial amounts in the gut and a key
regulator of nutrient sensing (including
signaling from gut to brain also emphasize the continued need for animal-model studies to advance glucose regulation), meal initiation, and
our understanding of the role of interoceptive signaling in the control of feeding, particularly given appetite.
the lack of effective methods to assess interoceptive signals from the gut in humans. Homeostasis: physiological regulatory
processes that react to current needs
and can occur with or without CNS
Interoception and Urinary Function
input. In this view, homeostatic changes
Urinary function provides an illustrative case of the role of interoception in a waste removal function, can be highly regular or temporally
another facet of energy regulation. Regulation of the lower urinary tract (LUT) engages auto- patterned, and in such cases regulation
nomic neural control, including both parasympathetic and sympathetic branches, as well as may require little modulation by the CNS.

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somatic neural control, and thus is yet another suitable system for studying how interoceptive feed- Lactate: a salt produced as a
byproduct of the breakdown of glucose
back regulates a complex behavior [41]. The role of pressure feedback in signaling bladder fullness under anaerobic conditions. In addition,
is well established, and this information is integrated with other exteroceptive signals to regulate be- lactate, although not typically a primary
havior. For example, urinary urgency is influenced by proximity to the entrance to one’s home, and fuel like glucose, may operate as a
such cues generated stronger urge responses in persons with overactive bladder than in healthy glucose-sparing alternative fuel under
conditions such as intense exercise
individuals [42]. More generally, the integration of bladder fullness and other interoceptive and ex- where lactate levels in blood and brain
teroceptive signals influences the perception of urinary urgency, and symptoms of urinary inconti- increase.
nence are amplified by psychological stress [43], anxiety [44], and depression [45]. Leptin: a peptide released
predominantly by adipose tissue, which
is a key regulator of meal initiation and
Regulation of the LUT also relies on multisensory integration and, in addition to bladder pressure appetite. Circulating leptin levels are
or fullness, recent results highlight the importance of feedback from the urethra in regulating LUT typically higher in those with a higher
function. The sensory innervation of the urethra transmits information related to flow [46] and dis- body mass index (BMI) and the brain is
less sensitive to leptin in those with
ruption of flow-related feedback reduces the efficiency of bladder voiding [47,48]. Electrical nerve
higher BMI than those with lower BMI.
stimulation can restore bladder emptying efficiency following disruption of flow-related feedback Lower urinary tract (LUT): comprises
[49], and this has potential clinical implications for urinary retention – the inability to empty the the bladder, urethra, and, in males, the
bladder completely [50] – because loss of urethral sensitivity may contribute to inefficient voiding prostate.
Microneurography: method for
[51]. recording from peripheral nerves that lie
close to the skin’s surface in humans. An
Flow-related feedback from urethral afferents accommodates rapidly [46], illustrating a ubiquitous experimenter uses a very-small-
feature of primary sensory neurons (both exteroceptive and interoceptive): adaptation during a diameter needle to impale a nerve
underlying the skin. The needle has a
persistent stimulus. How is it, then, that only transient flow-related feedback has such profound small, exposed tip and is used to record
effects on efficient bladder emptying? Many species, including mice, rats, and dogs, paradoxi- multiunit neural activity without the need
cally exhibit increased phasic activity of the external urethral sphincter (EUS) during voiding, for anesthesia.
Multisensory integration: the process
which transiently occludes the urethra. Surprisingly, disruption of this phasic EUS activity reduces
by which sense data from two or more
voiding efficiency in the rat [47,48] and dog [52], revealing that phasic bursting of the EUS serves modalities are combined to form a
as a sensory amplifier. Specifically, transient closure of the urethra increases the activity in flow- product that is distinct from, and thus
responsive afferents (i.e., reduces accommodation [46]), and this increased sensory activity en- cannot be easily ‘deconstructed’ to
reconstitute, the components from
ables more efficient voiding [48]. Further, the imposition of artificially induced phasic bursting of
which it is created (also called
the EUS in cats, which normally exhibit EUS relaxation during voiding, promoted more efficient multimodal integration).
voiding by increasing sensory feedback [48]. These data suggest a possible approach to en- Satiation: refers to the cessation of
hance bladder emptying in urinary retention in humans [50]. additional desire to continue eating.
Satiety: the physical feeling of being fed
to or beyond one’s capacity (i.e., a
Emerging research tools enable addressing the challenge of establishing the role of interoceptive feeling of being full).
feedback on LUT function without the confounding effects of anesthesia. These include the use of
awake cystometry in lightly restrained animals [53], the use of implanted sensors and metabolic
cages to quantify the effects of phasic EUS activity on voiding efficiency [54], and wireless im-
planted telemeters to monitor bladder pressure [55]. The state-of-the-art for rodent studies com-
bines a strain gauge to measure bladder distension and integrated light-emitting diodes opposed
to the bladder to illuminate light-sensitive optogenetic channels and modulate sensory nerve ac-
tivity [56]. In humans, the tools available to assess interoceptive function in the LUT are much
more limited and include primarily urethral stimulation [57] and anesthesia [58]. Further, epidural
electrodes implanted for restoration of function [59] may also enable the mapping of human
LUT function [60].

Interoception and Memory

Emerging evidence reveals that learning, memory, and other cognitive processes are influenced by
interoceptive signaling [61]. Peripheral signals of energy status preferentially target neurons in the
hippocampus, thereby promoting learning and memory. The hippocampus is critical for remem-
bering the location and features of extrapersonal physical spaces (visuospatial and contextual
memory, respectively) and for declarative memory, the memory for facts and episodic events.

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These memory processes are crucial to foraging and eating behaviors because animals must be
able to accurately return to the location of a food source and recall episodic features of feeding
events, such as whether a particular food was nutritive, as well as diurnal and seasonal features
that influence predator and prey dynamics. Thus, it is reasonable to expect that the central neural
systems that receive interoceptive energy status signals are tightly linked anatomically and
functionally with those involved in remembering and learning about features of the environment
that optimize nutritive intake.

During food intake, afferent vagal fibers convey signals from the upper and lower gastrointestinal
tract that directly communicate satiation to the caudal brainstem and initiate meal termination [24].
Signals of gastric distension and intestinal nutrient infusion in rodents also cause increased cerebral
blood flow (CBF) to the hippocampus [62,63] and hippocampal CBF is increased following electrical
gastric vagal nerve stimulation (VNS) in humans [64]. The relevance of the gut–hippocampal pathway
to learning and memory function is also suggested by neurophysiological and neurochemical alter-
ations in hippocampal neurons following VNS in rodents, including the induction of long-term poten-
tiation [65] and increased expression of neurotrophic and neurogenic markers related to memory
[66]. A recent study confirmed a physiological role for gut-derived vagal afferent signaling in learning
and memory function by revealing that rats with selective ablation of vagal sensory inputs from the
upper gastrointestinal tract are impaired in hippocampus-dependent visuospatial working memory
and contextual episodic memory [39]. These findings illustrate the idea of the multisensory integra-
tion of information from both interoceptive (energy status signals from the gut) and exteroceptive
(visuospatial navigational and contextual cues) sources. A conceptual framework for these findings
posits that meal-derived vagal signaling primes the hippocampus to encode mnemonic details
associated with eating behavior (e.g., location of food source, episodic memory) to more efficiently
direct future feeding behaviors [34].

Other hormonal systems also provide interoceptive information about energy status and promote
enhanced memory function via direct action on hippocampal neurons. Receptors for leptin,
ghrelin, glucagon-like peptide-1 (GLP-1), and insulin are expressed in the hippocampus
(see also ‘Allostasis and Homeostasis’ earlier), fluctuate with energy status, and influence feeding
and metabolism. Further, the direct action of these signals on hippocampal neurons enhances
hippocampus-dependent learning and memory (see [34] for a further review). Among these
signals, ghrelin is unique in that it is a peripherally derived appetitive meal anticipation signal,
suggesting that the enhancement of hippocampus-dependent memory processes is not mediated
exclusively by interoceptive signals related to satiation (vagal signaling, GLP-1) but also includes
interoceptive signals of energy need [67]. Recent data thus illustrate that multisensory integration
of interoceptive and exteroceptive signaling regulates feeding behavior, including important
features of memory for prior feeding experiences that optimize the efficiency of energy regulation.

Affective and Emotional Experience

Affective and emotional experience represent phenomena that have been proposed to be impor-
tantly related to interoceptive signaling for at least the past 100 years (for reviews see [68,69]). We
refer to affective feelings as the lower-dimensional qualia of experience that are most commonly
described as having features of valence (pleasant vs unpleasant) and arousal (activated vs
deactivated). We consider emotional experience as arising from interoceptive sense data that
are categorized in a specific situation using an emotion concept such as ‘anger’ or ‘happiness’.
Although virtually all hypotheses about the nature of emotion view interoception as playing at
least some role in affect and emotion, the experimental evidence for the specific role is incomplete
because the phenomena are experiential and subjective and thus measurable only via self-report. A
key issue is that the design of many studies has blurred the important distinction between what

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participants believe or expect about their bodily changes versus actual changes in interoceptive
signaling. This has led to confusion about the specific role of interoceptive signals in affective and
emotional experience [70]. Early work such as [71] used physiological manipulations to alter inter-
oceptive signaling and thereby affect, but on the whole this work has been difficult to replicate, likely
due to the crucial additional role of the external context [72]. These studies also illustrate how diffi-
cult it is, with current interoceptive methods in humans, to study the specific impact of interoceptive
signals on affective and emotional experience. Several emotion hypotheses, including recent
construction-based approaches, propose that interoception is a basic function of the nervous sys-
tem and is not specific to emotional events or emotional experiences [73–75]. Rather, they propose
that interoceptive and exteroceptive sense data are continually predicted and used by the CNS to
maintain allostasis and, in the process, make meaning about the relationship between one’s body,
its predicted needs, and the external world (for a review of these constructionist approaches, see
[76]). Specifically, the active inference-based views of Barrett and colleagues [74,75] propose sig-
nificant multimodal integration across multiple interoceptive and exteroceptive signals. It was fur-
ther proposed that interoception is achieved by a combination of the prediction and encoding of
ascending interoceptive signals [75], such that the brain is always running an internal model of
the body to estimate body status, a model that is continually updated by changing ascending sen-
sory signals (i.e., interoceptive prediction errors). Other recent theoretical perspectives also sug-
gest that instances of emotion arise from active inference about the presumed causes of
interoceptive signals [77,78].

The strongest evidence for the role of interoception in emotional and affective experience is
provided by the striking overlap in the neuroanatomical substrates that underlie interoceptive
function, body regulation, and emotional and affective experience [75,79–82]. Other evidence
for a role for interoception in affective and emotional experience comes in the form of temporal
covariation of changes in peripheral physiology (e.g., heart rate, skin conductance) and changes
in affective experience while viewing affectively evocative pictures or other stimuli ([83],
see Study 4). A current methodological limitation is that one is constrained to use either temporal
or magnitude covariations, and these provide only indirect evidence for the role of interoceptive
signaling and interoceptive processes in affective experience. This reliance on correlational
evidence is a major limitation in understanding the role of interoceptive sense data in affect and
emotion. Two recent papers [76,84] proposed that the accessibility of C-tactile (CT) afferent
nerve endings in the skin that mediate so-called affective touch may provide an externally acces-
sible experimental channel for manipulation of sensory input that, by virtue of its anatomy,
appears ‘interoceptive’ (see Box 1 for a description of affective touch). Applying this approach
and perhaps other new methods to directly manipulate interoceptive sense data would be instru-
mental in examining how exactly interoceptive signals impact affect and emotional experience.

Box 1. Affective Touch

Studies demonstrate that the hairy skin of mammals contains CT afferent fibers that are preferentially activated by stroking
at a force, velocity and temperature similar to that typically used when primates stroke one another [112,115]. Importantly,
stroking that activates these fibers is rated as affectively pleasant. These fibers have many features consistent with those of
interoceptive afferents (i.e., they are thin, unmyelinated, and diffusely arrayed). Critically, in a patient with selective loss of
large-diameter myelinated sensory afferents in hairy skin, the activation of intact CT afferent fibers activated the dorsal pos-
terior insula, much like other interoceptive afferents, but did not activate the primary or secondary somatosensory cortex
as would be expected with exteroceptive signals [113]. Because CT afferents are located in the skin, these sensors are
much more accessible to experimental manipulation, and recordings from these afferents can be made in humans using
microneurography [115]. Manipulation of affective touch represents a potentially promising way in which researchers
can study interoceptive signaling in humans [84]. The co-mingling of many different afferent fibers, both myelinated and
unmyelinated, in the hairy skin of mammals also serves as an example of how touch sensations can easily blur the classical
distinction between interoceptive and exteroceptive processes.

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Interoception and the Psychological Sense of Self

From the perspective of psychology, the question of selfhood is intimately linked to the question of
body awareness. However, much of the early work on body awareness focused on the perception
of one’s own and others’ bodies from the outside, in terms of exteroceptive, observable sensory
and motor events. A prototypical example of this exteroceptive route to selfhood is mirror self-
recognition [85], an ability considered a hallmark of self-awareness. The sense of body ownership
has also been studied in the context of exteroceptive multisensory integration; in particular, visual
and tactile integration. In the Rubber Hand Illusion (RHI), an influential experimental model of
embodiment, watching a rubber hand being stroked synchronously with one’s own unseen
hand causes a person to experience the rubber hand as part of their body [6]. Such evidence sug-
gests that self-awareness is highly malleable and subject to the perception of the body from the
outside.

More recently, research has increasingly begun to consider the role that interoceptive signals
and their awareness play in shaping self-awareness. From the somatic-marker hypothesis
[86] and the neuroanatomical and functional focus on the insula [87] to more recent predictive
coding and computational models of interoception [88,89], current views on the bodily basis of
selfhood instead consider the visceral body and its cortical representation to be a core element
of the self.

A study that aimed to examine the relationship between interoceptive and exteroceptive awareness of
the body reported observing a negative correlation between levels of interoceptive awareness and the
malleability of self-awareness as a result of multisensory exteroceptive input in the classic RHI [90].
Participants with lower interoceptive awareness experienced a stronger alteration in body ownership,
suggesting that, in the absence of accurate interoceptive representations, one’s model of self is dom-
inated by exteroceptive input (see also [91–94]). Beyond the conscious aspect of interoception, other
studies used a combination of concurrent interoceptive and exteroceptive signals to study how these
are integrated in body awareness [95–97] and how interoceptive signals may impact self-processing
[98,99] as well as a range of cognitive [100–103] and social-affective processes [104,105].

Within predictive coding accounts of bodily self-awareness, individuals may differ in interoceptive
accuracy and awareness in part due to the relative precision of incoming interoceptive versus ex-
teroceptive signals used to compute the relative probabilities that a given sensory signal is related
to one’s own body [106]. In this context, multisensory integration contributes to the perception of
exteroceptive signals alongside an ever-present flow of interoceptive sense data. Although intero-
ceptive signals are typically in the background of phenomenal awareness (i.e., one does not focus
attention on activity in one’s gut during all waking hours), interoceptive signals can sometimes be
more or less foregrounded in attentional awareness.

Despite the growing research on interoception in adulthood, questions of when and how intero-
ceptive awareness emerges in early life remain unexplored, partly because of the limited-range
interoceptive measures for use in humans, especially in children [107]. However, with new mea-
sures [108] and experimental tasks [107] and insights from studies of psychophysiological cou-
pling between caregivers and infants [109], researchers can now begin to test hypotheses
[110,111] about the inherently social origins of interoceptive awareness. Given that key allostatic
and homeostatic processes are still emerging in infants, caregivers play a key role in both inferring
the infant’s hidden interoceptive perturbations that give rise to behavioral expressions of affective
feelings and in providing an appropriate response to assist in regulating the infant’s needs. It is
through such embodied interactions that the infant’s brain will slowly start to mentalize her own
interoceptive sensations and eventually take appropriate actions [110].

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Concluding Remarks Outstanding Questions

As the preceding attests, interoception plays a role in a wide array of human functions, from how How does the brain use interoceptive
we gather energetic resources and remove waste to optimally support our energetic needs to signals from across different organ
systems to estimate the current
how we view ourselves as distinct from others and the world around us. Although there are dis- energetic status of the body?
tinctive features of interoceptive and exteroceptive sensory anatomy (see [5]), real-world sensa-
tions occur in the context of continual and extensive multisensory integration across both How does the brain integrate its
ongoing (predictive) model of the
interoceptive and exteroceptive systems with impacts on every function reviewed here. Recent
body with ascending interoceptive
studies have broadened the scientific perspective on the important role that interoceptive modal- signals?
ities play in multisensory integration in addition to the more well-studied exteroceptive modalities.
Our review, while selective rather than comprehensive, examined research across a number of How does the brain transform
interoceptive signals into affective
interoceptive functions to illustrate both how interoceptive sense data are integrated with other
feelings and emotional episodes, with
sensory modalities as well as the difficulties inherent in the manipulation and measurement of in- and without emotional experiences?
teroceptive signaling in humans. The hope is that new techniques, such as electrical stimulation of
the vagus nerve, recording from the vagus nerve in humans [114], or the use of methods to ma- How is interoceptive signaling affected by
the widespread neural, hormonal, and
nipulate affective touch, may provide additional tools to study interoceptive processes in humans other physiological changes occurring
(see Outstanding Questions). across different developmental periods?
Specifically, what are key developmental
Acknowledgments features of interoceptive signaling and
Work by K.S.Q. and L.F.B. on the manuscript was supported by grant W911NF-16-1-0191 from the Army Research interoceptive awareness during life
Institute (to K.S.Q.) and National Institutes of Health (NIH) grants R01MH113234 and 1U01CA193632-01A1 (to L.F.B.). stages such as infancy and childhood,
old age, or during puberty, a period that
We also acknowledge helpful discussions on affective touch with Dr Mary Burleson. M.T. was supported by the European
is especially critical for mental health?
Research Council Consolidator Grant (ERC-2016-CoG-724537) under the FP7.

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