title: Amygdala lesions do not compromise the cortical network for false-belief reasoning.
abstract: The amygdala plays an integral role in human social cognition and behavior, with clear links to emotion recognition, trust judgments, anthropomorphization, and psychiatric disorders ranging from social phobia to autism. A central feature of human social cognition is a theory-of-mind (ToM) that enables the representation other people's mental states as distinct from one's own. Numerous neuroimaging studies of the best studied use of ToM--false-belief reasoning--suggest that it relies on a specific cortical network; moreover, the amygdala is structurally and functionally connected with many components of this cortical network. It remains unknown whether the cortical implementation of any form of ToM depends on amygdala function. Here we investigated this question directly by conducting functional MRI on two patients with rare bilateral amygdala lesions while they performed a neuroimaging protocol standardized for measuring cortical activity associated with false-belief reasoning. We compared patient responses with those of two healthy comparison groups that included 480 adults. Based on both univariate and multivariate comparisons, neither patient showed any evidence of atypical cortical activity or any evidence of atypical behavioral performance; moreover, this pattern of typical cortical and behavioral response was replicated for both patients in a follow-up session. These findings argue that the amygdala is not necessary for the cortical implementation of ToM in adulthood and suggest a reevaluation of the role of the amygdala and its cortical interactions in human social cognition.
authors.affiliation: Division of Humanities and Social Sciences, California Institute of Technology, Pasadena, CA 91125; spunt@caltech.edu.
authors.forename: Robert P
authors.identifier: http://orcid.org/0000-0003-2975-4597
authors.initials: RP
authors.lastname: Spunt
authors.affiliation: Division of Humanities and Social Sciences, California Institute of Technology, Pasadena, CA 91125; Institute of Child Development, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Jed T
authors.initials: JT
authors.lastname: Elison
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; and.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Dufour
authors.affiliation: Department of Psychiatry, University of Bonn, 53113 Bonn, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Hurlemann
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; and.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Saxe
authors.affiliation: Division of Humanities and Social Sciences, California Institute of Technology, Pasadena, CA 91125;
authors.forename: Ralph
authors.initials: R
authors.lastname: Adolphs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000679:Amygdala / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000502:physiology*; D003071:Cognition / Q000502:physiology; D003469:Culture; D005260:Female; D006801:Humans; D007600:Judgment / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D056345:Theory of Mind; D055815:Young Adult
keywords: amygdala; fMRI; false-belief; lesions; theory-of-mind
references.citation: Neuron. 2007 Aug 16;55(4):545-55
references.pmid: 17698008
references.citation: Neuroimage. 2011 Mar 15;55(2):705-12
references.pmid: 21182967
references.citation: Child Dev. 2001 May-Jun;72(3):655-84
references.pmid: 11405571
references.citation: Proc Natl Acad Sci U S A. 2004 May 11;101(19):7487-91
references.pmid: 15123799
references.citation: Dev Sci. 2013 Mar;16(2):186-97
references.pmid: 23432829
references.citation: Neuropsychologia. 1999 Sep;37(10):1111-7
references.pmid: 10509833
references.citation: Trends Cogn Sci. 2003 Feb;7(2):77-83
references.pmid: 12584026
references.citation: Hum Brain Mapp. 2009 Aug;30(8):2313-35
references.pmid: 19034900
references.citation: Neuroimage. 2001 Aug;14(2):253-7
references.pmid: 11467900
references.citation: Acta Derm Venereol Suppl (Stockh). 1973;53:1-52
references.pmid: 4590183
references.citation: Curr Biol. 2007 Aug 21;17(16):R724-32
references.pmid: 17714666
references.citation: Neurosci Biobehav Rev. 2014 May;42:9-34
references.pmid: 24486722
references.citation: Trends Cogn Sci. 2012 Nov;16(11):559-72
references.pmid: 23047070
references.citation: Behav Neurosci. 2001 Jun;115(3):515-44
references.pmid: 11439444
references.citation: PLoS One. 2013;8(9):e75468
references.pmid: 24073267
references.citation: Trends Cogn Sci. 2015 Feb;19(2):65-72
references.pmid: 25496670
references.citation: J Neurol Neurosurg Psychiatry. 2004 Jul;75(7):945-8
references.pmid: 15201345
references.citation: Curr Biol. 2011 Jan 11;21(1):34-8
references.pmid: 21167712
references.citation: J Neurophysiol. 2007 Feb;97(2):1671-83
references.pmid: 17093126
references.citation: Arch Gen Psychiatry. 2010 Aug;67(8):830-40
references.pmid: 20679591
references.citation: Behav Brain Sci. 2005 Oct;28(5):675-91; discussion 691-735
references.pmid: 16262930
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 13;107(15):6753-8
references.pmid: 20351278
references.citation: Ann N Y Acad Sci. 2010 Mar;1191:42-61
references.pmid: 20392275
references.citation: Nature. 1994 Dec 15;372(6507):669-72
references.pmid: 7990957
references.citation: Neuropsychologia. 2003;41(2):209-20
references.pmid: 12459219
references.citation: Neuroimage. 2009 Nov 15;48(3):564-84
references.pmid: 19524046
references.citation: Nat Rev Neurosci. 2006 Apr;7(4):268-77
references.pmid: 16552413
references.citation: Brain. 2004 Apr;127(Pt 4):914-28
references.pmid: 14998913
references.citation: Ment Retard Dev Disabil Res Rev. 2004;10(4):259-71
references.pmid: 15666336
references.citation: Neuroimage. 2014 Oct 1;99:301-11
references.pmid: 24844746
references.citation: Nat Neurosci. 2004 May;7(5):499-500
references.pmid: 15077111
references.citation: Cognition. 2000 Oct 16;77(1):B25-31
references.pmid: 10980256
references.citation: Nat Neurosci. 2009 Oct;12(10):1226-7
references.pmid: 19718035
references.citation: Neuroimage. 2002 Jan;15(1):273-89
references.pmid: 11771995
references.citation: Cereb Cortex. 2000 Mar;10(3):206-19
references.pmid: 10731217
references.citation: Neuron. 2014 Jan 22;81(2):428-37
references.pmid: 24462103
references.citation: Curr Biol. 2011 Oct 11;21(19):1654-60
references.pmid: 21962712
references.citation: Brain. 2004 Jul;127(Pt 7):1535-48
references.pmid: 15155523
references.citation: Biol Psychiatry. 2012 Jul 1;72(1):70-7
references.pmid: 22218285
references.citation: Neuroimage. 2003 Aug;19(4):1835-42
references.pmid: 12948738
references.citation: Annu Rev Psychol. 2011;62:103-34
references.pmid: 21126178
references.citation: Dev Cogn Neurosci. 2014 Apr;8:153-63
references.pmid: 24139023
references.citation: Nature. 1998 Jun 4;393(6684):470-4
references.pmid: 9624002
references.citation: J Cogn Neurosci. 2009 Mar;21(3):489-510
references.pmid: 18510452
references.citation: Biol Psychiatry. 2013 Apr 1;73(7):e9-11
references.pmid: 23245746
references.citation: Behav Neurosci. 2006 Aug;120(4):761-86
references.pmid: 16893284
references.citation: Philos Trans R Soc Lond B Biol Sci. 2003 Feb 28;358(1430):415-27
references.pmid: 12639338
references.citation: Brain. 2001 Feb;124(Pt 2):287-98
references.pmid: 11157556
references.citation: Neuron. 2010 Feb 11;65(3):298-308
references.pmid: 20159444