Archival Report|Articles in Press

A lesion-derived brain network for emotion regulation

  • Jing Jiang
    Corresponding author: Jing Jiang, Ph.D. 200 Hawkins Drive, Iowa City, Iowa 52242,
    Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa, IA, USA

    Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa, IA, USA

    Center for Brain Circuit Therapeutics, Brigham & Women’s Hospital, Boston, MA, USA

    Department of Neurology, Harvard Medical School, Boston, MA, USA
    Search for articles by this author
  • Michael A. Ferguson
    Center for Brain Circuit Therapeutics, Brigham & Women’s Hospital, Boston, MA, USA

    Department of Neurology, Harvard Medical School, Boston, MA, USA

    Center for the Study of World Religions, Harvard Divinity School, MA, USA
    Search for articles by this author
  • Jordan Grafman
    Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Shirley Ryan Ability Lab, Chicago, IL, USA
    Search for articles by this author
  • Author Footnotes
    # Contributed equally to this work
    Alexander L. Cohen
    # Contributed equally to this work
    Center for Brain Circuit Therapeutics, Brigham & Women’s Hospital, Boston, MA, USA

    Department of Neurology, Harvard Medical School, Boston, MA, USA

    Center for the Study of World Religions, Harvard Divinity School, MA, USA
    Search for articles by this author
  • Author Footnotes
    # Contributed equally to this work
    Michael D. Fox
    # Contributed equally to this work
    Center for Brain Circuit Therapeutics, Brigham & Women’s Hospital, Boston, MA, USA

    Department of Neurology, Harvard Medical School, Boston, MA, USA
    Search for articles by this author
  • Author Footnotes
    # Contributed equally to this work
Published:February 14, 2023DOI:



      Emotion regulation has been linked to specific brain networks based on functional neuroimaging, but networks causally involved in emotion regulation remain unknown.


      We studied patients with focal brain damage (n=167) who completed the “managing emotion” subscale of the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), a measure of emotion regulation. First, we tested whether patients with lesions to an a priori network derived from functional neuroimaging showed impaired emotion regulation. Next, we leveraged lesion network mapping to derive a de novo brain network for emotion regulation. Finally, we used an independent lesion database (n=629) to test whether damage to this lesion-derived network would increase the risk of neuropsychiatric conditions associated with emotion regulation impairment.


      First, patients with lesions intersecting the a priori emotion regulation network derived from functional neuroimaging showed impairments in the managing emotion subscale of the MSCEIT. Next, our de novo brain network for emotion regulation derived from lesion data was defined by functional connectivity (FC) to the left ventrolateral prefrontal cortex (vlPFC). Finally, lesions from the independent database associated with mania, criminality, and depression intersected this de novo brain network more than lesions associated with other disorders.


      The findings suggest that emotion regulation maps to a connected brain network centered on the left vlPFC. Lesion damage to part of this network is associated with reported difficulties in managing emotions and is related to increased likelihood of having one of several neuropsychiatric disorders.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. Mayer JD, Salovey P, Caruso DR, Sitarenios G (2003): Measuring emotional intelligence with the MSCEIT V2. 0. Emotion. 3:97.

        • Gross J.J.
        • John O.P.
        Individual differences in two emotion regulation processes: implications for affect, relationships, and well-being.
        Journal of personality and social psychology. 2003; 85: 348
        • Berking M.
        • Wupperman P.
        Emotion regulation and mental health: recent findings, current challenges, and future directions.
        Current opinion in psychiatry. 2012; 25: 128-134
        • Etkin A.
        • Schatzberg A.F.
        Common abnormalities and disorder-specific compensation during implicit regulation of emotional processing in generalized anxiety and major depressive disorders.
        American Journal of Psychiatry. 2011; 168: 968-978
        • Phillips M.L.
        • Ladouceur C.D.
        • Drevets W.C.
        A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder.
        Molecular psychiatry. 2008; 13: 833-857
        • Mazefsky C.A.
        • Herrington J.
        • Siegel M.
        • Scarpa A.
        • Maddox B.B.
        • Scahill L.
        • et al.
        The role of emotion regulation in autism spectrum disorder.
        Journal of the American Academy of Child & Adolescent Psychiatry. 2013; 52: 679-688
        • Sloan E.
        • Hall K.
        • Moulding R.
        • Bryce S.
        • Mildred H.
        • Staiger P.K.
        Emotion regulation as a transdiagnostic treatment construct across anxiety, depression, substance, eating and borderline personality disorders: A systematic review.
        Clinical psychology review. 2017; 57: 141-163
        • Bufkin J.L.
        • Luttrell V.R.
        Neuroimaging studies of aggressive and violent behavior: current findings and implications for criminology and criminal justice.
        Trauma, Violence, & Abuse. 2005; 6: 176-191
        • Morawetz C.
        • Riedel M.C.
        • Salo T.
        • Berboth S.
        • Eickhoff S.
        • Laird A.R.
        • et al.
        Multiple large-scale neural networks underlying emotion regulation.
        Neuroscience & Biobehavioral Reviews. 2020;
        • Buhle J.T.
        • Silvers J.A.
        • Wager T.D.
        • Lopez R.
        • Onyemekwu C.
        • Kober H.
        • et al.
        Cognitive reappraisal of emotion: a meta-analysis of human neuroimaging studies.
        Cerebral cortex. 2014; 24: 2981-2990
        • Frank D.
        • Dewitt M.
        • Hudgens-Haney M.
        • Schaeffer D.
        • Ball B.
        • Schwarz N.
        • et al.
        Emotion regulation: quantitative meta-analysis of functional activation and deactivation.
        Neuroscience & Biobehavioral Reviews. 2014; 45: 202-211
        • Kohn N.
        • Eickhoff S.B.
        • Scheller M.
        • Laird A.R.
        • Fox P.T.
        • Habel U.
        Neural network of cognitive emotion regulation—an ALE meta-analysis and MACM analysis.
        Neuroimage. 2014; 87: 345-355
        • Messina I.
        • Bianco S.
        • Sambin M.
        • Viviani R.
        Executive and semantic processes in reappraisal of negative stimuli: insights from a meta-analysis of neuroimaging studies.
        Frontiers in Psychology. 2015; 6: 956
        • Morawetz C.
        • Bode S.
        • Derntl B.
        • Heekeren H.R.
        The effect of strategies, goals and stimulus material on the neural mechanisms of emotion regulation: a meta-analysis of fMRI studies.
        Neuroscience & Biobehavioral Reviews. 2017; 72: 111-128
        • Smith R.
        • Lane R.D.
        The neural basis of one's own conscious and unconscious emotional states.
        Neuroscience & Biobehavioral Reviews. 2015; 57: 1-29
        • Etkin A.
        • Büchel C.
        • Gross J.J.
        The neural bases of emotion regulation.
        Nature reviews neuroscience. 2015; 16: 693-700
        • Silvers J.A.
        • Moreira J.F.G.
        Capacity and tendency: A neuroscientific framework for the study of emotion regulation.
        Neuroscience letters. 2019; 693: 35-39
        • Dixon M.L.
        • Thiruchselvam R.
        • Todd R.
        • Christoff K.
        Emotion and the prefrontal cortex: An integrative review.
        Psychological bulletin. 2017; 143: 1033
        • Ochsner K.N.
        • Silvers J.A.
        • Buhle J.T.
        Functional imaging studies of emotion regulation: a synthetic review and evolving model of the cognitive control of emotion.
        Annals of the new York Academy of Sciences. 2012; 1251: E1
        • Adolphs R.
        Human lesion studies in the 21st century.
        Neuron. 2016; 90: 1151-1153
        • Fox M.D.
        Mapping Symptoms to Brain Networks with the Human Connectome.
        N Engl J Med. 2018; 379: 2237-2245
      2. Siddiqi S, K K, J P, MD F (2021): Causal Mapping of Human Brain Function Nature Reviews Neuroscience In Press.

        • Salas C.E.
        • Radovic D.
        • Yuen K.S.
        • Yeates G.N.
        • Castro O.
        • Turnbull O.H.
        Opening an emotional dimension in me”: Changes in emotional reactivity and emotion regulation in a case of executive impairment after left fronto-parietal damage.
        Bulletin of the Menninger Clinic. 2014; 78: 301-334
        • Maier M.E.
        • Di Pellegrino G.
        Impaired conflict adaptation in an emotional task context following rostral anterior cingulate cortex lesions in humans.
        Journal of cognitive neuroscience. 2012; 24: 2070-2079
        • Motzkin J.C.
        • Philippi C.L.
        • Wolf R.C.
        • Baskaya M.K.
        • Koenigs M.
        Ventromedial prefrontal cortex is critical for the regulation of amygdala activity in humans.
        Biological psychiatry. 2015; 77: 276-284
        • Motzkin J.C.
        • Philippi C.L.
        • Oler J.A.
        • Kalin N.H.
        • Baskaya M.K.
        • Koenigs M.
        Ventromedial prefrontal cortex damage alters resting blood flow to the bed nucleus of stria terminalis.
        cortex. 2015; 64: 281-288
        • Salas C.E.
        • Castro O.
        • Yuen K.S.
        • Radovic D.
        • d’Avossa G.
        • Turnbull O.H.
        ‘Just can’t hide it’: a behavioral and lesion study on emotional response modulation after right prefrontal damage.
        Social Cognitive and Affective Neuroscience. 2016; 11: 1528-1540
        • Salas C.E.
        • Gross J.J.
        • Rafal R.D.
        • Viñas-Guasch N.
        • Turnbull O.H.
        Concrete behaviour and reappraisal deficits after a left frontal stroke: A case study.
        Neuropsychological rehabilitation. 2013; 23: 467-500
        • Falquez R.
        • Couto B.
        • Ibanez A.
        • Freitag M.T.
        • Berger M.
        • Arens E.A.
        • et al.
        Detaching from the negative by reappraisal: the role of right superior frontal gyrus (BA9/32).
        Frontiers in Behavioral Neuroscience. 2014; 8: 165
        • Salas C.E.
        • Gross J.J.
        • Turnbull O.H.
        Using the process model to understand emotion regulation changes after brain injury.
        Psychology & Neuroscience. 2019; 12: 430
        • Turnbull O.H.
        • Salas C.E.
        The Neuropsychology of Emotion and Emotion Regulation: The Role of Laterality and Hierarchy.
        Brain Sciences. 2021; 11: 1075
        • Boes A.D.
        • Prasad S.
        • Liu H.
        • Liu Q.
        • Pascual-Leone A.
        • Caviness Jr., V.S.
        • et al.
        Network localization of neurological symptoms from focal brain lesions.
        Brain. 2015; 138: 3061-3075
      3. Caveness W, WF C (1979): Incidence of craniocerebral trauma in the United States in 1976 with trend from 1970 to 1975.

        • Raymont V.
        • Salazar A.
        • Krueger F.
        • Grafman J.
        Studying injured minds”–the Vietnam head injury study and 40 years of brain injury research.
        Frontiers in Neurology. 2011; 2: 15
        • Krueger F.
        • Barbey A.K.
        • McCabe K.
        • Strenziok M.
        • Zamboni G.
        • Solomon J.
        • et al.
        The neural bases of key competencies of emotional intelligence.
        Proceedings of the National Academy of Sciences. 2009; 106: 22486-22491
        • Barbey A.K.
        • Colom R.
        • Paul E.J.
        • Chau A.
        • Solomon J.
        • Grafman J.H.
        Lesion mapping of social problem solving.
        Brain. 2014; 137: 2823-2833
      4. Mayer JD, Salovey P, Caruso DR (2002): Mayer-Salovey-Caruso emotional intelligence test (MSCEIT) item booklet.

        • Lopes P.N.
        • Salovey P.
        • Côté S.
        • Beers M.
        • Petty R.E.
        Emotion regulation abilities and the quality of social interaction.
        Emotion. 2005; 5: 113
        • Ehring T.
        • Ehlers A.
        Does rumination mediate the relationship between emotion regulation ability and posttraumatic stress disorder?.
        European journal of psychotraumatology. 2014; 523547
        • Kimhy D.
        • Vakhrusheva J.
        • Jobson-Ahmed L.
        • Tarrier N.
        • Malaspina D.
        • Gross J.J.
        Emotion awareness and regulation in individuals with schizophrenia: Implications for social functioning.
        Psychiatry research. 2012; 200: 193-201
        • Kerns C.E.
        • Mennin D.S.
        • Farach F.J.
        • Nocera C.C.
        Utilizing an ability-based measure to detect emotion regulation deficits in generalized anxiety disorder.
        Journal of Psychopathology and Behavioral Assessment. 2014; 36: 115-123
        • Hertel J.
        • Schütz A.
        • Lammers C.H.
        Emotional intelligence and mental disorder.
        Journal of clinical psychology. 2009; 65: 942-954
        • Ludwig L.
        • Werner D.
        • Lincoln T.M.
        The relevance of cognitive emotion regulation to psychotic symptoms–a systematic review and meta-analysis.
        Clinical psychology review. 2019; 72101746
        • Peña-Sarrionandia A.
        • Mikolajczak M.
        • Gross J.J.
        Integrating emotion regulation and emotional intelligence traditions: a meta-analysis.
        Frontiers in psychology. 2015; 6: 160
        • Lopes P.N.
        • Nezlek J.B.
        • Extremera N.
        • Hertel J.
        • Fernández‐Berrocal P.
        • Schütz A.
        • et al.
        Emotion regulation and the quality of social interaction: Does the ability to evaluate emotional situations and identify effective responses matter?.
        Journal of personality. 2011; 79: 429-467
        • Brackett M.A.
        • Salovey P.
        Measuring emotional intelligence with the mayer-salovery-caruso emotional intelligence test (MSCEIT).
        Psicothema. 2006; 18: 34-41
      5. Mayer J (2002): MSCEIT: Mayer-Salovey-Caruso emotional intelligence test. Toronto, Canada: Multi-Health Systems.

        • Gratz K.L.
        • Roemer L.
        Multidimensional assessment of emotion regulation and dysregulation: Development, factor structure, and initial validation of the difficulties in emotion regulation scale.
        Journal of psychopathology and behavioral assessment. 2004; 26: 41-54
        • Lopes P.N.
        • Salovey P.
        • Straus R.
        Emotional intelligence, personality, and the perceived quality of social relationships.
        Personality and individual Differences. 2003; 35: 641-658
        • Mayer J.D.
        • Salovey P.
        • Caruso D.R.
        The validity of the MSCEIT: Additional analyses and evidence.
        Emotion review. 2012; 4: 403-408
        • Brackett M.A.
        • Mayer J.D.
        Convergent, discriminant, and incremental validity of competing measures of emotional intelligence.
        Personality and social psychology bulletin. 2003; 29: 1147-1158
        • Megías-Robles A.
        • Gutiérrez-Cobo M.J.
        • Gómez-Leal R.
        • Cabello R.
        • Gross J.J.
        • Fernández-Berrocal P.
        Emotionally intelligent people reappraise rather than suppress their emotions.
        PloS one. 2019; 14e0220688
        • Curci A.
        • Lanciano T.
        • Soleti E.
        • Zammuner V.L.
        • Salovey P.
        Construct validity of the Italian version of the Mayer–Salovey–Caruso emotional intelligence test (MSCEIT) v2. 0.
        Journal of personality assessment. 2013; 95: 486-494
        • Mitsopoulou E.
        • Kafetsios K.
        • Karademas E.
        • Papastefanakis E.
        • Simos P.G.
        The Greek version of the Difficulties in Emotion Regulation Scale: Testing the factor structure, reliability and validity in an adult community sample.
        Journal of Psychopathology and Behavioral Assessment. 2013; 35: 123-131
        • Ferguson M.A.
        • Lim C.
        • Cooke D.
        • Darby R.R.
        • Wu O.
        • Rost N.S.
        • et al.
        A human memory circuit derived from brain lesions causing amnesia.
        Nat Commun. 2019; 10: 3497
        • Cohen A.L.
        • Soussand L.
        • Corrow S.L.
        • Martinaud O.
        • Barton J.J.S.
        • Fox M.D.
        Looking beyond the face area: lesion network mapping of prosopagnosia.
        Brain. 2019; 142: 3975-3990
        • Yeo B.T.
        • Krienen F.M.
        • Sepulcre J.
        • Sabuncu M.R.
        • Lashkari D.
        • Hollinshead M.
        • et al.
        The organization of the human cerebral cortex estimated by intrinsic functional connectivity.
        Journal of neurophysiology. 2011;
        • Holmes A.J.
        • Hollinshead M.O.
        • O’keefe T.M.
        • Petrov V.I.
        • Fariello G.R.
        • Wald L.L.
        • et al.
        Brain Genomics Superstruct Project initial data release with structural, functional, and behavioral measures.
        Scientific data. 2015; 2: 1-16
        • Padmanabhan J.L.
        • Cooke D.
        • Joutsa J.
        • Siddiqi S.H.
        • Ferguson M.
        • Darby R.R.
        • et al.
        A Human Depression Circuit Derived From Focal Brain Lesions.
        Biol Psychiatry. 2019; 86: 749-758
        • Joutsa J.
        • Moussawi K.
        • Siddiqi S.H.
        • Abdolahi A.
        • Drew W.
        • Cohen A.L.
        • et al.
        Brain lesions disrupting addiction map to a common human brain circuit.
        Nature medicine. 2022; 28: 1249-1255
        • Ferguson M.A.
        • Schaper F.L.
        • Cohen A.
        • Siddiqi S.
        • Merrill S.M.
        • Nielsen J.A.
        • et al.
        A neural circuit for spirituality and religiosity derived from patients with brain lesions.
        Biological psychiatry. 2022; 91: 380-388
        • Siddiqi S.H.
        • Kording K.P.
        • Parvizi J.
        • Fox M.D.
        Causal mapping of human brain function.
        Nature reviews neuroscience. 2022; 23: 361-375
        • Cotovio G.
        • Talmasov D.
        • Barahona-Correa J.B.
        • Hsu J.
        • Senova S.
        • Ribeiro R.
        • et al.
        Mapping mania symptoms based on focal brain damage.
        J Clin Invest. 2020; 130: 5209-5222
        • Darby R.R.
        • Horn A.
        • Cushman F.
        • Fox M.D.
        Lesion network localization of criminal behavior.
        Proc Natl Acad Sci U S A. 2018; 115: 601-606
        • Adamaszek M.
        • D’Agata F.
        • Ferrucci R.
        • Habas C.
        • Keulen S.
        • Kirkby K.
        • et al.
        Consensus paper: cerebellum and emotion.
        The Cerebellum. 2017; 16: 552-576
        • Schutter D.J.
        • van Honk J.
        The cerebellum in emotion regulation: a repetitive transcranial magnetic stimulation study.
        The Cerebellum. 2009; 8: 28-34
        • Ferrucci R.
        • Giannicola G.
        • Rosa M.
        • Fumagalli M.
        • Boggio P.S.
        • Hallett M.
        • et al.
        Cerebellum and processing of negative facial emotions: cerebellar transcranial DC stimulation specifically enhances the emotional recognition of facial anger and sadness.
        Cognition & emotion. 2012; 26: 786-799
        • Thompson-Schill S.L.
        • D’Esposito M.
        • Aguirre G.K.
        • Farah M.J.
        Role of left inferior prefrontal cortex in retrieval of semantic knowledge: a reevaluation.
        Proceedings of the National Academy of Sciences. 1997; 94: 14792-14797
        • Moss H.
        • Abdallah S.
        • Fletcher P.
        • Bright P.
        • Pilgrim L.
        • Acres K.
        • et al.
        Selecting among competing alternatives: selection and retrieval in the left inferior frontal gyrus.
        Cerebral Cortex. 2005; 15: 1723-1735
        • Morawetz C.
        • Bode S.
        • Baudewig J.
        • Kirilina E.
        • Heekeren H.R.
        Changes in effective connectivity between dorsal and ventral prefrontal regions moderate emotion regulation.
        Cerebral Cortex. 2016; 26: 1923-1937
        • He Z.
        • Liu Z.
        • Zhao J.
        • Elliott R.
        • Zhang D.
        Improving emotion regulation of social exclusion in depression-prone individuals: a tDCS study targeting right VLPFC.
        Psychological medicine. 2020; 50: 2768-2779
        • Feeser M.
        • Prehn K.
        • Kazzer P.
        • Mungee A.
        • Bajbouj M.
        Transcranial direct current stimulation enhances cognitive control during emotion regulation.
        Brain stimulation. 2014; 7: 105-112
        • Carrera E.
        • Tononi G.
        Diaschisis: past, present, future.
        Brain. 2014; 137: 2408-2422
        • Aldao A.
        • Gee D.G.
        • De Los Reyes A.
        • Seager I.
        Emotion regulation as a transdiagnostic factor in the development of internalizing and externalizing psychopathology: Current and future directions.
        Development and psychopathology. 2016; 28: 927-946
        • Fernandez K.C.
        • Jazaieri H.
        • Gross J.J.
        Emotion regulation: a transdiagnostic perspective on a new RDoC domain.
        Cognitive therapy and research. 2016; 40: 426-440
        • McGrogan C.L.
        • Dodd A.L.
        • Smith M.A.
        Emotion regulation strategies in mania risk: a systematic review.
        Journal of clinical psychology. 2019; 75: 2106-2118
        • Sharma N.
        • Prakash O.
        • Sengar K.
        • Chaudhury S.
        • Singh A.R.
        The relation between emotional intelligence and criminal behavior: A study among convicted criminals.
        Industrial psychiatry journal. 2015; 24: 54
        • Joormann J.
        • Gotlib I.H.
        Emotion regulation in depression: Relation to cognitive inhibition.
        Cognition and Emotion. 2010; 24: 281-298
        • Berking M.
        • Wirtz C.M.
        • Svaldi J.
        • Hofmann S.G.
        Emotion regulation predicts symptoms of depression over five years.
        Behaviour research and therapy. 2014; 57: 13-20
        • Megreya A.M.
        • Latzman R.D.
        Individual differences in emotion regulation and face recognition.
        Plos one. 2020; 15e0243209
      6. Bloch L, Moran EK, Kring AM (2010): On the need for conceptual and definitional clarity in emotion regulation research on psychopathology. Emotion regulation and psychopathology: A transdiagnostic approach to etiology and treatment.88-104.

        • Eisenberg N.
        • Spinrad T.L.
        Emotion‐related regulation: Sharpening the definition.
        Child development. 2004; 75: 334-339
        • Cole P.M.
        • Martin S.E.
        • Dennis T.A.
        Emotion regulation as a scientific construct: Methodological challenges and directions for child development research.
        Child development. 2004; 75: 317-333
        • Bridges L.J.
        • Denham S.A.
        • Ganiban J.M.
        Definitional issues in emotion regulation research.
        Child development. 2004; 75: 340-345
        • Cohen A.L.
        • Mulder B.P.
        • Prohl A.K.
        • Soussand L.
        • Davis P.
        • Kroeck M.R.
        • et al.
        Tuber Locations Associated with Infantile Spasms Map to a Common Brain Network.
        Annals of Neurology. 2021; 89: 726-739