The dorsal anterior cingulate cortex is selective for pain: Results from large-scale reverse inference

Significance No neural region has been associated with more conflicting accounts of its function than the dorsal anterior cingulate cortex (dACC), with claims that it contributes to executive processing, conflict monitoring, pain, and salience. However, these claims are based on forward inference analysis, which is the wrong tool for making such claims. Using Neurosynth, an automated brainmapping database, we performed reverse inference analyses to explore the best psychological account of dACC function. Although forward inference analyses reproduced the findings that many processes activate the dACC, reverse inference analyses demonstrated that the dACC is selective for pain and that pain-related terms were the single best reverse inference for this region. This finding has implications for our understanding of pain and distress-related psychological disorders. Dorsal anterior cingulate cortex (dACC) activation is commonly observed in studies of pain, executive control, conflict monitoring, and salience processing, making it difficult to interpret the dACC’s specific psychological function. Using Neurosynth, an automated brainmapping database [of over 10,000 functional MRI (fMRI) studies], we performed quantitative reverse inference analyses to explore the best general psychological account of the dACC function P(Ψ process|dACC activity). Results clearly indicated that the best psychological description of dACC function was related to pain processing—not executive, conflict, or salience processing. We conclude by considering that physical pain may be an instance of a broader class of survival-relevant goals monitored by the dACC, in contrast to more arbitrary temporary goals, which may be monitored by the supplementary motor area.

[1]  M Liotti,et al.  Brain responses associated with consciousness of breathlessness (air hunger). , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[2]  山村 宏嘉 Morphological and electrophysiological properties of ACCx nociceptive neurons in rats(ラット前帯状回侵害受容性ニューロンの反応,形態および局在) , 1997 .

[3]  S. Schulman The Astonishing Hypothesis: The Scientific Search for the Soul , 1994 .

[4]  Gwenn W. Gröndal,et al.  Meta-analytic procedures for social research , 1993 .

[5]  A. Craig A new view of pain as a homeostatic emotion , 2003, Trends in Neurosciences.

[6]  R. Davidson,et al.  The integration of negative affect, pain and cognitive control in the cingulate cortex , 2011, Nature Reviews Neuroscience.

[7]  Kenneth Knoblauch,et al.  The Location of Feedback-Related Activity in the Midcingulate Cortex Is Predicted by Local Morphology , 2013, The Journal of Neuroscience.

[8]  M. Lindquist,et al.  An fMRI-based neurologic signature of physical pain. , 2013, The New England journal of medicine.

[9]  R. Rosenthal Meta-analytic procedures for social research , 1984 .

[10]  M. Inzlicht,et al.  Emotional foundations of cognitive control , 2015, Trends in Cognitive Sciences.

[11]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.

[12]  H. Fields,et al.  The affective component of pain in rodents: Direct evidence for a contribution of the anterior cingulate cortex , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Peter T. Fox,et al.  Neuroimaging of genesis and satiation of thirst and an interoceptor-driven theory of origins of primary consciousness. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  G. Hajcak,et al.  Errors Are Aversive , 2008, Psychological science.

[15]  Timothy B. Smith,et al.  Social Relationships and Mortality Risk: A Meta-analytic Review , 2010, PLoS medicine.

[16]  Christian Büchel,et al.  Dyspnea and pain share emotion-related brain network , 2009, NeuroImage.

[17]  Russell A. Poldrack,et al.  Discovering Relations Between Mind, Brain, and Mental Disorders Using Topic Mapping , 2012, PLoS Comput. Biol..

[18]  V. Menon,et al.  Saliency, switching, attention and control: a network model of insula function , 2010, Brain Structure and Function.

[19]  B. Vogt,et al.  Nociceptive neurons in area 24 of rabbit cingulate cortex. , 1992, Journal of neurophysiology.

[20]  Matthew D. Lieberman,et al.  Why rejection hurts: a common neural alarm system for physical and social pain , 2004, Trends in Cognitive Sciences.

[21]  M. Barrot,et al.  The Anterior Cingulate Cortex Is a Critical Hub for Pain-Induced Depression , 2015, Biological Psychiatry.

[22]  Edward E. Smith,et al.  Neuroimaging studies of working memory: , 2003, Cognitive, affective & behavioral neuroscience.

[23]  F. Crick,et al.  The Astonishing Hypothesis: The Scientific Search for the Soul , 1994 .

[24]  Matthew D. Lieberman,et al.  The Phenomenology of Error Processing: The Dorsal ACC Response to Stop-signal Errors Tracks Reports of Negative Affect , 2012, Journal of Cognitive Neuroscience.

[25]  R. Poldrack Can cognitive processes be inferred from neuroimaging data? , 2006, Trends in Cognitive Sciences.

[26]  Luke J. Chang,et al.  Decoding the role of the insula in human cognition: functional parcellation and large-scale reverse inference. , 2013, Cerebral cortex.

[27]  G. F. Egan,et al.  The role of primordial emotions in the evolutionary origin of consciousness , 2009, Consciousness and Cognition.

[28]  P. Maruff,et al.  Hemispheric and gender-related differences in the gross morphology of the anterior cingulate/paracingulate cortex in normal volunteers: an MRI morphometric study. , 2001, Cerebral cortex.

[29]  G. Egan,et al.  Correlation of regional cerebral blood flow and change of plasma sodium concentration during genesis and satiation of thirst. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[30]  H. Garavan,et al.  Dissociable Executive Functions in the Dynamic Control of Behavior: Inhibition, Error Detection, and Correction , 2002, NeuroImage.

[31]  Alan C. Evans,et al.  Human cingulate and paracingulate sulci: pattern, variability, asymmetry, and probabilistic map. , 1996, Cerebral cortex.

[32]  M. Petrides,et al.  Neuroimaging evidence of the anatomo-functional organization of the human cingulate motor areas. , 2014, Cerebral cortex.

[33]  R. Baumeister,et al.  The need to belong: desire for interpersonal attachments as a fundamental human motivation. , 1995, Psychological bulletin.

[34]  Dennis Velakoulis,et al.  Variability of the paracingulate sulcus and morphometry of the medial frontal cortex: Associations with cortical thickness, surface area, volume, and sulcal depth , 2008, Human brain mapping.

[35]  Ouriel Grynszpan,et al.  A meta-analysis of the anterior cingulate contribution to social pain. , 2014, Social cognitive and affective neuroscience.

[36]  B. Shyu,et al.  Electrophysiological study of the connection between medial thalamus and anterior cingulate cortex in the rat , 1997, Neuroreport.

[37]  Karleyton C Evans,et al.  BOLD fMRI identifies limbic, paralimbic, and cerebellar activation during air hunger. , 2002, Journal of neurophysiology.

[38]  M. Bushnell,et al.  Pain affect encoded in human anterior cingulate but not somatosensory cortex. , 1997, Science.

[39]  Russell A. Poldrack,et al.  Large-scale automated synthesis of human functional neuroimaging data , 2011, Nature Methods.

[40]  S. Pappatà,et al.  Paracingulate sulcus morphology in men with early-onset schizophrenia , 2003, British Journal of Psychiatry.

[41]  E G Jones,et al.  Making brain connections: neuroanatomy and the work of TPS Powell, 1923-1996. , 1999, Annual review of neuroscience.

[42]  P. Maclean,et al.  Brain evolution relating to family, play, and the separation call. , 1985, Archives of general psychiatry.

[43]  G. Egan,et al.  Effect of aging on regional cerebral blood flow responses associated with osmotic thirst and its satiation by water drinking: A PET study , 2008, Proceedings of the National Academy of Sciences.

[44]  H. Heinze,et al.  The Role of Reward in Word Learning and Its Implications for Language Acquisition , 2014, Current Biology.

[45]  A. Mouraux,et al.  The pain matrix reloaded A salience detection system for the body , 2011, Progress in Neurobiology.

[46]  C. Olson,et al.  Functional heterogeneity in cingulate cortex: the anterior executive and posterior evaluative regions. , 1992, Cerebral cortex.

[47]  E. Ravussin,et al.  Neuroanatomical correlates of hunger and satiation in humans using positron emission tomography. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[48]  D L Rosene,et al.  Cingulate cortex of the rhesus monkey: I. Cytoarchitecture and thalamic afferents , 1987, The Journal of comparative neurology.

[49]  E L FOLTZ,et al.  Pain "relief" by frontal cingulumotomy. , 1962, Journal of neurosurgery.

[50]  M. Botvinick,et al.  The Contribution of the Anterior Cingulate Cortex to Executive Processes in Cognition , 1999, Reviews in the neurosciences.

[51]  G Rizzolatti,et al.  Parcellation of human mesial area 6: cytoarchitectonic evidence for three separate areas , 1998, The European journal of neuroscience.

[52]  T. Egner,et al.  Emotional processing in anterior cingulate and medial prefrontal cortex , 2011, Trends in Cognitive Sciences.

[53]  Jonathan D. Cohen,et al.  Conflict monitoring and anterior cingulate cortex: an update , 2004, Trends in Cognitive Sciences.

[54]  Francis Crick,et al.  Review of The Astonishing Hypothesis: The Scientific Search For The Soul by , 1995 .

[55]  Carter Wendelken,et al.  Meta-analysis: how does posterior parietal cortex contribute to reasoning? , 2015, Front. Hum. Neurosci..

[56]  Rebecca Saxe,et al.  Contributions of episodic retrieval and mentalizing to autobiographical thought: Evidence from functional neuroimaging, resting-state connectivity, and fMRI meta-analyses , 2014, NeuroImage.