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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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“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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
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“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
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“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
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“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
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In the citing paper
“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]
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In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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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Citations
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Dissociable intrinsic connectivity networks for salience processing and executive control
Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., Reiss, A. L., & Greicius, M. D. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5587-06.2007 · Cited by 7,426
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Interoception and Mental Health: A Roadmap.
Khalsa, S. S., Adolphs, R., Cameron, O. G., Critchley, H. D., Davenport, P. W., Feinstein, J. S., Feusner, J. D., Garfinkel, S. N., Lane, R. D., Mehling, W. E., et al. (2018) · Biological psychiatry. Cognitive neuroscience and neuroimaging · doi:10.1016/j.bpsc.2017.12.004 · Cited by 1,453
Self-citationThe theory of constructed emotion: an active inference account of interoception and categorization
Barrett, L. F. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsw154 · Cited by 1,426
Self-citationThe theory of constructed emotion: an active inference account of interoception and categorization
Barrett, L. F. (2017) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsx060 · Cited by 1,009
Self-citationCritchley, H. D., & Garfinkel, S. N. (2017) · Current Opinion in Psychology · doi:10.1016/j.copsyc.2017.04.020 · Cited by 899
“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
Metadata
- 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
- 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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