Preserved emotional awareness of pain in a patient with extensive bilateral damage to the insula, anterior cingulate, and amygdala
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Functional neuroimaging investigations of pain have discovered a reliable pattern of activation within limbic regions of a putative "pain matrix" that has been theorized to reflect the affective dimension of pain. To test this theory, we evaluated the experience of pain in a rare neurological patient with extensive bilateral lesions encompassing core limbic structures of the pain matrix, including the insula, anterior cingulate, and amygdala. Despite widespread damage to these regions, the patient's expression and experience of pain was intact, and at times excessive in nature. This finding was consistent across multiple pain measures including self-report, facial expression, vocalization, withdrawal reaction, and autonomic response. These results challenge the notion of a "pain matrix" and provide direct evidence that the insula, anterior cingulate, and amygdala are not necessary for feeling the suffering inherent to pain. The patient's heightened degree of pain affect further suggests that these regions may be more important for the regulation of pain rather than providing the decisive substrate for pain's conscious experience.
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Intact emotional and interoceptive abilities have been observed in patients with insula and ACC lesions during adulthood.
“One indication that online interoception may not be required is the observation of intact emotional and interoceptive abilities in patients with insula and ACC lesions during adulthood (Damasio et al., 2013; Feinstein et al., 2016).”
From Atypical interoception as a common risk factor for psychopathology: A review (2021) · cites this paper as Feinstein et al., 2016
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How do you feel — now? The anterior insula and human awareness
(Bud) Craig, A. D. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2555 · Cited by 6,657 · cited 2× · see citing works
“This is an important point since several investigators have recently claimed that the anterior insula is the necessary substrate underlying all forms of emotional awareness (Craig 2009; Gu et al. 2013).”
Ekman, P., & Friesen, W. V. (2019) · PsycTESTS Dataset · doi:10.1037/t27734-000 · Cited by 6,019 · 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
The validation of visual analogue scales as ratio scale measures for chronic and experimental pain
Price, D. D., McGrath, P. A., Rafii, A., & Buckingham, B. (1983) · Pain · doi:10.1016/0304-3959(83)90126-4 · Cited by 3,921 · see citing works
Does Rejection Hurt? An fMRI Study of Social Exclusion
Eisenberger, N. I., Lieberman, M. D., & Williams, K. D. (2003) · Science · doi:10.1126/science.1089134 · Cited by 3,849 · see citing works
Conflict monitoring and anterior cingulate cortex: an update
Botvinick, M. M., Cohen, J. D., & Carter, C. S. (2004) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2004.10.003 · Cited by 3,623 · see citing works
Functional neuroanatomy of emotion: A meta-analysis of emotion activation studies in PET and fMRI
Phan, K. L., Wager, T., Taylor, S. F., & Liberzon, I. (2002) · NeuroImage · doi:10.1006/nimg.2002.1087 · Cited by 3,502 · see citing works
DISCONNEXION SYNDROMES IN ANIMALS AND MAN
Geschwind, N. (1965) · Brain · doi:10.1093/brain/88.2.237 · Cited by 3,419 · see citing works
Looking at pictures: Affective, facial, visceral, and behavioral reactions
LANG, P. J., GREENWALD, M. K., BRADLEY, M. M., & HAMM, A. O. (1993) · Psychophysiology · doi:10.1111/j.1469-8986.1993.tb03352.x · Cited by 3,190 · see citing works
Pain Affect Encoded in Human Anterior Cingulate But Not Somatosensory Cortex
Rainville, P., Duncan, G. H., Price, D. D., Carrier, B., & Bushnell, M. C. (1997) · Science · doi:10.1126/science.277.5328.968 · Cited by 2,629 · cited 3× · see citing works
“…and a dissociation between neural systems subserving pain affect and pain sensation has been proposed, with limbic regions of the matrix encoding the emotional aspects of pain and primary sensory regions encoding the location and intensity of pain sensation (Price 2000; Rainville et al. 1997).”
Functional imaging of brain responses to pain. A review and meta-analysis (2000)
Peyron, R., Laurent, B., & García-Larrea, L. (2000) · Neurophysiologie Clinique/Clinical Neurophysiology · doi:10.1016/s0987-7053(00)00227-6 · Cited by 2,171 · see citing works
Psychological and neural mechanisms of the affective dimension of pain
Price, D. D. (2000) · Science · doi:10.1126/science.288.5472.1769 · Cited by 2,092 · see citing works
The integration of negative affect, pain and cognitive control in the cingulate cortex
Shackman, A. J., Salomons, T. V., Slagter, H. A., Fox, A. S., Winter, J. J., & Davidson, R. J. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn2994 · Cited by 2,082 · see citing works
Cognitive and emotional control of pain and its disruption in chronic pain
Bushnell, M. C., Čeko, M., & Low, L. A. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3516 · Cited by 2,076 · see citing works
Looking for Spinoza : Joy, Sorrow, and the Feeling Brain
Damásio, A. R. (2003) · Dominican Scholar (Dominican University of California) · Cited by 1,879 · see citing works
The Cerebral Signature for Pain Perception and Its Modulation
Tracey, I., & Mantyh, P. W. (2007) · Neuron · doi:10.1016/j.neuron.2007.07.012 · Cited by 1,843 · see citing works
DISCONNEXION SYNDROMES IN ANIMALS AND MAN
Geschwind, N. (1965) · Brain · doi:10.1093/brain/88.3.585 · Cited by 1,823 · see citing works
An fMRI-Based Neurologic Signature of Physical Pain
Wager, T. D., Atlas, L. Y., Lindquist, M. A., Roy, M., Woo, C.-W., & Kross, E. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1204471 · Cited by 1,597 · see citing works
Why rejection hurts: a common neural alarm system for physical and social pain
Eisenberger, N. I., & Lieberman, M. D. (2004) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2004.05.010 · Cited by 1,246 · see citing works
Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence
Critchley, H. D., Mathias, C. J., Josephs, O., O’Doherty, J., Zanini, S., Dewar, B., Cipolotti, L., Shallice, T., & Dolan, R. J. (2003) · Brain · doi:10.1093/brain/awg216 · Cited by 1,201 · see citing works
Pain intensity processing within the human brain: a bilateral, distributed mechanism
Coghill, R. C., Sang, C. N., Maisog, J. M., & Iadarola, M. J. (1999) · Journal of Neurophysiology · doi:10.1152/jn.1999.82.4.1934 · Cited by 1,077 · see citing works
Eisenberger, N. I. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3231 · Cited by 1,016 · see citing works
Hein, G., Silani, G., Preuschoff, K., Batson, C. D., & Singer, T. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.003 · Cited by 821 · see citing works
The amygdala and persistent pain
Neugebauer, V., Li, W., Bird, G. C., & Han, J. S. (2004) · The Neuroscientist · doi:10.1177/1073858403261077 · Cited by 719 · see citing works
Anterior insular cortex and emotional awareness
Gu, X., Hof, P. R., Friston, K. J., & Fan, J. (2013) · Journal of Comparative Neurology · doi:10.1002/cne.23368 · Cited by 712 · cited 1× · see citing works
“This is an important point since several investigators have recently claimed that the anterior insula is the necessary substrate underlying all forms of emotional awareness (Craig 2009; Gu et al. 2013).”
Social rejection shares somatosensory representations with physical pain
Kross, E., Berman, M. G., Mischel, W., Smith, E. E., & Wager, T. D. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102693108 · Cited by 689 · see citing works
Pain “relief” by frontal cingulumotomy
Foltz, E. L., & White, L. E. (1962) · Journal of Neurosurgery · doi:10.3171/jns.1962.19.2.0089 · Cited by 588 · see citing works
A multisensory investigation of the functional significance of the “pain matrix”
Mouraux, A., Diukova, A., Lee, M., Wise, R. G., & Iannetti, G. D. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.09.084 · Cited by 556 · see citing works
From the neuromatrix to the pain matrix (and back)
Iannetti, G. D., & Mouraux, A. (2010) · Experimental Brain Research · doi:10.1007/s00221-010-2340-1 · Cited by 554 · see citing works
The consistency of facial expressions of pain: a comparison across modalities
Prkachin, K. M. (1992) · Pain · doi:10.1016/0304-3959(92)90213-u · Cited by 532 · see citing works
Prkachin, K. M., & Solomon, P. E. (2008) · Pain · doi:10.1016/j.pain.2008.04.010 · Cited by 472 · see citing works
Asymbolia for pain: a sensory‐limbic disconnection syndrome
Berthier, M., Starkstein, S., & Leiguarda, R. (1988) · Annals of Neurology · doi:10.1002/ana.410240109 · Cited by 456 · see citing works
The Cold Pressor Test and Autonomic Function: A Review and Integration
Lovallo, W. (1975) · Psychophysiology · doi:10.1111/j.1469-8986.1975.tb01289.x · Cited by 409 · see citing works
The 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
Rainville, P., Feine, J. S., Bushnell, M. C., & Duncan, G. H. (1992) · Somatosensory & Motor Research · doi:10.3109/08990229209144776 · Cited by 383 · see citing works
Damásio, A. R. (2003) · Cited by 381 · see citing works
Localization of pain-related brain activation: A meta-analysis of neuroimaging data
Duerden, E. G., & Albanese, M. (2013) · Human Brain Mapping · doi:10.1002/hbm.21416 · Cited by 342 · see citing works
The amygdala between sensation and affect: a role in pain
Veinante, P., Yalçın, İ., & Barrot, M. (2013) · Journal of Molecular Psychiatry · doi:10.1186/2049-9256-1-9 · Cited by 321 · see citing works
Craving love? Enduring grief activates brain’s reward center
O'Connor, M.-F., Wellisch, D. K., Stanton, A. L., Eisenberger, N. I., Irwin, M. R., & Lieberman, M. D. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.04.256 · Cited by 317 · see citing works
Pain sensitivity alterations as a function of lesion location in the parasylvian cortex
Greenspan, J. D., Lee, R. R., & Lenz, F. A. (1999) · Pain · doi:10.1016/s0304-3959(99)00021-4 · Cited by 297 · see citing works
Roles of the Insular Cortex in the Modulation of Pain: Insights from Brain Lesions
Starr, C. J., Sawaki, L. A., Wittenberg, G. F., Burdette, J. H., Oshiro, Y., de Quevedo, A. S., & Coghill, R. C. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5173-08.2009 · Cited by 283 · see citing works
Persistence of feelings and sentience after bilateral damage of the insula
Damasio, A., Damasio, H., & Tranel, D. (2013) · Cerebral Cortex · doi:10.1093/cercor/bhs077 · Cited by 282 · see citing works
Decety, J., Skelly, L. R., & Kiehl, K. A. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.27 · Cited by 267 · see citing works
The human amygdala and pain: Evidence from neuroimaging
Simons, L. E., Moulton, E. A., Linnman, C., Carpino, E. A., Becerra, L. R., & Borsook, D. (2012) · Human Brain Mapping · doi:10.1002/hbm.22199 · Cited by 251 · see citing works
How Do You Feel?: An Interoceptive Moment with Your Neurobiological Self
Craig, A. D. (2015) · doi:10.1515/9781400852727 · Cited by 231 · see citing works
Hebben, N., Corkin, S., Eichenbaum, H., & Shedlack, K. J. (1985) · Behavioral Neuroscience · doi:10.1037/0735-7044.99.6.1031 · Cited by 220 · see citing works
Hebben, N., Corkin, S., Eichenbaum, H., & Shedlack, K. J. (1985) · Behavioral Neuroscience · doi:10.1037//0735-7044.99.6.1031 · Cited by 218 · see citing works
Danziger, N., Faillenot, I., & Peyron, R. (2009) · Neuron · doi:10.1016/j.neuron.2008.11.023 · Cited by 215 · see citing works
How Do You Feel?: An Interoceptive Moment with Your Neurobiological Self
Craig, A. (2014) · Cited by 199 · see citing works
Mechanisms and consequences of widespread random monoallelic expression
Chess, A. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3239 · Cited by 186 · see citing works
Operculo-insular pain (parasylvian pain): a distinct central pain syndrome
Garcı́a-Larrea, L., Perchet, C., Créac’h, C., Convers, P., Peyron, R., Laurent, B., Mauguı̀ere, F., & Magnin, M. (2010) · Brain · doi:10.1093/brain/awq220 · Cited by 180 · see citing works
Beyond metaphor: Contrasting mechanisms of social and physical pain
Iannetti, G. D., Salomons, T. V., Moayedi, M., Mouraux, A., & Davis, K. D. (2013) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2013.06.002 · Cited by 166 · see citing works
Bilateral Anterior Cingulate Gyrus Lesions
Barris, R. W., & Schuman, H. R. (1953) · Neurology · doi:10.1212/wnl.3.1.44 · Cited by 163 · see citing works
Stereotactic Anterior Cingulate Lesions for Persistent Pain: A Report on 68 Cases
Hurt, W. R., & Ballantine, T. H. (1974) · Neurosurgery · doi:10.1093/neurosurgery/21.cn_suppl_1.334 · Cited by 155 · see citing works
The posterior insular-opercular region and the search of a primary cortex for pain
Garcı́a-Larrea, L. (2012) · Neurophysiologie Clinique · doi:10.1016/j.neucli.2012.06.001 · Cited by 154 · see citing works
The Conduction of Pain Above the Level of the Thalamus Opticus
Biemond, A. (1956) · Archives of Neurology And Psychiatry · doi:10.1001/archneurpsyc.1956.02330210011001 · Cited by 152 · see citing works
The neural circuitry of pain as explored with functional MRI
Davis, K. D. (2000) · Neurological Research · doi:10.1080/01616412.2000.11740676 · Cited by 150 · see citing works
Philippi, C. L., Feinstein, J. S., Khalsa, S. S., Damasio, A., Tranel, D., Landini, G., Williford, K., & Rudrauf, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038413 · Cited by 144 · see citing works
Brain correlates of subjective reality of physically and psychologically induced pain
Raij, T. T., Numminen, J., Närvänen, S., Hiltunen, J., & Hari, R. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409542102 · Cited by 143 · see citing works
Davis, K. D., Hutchison, W. D., Lozano, A. M., & Dostrovsky, J. O. (1994) · Pain · doi:10.1016/0304-3959(94)90071-x · Cited by 110 · see citing works
Breaking down the Barriers: fMRI Applications in Pain, Analgesia and Analgesics
Borsook, D., & Becerra, L. R. (2006) · Molecular Pain · doi:10.1186/1744-8069-2-30 · Cited by 108 · see citing works
Emotional and personality changes following cingulotomy
Cohen, R. A., Paul, R., Zawacki, T. M., Moser, D. J., Sweet, L., & Wilkinson, H. (2001) · Emotion · doi:10.1037/1528-3542.1.1.38 · Cited by 93 · see citing works
Reduced Perception of Dyspnea and Pain after Right Insular Cortex Lesions
Schön, D., Rosenkranz, M., Regelsberger, J., Dahme, B., Büchel, C., & von Leupoldt, A. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200805-731oc · Cited by 91 · see citing works
Hierons, R., Janota, I., & Corsellis, J. (1978) · Psychological Medicine · doi:10.1017/s0033291700006607 · Cited by 88 · see citing works
Bilateral lesions of the anterior cingulate gyri; report of case.
NIELSEN, J. M., & Jacobs, L. (1951) · PubMed · Cited by 82 · see citing works
Rudrauf, D. (2014) · Advances in Neuroscience · doi:10.1155/2014/462765 · Cited by 74 · see citing works
Lee, J. E., Watson, D., & Law, L. A. F. (2010) · Journal of Pain · doi:10.1016/j.jpain.2009.10.013 · Cited by 61 · see citing works
Bilateral limbic system destruction in man
Feinstein, J. S., Rudrauf, D., Khalsa, S. S., Cassell, M. D., Bruss, J., Grabowski, T. J., & Tranel, D. (2009) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803390903066873 · Cited by 61 · see citing works
Insula and sensory insular cortex and somatosensory control in patients with insular stroke
Baier, B., zu Eulenburg, P., Geber, C., Rohde, F., Rolke, R., Maihöfner, C., Birklein, F., & Dieterich, M. (2014) · European Journal of Pain · doi:10.1002/j.1532-2149.2014.501.x · Cited by 59 · see citing works
Lesion studies of human emotion and feeling
Feinstein, J. S. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2012.12.007 · Cited by 55 · see citing works
Altered pain and thermal sensation in subjects with isolated parietal and insular cortical lesions
Veldhuijzen, D. S., Greenspan, J. D., Kim, J. H., & Lenz, F. A. (2009) · European Journal of Pain · doi:10.1016/j.ejpain.2009.10.002 · Cited by 53 · see citing works
De novo artistic activity following insular–SII ischemia
Thomas-Antérion, C., Créac’h, C., Dionet, E., Borg, C., Extier, C., Faillenot, I., & Peyron, R. (2010) · Pain · doi:10.1016/j.pain.2010.04.010 · Cited by 30 · see citing works
Greenspan, J. D., Coghill, R. C., Gilron, I., Sarlani, E., Veldhuijzen, D. S., & Lenz, F. A. (2008) · European Journal of Pain · doi:10.1016/j.ejpain.2008.01.007 · Cited by 27 · see citing works
The Adaptation of Pain Aroused by Cold
Edes, B., & Dallenbach, K. M. (1936) · The American Journal of Psychology · doi:10.2307/1415749 · Cited by 21 · see citing works
Somatic Sensation and the Insular-Opercular Cortex: Relationship to Central Pain
Bowsher, D. R. (2006) · European Neurology · doi:10.1159/000093575 · Cited by 20 · see citing works
Turning on the alarm: The neural mechanisms of the transition from innocuous to painful sensation
Johnstone, T., Salomons, T. V., Bačkonja, M., & Davidson, R. J. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.08.083 · Cited by 20 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Damasio AR, Van Hoesen GW (1983) Emotional disturbances associated with focal lesions of the limbic frontal lobe. In: Heilman KM, Satz P (eds) Neuropsychology of Human Emotion, Guilford Press, pp 85–110
Cited by
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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
Using Neuroscience to Help Understand Fear and Anxiety: A Two-System Framework
LeDoux, J. E., & Pine, D. S. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2016.16030353 · Cited by 1,035 · see citing works
Understanding Emotions: Origins and Roles of the Amygdala
Šimić, G., Tkalčić, M., Vukić, V., Mulc, D., Španić, E., Šagud, M., Olucha-Bordonau, F., Vukšić, M., & Hof, P. R. (2021) · Biomolecules · doi:10.3390/biom11060823 · Cited by 464 · see citing works
Interoception and psychopathology: A developmental neuroscience perspective
Murphy, J., Brewer, R., Catmur, C., & Bird, G. (2017) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2016.12.006 · Cited by 404 · see citing works
An Active Inference Approach to Interoceptive Psychopathology
Paulus, M. P., Feinstein, J. S., & Khalsa, S. S. (2019) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-050718-095617 · Cited by 366 · see citing works
Key, B. (2016) · Animal Sentience · doi:10.51291/2377-7478.1011 · Cited by 318 · see citing works
Mapping neuroplastic potential in brain-damaged patients
Herbet, G., Maheu, M., Costi, E., Lafargue, G., & Duffau, H. (2016) · Brain · doi:10.1093/brain/awv394 · Cited by 289 · see citing works
When pain gets stuck: the evolution of pain chronification and treatment resistance
Borsook, D., Youssef, A. M., Simons, L., Elman, I., & Eccleston, C. (2018) · Pain · doi:10.1097/j.pain.0000000000001401 · Cited by 281 · see citing works
Insects have the capacity for subjective experience
Klein, C., & Barron, A. B. (2016) · Animal Sentience · doi:10.51291/2377-7478.1113 · Cited by 243 · see citing works
Murphy, J., Catmur, C., & Bird, G. (2017) · Journal of Experimental Psychology General · doi:10.1037/xge0000366 · Cited by 210 · see citing works
Atypical interoception as a common risk factor for psychopathology: A review
Brewer, R., Murphy, J., & Bird, G. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.07.036 · Cited by 180 · see citing works
Panksepp, J., Lane, R. D., Solms, M., & Smith, R. S. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.09.010 · Cited by 167 · see citing works
The Edge of Sentience: Risk and Precaution in Humans, Other Animals, and AI
Birch, J. (2024) · doi:10.1093/9780191966729.001.0001 · Cited by 236 · see citing works
The integrated information theory of consciousness: A case of mistaken identity
Merker, B. H., Williford, K., & Rudrauf, D. (2021) · Behavioral and Brain Sciences · doi:10.1017/s0140525x21000881 · Cited by 140 · see citing works
Torta, D. M. E., Legrain, V., Mouraux, A., & Valentini, E. (2017) · Cortex · doi:10.1016/j.cortex.2017.01.010 · Cited by 127 · see citing works
The Distributed Nociceptive System: A Framework for Understanding Pain
Coghill, R. C. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.07.004 · Cited by 119 · see citing works
Acquired alexithymia following damage to the anterior insula
Hogeveen, J., Bird, G., Chau, A., Krueger, F., & Grafman, J. (2016) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2016.01.021 · Cited by 116 · see citing works
Social information processing following resection of the insular cortex
Boucher, O., Rouleau, I., Lassonde, M. C., Leporé, F., Bouthillier, A., & Nguyen, D. K. (2015) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2015.03.008 · Cited by 99 · see citing works
Derbyshire, S. W. G., & Bockmann, J. C. (2020) · Journal of Medical Ethics · doi:10.1136/medethics-2019-105701 · Cited by 98 · see citing works
Duffau, H. (2017) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2017.04.003 · Cited by 86 · see citing works
A Return to the Psychiatric Dark Ages with a Two-System Framework for Fear
Fanselow, M., & Pennington, Z. T. (2017) · Behaviour Research and Therapy · doi:10.1016/j.brat.2017.10.012 · Cited by 79 · see citing works
Emotional Experience and Awareness of Self: Functional MRI Studies of Depersonalization Disorder
Medford, N., Sierra, M., Stringaris, A. K., Giampietro, V., Brammer, M. J., & David, A. S. (2016) · Frontiers in Psychology · doi:10.3389/fpsyg.2016.00432 · Cited by 81 · see citing works
McLennan, K. M., Miller, A. L., Costa, E. D., Stucke, D., Corke, M. J., Broom, D. M., & Leach, M. C. (2019) · Applied Animal Behaviour Science · doi:10.1016/j.applanim.2019.06.001 · Cited by 81 · see citing works
Nociceptive Local Field Potentials Recorded from the Human Insula Are Not Specific for Nociception
Liberati, G., Klöcker, A., Safronova, M. M., Santos, S. F., Vaz, J.-G. R., Raftopoulos, C., & Mouraux, A. (2016) · PLoS Biology · doi:10.1371/journal.pbio.1002345 · Cited by 68 · see citing works
From Extinction Learning to Anxiety Treatment: Mind the Gap
Carpenter, J. K., Pinaire, M., & Hofmann, S. G. (2019) · Brain Sciences · doi:10.3390/brainsci9070164 · Cited by 69 · see citing works
Lenoir, C., Algoet, M., & Mouraux, A. (2018) · The Journal of Physiology · doi:10.1113/jp276359 · Cited by 64 · see citing works
Evidence against pain specificity in the dorsal posterior insula
Davis, K. D., Bushnell, M. C., Iannetti, G. D., Lawrence, K. S., & Coghill, R. C. (2015) · F1000Research · doi:10.12688/f1000research.6833.1 · Cited by 62 · see citing works
Lee, I., Necka, E. A., & Atlas, L. Y. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.116254 · Cited by 58 · see citing works
Gamma-Band Oscillations Preferential for Nociception can be Recorded in the Human Insula
Liberati, G., Klöcker, A., Algoet, M., Mulders, D., Safronova, M. M., Santos, S. F., Vaz, J.-G. R., Raftopoulos, C., & Mouraux, A. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx237 · Cited by 56 · see citing works
Analgesia for fetal pain during prenatal surgery: 10 years of progress
Bellieni, C. V. (2020) · Pediatric Research · doi:10.1038/s41390-020-01170-2 · Cited by 54 · see citing works
Ross, P., & Atkinson, A. (2020) · Frontiers in Psychology · doi:10.3389/fpsyg.2020.00309 · Cited by 44 · see citing works
A neurobiologist’s attempt to understand persistent pain
Brodal, P. (2017) · Scandinavian Journal of Pain · doi:10.1016/j.sjpain.2017.03.001 · Cited by 47 · see citing works
Anterior insular cortex stimulation and its effects on emotion recognition
Motomura, K., Terasawa, Y., Natsume, A., Iijima, K., Chalise, L., Sugiura, J., Yamamoto, H., Koyama, K., Wakabayashi, T., & Umeda, S. (2019) · Brain Structure and Function · doi:10.1007/s00429-019-01895-9 · Cited by 44 · see citing works
Pain Asymbolia as Depersonalization for Pain Experience. An Interoceptive Active Inference Account
Gerrans, P. (2020) · Frontiers in Psychology · doi:10.3389/fpsyg.2020.523710 · Cited by 43 · see citing works
Depersonalization Disorder, Affective Processing and Predictive Coding
Gerrans, P. (2018) · Review of Philosophy and Psychology · doi:10.1007/s13164-018-0415-2 · Cited by 41 · see citing works
Applications of dynamic functional connectivity to pain and its modulation
Necka, E. A., Lee, I., Kucyi, A., Cheng, J. C., Yu, Q., & Atlas, L. Y. (2019) · PAIN Reports · doi:10.1097/pr9.0000000000000752 · Cited by 40 · see citing works
Preserved metacognitive ability despite unilateral or bilateral anterior prefrontal resection
Lemaitre, A., Herbet, G., Duffau, H., & Lafargue, G. (2017) · Brain and Cognition · doi:10.1016/j.bandc.2017.10.004 · Cited by 35 · see citing works
Sutterer, M. J., & Tranel, D. (2017) · Neuropsychology · doi:10.1037/neu0000408 · Cited by 32 · see citing works
Modality-specific effects of aversive expectancy in the anterior insula and medial prefrontal cortex
Sharvit, G., Corradi‐Dell’Acqua, C., & Vuilleumier, P. O. (2018) · Pain · doi:10.1097/j.pain.0000000000001237 · Cited by 31 · see citing works
The emotional brain: Fundamental questions and strategies for future research
Shackman, A. J., & Wager, T. D. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.10.012 · Cited by 29 · see citing works
A role for the anterior insular cortex in the global neuronal workspace model of consciousness
Michel, M. (2017) · Consciousness and Cognition · doi:10.1016/j.concog.2017.02.004 · Cited by 29 · see citing works
MacCormack, J. K., Bonar, A. S., & Lindquist, K. A. (2023) · Emotion · doi:10.1037/emo0001270 · Cited by 27 · see citing works
Basic emotions and adaptation. A computational and evolutionary model
Pacella, D., Ponticorvo, M., Gigliotta, O., & Miglino, O. (2017) · PLoS ONE · doi:10.1371/journal.pone.0187463 · Cited by 26 · see citing works
Designing Brains for Pain: Human to Mollusc
Key, B., & Brown, D. J. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01027 · Cited by 25 · see citing works
Emotions Are Rising: The Growing Field of Affect Neuropsychology
McDonald, S. (2017) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617717000844 · Cited by 25 · see citing works
MacCormack, J. K., Stein, A. G., Kang, J., Giovanello, K. S., Satpute, A. B., & Lindquist, K. A. (2020) · Affective Science · doi:10.1007/s42761-020-00016-8 · Cited by 24 · see citing works
Marins, F. R., Iddings, J. A., Fontes, M. A. P., & Filosa, J. A. (2017) · Physiological Reports · doi:10.14814/phy2.13156 · Cited by 21 · see citing works
Contributions of Nociresponsive Area 3a to Normal and Abnormal Somatosensory Perception
Whitsel, B. L., Vierck, C. J., Waters, R. S., Tommerdahl, M., & Favorov, O. V. (2018) · Journal of Pain · doi:10.1016/j.jpain.2018.08.009 · Cited by 22 · see citing works
Segerdahl, A. R., Mezue, M., Okell, T. W., Farrar, J. T., & Tracey, I. (2015) · F1000Research · doi:10.12688/f1000research.7287.1 · Cited by 18 · see citing works
Fetal Pain in the First Trimester
Thill, B. (2021) · The Linacre Quarterly · doi:10.1177/00243639211059245 · Cited by 25 · see citing works
Thill, B. (2023) · Frontiers in Pain Research · doi:10.3389/fpain.2023.1128530 · Cited by 24 · see citing works
Might pain be experienced in the brainstem rather than in the cerebral cortex?
Baron, M. S., & Devor, M. G. (2022) · Behavioural Brain Research · doi:10.1016/j.bbr.2022.113861 · Cited by 17 · see citing works
Fetal pain and its relevance to abortion policy
Salomons, T. V., & Iannetti, G. D. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01188-1 · Cited by 13 · see citing works
Mechanical pain sensitivity is associated with hippocampal structural integrity
Ayoub, L. J., Honigman, L., Barnett, A. J., McAndrews, M. P., & Moayedi, M. (2024) · Pain · doi:10.1097/j.pain.0000000000003221 · Cited by 12 · see citing works
Behavioral evidence suggestive of frontal lobe pathology in the amnesic H.M.
Winter, W. (2018) · Brain and Cognition · doi:10.1016/j.bandc.2018.03.005 · Cited by 11 · see citing works
Amygdala but not hippocampal damage associated with smaller social network size
Beadle, J. N., Heller, A. M., Rosenbaum, R. S., Davidson, P. S. R., Tranel, D., & Duff, M. C. (2022) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2022.108311 · Cited by 10 · see citing works
What does brain imaging tell us about itch?
Mochizuki, H., Hernandez, L. E. D. L. C., & Yosipovitch, G. (2019) · Itch · doi:10.1097/itx.0000000000000023 · Cited by 11 · see citing works
A vessel without a pilot: Bodily and affective experience in the Cotard delusion of inexistence
Gerrans, P. (2022) · Mind & Language · doi:10.1111/mila.12441 · Cited by 10 · see citing works
Do Animals Feel Pain in a Morally Relevant Sense?
Miller, C. (2020) · Philosophia · doi:10.1007/s11406-020-00254-x · Cited by 9 · see citing works
Matsuzaki, J., Kagitani‐Shimono, K., Aoki, S., Hanaie, R., Kato, Y., Nakanishi, M., Tatsumi, A., Tominaga, K., Yamamoto, T., Nagai, Y., et al. (2021) · Brain and Development · doi:10.1016/j.braindev.2021.08.007 · Cited by 8 · see citing works
Gao, M., Li, A., Yu, Y., Wang, J., Hou, Y., Xu, Q., Ren, L., & Gao, D. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.856443 · Cited by 7 · see citing works
Interoceptive sensibility in stroke patients: Latent profile analysis and influencing factors
Guo, Y., Feng, X., Yu, S. L., Peng, S., Yan, X., & Zhou, Q. (2025) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2025.112313 · Cited by 7 · see citing works
Cortex necessary for pain — but not in sense that matters
Shriver, A. (2016) · Animal Sentience · doi:10.51291/2377-7478.1051 · Cited by 7 · see citing works
Against Neo-Cartesianism: Neurofunctional Resilience and Animal Pain
Halper, P., Williford, K., Rudrauf, D., & Fuchs, P. N. (2021) · Philosophical Psychology · doi:10.1080/09515089.2021.1914829 · Cited by 6 · see citing works
The Human Locomotor System: Physiological and Technological Foundations
Sarkodie-Gyan, T., & Yu, H. (2023) · Springer eBooks · doi:10.1007/978-3-031-32781-0_1 · Cited by 5 · see citing works
Anxiety-related circuitry in affective neuroscience
Cacha, L. A., Poznański, R. R., Salleh, S. H. S., Latif, A. Z. A., & Ariff, T. M. (2020) · Journal of Molecular and Clinical Medicine · doi:10.31083/j.jmcm.2020.03.806 · Cited by 4 · see citing works
The distributed nociceptive system: a novel framework for understanding pain
Coghill, R. C. (2022) · Scandinavian Journal of Pain · doi:10.1515/sjpain-2022-0097 · Cited by 4 · see citing works
Devor, M. G. (2016) · Animal Sentience · doi:10.51291/2377-7478.1071 · Cited by 4 · see citing works
Brain imaging in experimental pain
Moayedi, M., & Salomons, T. V. (2016) · Wiley eBooks · doi:10.1002/9781118455968.ch8 · Cited by 3 · see citing works
Representation and Regulation in Emotional Theory
Gerrans, P. (2024) · Journal of Philosophy of Emotion · doi:10.33497/2024.winter.5 · Cited by 2 · see citing works
Gerrans, P. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198872221.003.0009 · Cited by 2 · see citing works
Birch, J. (2024) · The Edge of Sentience · doi:10.1093/9780191966729.003.0003 · Cited by 1 · see citing works
Rosa, L. A. (2018) · Cognitive Neuropsychiatry · doi:10.1080/13546805.2018.1527217 · Cited by 1 · see citing works
Summary of the Framework and Proposals
Birch, J. (2024) · doi:10.1093/9780191966729.003.0001 · Cited by 1 · see citing works
Large Language Models and the Gaming Problem
Birch, J. (2024) · doi:10.1093/9780191966729.003.0017 · Cited by 1 · see citing works
Bellieni, C. V., & Anand, K. J. S. (2025) · Early Human Development · doi:10.1016/j.earlhumdev.2025.106196 · Cited by 1 · see citing works
Deference, development, and large language models: Issues at the edge of sentience
Bayne, T. (2025) · Mind & Language · doi:10.1111/mila.12537 · Cited by 1 · see citing works
The Functional Role of the Anterior Insular Cortex in Cognitive Control
Yu, C. (2020) · CUNY Academic Works (City University of New York)
Adams, J. (2021) · eScholarship@McGill (McGill) · doi:10.82308/22873
Canavero, S., & Bonicalzi, V. (2018) · Springer eBooks · doi:10.1007/978-3-319-56765-5_8
Neuronal circuits of stress and their dynamic interactions: a biopsychological framework
Integrative Neuroscience Initiative, M., Cacha, L. A., & Poznanski, R. R. (2022) · Journal of Multiscale Neuroscience · doi:10.56280/1531631243
Birch, J. (2024) · doi:10.1093/9780191966729.003.0011
Birch, J. (2024) · doi:10.1093/9780191966729.003.0009
Birch, J. (2024) · doi:10.1093/9780191966729.003.0015
Birch, J. (2024) · doi:10.1093/9780191966729.003.0019
Birch, J. (2024) · doi:10.1093/9780191966729.003.0004
Birch, J. (2024) · doi:10.1093/9780191966729.003.0025
Birch, J. (2024) · doi:10.1093/9780191966729.003.0005
Birch, J. (2024) · doi:10.1093/9780191966729.003.0008
Birch, J. (2024) · doi:10.1093/9780191966729.002.0006
Birch, J. (2024) · doi:10.1093/9780191966729.003.0027
Birch, J. (2024) · doi:10.1093/9780191966729.003.0012
Birch, J. (2024) · doi:10.1093/9780191966729.003.0007
People with Disorders of Consciousness
Birch, J. (2024) · doi:10.1093/9780191966729.003.0010
Birch, J. (2024) · doi:10.1093/9780191966729.003.0018
Birch, J. (2024) · doi:10.1093/9780191966729.003.0026
Birch, J. (2024) · doi:10.1093/9780191966729.003.0016
Birch, J. (2024) · doi:10.1093/9780191966729.003.0013
Birch, J. (2024) · doi:10.1093/9780191966729.003.0002
- Authors
- Feinstein, J. S., Khalsa, S. S., Salomons, T. V., Prkachin, K. M., Frey-Law, L. A., Lee, J. E., Tranel, D., & Rudrauf, D.
- Affiliations
- University of Iowa (US)
- University of Reading (GB)
- University of Northern British Columbia (CA)
- Corresponding author
- Feinstein, Justin S.
- ORCID
- Venue
- Brain Structure and Function
- Published
- 2015-01-11
- Volume
- 221
- Issue
- 3
- Pages
- 1499-1511
- ISSN
- 1863-2653 (ISSN-L)
- 1863-2661
- PMC
- PMC4734900
- OpenAlex
- W2070127106
- Cited by
- 108
- References
- 76
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 29 · 2023: 3 · 2022: 8 · 2021: 7 · 2020: 9 · 2019: 7 · 2018: 10 · 2017: 12 · 2016: 12 · 2015: 4
- FWCI
- 9.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Brain Structure and Function (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CentAUR (University of Reading) (submittedVersion, other-oa)
- Funders
- William K. Warren Foundation
- National Institutes of Health (5p50ns019632-28, P50 NS19632)
- National Institute of Neurological Disorders and Stroke (P50-NS019632, P50NS19632, NS-19632, NINDS P50 NS19632)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Keywords
- pain matrix, affective dimension of pain, insula, anterior cingulate cortex, amygdala, bilateral brain lesions, pain experience, pain modulation, facial expressions of pain
- MeSH terms
- Amygdala, Cerebral Cortex, Emotions, Facial Expression, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Pain Measurement, Self Report, Pain Perception
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