Evidence for a large-scale brain system supporting allostasis and interoception in humans
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Abstract
Large-scale intrinsic brain systems have been identified for exteroceptive senses (such as sight, hearing and touch). We introduce an analogous system for representing sensations from within the body, called interoception, and demonstrate its relation to regulating peripheral systems in the body, called allostasis. Employing the recently introduced Embodied Predictive Interoception Coding (EPIC) model, we used tract-tracing studies of macaque monkeys, followed by two intrinsic functional magnetic resonance imaging samples (N = 280 and N = 270) to evaluate the existence of an intrinsic allostatic–interoceptive system in the human brain. Another sample (N = 41) allowed us to evaluate the convergent validity of the hypothesized allostatic–interoceptive system by showing that individuals with stronger connectivity between system hubs performed better on an implicit index of interoceptive ability related to autonomic fluctuations. Implications include insights for the brain’s functional architecture, dissolving the artificial boundary between mind and body, and unifying mental and physical illness.
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Different interoceptive channels share common regional neural substrates that likely permit integrative processing towards predictive representations that might ultimately direct adaptive behaviour.
“Within the brain, different interoceptive channels share common regional neural substrates that likely permit integrative processing towards (predictive) representations that might ultimately direct adaptive behaviour [10].”
From Interoception and emotion. (2017) · cites this paper as [10]
The Anatomical evidence section describes interconnected regions exchanging interoceptive predictions, and the Discussion says interoceptive inputs and visceromotor control are integrated within one system. However, the paper does not establish that different interoceptive channels share regional substrates; the Discussion also says the system’s predictive-coding features remain to be tested. Pages are not available in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredEach network is comprised of cortical and subcortical regions interconnected by hub regions, including the aMCC.
“Each network is comprised of cortical and subcortical regions interconnected by the brain’s hub regions, including but not limited to regions important for motivation such as the anterior subregion of the mid-cingulate cortex (aMCC) (Kleckner et al., 2017).”
From Motivation in the Service of Allostasis: The Role of Anterior Mid-Cingulate Cortex (2019) · cites this paper as Kleckner et al., 2017
The Results section on cortical connectivity describes two networks connected through overlapping regions, and the Results section on subcortical connectivity links their cortical hubs to non-cortical regions. The Results section on validation identifies the aMCC as part of the connected allostatic/interoceptive system, but the passages do not establish that the aMCC is itself a connector hub or characterize it as important for motivation. No page numbers are provided in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredRecent neuroscience research points to a large-scale system in the brain supporting allostasis, which connects predictions about energy requirements to systems that monitor and regulate the state of the body.
“Recent neuroscience research points to a large-scale system in the brain supporting allostasis, which connects predictions about energy requirements to systems that monitor and regulate the state of the body (Kleckner et al., 2017).”
From Motivation in the Service of Allostasis: The Role of Anterior Mid-Cingulate Cortex (2019) · cites this paper as Kleckner et al., 2017
The aMCC participates in systems associated with visceromotor functions (salience, allostatic-interoceptive) and executive function, attention, and motor control (frontoparietal control, ventral attention, cingulo-operculum control).
“Evidence from brain connectivity studies show that the aMCC participates in systems associated with visceromotor functions such as the “salience” (Seeley et al., 2007; Touroutoglou et al., 2012) and “allostatic-interoceptive” networks (Kleckner et al., 2017) as well as networks associated with executive function, attention, and motor control such as “frontoparietal control” (Vincent et al., 2008),”
From Motivation in the Service of Allostasis: The Role of Anterior Mid-Cingulate Cortex (2019) · cites this paper as Kleckner et al., 2017
This system includes two of the brain's major intrinsic networks involved in sensing, thinking, and feeling (salience and default mode network).
“This system includes two of the brain’s major intrinsic networks involved in sensing, thinking, and feeling (known as the salience and default mode network) (see Figure 1; (Kleckner et al., 2017).”
From Motivation in the Service of Allostasis: The Role of Anterior Mid-Cingulate Cortex (2019) · cites this paper as Kleckner et al., 2017
Interoception seemingly involves a high degree of connectivity within the brain.
“Interoception seemingly involves a high degree of connectivity within the brain (135).”
From Interoception and Mental Health: A Roadmap. (2018) · cites this paper as [135]
Beyond allostasis, the predictive coding framework proposes that estimating the most likely cause of changes in internal bodily parameters, given a certain exteroceptive context, gives rise to emotional feelings, with a particular role for anterior cingulate and anterior insular cortices to generate visceral predictions.
“Beyond allostasis, the predictive coding framework proposes that estimating the most likely cause of changes in internal bodily parameters, given a certain exteroceptive context, gives rise to emotional feelings 209-211 , with a particular role for anterior cingulate and anterior insular cortices to generate visceral predictions 212 .”
From Interoceptive rhythms in the brain (2023) · cites this paper as [212]
Interoception impairment is a core feature that can occur in multiple clinical conditions.
“Interoception impairment (i.e., difficulties in the sensing, perceiving, and anticipating of signals arising from within the body) is a core feature that can occur in multiple clinical conditions.1, 2, 3”
From Altered spatiotemporal brain dynamics of interoception in behavioural-variant frontotemporal dementia (2025) · cites this paper as [3]
Allostatic-interoception is underpinned by the Allostatic-Interoceptive Network (AIN), a large-scale domain-general network including the anterior cingulate cortex, insula, orbitofrontal cortex, amygdala, thalamus, hippocampus, ventral striatum, and angular gyrus.
“Allostatic-interoception is underpinned by the Allostatic-Interoceptive Network (AIN), a large-scale domain-general network including the anterior cingulate cortex, insula, orbitofrontal cortex, amygdala, thalamus, hippocampus, ventral striatum, and angular gyrus.1,3,14”
From Altered spatiotemporal brain dynamics of interoception in behavioural-variant frontotemporal dementia (2025) · cites this paper as [3]
Allostasis is deeply intertwined with interoception.
“Allostasis (i.e., the brain's continual prediction, anticipation, and adaptation to meet the body's needs before they arise or become urgent)13 is deeply intertwined with interoception.3”
From Altered spatiotemporal brain dynamics of interoception in behavioural-variant frontotemporal dementia (2025) · cites this paper as [3]
Both atrophy and functional connectivity alterations observed in people with bvFTD substantially overlap with the AIN.
“Moreover, both atrophy and functional connectivity alterations observed in people with bvFTD14,17,24 substantially overlap with the AIN.3”
From Altered spatiotemporal brain dynamics of interoception in behavioural-variant frontotemporal dementia (2025) · cites this paper as [3]
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Interoception and Mental Health: A Roadmap.
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Self-citationThe theory of constructed emotion: an active inference account of interoception and categorization
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Self-citationThe theory of constructed emotion: an active inference account of interoception and categorization
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“Within the brain, different interoceptive channels share common regional neural substrates that likely permit integrative processing towards (predictive) representations that might ultimately direct adaptive behaviour [10].”
BackgroundChen, W. G., Schloesser, D., Arensdorf, A. M., Simmons, J. M., Cui, C., Valentino, R., Gnadt, J. W., Nielsen, L., Hillaire-Clarke, C. S., Spruance, V., et al. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2020.10.007 · Cited by 707 · see citing works
An active inference theory of allostasis and interoception in depression
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Self-citationConnecting minds and sharing emotions through mimicry: A neurocognitive model of emotional contagion
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“In support of NMEC, researchers began to identify analogous introspective mechanisms for representing sensations from within the body (Kleckner et al., 2017).”
InfluentialVisceral Signals Shape Brain Dynamics and Cognition
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Hutchinson, J. B., & Barrett, L. F. (2019) · Current Directions in Psychological Science · doi:10.1177/0963721419831992 · Cited by 216 · see citing works
Pace-Schott, E. F., Amole, M. C., Aue, T., Balconi, M., Bylsma, L. M., Critchley, H., Demaree, H. A., Friedman, B. H., Gooding, A. E. K., Gosseries, O., et al. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.05.002 · Cited by 221 · see citing works
“Following influential reviews (Cameron, 2001; Craig, 2002, 2016; Critchley, 2005), the study of interoception in relation to normal emotion has blossomed (Barrett, 2017c; Craig, 2010; Critchley and Garfinkel, 2017; Kleckner et al., 2017; Krautwurst et al., 2016; Strigo and Craig, 2016).”
Interoceptive rhythms in the brain
Engelen, T., Solcà, M., & Tallon-Baudry, C. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01425-1 · Cited by 207 · see citing works
Anterior insular cortex plays a critical role in interoceptive attention
Wang, X., Wu, Q., Egan, L., Gu, X., Liu, P., Gu, H., Yang, Y., Luo, J., Wu, Y., Gao, Z., et al. (2019) · eLife · doi:10.7554/elife.42265 · Cited by 204 · see citing works
The sense of should: A biologically-based framework for modeling social pressure
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Self-citationHistorical pitfalls and new directions in the neuroscience of emotion
Barrett, L. F., & Satpute, A. B. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2017.07.045 · Cited by 180 · see citing works
The influence of physiological signals on cognition
Critchley, H. D., & Garfinkel, S. N. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2017.08.014 · Cited by 178 · see citing works
Kraynak, T. E., Marsland, A. L., Wager, T. D., & Gianaros, P. J. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.07.013 · Cited by 165 · see citing works
Interoception primes emotional processing: multimodal evidence from neurodegeneration
Salamone, P. C., Legaz, A., Sedeño, L., Moguilner, S., Fraile-Vazquez, M., Campo, C. G., Fittipaldi, S., Yoris, A., Miranda, M., Birba, A., et al. (2021) · The Journal of Neuroscience · doi:10.1523/jneurosci.2578-20.2021 · Cited by 103 · see citing works
Interoception as modeling, allostasis as control
Sennesh, E., Theriault, J., Brooks, D., van de Meent, J.-W., Barrett, L. F., & Quigley, K. S. (2022) · Biological Psychology · doi:10.1016/j.biopsycho.2021.108242 · Cited by 107 · see citing works
Self-citationConcepts, goals and the control of survival-related behaviors
Feldman Barrett, L., & Finlay, B. L. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.10.001 · Cited by 89 · see citing works
Self-citationAinley, V., Tsakiris, M., Pollatos, O., Schulz, A., & Herbert, B. M. (2020) · Biological Psychology · doi:10.1016/j.biopsycho.2020.107870 · Cited by 88 · see citing works
Allostasis, action and affect in depression: Insights from the theory of constructed emotion
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Self-citationHeartbeat and somatosensory perception
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Allostasis as a core feature of hierarchical gradients in the human brain
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Self-citationThe Peripersonal Space in a social world
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“For instance, the default mode and salience networks support interoception and allostasis and continuously interact with other networks underlying different cognitive functions (Khalsa et al., 2018; Kleckner et al., 2017).”
BackgroundA predictive coding framework of allostatic–interoceptive overload in frontotemporal dementia
Migeot, J. A., Duran-Aniotz, C. A., Signorelli, C. M., Piguet, O., & Ibáñez, A. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.08.005 · Cited by 76 · see citing works
Generating meaning: active inference and the scope and limits of passive AI
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Active information sampling varies across the cardiac cycle
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Allostatic interoceptive overload in frontotemporal dementia
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A synergetic turn in cognitive neuroscience of brain diseases
Ibanez, A., Kringelbach, M. L., & Deco, G. (2024) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2023.12.006 · Cited by 65 · see citing works
Allostatic Interoceptive Overload Across Psychiatric and Neurological Conditions
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Intrinsic functional connectivity is organized as three interdependent gradients
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Pain Asymbolia as Depersonalization for Pain Experience. An Interoceptive Active Inference Account
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Intrinsic timescales and predictive allostatic interoception in brain health and disease
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Motivation in the Service of Allostasis: The Role of Anterior Mid-Cingulate Cortex
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“, 2012) and “allostatic-interoceptive” networks (Kleckner et al., 2017) as well as networks associated with executive function, attention, and motor control such as “frontoparietal control” (Vincent et al.”
BackgroundInfluentialSelf-citationAllostasis, health, and development in Latin America
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Allostatic-interoceptive anticipation of social rejection
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“In illness states—including FND—illness-promoting thoughts and feelings generated The stress system maintains energy regulation (allostasis) [45,46], regulates the physiological state of the body (milieu intérieur) [47], and modulates the brain–body stress system in response to threat and the…”
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Maternal dopamine encodes affective signals of human infants
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Allostatic interoception and brain health: From neurodegeneration to social adversities
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Generating Meaning: Active Inference and the Scope and Limits of Passive AI
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- Authors
- Kleckner, I. R., Zhang, J., Touroutoglou, A., Chanes, L., Xia, C., Simmons, W. K., Quigley, K. S., Dickerson, B. C., & Feldman Barrett, L.
- Affiliations
- Northeastern University (US)
- Harvard University (US)
- Laureate Institute for Brain Research (US)
- Corresponding author
- Kleckner, Ian R.
- ORCID
- Venue
- Nature Human Behaviour
- Published
- 2017-04-24
- Volume
- 1
- Issue
- 5
- ISSN
- 2397-3374 (ISSN-L)
- PMC
- PMC5624222
- OpenAlex
- W2949653992
- Semantic Scholar
- 79ae92da636496383feb502c600494d896c27829
- Cited by
- 641
- References
- 248
- Citations by year
- 2026: 80 · 2025: 74 · 2024: 83 · 2023: 70 · 2022: 67 · 2021: 70 · 2020: 87 · 2019: 51 · 2018: 34 · 2017: 20 · 2016: 3
- FWCI
- 30.15
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Human Behaviour (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute on Aging (R01AG030311)
- National Institute of Mental Health (F32MH096533, K01MH096175)
- National Cancer Institute (R25CA102618, U01CA193632, UG1CA189961)
- Army Research Institute for the Behavioral and Social Sciences (W5J9CQ-11-C-0046, W5J9CQ-12-C-0049)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- allostasis, interoception, brain connectivity, convergent validity, mind-body problem, brain functional architecture
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