Major Depressive Disorder Is Associated With Abnormal Interoceptive Activity and Functional Connectivity in the Insula
Open accessAbstract
Background Somatic complaints and altered interoceptive awareness are common features in the clinical presentation of major depressive disorder (MDD). Recently, neurobiological evidence has accumulated demonstrating that the insula is one of the primary cortical structures underlying interoceptive awareness. Abnormal interoceptive representation within the insula may thus contribute to the pathophysiology and symptomatology of MDD. Methods We compared fMRI blood oxygenation level-dependent (BOLD) responses between twenty unmedicated adults with MDD and twenty healthy control participants during a task requiring attention to visceral interoceptive sensations and also assessed the relationship of this BOLD response to depression severity, as rated using the Hamilton Depression Rating Scale (HDRS). Additionally, we examined between-group differences in insula resting-state functional connectivity, and its relationship to HDRS ratings of depression severity. Results Relative to the healthy controls, unmedicated MDD subjects exhibited decreased activity bilaterally in the dorsal mid-insula cortex (dmIC) during interoception, as well as within a network of brain regions implicated previously in emotion and visceral control. Activity within the insula during the interoceptive attention task was negatively correlated with both depression severity and somatic symptom severity in depressed subjects. MDD also was associated with greater resting-state functional connectivity between the dmIC and limbic brain regions implicated previously in MDD, including the amygdala, subgenual prefrontal cortex, and orbitofrontal cortex. Moreover, functional connectivity between these regions and the dmIC was positively correlated with depression severity. Conclusions MDD and the somatic symptoms of depression are associated with abnormal interoceptive representation within the insula.
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Individuals suffering from depression exhibit significantly decreased interoceptive sensitivity.
“Indeed, recent studies indicate that individuals suffering from depression exhibit significantly decreased interoceptive sensitivity (Avery et al., 2014).”
From Motivation in the Service of Allostasis: The Role of Anterior Mid-Cingulate Cortex (2019) · cites this paper as Avery et al., 2014
The Results (Imaging Results; page unavailable) report significantly lower brain activity during interoceptive attention in depressed subjects, not a direct measure of interoceptive sensitivity. The Introduction (page unavailable) reports earlier findings of decreased heartbeat-perception accuracy in depression but cautions that those findings were mixed and difficult to interpret. Thus the source supports an interoceptive difference, but not the unqualified claim of significantly decreased sensitivity. (LLM, conf=0.84)
Experimental — accuracy not yet measuredQualitative synthesis found reduced activity in the insular cortex in major depressive disorder across multiple task modalities, with specific reductions in the posterior, dorsal mid- and anterior insula.
“The most consistent finding was reduced activity in the insular cortex in MDD [36–38, 41, 42]. The effect was observed across multiple task modalities, including VIA, heartbeat, and CO2 reactivity, with specific reductions reported in the posterior, dorsal mid- and anterior insula.”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [36]
The Results (Imaging Results; page not provided) report reduced bilateral dorsal mid-insula activity in MDD during heartbeat attention, and reduced activity in the same region during stomach and bladder attention. This supports the source’s contribution to the multi-citation sentence, but the paper does not report the claimed reductions in posterior and anterior insula or findings from VIA and CO2-reactivity tasks. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAll three whole-brain VIA studies reported decreased caudate nucleus activation in major depressive disorder.
“All three studies reported decreased caudate nucleus activation in MDD.”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [36]
The Results (Imaging Results; page not provided) report significantly lower right caudate BOLD activity in depressed subjects during attention to heartbeat sensations. This supports the finding for this study, but the paper does not establish that the other two studies also reported decreased caudate activation. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAvery et al. found that insula activity in individuals with major depressive disorder was negatively correlated with both affective and somatic symptom severity.
“Supporting this view, Avery et al. found that insula activity in individuals with MDD was negatively correlated with both affective and somatic symptom severity, highlighting its potential role in linking disrupted bodily state processing to symptom expression [36].”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [36]
The Results (Imaging Results; page not provided) report negative correlations between insula activity during heartbeat attention and both overall depression severity and somatic symptom severity in participants with MDD. They do not establish a separate correlation with affective symptom severity: only the HDRS somatization subscale was significantly related to dorsal mid-insula activity, while the other subscales were not. (LLM, conf=0.87)
Experimental — accuracy not yet measuredCompromised interoceptive function is linked to psychiatric disorders including depression, anxiety, and addiction.
“Clear links have been found between compromised interoceptive function and psychiatric disorders, including depression (Avery et al., 2013), anxiety (Paulus and Stein, 2010) and addiction (May et al., 2014).”
From Somatic experiencing: using interoception and proprioception as core elements of trauma therapy (2015) · cites this paper as Avery et al., 2013
Avery et al. and Burrows et al. found reduced right amygdala activity in major depressive disorder.
“Both Avery et al. and Burrows et al. also found reduced right amygdala activity [36, 37].”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [36]
In whole-brain VIA studies, Burrows et al. and Avery et al. identified reduced dorsal mid-insula activation in major depressive disorder, and Park et al. found reduced left insula activation.
“More specifically, Burrows et al. and Avery et al. identified reduced activation in the dorsal mid-insula [36, 37] and Park et al. found reduced activation of the left insula [38].”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [36]
All three whole-brain VIA studies reported decreased insula activation in major depressive disorder compared with healthy controls.
“Three studies utilized a VIA task to examine interoception in MDD with whole-brain analysis [36–38]. All studies reported decreased insula activation in MDD compared to healthy controls.”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [36]
In non-medicated depressed patients, functional connectivity during rest between mid-insula and SGC, OFC and amygdala was increased and correlated with depression severity.
“additionally functional connectivity during unconstrained cognition (rest) between mid-insula and SGC, OFC and amygdala was increased in patients and correlated with depression severity.”
From Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced Fatigue and Depression (2016) · cites this paper as Avery et al., 2014
In non-medicated depressed patients, mid-insula activity during an interoceptive attention task was negatively correlated with severity of depression and somatic symptoms.
“Concerning depression, Avery et al. (2014) examined non-medicated patients with fMRI and found that mid-insula activity during an interoceptive attention task was negatively correlated with the severity of depression and somatic symptoms;”
From Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced Fatigue and Depression (2016) · cites this paper as Avery et al., 2014
The findings are consistent with the insula's role in brain regulation of somatic symptoms.
“Thus these findings are consistent with the insula's role in brain regulation of somatic symptoms (Avery et al. 2014).”
From Brain Activity and Functional Connectivity Associated with Hypnosis (2016) · cites this paper as Avery et al. 2014
Mind-body exercise combines the mental and physical aspects of exercise, which may result in similar antidepressive effects to higher intensity exercise.
“Rather, mind-body exercise combines the mental and physical aspects of exercise, which may result in similar antidepressive effects to higher intensity exercise 135, 136 .”
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Cites
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817 · see citing works
Co-Planar Stereotaxic Atlas of the Human Brain
Talairach, J., & Tournoux, P. (1988) · Medical Entomology and Zoology · Cited by 11,798 · see citing works
The assessment of anxiety states by rating
HAMILTON, M. (1959) · British Journal of Medical Psychology · doi:10.1111/j.2044-8341.1959.tb00467.x · Cited by 11,455 · see citing works
Co-planar stereotaxic atlas of the human brain
Laitinen, L. (1989) · Clinical Neurology and Neurosurgery · doi:10.1016/0303-8467(89)90128-5 · Cited by 7,565 · see citing works
How do you feel? Interoception: The sense of the physiological condition of the body
Craig, A. D. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn894 · Cited by 6,006 · see citing works
Deep Brain Stimulation for Treatment-Resistant Depression
Mayberg, H. S., Lozano, A. M., Voon, V., McNeely, H. E., Seminowicz, D., Hamani, C., Schwalb, J. M., & Kennedy, S. H. (2005) · Neuron · doi:10.1016/j.neuron.2005.02.014 · Cited by 4,059 · see citing works
Empathy for Pain Involves the Affective but not Sensory Components of Pain
Singer, T., Seymour, B., O'Doherty, J., Kaube, H., Dolan, R. J., & Frith, C. D. (2004) · Science · doi:10.1126/science.1093535 · Cited by 3,929 · see citing works
Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression
Miller, A. H., Maletic, V., & Raison, C. L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.029 · Cited by 3,848 · see citing works
Neural systems supporting interoceptive awareness
Critchley, H. D., Wiens, S., Rotshtein, P., Öhman, A., & Dolan, R. J. (2004) · Nature Neuroscience · doi:10.1038/nn1176 · Cited by 3,406 · see citing works
The somatic marker hypothesis and the possible functions of the prefrontal cortex
Damasio, A. R. (1996) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.1996.0125 · Cited by 2,847 · see citing works
Subgenual prefrontal cortex abnormalities in mood disorders
Drevets, W. C., Price, J. L., Simpson, J. R., Todd, R. D., Reich, T., Vannier, M., & Raichle, M. E. (1997) · Nature · doi:10.1038/386824a0 · Cited by 2,693 · see citing works
Self-citationOngur, D. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.3.206 · Cited by 2,627 · see citing works
Greicius, M. D., Flores, B. H., Menon, V., Glover, G. H., Solvason, H. B., Kenna, H., Reiss, A. L., & Schatzberg, A. F. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.09.020 · Cited by 2,214 · see citing works
Drevets, W. C., Price, J. L., & Furey, M. L. (2008) · Brain Structure and Function · doi:10.1007/s00429-008-0189-x · Cited by 2,209 · cited 5× · see citing works
“Similarly, volumetric abnormalities as well as increased regional cerebral blood flow and metabolism in the OFC have been reported in neuroimaging and postmortem neuropathological studies of MDD (33,39,68), and lesions of the OFC increase the risk for developing MDD (69).”
BackgroundResultInfluentialSelf-citationNeurobiology of emotion perception I: the neural basis of normal emotion perception
Phillips, M. L., Drevets, W. C., Rauch, S. L., & Lane, R. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00168-9 · Cited by 2,173 · see citing works
Self-citationCircuitry and functional aspects of the insular lobe in primates including humans
AUGUSTINE, J. (1996) · Brain Research Reviews · doi:10.1016/s0165-0173(96)00011-2 · Cited by 1,776 · see citing works
Neurocircuitry of Mood Disorders
Price, J. L., & Drevets, W. C. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.104 · Cited by 1,606 · cited 5× · see citing works
“org/journal in the putative prelimbic region corresponding to Brodmann area [BA] 32pl) (38,49), lateral OFC, posterior OFC (BA13a; located near the caudal part of the olfactory sulcus), and right caudate nucleus (Figure 1, Table 2).”
BackgroundResultInfluentialSelf-citationGlial reduction in the subgenual prefrontal cortex in mood disorders
Öngür, D., Drevets, W. C., & Price, J. L. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.22.13290 · Cited by 1,525 · see citing works
Self-citationNeuroimaging studies of mood disorders
Drevets, W. C. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(00)01020-9 · Cited by 1,313 · see citing works
Self-citationKurth, F., Zilles, K., Fox, P. T., Laird, A. R., & Eickhoff, S. B. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0255-z · Cited by 1,293 · see citing works
A functional anatomical study of unipolar depression
Drevets, W., Videen, T., Price, J., Preskorn, S., Carmichael, S., & Raichle, M. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-09-03628.1992 · Cited by 1,266 · see citing works
Self-citationThe subgenual anterior cingulate cortex in mood disorders
Drevets, W. C., Savitz, J., & Trimble, M. (2008) · CNS Spectrums · doi:10.1017/s1092852900013754 · Cited by 1,109 · see citing works
Self-citationInsula of the old world monkey. III: Efferent cortical output and comments on function
Mesulam, M. ‐., & Mufson, E. J. (1982) · Journal of Comparative Neurology · doi:10.1002/cne.902120104 · Cited by 1,013 · see citing works
Thermosensory activation of insular cortex
Craig, A. D., Chen, K., Bandy, D., & Reiman, E. M. (2000) · Nature Neuroscience · doi:10.1038/72131 · Cited by 1,004 · see citing works
Interoception in anxiety and depression
Paulus, M. P., & Stein, M. B. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0258-9 · Cited by 952 · see citing works
Architectonic subdivision of the human orbital and medial prefrontal cortex
Öngür, D., Ferry, A. T., & Price, J. L. (2003) · Journal of Comparative Neurology · doi:10.1002/cne.10609 · Cited by 944 · see citing works
Medically Unexplained Physical Symptoms, Anxiety, and Depression: A Meta-Analytic Review
Henningsen, P., Zimmermann, T., & Sattel, H. (2003) · Psychosomatic Medicine · doi:10.1097/01.psy.0000075977.90337.e7 · Cited by 829 · see citing works
Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys
Carmichael, S. T., & Price, J. L. (1995) · Journal of Comparative Neurology · doi:10.1002/cne.903630409 · Cited by 678 · see citing works
Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression
Drevets, W. C. (2000) · Progress in Brain Research · doi:10.1016/s0079-6123(00)26027-5 · Cited by 659 · see citing works
Self-citationFunctional MRI reveals spatially specific attentional modulation in human primary visual cortex
Somers, D. C., Dale, A. M., Seiffert, A. E., & Tootell, R. B. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.4.1663 · Cited by 653 · see citing works
Domschke, K., Stevens, S., Pfleiderer, B., & Gerlach, A. L. (2010) · Clinical Psychology Review · doi:10.1016/j.cpr.2009.08.008 · Cited by 580 · see citing works
Toward a Neuroimaging Treatment Selection Biomarker for Major Depressive Disorder
McGrath, C. L., Kelley, M. E., Holtzheimer, P. E., Dunlop, B. W., Craighead, W. E., Franco, A. R., Craddock, R. C., & Mayberg, H. S. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.143 · Cited by 561 · see citing works
Lorenzetti, V., Allen, N. B., Fornito, A., & Yücel, M. (2009) · Journal of Affective Disorders · doi:10.1016/j.jad.2008.11.021 · Cited by 553 · see citing works
Neuroimaging Abnormalities in the Amygdala in Mood Disorders
DREVETS, W. C. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb07098.x · Cited by 544 · see citing works
Self-citationBurgos-Robles, A., Vidal-Gonzalez, I., & Quirk, G. J. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0378-09.2009 · Cited by 530 · see citing works
The nucleus of the solitary tract in the monkey: Projections to the thalamus and brain stem nuclei
Beckstead, R. M., Morse, J. R., & Norgren, R. (1980) · The Journal of Comparative Neurology · doi:10.1002/cne.901900205 · Cited by 445 · see citing works
The Neural Basis of Mood-Congruent Processing Biases in Depression
Elliott, R., Rubinsztein, J. S., Sahakian, B. J., & Dolan, R. J. (2002) · Archives of General Psychiatry · doi:10.1001/archpsyc.59.7.597 · Cited by 440 · see citing works
Simmons, W. K., Avery, J. A., Barcalow, J. C., Bodurka, J., Drevets, W. C., & Bellgowan, P. (2013) · Human Brain Mapping · doi:10.1002/hbm.22113 · Cited by 401 · see citing works
Self-citationThe pathways of interoceptive awareness
Khalsa, S. S., Rudrauf, D., Feinstein, J. S., & Tranel, D. (2009) · Nature Neuroscience · doi:10.1038/nn.2411 · Cited by 387 · see citing works
The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort
Giesecke, T., Gracely, R. H., Williams, D. A., Geisser, M. E., Petzke, F. W., & Clauw, D. J. (2005) · Arthritis & Rheumatism · doi:10.1002/art.21008 · Cited by 377 · see citing works
A convergent functional architecture of the insula emerges across imaging modalities
Kelly, C., Toro, R., Di Martino, A., Cox, C. L., Bellec, P., Castellanos, F. X., & Milham, M. P. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.03.021 · Cited by 374 · see citing works
Brain structures mediating cardiovascular arousal and interoceptive awareness
Pollatos, O., Schandry, R., Auer, D. P., & Kaufmann, C. (2007) · Brain Research · doi:10.1016/j.brainres.2007.01.026 · Cited by 351 · see citing works
Neural Origins of Human Sickness in Interoceptive Responses to Inflammation
Harrison, N. A., Brydon, L., Walker, C., Gray, M. A., Steptoe, A., Dolan, R. J., & Critchley, H. D. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.03.007 · Cited by 345 · see citing works
A Treatment-Resistant Default Mode Subnetwork in Major Depression
Li, B., Liu, L., Friston, K. J., Shen, H., Wang, L., Zeng, L.-L., & Hu, D. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.11.007 · Cited by 333 · see citing works
Neural systems connecting interoceptive awareness and feelings
Pollatos, O., Gramann, K., & Schandry, R. (2007) · Human Brain Mapping · doi:10.1002/hbm.20258 · Cited by 301 · see citing works
Gastric distention activates satiety circuitry in the human brain
Wang, G.-J., Tomasi, D., Backus, W., Wang, R., Telang, F., Geliebter, A., Korner, J., Bauman, A., Fowler, J. S., Thanos, P. K., et al. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2007.11.008 · Cited by 297 · see citing works
Projections of thalamic gustatory and lingual areas in the monkey, Macaca fascicularis
Pritchard, T. C., Hamilton, R. B., Morse, J. R., & Norgren, R. (1986) · The Journal of Comparative Neurology · doi:10.1002/cne.902440208 · Cited by 292 · see citing works
Herbert, B. M., Muth, E. R., Pollatos, O., & Herbert, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036646 · Cited by 287 · see citing works
Resting-State Brain Activity in Schizophrenia and Major Depression: A Quantitative Meta-Analysis
Kühn, S., & Gallinat, J. (2011) · Schizophrenia Bulletin · doi:10.1093/schbul/sbr151 · Cited by 287 · see citing works
The epidemiology of pain in depression
Lépine, J., & Briley, M. (2004) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.618 · Cited by 275 · see citing works
Differential effects of anxiety and depression on interoceptive accuracy
Pollatos, O., Traut-Mattausch, E., & Schandry, R. (2009) · Depression and Anxiety · doi:10.1002/da.20504 · Cited by 274 · see citing works
Jäncke, L., Mirzazade, S., & Shah, N. J. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00288-8 · Cited by 264 · see citing works
Interoceptive sensitivity and emotion processing: An EEG study
Herbert, B. M., Pollatos, O., & Schandry, R. (2007) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2007.04.007 · Cited by 258 · see citing works
Alexithymia and Depression: A Prospective Study of Patients With Major Depressive Disorder
Honkalampi, K. M., Hintikka, J. J., Laukkanen, E., & Viinamäki, J. L. H. (2001) · Psychosomatics · doi:10.1176/appi.psy.42.3.229 · Cited by 249 · see citing works
Heartbeat evoked potentials mirror altered body perception in depressed patients
Terhaar, J., Viola, F. C., Bär, K., & Debener, S. (2012) · Clinical Neurophysiology · doi:10.1016/j.clinph.2012.02.086 · Cited by 238 · see citing works
Attentional modulation of primary interoceptive and exteroceptive cortices.
Farb, N. A. S., Segal, Z. V., & Anderson, A. K. (2013) · Cerebral Cortex · doi:10.1093/cercor/bhr385 · Cited by 235 · see citing works
Heartbeat perception in depression
Dunn, B. D., Dalgleish, T., Ogilvie, A. D., & Lawrence, A. D. (2007) · Behaviour Research and Therapy · doi:10.1016/j.brat.2006.09.008 · Cited by 218 · see citing works
Neural aspects of immunomodulation: Focus on the vagus nerve
Thayer, J. F., & Sternberg, E. M. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.07.247 · Cited by 200 · see citing works
Henderson, L. A., Gandevia, S. C., & Macefield, V. G. (2007) · Pain · doi:10.1016/j.pain.2006.08.013 · Cited by 177 · see citing works
The insular cortex and the neuroanatomy of major depression
Sprengelmeyer, R., Steele, J. D., Mwangi, B., Kumar, P., Christmas, D. M., Milders, M. M., & Matthews, K. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.04.004 · Cited by 176 · see citing works
Attention to touch modulates activity in both primary and secondary somatosensory areas
Johansen‐Berg, H., Christensen, V., Woolrich, M. W., & Matthews, P. M. (2000) · Neuroreport · doi:10.1097/00001756-200004270-00019 · Cited by 171 · see citing works
Medial orbital frontal lesions in late-onset depression
MacFall, J. R., Payne, M. E., Provenzale, J. E., & Krishnan, K. R. R. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(00)01113-6 · Cited by 163 · see citing works
Serial Vagus Nerve Stimulation Functional MRI in Treatment-Resistant Depression
Nahas, Z. H., Tenebäck, C. C., Chae, J., Mu, Q., Molnar, C., Kozel, F. A., Walker, J., Anderson, B. S., Koola, J., Köse, S., et al. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301288 · Cited by 154 · see citing works
Heartbeat perception in panic disorder: a reanalysis
Van der Does, A. J. W., Antony, M. M., Ehlers, A., & Barsky, A. J. (2000) · Behaviour Research and Therapy · doi:10.1016/s0005-7967(98)00184-3 · Cited by 152 · see citing works
Projections of thalamic gustatory and lingual areas in the rat
Norgren, R., & Wolf, G. (1975) · Brain Research · doi:10.1016/0006-8993(75)90531-4 · Cited by 151 · see citing works
Interoceptive awareness, positive affect, and decision making in Major Depressive Disorder
Furman, D. J., Waugh, C. E., Bhattacharjee, K., Thompson, R. J., & Gotlib, I. H. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.06.044 · Cited by 142 · see citing works
Heart Beat Perception in Patients with Depressive, Somatoform, and Personality Disorders
Mussgay, L., Klinkenberg, N., & Rüddel, H. (1999) · Journal of Psychophysiology · doi:10.1027//0269-8803.13.1.27 · Cited by 119 · see citing works
Functional neuroimaging of gastric distention
Stephan, E., Pardo, J. V., Faris, P. L., Hartman, B. K., Kim, S. W., Ivanov, E. H., Daughters, R. S., Costello, P. A., & Goodale, R. L. (2003) · Journal of Gastrointestinal Surgery · doi:10.1016/s1091-255x(03)00071-4 · Cited by 116 · see citing works
Category-specific integration of homeostatic signals in caudal but not rostral human insula
Simmons, W. K., Rapuano, K. M., Kallman, S., Ingeholm, J. E., Miller, B. V., Gotts, S. J., Avery, J. A., Hall, K. D., & Martin, A. D. (2013) · Nature Neuroscience · doi:10.1038/nn.3535 · Cited by 106 · see citing works
Self-citationPain and emotion in the insular cortex: evidence for functional reorganization in major depression
Mutschler, I., Tonio Ball, A., Wankerl, J., & Strigo, I. A. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.03.095 · Cited by 98 · see citing works
Cameron, O. G., Huang, G., Nichols, T. E., Koeppe, R. A., Minoshima, S., Rose, D. S., & Frey, K. A. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.7.793 · Cited by 90 · see citing works
Strigo, I. A., Simmons, A. N., Matthews, S. C., Craig, A. D. B., & Paulus, M. P. (2008) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181656a48 · Cited by 73 · see citing works
Jabbi, M., Kippenhan, J. S., Kohn, P. D., Marenco, S., Mervis, C. Β., Morris, C. A., Meyer‐Lindenberg, A., & Berman, K. F. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114774109 · Cited by 52 · see citing works
Neurometabolic correlates of depression and disability in episodic cluster headache
Seifert, C. L., Valet, M., Pfaffenrath, V., Boecker, H., Rüther, K. V., Tölle, T. R., & Sprenger, T. (2010) · Journal of Neurology · doi:10.1007/s00415-010-5704-3 · Cited by 22 · see citing works
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Interoceptive predictions in the brain
Barrett, L. F., & Simmons, W. K. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3950 · Cited by 1,766 · see citing works
Self-citationInteroception 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 · see citing works
Self-citationSetiawan, E., Wilson, A. A., Mizrahi, R., Rusjan, P. M., Miler, L., Rajkowska, G., Suridjan, I., Kennedy, J. L., Rekkas, P. V., Houle, S., et al. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.2427 · Cited by 939 · see citing works
Resting-state functional connectivity in major depressive disorder: A review
Mulders, P. C., van Eijndhoven, P. F., Schene, A. H., Beckmann, C. F., & Tendolkar, I. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.07.014 · Cited by 884 · see citing works
Chen, 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
Wise, T., Radua, J., Via, E., Cardoner, N., Abe, O., Adams, T. M., Amico, F., Cheng, Y., Cole, J. H., de Azevedo Marques Périco, C., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.72 · Cited by 606 · see citing works
Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced Fatigue and Depression
Stephan, K. E., Manjaly, Z. M., Mathys, C. D., Weber, L. A. E., Paliwal, S., Gard, T., Tittgemeyer, M., Fleming, S. M., Haker, H., Seth, A. K., et al. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00550 · Cited by 437 · see citing works
“Concerning depression, Avery et al. (2014) examined non-medicated patients with fMRI and found that mid-insula activity during an interoceptive attention task was negatively correlated with the severity of depression and somatic symptoms; additionally functional connectivity during unconstrained…”
BackgroundMindfulness and Behavior Change
Schuman-Olivier, Z., Trombka, M., Lovas, D. A., Brewer, J. A., Vago, D. R., Gawande, R., Dunne, J. P., Lazar, S. W., Loucks, E. B., & Fulwiler, C. (2020) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000277 · Cited by 435 · see citing works
Can interoception improve the pragmatic search for biomarkers in psychiatry?
Khalsa, S. S., & Lapidus, R. C. (2016) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2016.00121 · Cited by 366 · see citing works
Somatic experiencing: using interoception and proprioception as core elements of trauma therapy
Payne, P., Levine, P. A., & Crane-Godreau, M. A. (2015) · Frontiers in Psychology · doi:10.3389/fpsyg.2015.00093 · Cited by 344 · see citing works
“including depression (Avery et al., 2013), anxiety (Paulus and Stein, 2010) and addiction (May et al., 2014). Mindfulness meditation practices have been shown to improve insular functioning and connectivity (Holzel et al., 2011) and to increase interoception (Farb et al., 2013), and insular function has been linked wi…”
BackgroundAversive state processing in the posterior insular cortex
Gehrlach, D. A., Dolensek, N., Klein, A. S., Roy Chowdhury, R., Matthys, A., Junghänel, M., Gaitanos, T. N., Podgornik, A., Black, T. D., Reddy Vaka, N., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0469-1 · Cited by 303 · see citing works
Harshaw, C. (2015) · Psychological Bulletin · doi:10.1037/a0038101 · Cited by 302 · see citing works
Towards a comprehensive assessment of interoception in a multi-dimensional framework
Suksasilp, C., & Garfinkel, S. N. (2022) · Biological Psychology · doi:10.1016/j.biopsycho.2022.108262 · Cited by 288 · see citing works
Interoception, homeostatic emotions and sympathovagal balance
Strigo, I. A., & Craig, A. D. (. (2016) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2016.0010 · Cited by 281 · see citing works
Brain Activity and Functional Connectivity Associated with Hypnosis
Jiang, H., White, M. P., Greicius, M. D., Waelde, L. C., & Spiegel, D. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw220 · Cited by 239 · see citing works
Schulz, S. M. (2016) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2016.0018 · Cited by 205 · 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
Interoceptive pathways to understand and treat mental health conditions
Nord, C. L., & Garfinkel, S. N. (2022) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2022.03.004 · Cited by 199 · see citing works
Khalsa, S. S., Craske, M. G., Li, W., Vangala, S., Strober, M., & Feusner, J. D. (2015) · International Journal of Eating Disorders · doi:10.1002/eat.22387 · Cited by 191 · see citing works
Evans, J. W., Szczepanik, J., Brutsché, N., Park, L. T., Nugent, A. C., & Zarate, C. A. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.01.027 · Cited by 173 · see citing works
Neuronal connectivity in major depressive disorder: a systematic review
Helm, K., Viol, K., Weiger, T. M., Tass, P. A., Grefkes, C., del Monte, D., & Schiepek, G. (2018) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s170989 · Cited by 164 · see citing works
Kerr, K. L., Moseman, S. E., Avery, J. A., Bodurka, J., Zucker, N. L., & Simmons, W. K. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.174 · Cited by 159 · see citing works
Self-citationThe insular cortex dynamically maps changes in cardiorespiratory interoception
Hassanpour, M. S., Simmons, W. K., Feinstein, J. S., Luo, Q., Lapidus, R. C., Bodurka, J., Paulus, M. P., & Khalsa, S. S. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.154 · Cited by 130 · see citing works
Self-citationFissler, M., Winnebeck, E., Schroeter, T., Gummersbach, M., Huntenburg, J. M., Gaertner, M., & Barnhofer, T. (2016) · Mindfulness · doi:10.1007/s12671-016-0559-z · Cited by 132 · see citing works
Interoceptive awareness changes the posterior insula functional connectivity profile.
Kuehn, E., Mueller, K., Lohmann, G., & Schuetz-Bosbach, S. (2016) · Brain Structure and Function · doi:10.1007/s00429-015-0989-8 · Cited by 125 · see citing works
Increased anterior insula activity in anxious individuals is linked to diminished perceived control
Alvarez, R. P., Kirlic, N., Misaki, M., Bodurka, J., Rhudy, J. L., Paulus, M. P., & Drevets, W. C. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.84 · Cited by 113 · see citing works
Self-citationRayner, G., Jackson, G., & Wilson, S. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.09.022 · Cited by 104 · see citing works
Wiebking, C., de Greck, M., Duncan, N. W., Tempelmann, C., Bajbouj, M., & Northoff, G. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00082 · Cited by 90 · see citing works
Wang, T., Zhang, X., Li, A., Zhu, M., Liu, S., Qin, W., Li, J., Yu, C., Jiang, T., & Liu, B. (2017) · NeuroImage: Clinical · doi:10.1016/j.nicl.2017.02.011 · Cited by 88 · see citing works
Gong, L., Yin, Y., He, C., Ye, Q., Bai, F., Yuan, Y., Zhang, H., Lv, L., Zhang, H., Xie, C., et al. (2017) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.09.016 · Cited by 82 · see citing works
Altered food-cue processing in chronically ill and recovered women with anorexia nervosa
Sanders, N., Smeets, P. A. M., van Elburg, A. A., Danner, U. N., van Meer, F., Hoek, H. W., & Adan, R. A. H. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00046 · Cited by 72 · see citing works
“Keywords: anorexia nervosa, recovery, functional magnetic resonance imaging, food viewing”
BackgroundRay, D., Bezmaternykh, D., Mel’nikov, M., Friston, K. J., & Das, M. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2105730118 · Cited by 73 · see citing works
Wu, X., Lin, P., Yang, J., Song, H., Yang, R., & Yang, J. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.04.046 · Cited by 73 · see citing works
Yoris, A., Abrevaya, S., Esteves, S., Salamone, P., Lori, N., Martorell, M., Legaz, A., Alifano, F., Petroni, A., Sánchez, R., et al. (2018) · Human Brain Mapping · doi:10.1002/hbm.23933 · Cited by 66 · see citing works
Hassanpour, M. S., Yan, L., Wang, D. J. J., Lapidus, R. C., Arevian, A. C., Simmons, W. K., Feusner, J. D., & Khalsa, S. S. (2016) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2016.0017 · Cited by 70 · see citing works
Self-citationLiu, C.-H., Ma, X., Song, L.-P., Fan, J., Wang, W.-D., Lv, X.-Y., Zhang, Y., Li, F., Wang, L., & Wang, C.-Y. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.11.047 · Cited by 71 · see citing works
Allostatic Interoceptive Overload Across Psychiatric and Neurological Conditions
Santamaría-García, H., Migeot, J., Medel, V., Hazelton, J. L., Teckentrup, V., Romero-Ortuno, R., Piguet, O., Lawor, B., Northoff, G., & Ibanez, A. (2025) · Biological Psychiatry · doi:10.1016/j.biopsych.2024.06.024 · Cited by 65 · see citing works
Li, H., Wei, D., Browning, M., Du, X., Zhang, Q., & Qiu, J. (2016) · Psychological Medicine · doi:10.1017/s003329171500238x · Cited by 59 · see citing works
Forrest, L. N., Zuromski, K. L., Dodd, D. R., & Smith, A. R. (2017) · International Journal of Eating Disorders · doi:10.1002/eat.22582 · Cited by 57 · see citing works
Hao, Z. Y., Zhong, Y., Ma, Z. J., Xu, H. Z., Kong, J. Y., Wu, Z., Wu, Y., Li, J., Lu, X., Zhang, N., et al. (2020) · BMC Psychiatry · doi:10.1186/s12888-020-02490-7 · Cited by 54 · see citing works
Limbic Intrinsic Connectivity in Depressed and High-Risk Youth
Singh, M. K., Leslie, S. M., Packer, M. M., Weisman, E. F., & Gotlib, I. H. (2018) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2018.06.017 · Cited by 54 · see citing works
Increasing Our Insular World View: interoception and Psychopathology for Psychotherapists.
Duquette, P. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00135 · Cited by 54 · see citing works
Pinter, A., Szatmari Jr, S., Horvath, T., Penzlin, A. I., Barlinn, K., Siepmann, M., & Siepmann, T. (2019) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s200360 · Cited by 53 · see citing works
Richter, F., García, A. M., Rodriguez Arriagada, N., Yoris, A., Birba, A., Huepe, D., Zimmer, H., Ibáñez, A., & Sedeño, L. (2021) · Human Brain Mapping · doi:10.1002/hbm.25288 · Cited by 46 · see citing works
Cayoun, B., Simmons, A., & Shires, A. (2020) · Mindfulness · doi:10.1007/s12671-017-0823-x · Cited by 48 · see citing works
Chen, H., Dong, G., & Li, K. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1094583 · Cited by 47 · see citing works
Distinct functional connectivities predict clinical response with emotion regulation therapy
Fresco, D. M., Roy, A. K., Adelsberg, S., Seeley, S., García-Lesy, E., Liston, C., & Mennin, D. S. (2017) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2017.00086 · Cited by 43 · see citing works
“…targets of treatment for GAD with and without co-occurring MDD. Keywords: generalized anxiety disorder, major depressive disorder, worry, somatic anxiety, decentering, resting state functional connectivity Frontiers in Human Neuroscience | www.frontiersin.org 1 March 2017 | Volume 11 | Article 86”
BackgroundMiller, K. J., Areerob, P., Hennessy, D., Gonçalves-Bradley, D. C., Mesagno, C., & Grace, F. (2020) · F1000Research · doi:10.12688/f1000research.27123.1 · Cited by 41 · see citing works
Cayoun, B. A., & Shires, A. G. (2020) · Frontiers in Psychology · doi:10.3389/fpsyg.2020.545945 · Cited by 36 · see citing works
Datko, M., Lutz, J., Gawande, R., Comeau, A., To, M. N., Desel, T., Gan, J., Desbordes, G., Napadow, V., & Schuman-Olivier, Z. (2022) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2022.111559 · Cited by 35 · see citing works
Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review
Demchenko, I., Tassone, V. K., Kennedy, S. H., Dunlop, K., & Bhat, V. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.864902 · Cited by 29 · see citing works
Opel, N., Redlich, R., Grotegerd, D., Dohm, K., Zaremba, D., Meinert, S., Bürger, C., Plümpe, L., Alferink, J., Heindel, W., et al. (2017) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.160198 · Cited by 28 · see citing works
Impact of serotonergic medication on interoception in major depressive disorder
Burrows, K., DeVille, D. C., Cosgrove, K. T., Kuplicki, R. T., Paulus, M. P., Aupperle, R., Khalsa, S. S., Stewart, J. L., Bodurka, J., Guinjoan, S., et al. (2022) · Biological Psychology · doi:10.1016/j.biopsycho.2022.108286 · Cited by 24 · see citing works
Self-citationMotivation in the Service of Allostasis: The Role of Anterior Mid-Cingulate Cortex
Touroutoglou, A., Andreano, J. M., Adebayo, M., Lyons, S., & Barrett, L. F. (2019) · Advances in Motivation Science · doi:10.1016/bs.adms.2018.09.002 · Cited by 25 · see citing works
“Indeed, recent studies indicate that individuals suffering from depression exhibit significantly decreased interoceptive sensitivity (Avery et al., 2014).”
BackgroundPagni, B. A., Walsh, M. J. M., Foldes, E., Sebren, A., Dixon, M. V., Guerithault, N., & Braden, B. B. (2020) · Journal of Neuroscience Research · doi:10.1002/jnr.24600 · Cited by 25 · see citing works
A dimensional approach to functional movement disorders: Heresy or opportunity
Spagnolo, P. A., Garvey, M., & Hallett, M. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.04.005 · Cited by 23 · see citing works
Park, H., Sanchez, S. M., Kuplicki, R., Tsuchiyagaito, A., Khalsa, S. S., Paulus, M. P., & Guinjoan, S. M. (2022) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2022.10.020 · Cited by 20 · see citing works
Miller, K. J., Areerob, P., Hennessy, D., Gonçalves-Bradley, D. C., Mesagno, C., & Grace, F. (2021) · F1000Research · doi:10.12688/f1000research.27123.2 · Cited by 20 · see citing works
Jamieson, A. J., Davey, C. G., Pujol, J., Blanco-Hinojo, L., & Harrison, B. J. (2025) · Psychological Medicine · doi:10.1017/s0033291725000510 · Cited by 2 · see citing works
Bednarek, L., Harrison, B. J., Davey, C. G., Steward, T., & Jamieson, A. J. (2026) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-026-02201-5 · Cited by 1 · see citing works
“VIA task : Three studies used variations of the VIA task [ 36 – 38 ].”
Influential
- Authors
- Avery, J. A., Drevets, W. C., Moseman, S. E., Bodurka, J., Barcalow, J. C., & Simmons, W. K.
- Affiliations
- Laureate Institute for Brain Research (US)
- Johnson & Johnson (United States) (US)
- Laureate Psychiatric Clinic and Hospital (US)
- Corresponding author
- Simmons, W. Kyle
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 76
- Issue
- 3
- Pages
- 258-266
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4048794
- OpenAlex
- W2015741558
- Semantic Scholar
- eb447f60b63391b605ce831c0840737510393d38
- Cited by
- 442
- References
- 74
- Citations by year
- 2026: 35 · 2025: 40 · 2024: 37 · 2023: 30 · 2022: 30 · 2021: 57 · 2020: 46 · 2019: 38 · 2018: 31 · 2017: 34 · 2016: 27 · 2015: 29 · 2014: 7
- FWCI
- 14.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (K01MH096175)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- major depressive disorder, interoception, insula, resting-state functional connectivity, somatic symptoms, interoceptive attention, depression severity, amygdala, subgenual prefrontal cortex, orbitofrontal cortex, limbic system
- MeSH terms
- Adult, Attention, Brain, Brain Mapping, Cerebral Cortex, Major Depressive Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net, Young Adult, Interoception
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