Abstract
Intuition suggests that perception follows sensation and therefore bodily feelings originate in the body. However, recent evidence goes against this logic: interoceptive experience may largely reflect limbic predictions about the expected state of the body that are constrained by ascending visceral sensations. In this Opinion article, we introduce the Embodied Predictive Interoception Coding model, which integrates an anatomical model of corticocortical connections with Bayesian active inference principles, to propose that agranular visceromotor cortices contribute to interoception by issuing interoceptive predictions. We then discuss how disruptions in interoceptive predictions could function as a common vulnerability for mental and physical illness.
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References
- 1
Friston, K. The free-energy principle: a unified brain theory? Nat. Rev. Neurosci. 11, 127–138 (2010).
- 2
Clark, A. Whatever next? Predictive brains, situated agents, and the future of cognitive science. Behav. Brain Sci. 36, 181–204 (2013).
- 3
Mesulam, M. M. From sensation to cognition. Brain 121, 1013–1052 (1998).
- 4
Kok, P. & de Lange, F. P. Shape perception simultaneously up- and downregulates neural activity in the primary visual cortex. Curr. Biol. 24, 1531–1535 (2014).
- 5
Chennu, S. et al. Expectation and attention in hierarchical auditory prediction. J. Neurosci. 33, 11194–11205 (2013).
- 6
Craig, A. D. How do you feel — now? The anterior insula and human awareness. Nat. Rev. Neurosci. 10, 59–70 (2009).
- 7
Paulus, M. P. & Stein, M. B. An insular view of anxiety. Biol. Psychiatry 60, 383–387 (2006).
- 8
Paulus, M. P. & Stewart, J. L. Interoception and drug addiction. Neuropharmacology 76, 342–350 (2014).
- 9
Avery, J. A. et al. Major depressive disorder is associated with abnormal interoceptive activity and functional connectivity in the insula. Biol. Psychiatry 76, 258–266 (2014).
- 10
Simmons, W. K. et al. Keeping the body in mind: insula functional organization and functional connectivity integrate interoceptive, exteroceptive, and emotional awareness. Hum. Brain Mapp. 34, 2944–2958 (2013).
- 11
Barbas, H. & Rempel-Clower, N. Cortical structure predicts the pattern of corticocortical connections. Cereb. Cortex 7, 635–646 (1997).
- 12
Gu, X., Hof, P. R., Friston, K. J. & Fan, J. Anterior insular cortex and emotional awareness. J. Comp. Neurol. 521, 3371–3388 (2013).
- 13
Seth, A. K. Interoceptive inference, emotion, and the embodied self. Trends Cogn. Sci. 17, 565–573 (2013).
- 14
Seth, A. K., Suzuki, K. & Critchley, H. D. An interoceptive predictive coding model of conscious presence. Front. Psychol. 2, 395 (2011).
- 15
Singer, T., Critchley, H. D. & Preuschoff, K. A common role of insula in feelings, empathy and uncertainty. Trends Cogn. Sci. 13, 334–340 (2009).
- 16
Mumford, D. On the computational architecture of the neocortex. I. The role of the thalamo-cortical loop. Biol. Cybern. 65, 135–145 (1991).
- 17
Bastos, A. M. et al. Canonical microcircuits for predictive coding. Neuron 76, 695–711 (2012).
- 18
Carmichael, S. T. & Price, J. L. Connectional networks within the orbital and medial prefrontal cortex of macaque monkeys. J. Comp. Neurol. 371, 179–207 (1996).
- 19
Evrard, H. C., Logothetis, N. K. & Craig, A. D. Modular architectonic organization of the insula in the macaque monkey. J. Comp. Neurol. 522, 64–97 (2014).
- 20
Mufson, E. J. & Mesulam, M. M. Insula of the old world monkey. II: afferent cortical input and comments on the claustrum. J. Comp. Neurol. 212, 23–37 (1982).
- 21
Öngür, D., Ferry, A. T. & Price, J. L. Architectonic subdivision of the human orbital and medial prefrontal cortex. J. Comp. Neurol. 460, 425–449 (2003).
- 22
Öngür, D. & Price, J. L. The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb. Cortex 10, 206–219 (2000).
- 23
Saleem, K. S., Kondo, H. & Price, J. L. Complementary circuits connecting the orbital and medial prefrontal networks with the temporal, insular, and opercular cortex in the macaque monkey. J. Comp. Neurol. 506, 659–693 (2008).
- 24
Semendeferi, K. & Damasio, H. The brain and its main anatomical subdivisions in living hominoids using magnetic resonance imaging. J. Hum. Evol. 38, 317–332 (2000).
- 25
Vogt, B. A. & Pandya, D. N. Cingulate cortex of the rhesus monkey: II. Cortical afferents. J. Comp. Neurol. 262, 271–289 (1987).
- 26
Vogt, B. A., Pandya, D. N. & Rosene, D. L. Cingulate cortex of the rhesus monkey: I. Cytoarchitecture and thalamic afferents. J. Comp. Neurol. 262, 256–270 (1987).
- 27
Barbas, H. & Hilgetag, C. C. Rules relating connections to cortical structure in primate prefrontal cortex. Neurocomputing 44–46, 301–308 (2002).
- 28
Shipp, S., Adams, R. A. & Friston, K. J. Reflections on agranular architecture: predictive coding in the motor cortex. Trends Neurosci. 36, 706–716 (2013).
- 29
Larkum, M. A cellular mechanism for cortical associations: an organizing principle for the cerebral cortex. Trends Neurosci. 36, 141–151 (2013).
- 30
Sherman, S. M. The thalamus is more than just a relay. Curr. Opin. Neurobiol. 17, 417–422 (2007).
- 31
Barsalou, L. W. Grounded cognition. Annu. Rev. Psychol. 59, 617–645 (2008).
- 32
Adams, R. A., Shipp, S. & Friston, K. J. Predictions not commands: active inference in the motor system. Brain Struct. Funct. 218, 611–643 (2013).
- 33
Corbetta, M. & Shulman, G. L. Control of goal-directed and stimulus-driven attention in the brain. Nat. Rev. Neurosci. 3, 201–215 (2002).
- 34
Fox, M. D., Corbetta, M., Snyder, A. Z., Vincent, J. L. & Raichle, M. E. Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. Proc. Natl Acad. Sci. USA 103, 10046–10051 (2006).
- 35
Fox, M. D. et al. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc. Natl Acad. Sci. USA 102, 9673–9678 (2005).
- 36
Seeley, W. W. et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J. Neurosci. 27, 2349–2356 (2007).
- 37
Vincent, J. L., Kahn, I., Snyder, A. Z., Raichle, M. E. & Buckner, R. L. Evidence for a frontoparietal control system revealed by intrinsic functional connectivity. J. Neurophysiol. 100, 3328–3342 (2008).
- 38
Yeo, B. T. et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J. Neurophysiol. 106, 1125–1165 (2011).
- 39
Feldman, H. & Friston, K. J. Attention, uncertainty, and free-energy. Front. Hum. Neurosci. 4, 215 (2010).
- 40
Friston, K. The free-energy principle: a rough guide to the brain? Trends Cogn. Sci. 13, 293–301 (2009).
- 41
Shipp, S. The importance of being agranular: a comparative account of visual and motor cortex. Phil. Trans. R. Soc. B 360, 797–814 (2005).
- 42
Wolpert, D. M. & Kawato, M. Multiple paired forward and inverse models for motor control. Neural Netw. 11, 1317–1329 (1998).
- 43
Crapse, T. B. & Sommer, M. A. Corollary discharge across the animal kingdom. Nat. Rev. Neurosci. 9, 587–600 (2008).
- 44
Barbas, H., García-Cabezas, M. Á. & Zikopoulos, B. Frontal–thalamic circuits associated with language. Brain Lang. 126, 49–61 (2013).
- 45
McFarland, N. R. & Haber, S. N. Thalamic relay nuclei of the basal ganglia form both reciprocal and nonreciprocal cortical connections, linking multiple frontal cortical areas. J. Neurosci. 22, 8117–8132 (2002).
- 46
Barbas, H. & García-Cabezas, M. Á. Motor cortex layer 4: less is more. Trends Neurosci. 38, 259–261 (2015).
- 47
Carmichael, S. T. & Price, J. L. Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys. J. Comp. Neurol. 363, 615–641 (1995).
- 48
Mesulam, M. M. & Mufson, E. J. Insula of the old world monkey. III: efferent cortical output and comments on function. J. Comp. Neurol. 212, 38–52 (1982).
- 49
Freedman, L. J., Insel, T. R. & Smith, Y. Subcortical projections of area 25 (subgenual cortex) of the macaque monkey. J. Comp. Neurol. 421, 172–188 (2000).
- 50
Vogt, B. A. Pain and emotion interactions in subregions of the cingulate gyrus. Nat. Rev. Neurosci. 6, 533–544 (2005).
- 51
Hsu, D. T. & Price, J. L. Midline and intralaminar thalamic connections with the orbital and medial prefrontal networks in macaque monkeys. J. Comp. Neurol. 504, 89–111 (2007).
- 52
Chiba, T., Kayahara, T. & Nakano, K. Efferent projections of infralimbic and prelimbic areas of the medial prefrontal cortex in the Japanese monkey, Macaca fuscata. Brain Res. 888, 83–101 (2001).
- 53
Mesulam, M. M. & Mufson, E. J. Insula of the old world monkey. I. Architectonics in the insulo–orbito–temporal component of the paralimbic brain. J. Comp. Neurol. 212, 1–22 (1982).
- 54
Craig, A. D. How do you feel? Interoception: the sense of the physiological condition of the body. Nat. Rev. Neurosci. 33, 655–666 (2002).
- 55
Zikopoulos, B. & Barbas, H. Prefrontal projections to the thalamic reticular nucleus form a unique circuit for attentional mechanisms. J. Neurosci. 26, 7348–7361 (2006).
- 56
Haber, S. N. & Behrens, T. E. The neural network underlying incentive-based learning: implications for interpreting circuit disruptions in psychiatric disorders. Neuron 83, 1019–1039 (2014).
- 57
Ghashghaei, H. T., Hilgetag, C. C. & Barbas, H. Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala. Neuroimage 34, 905–923 (2007).
- 58
Hamani, C. et al. The subcallosal cingulate gyrus in the context of major depression. Biol. Psychiatry 69, 301–308 (2011).
- 59
Timbie, C. & Barbas, H. Specialized pathways from the primate amygdala to posterior orbitofrontal cortex. J. Neurosci. 34, 8106–8118 (2014).
- 60
Zikopoulos, B. & Barbas, H. Parallel driving and modulatory pathways link the prefrontal cortex and thalamus. PLoS ONE 2, e848 (2007).
- 61
Damasio, A. & Carvalho, G. B. The nature of feelings: evolutionary and neurobiological origins. Nat. Rev. Neurosci. 14, 143–152 (2013).
- 62
Hoffman, H. H. & Schnitzlein, H. N. The numbers of nerve fibers in the vagus nerve of man. Anat. Rec. 139, 429–435 (1961).
- 63
Sapolsky, R. M. Monkeyluv: And Other Essays on Our Lives as Animals (Scribner, 2006).
- 64
Simmons, W. K. et al. Category-specific integration of homeostatic signals in caudal but not rostral human insula. Nat. Neurosci. 16, 1551–1552 (2013).
- 65
van den Heuvel, M. P., Stam, C. J., Boersma, M. & Hulshoff Pol, H. E. Small-world and scale-free organization of voxel-based resting-state functional connectivity in the human brain. Neuroimage 43, 528–539 (2008).
- 66
Zippo, A. G. et al. Small-world networks in neuronal populations: a computational perspective. Neural Netw. 44, 143–156 (2013).
- 67
van den Heuvel, M. P. & Sporns, O. An anatomical substrate for integration among functional networks in human cortex. J. Neurosci. 33, 14489–14500 (2013).
- 68
van den Heuvel, M. P. & Sporns, O. Rich-club organization of the human connectome. J. Neurosci. 31, 15775–15786 (2011).
- 69
Dosenbach, N. U. et al. Distinct brain networks for adaptive and stable task control in humans. Proc. Natl Acad. Sci. USA 104, 11073–11078 (2007).
- 70
Dosenbach, N. U., Fair, D. A., Cohen, A. L., Schlaggar, B. L. & Petersen, S. E. A dual-networks architecture of top-down control. Trends Cogn. Sci. 12, 99–105 (2008).
- 71
Seubert, J., Freiherr, J., Djordjevic, J. & Lundström, J. N. Statistical localization of human olfactory cortex. Neuroimage 66, 333–342 (2013).
- 72
Veldhuizen, M. G. et al. Identification of human gustatory cortex by activation likelihood estimation. Hum. Brain Mapp. 32, 2256–2266 (2011).
- 73
Sepulcre, J., Sabuncu, M. R., Yeo, T. B., Liu, H. & Johnson, K. A. Stepwise connectivity of the modal cortex reveals the multimodal organization of the human brain. J. Neurosci. 32, 10649–10661 (2012).
- 74
Paulus, M. P., Tapert, S. F. & Schulteis, G. The role of interoception and alliesthesia in addiction. Pharmacol. Biochem. Behav. 94, 1–7 (2009).
- 75
van Elk, M., Lenggenhager, B., Heydrich, L. & Blanke, O. Suppression of the auditory N1-component for heartbeat-related sounds reflects interoceptive predictive coding. Biol. Psychol. 99, 172–182 (2014).
- 76
Oosterwijk, S. et al. States of mind: emotions, body feelings, and thoughts share distributed neural networks. Neuroimage 62, 2110–2128 (2012).
- 77
Blanke, O. Multisensory brain mechanisms of bodily self-consciousness. Nat. Rev. Neurosci. 13, 556–571 (2012).
- 78
Andrews-Hanna, J. R., Smallwood, J. & Spreng, R. N. The default network and self-generated thought: component processes, dynamic control, and clinical relevance. Ann. NY Acad. Sci. 1316, 29–52 (2014).
- 79
Barrett, L. F. & Satpute, A. B. Large-scale brain networks in affective and social neuroscience: towards an integrative functional architecture of the brain. Curr. Opin. Neurobiol. 23, 361–372 (2013).
- 80
Binder, J. R., Desai, R. H., Graves, W. W. & Conant, L. L. Where is the semantic system? A critical review and meta-analysis of 120 functional neuroimaging studies. Cereb. Cortex 19, 2767–2796 (2009).
- 81
Clithero, J. A. & Rangel, A. Informatic parcellation of the network involved in the computation of subjective value. Soc. Cogn. Affect. Neurosci. 9, 1289–1302 (2014).
- 82
Roy, M., Shohamy, D. & Wager, T. D. Ventromedial prefrontal–subcortical systems and the generation of affective meaning. Trends Cogn. Sci. 16, 147–156 (2012).
- 83
Wilson-Mendenhall, C. D., Barrett, L. F. & Barsalou, L. W. Situating emotional experience. Front. Hum. Neurosci. 7, 764 (2013).
- 84
Barrett, L. F. Solving the emotion paradox: categorization and the experience of emotion. Pers. Soc. Psychol. Rev. 10, 20–46 (2006).
- 85
Barrett, L. F. & Bliss-Moreau, E. Affect as a psychological primitive. Adv. Exp. Soc. Psychol. 41, 167–218 (2009).
- 86
Quattrocki, E. & Friston, K. Autism, oxytocin and interoception. Neurosci. Biobehav. Rev. 47, 410–430 (2014).
- 87
Sinha, P. et al. Autism as a disorder of prediction. Proc. Natl Acad. Sci. USA 111, 15220–15225 (2014).
- 88
Menon, V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn. Sci. 15, 483–506 (2011).
- 89
Crossley, N. A. et al. The hubs of the human connectome are generally implicated in the anatomy of brain disorders. Brain 137, 2382–2395 (2014).
- 90
Goodkind, M. et al. Identification of a common neurobiological substrate for mental illness. JAMA Psychiatry 72, 305–315 (2015).
- 91
Price, J. L. & Drevets, W. C. Neurocircuitry of mood disorders. Neuropsychopharmacology 35, 192–216 (2010).
- 92
Drevets, W. C. et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 386, 824–827 (1997).
- 93
Boes, A. D., McCormick, L. M., Coryell, W. H. & Nopoulos, P. Rostral anterior cingulate cortex volume correlates with depressed mood in normal healthy children. Biol. Psychiatry 63, 391–397 (2008).
- 94
Levesque, M. L. et al. Altered patterns of brain activity during transient sadness in children at familial risk for major depression. J. Affect. Disord. 135, 410–413 (2011).
- 95
Nieuwenhuizen, A. G. & Rutters, F. The hypothalamic–pituitary–adrenal-axis in the regulation of energy balance. Physiol. Behav. 94, 169–177 (2008).
- 96
Gold, P. W. & Chrousos, G. P. Organization of the stress system and its dysregulation in melancholic and atypical depression: high versus low CRH/NE states. Mol. Psychiatry 7, 254–275 (2002).
- 97
Carroll, B. J. et al. Pathophysiology of hypercortisolism in depression: pituitary and adrenal responses to low glucocorticoid feedback. Acta Psychiatr. Scand. 125, 478–491 (2012).
- 98
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W. & Kelley, K. W. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat. Rev. Neurosci. 9, 46–56 (2008).
- 99
Critchley, H. D. & Harrison, N. A. Visceral influences on brain and behavior. Neuron 77, 624–638 (2013).
- 100
Harrison, N. A. et al. Neural origins of human sickness in interoceptive responses to inflammation. Biol. Psychiatry 66, 415–422 (2009).
- 101
Paulus, M. P. & Stein, M. B. Interoception in anxiety and depression. Brain Struct. Funct. 214, 451–463 (2010).
- 102
Ryan, J. P., Sheu, L. K., Critchley, H. D. & Gianaros, P. J. A neural circuitry linking insulin resistance to depressed mood. Psychosom. Med. 74, 476–482 (2012).
- 103
Buckholtz, J. W. et al. Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality. Mol. Psychiatry 13, 313–324 (2008).
- 104
Raison, C. L. & Miller, A. H. Malaise, melancholia and madness: the evolutionary legacy of an inflammatory bias. Brain Behav. Immun. 31, 1–8 (2013).
- 105
Dantzer, R., Heijnen, C. J., Kavelaars, A., Laye, S. & Capuron, L. The neuroimmune basis of fatigue. Trends Neurosci. 37, 39–46 (2014).
- 106
Etkin, A. & Wager, T. D. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am. J. Psychiatry 164, 1476–1488 (2007).
- 107
Mayberg, H. S. et al. Deep brain stimulation for treatment-resistant depression. Neuron 45, 651–660 (2005).
- 108
Kennedy, S. H. et al. Deep brain stimulation for treatment-resistant depression: follow-up after 3 to 6 years. Am. J. Psychiatry 168, 502–510 (2011).
- 109
Riva-Posse, P. et al. Defining critical white matter pathways mediating successful subcallosal cingulate deep brain stimulation for treatment-resistant depression. Biol. Psychiatry 76, 963–969 (2014).
- 110
Hamani, C. et al. Deep brain stimulation of the subcallosal cingulate gyrus for depression: anatomical location of active contacts in clinical responders and a suggested guideline for targeting. J. Neurosurg. 111, 1209–1215 (2009).
- 111
Goldapple, K. et al. Modulation of cortical–limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch. Gen. Psychiatry 61, 34–41 (2004).
- 112
Aupperle, R. L. et al. Neural responses during emotional processing before and after cognitive trauma therapy for battered women. Psychiatry Res. 214, 48–55 (2013).
- 113
McGrath, C. L. et al. Toward a neuroimaging treatment selection biomarker for major depressive disorder. JAMA Psychiatry 70, 821–829 (2013).
- 114
McGrath, C. L. et al. Pretreatment brain states identify likely nonresponse to standard treatments for depression. Biol. Psychiatry 76, 527–535 (2014).
- 115
Moussavi, S. et al. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet 370, 851–858 (2007).
- 116
Smallwood, R. F. et al. Structural brain anomalies and chronic pain: a quantitative meta-analysis of gray matter volume. J. Pain 14, 663–675 (2013).
- 117
Ganzel, B. L., Morris, P. A. & Wethington, E. Allostasis and the human brain: integrating models of stress from the social and life sciences. Psychol. Rev. 117, 134–174 (2010).
- 118
Piazza, J. R., Charles, S. T., Sliwinski, M. J., Mogle, J. & Almeida, D. M. Affective reactivity to daily stressors and long-term risk of reporting a chronic physical health condition. Ann. Behav. Med. 45, 110–120 (2013).
- 119
Dannlowski, U. et al. Limbic scars: long-term consequences of childhood maltreatment revealed by functional and structural magnetic resonance imaging. Biol. Psychiatry 71, 286–293 (2012).
- 120
Teff, K. L. How neural mediation of anticipatory and compensatory insulin release helps us tolerate food. Physiol. Behav. 103, 44–50 (2011).
- 121
Levinthal, D. J. & Strick, P. L. The motor cortex communicates with the kidney. J. Neurosci. 32, 6726–6731 (2012).
- 122
Deco, G., Jirsa, V. K. & McIntosh, A. R. Emerging concepts for the dynamical organization of resting-state activity in the brain. Nat. Rev. Neurosci. 12, 43–56 (2011).
- 123
Hermundstad, A. M. et al. Structural foundations of resting-state and task-based functional connectivity in the human brain. Proc. Natl Acad. Sci. USA 110, 6169–6174 (2013).
- 124
Pernice, V., Staude, B., Cardanobile, S. & Rotter, S. How structure determines correlations in neuronal networks. PLoS Comput. Biol. 7, e1002059 (2011).
- 125
van den Heuvel, M. P., Mandl, R. C., Kahn, R. S. & Hulshoff Pol, H. E. Functionally linked resting-state networks reflect the underlying structural connectivity architecture of the human brain. Hum. Brain Mapp. 30, 3127–3141 (2009).
- 126
Huber, L. et al. Cortical lamina-dependent blood volume changes in human brain at 7T. Neuroimage 107, 23–33 (2015).
- 127
de-Wit, L., Machilsen, B. & Putzeys, T. Predictive coding and the neural response to predictable stimuli. J. Neurosci. 30, 8702–8703 (2010).
- 128
Rempel-Clower, N. L. & Barbas, H. The laminar pattern of connections between prefrontal and anterior temporal cortices in the rhesus monkey is related to cortical structure and function. Cereb. Cortex 10, 851–865 (2000).
- 129
Medalla, M. & Barbas, H. Specialized prefrontal “auditory fields”: organization of primate prefrontal–temporal pathways. Front. Neurosci. 8, 77 (2014).
- 130
Medalla, M. & Barbas, H. Diversity of laminar connections linking periarcuate and lateral intraparietal areas depends on cortical structure. Eur. J. Neurosci. 23, 161–179 (2006).
- 131
Hilgetag, C. C. & Grant, S. Cytoarchitectural differences are a key determinant of laminar projection origins in the visual cortex. Neuroimage 51, 1006–1017 (2010).
- 132
Goulas, A., Uylings, H. B. & Stiers, P. Mapping the hierarchical layout of the structural network of the macaque prefrontal cortex. Cereb. Cortex 24, 1178–1194 (2014).
- 133
Felleman, D. J. & Vas Essen, D. C. Distributed hierarchical processing in the primate cerebral cortex. Cereb. Cortex 1, 1–47 (1991).
- 134
Markov, N. T. et al. Cortical high-density counterstream architectures. Science 342, 1238406 (2013).
- 135
Sanides, F. in Advances in Primatology (eds Noback, C. H. & Montagna, W.) 137–208 (Appleton-Century-Crofts, 1970).
- 136
Nieuwenhuys, R. The insular cortex: a review. Prog. Brain Res. 195, 123–163 (2012).
- 137
Lovero, K. L., Simmons, A. N., Aron, J. L. & Paulus, M. P. Anterior insular cortex anticipates impending stimulus significance. Neuroimage 45, 976–983 (2009).
- 138
Holtz, K., Pane-Farre, C. A., Wendt, J., Lotze, M. & Hamm, A. O. Brain activation during anticipation of interoceptive threat. Neuroimage 61, 857–865 (2012).
- 139
Wise, S. P. Forward frontal fields: phylogeny and fundamental function. Trends Neurosci. 31, 599–608 (2008).
- 140
Terasawa, Y., Shibata, M., Moriguchi, Y. & Umeda, S. Anterior insular cortex mediates bodily sensibility and social anxiety. Soc. Cogn. Affect. Neurosci. 8, 259–266 (2013).
- 141
Price, C. J. & Friston, K. J. Degeneracy and cognitive anatomy. Trends Cogn. Sci. 6, 416–421 (2002).
- 142
Edelman, G. M. & Gally, J. A. Degeneracy and complexity in biological systems. Proc. Natl Acad. Sci. USA 98, 13763–13768 (2001).
- 143
Feinstein, J. S. et al. Preserved emotional awareness of pain in a patient with extensive bilateral damage to the insula, anterior cingulate, and amygdala. Brain Struct. Funct. http://dx.doi.org/10.1007/s00429-014-0986-3 (2015).
- 144
Philippi, C. L. et al. Preserved self-awareness following extensive bilateral brain damage to the insula, anterior cingulate, and medial prefrontal cortices. PLoS ONE 7, e38413 (2012).
- 145
Damasio, A., Damasio, H. & Tranel, D. Persistence of feelings and sentience after bilateral damage of the insula. Cereb. Cortex 23, 833–846 (2013).
- 146
Khalsa, S. S., Rudrauf, D., Feinstein, J. S. & Tranel, D. The pathways of interoceptive awareness. Nat. Neurosci. 12, 1494–1496 (2009).
- 147
Markov, N. T. et al. A weighted and directed interareal connectivity matrix for macaque cerebral cortex. Cereb. Cortex 24, 17–36 (2014).
- 148
Finlay, B. L. & Uchiyama, R. Developmental mechanisms channeling cortical evolution. Trends Neurosci. 38, 69–76 (2015).
- 149
Barbas, H. General cortical and special prefrontal connections: principles from structure to function. Ann. Rev. Neurosci. http://dx.doi.org/10.1146/annurev-neuro-071714-033936 (2015).
Acknowledgements
The authors thank M. Á. García-Cabezas for helpful discussions and advice in preparing figure 1. They also thank K. Friston, H. Barbas, B. Finlay, H. Mayberg, J. Feinstein, S. Khalsa, J. Avery, M. Paulus, A. Satpute, L. Chanes, A. Touroutoglou and I. Kleckner for helpful discussions about the EPIC model and comments offered on the manuscript. In addition, they thank L. Chanes, A. Touroutoglou and J. Zhang for their assistance in summarizing the interoceptive system from the macaque tract-tracing literature. This work was supported by a US National Institute on Aging grant (R01AG030311), a US National Science Foundation grant (BCS-1052790) and contracts from the US Army Research Institute for the Behavioural and Social Sciences (contracts W5J9CQ-12-C-0049 and W5J9CQ-11-C-0046) to L.F.B., as well as a US National Institute of Mental Health grant (K01MH096175-01), a US National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award, and funding from the Oklahoma Tobacco Research Center to W.K.S. The views, opinions and findings contained in this article are those of the authors and should not be construed as an official position, policy or decision of the US National Institutes of Health or Department of the Army unless so designated by other documents.
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Supplementary information
Supplementary information S1
Strengths of the structural model (PDF 169 kb)
Supplementary information S2
An example of how interoceptive perceptions arise in the brain (PDF 105 kb)
Supplementary information S3
Implications for Theories of Emotion (PDF 205 kb)
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Glossary
- Agranular cortex
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An isocortical region with a relatively undifferentiated layer II and layer III and lacking a fully expressed layer IV.
- Allostasis
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The process of activating physiological systems (such as hormonal, autonomic or immune systems) with the aim of returning the body to homeostasis.
- Bayesian approach to probability
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Models for assessing the probability of an event (that is, the posterior probability) based on the prior likelihood of an event and the evidence currently available as to its existence.
- Centrifugal
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A proposed hierarchical organization whereby the agranular and heteromodal association cortices form a collection of hubs, from which connections to unimodal sensory systems can be depicted as concentric rings.
- Corollary discharge
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Signals generated by the motor cortex that influence or inhibit the sensory processing of self-generated motor actions. Such signals convey simultaneous 'efference copies' of motor commands to sensory regions.
- Default mode network
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(DMN). A collection of midline and parietal brain regions that show more activity when people are constructing representations of the past and the future, simulating the present or processing semantic and conceptual content.
- Degeneracy
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The capacity of a system to perform identical functions or yield identical outputs with structurally different sets of elements.
- Deterministic models
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Mathematical models in which, given initial conditions or parameter values, there is no variation in the outcome.
- Dysgranular cortex
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An isocortical region defined by the presence of a differentiated layer II and layer III, and a rudimentary layer IV that contains stellate granule cells receiving thalamocortical inputs.
- Granular cortex
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An isocortical region with six differentiated layers, including a well-defined layer IV that contains many stellate granule cells receiving thalamocortical inputs.
- Homeostasis
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A set of dynamic functions (not a single set point) that interact to maintain an optimal use of energy in the body across all conditions at all times.
- Interoception
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The perception and integration of autonomic, hormonal, visceral and immunological homeostatic signals that collectively describe the physiological state of the body.
- Interoceptive sensations
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Activity within the nervous system indexing the autonomic, hormonal, visceral and immunological homeostatic signals that collectively describe the physiological state of the body — for example, concerning vagal signals, levels of insulin or cortisol, heart rate, gastric distension or inflammatory cytokine levels.
- Lamina I pathway
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Small-diameter sensory fibres that carry ascending interoceptive sensory signals (about muscle contractions in blood vessels, temperature, pain, hormonal activity, immunological inflammation and other variables) in the lateral spinothalamic pathway.
- Positive alliesthesia
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Transformation of a sensation from aversive to pleasurable, depending on the homeostatic needs of the body.
- Precision units
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Pyramidal cells that represent prediction-error signals; these cells modulate the activity of other neurons within a cortical column according to confidence in the predictions or the reliability of the incoming sensory signals.
- Vagus nerve
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Cranial nerve X, which carries ascending interoceptive sensory information about internal organs and the enteric nervous system.
- Visceromotor cortices
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Agranular regions of isocortex and allocortex that modulate the regulation of the autonomic nervous system as well as of the hormonal and immune systems.
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Barrett, L., Simmons, W. Interoceptive predictions in the brain. Nat Rev Neurosci 16, 419–429 (2015). https://doi.org/10.1038/nrn3950
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