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Amygdala and Insula Connectivity Changes Following Psychotherapy for Posttraumatic Stress Disorder: A Randomized Clinical Trial

  • Author Footnotes
    1 GAF and MSG contributed equally to this work as joint first authors.
    Gregory A. Fonzo
    Footnotes
    1 GAF and MSG contributed equally to this work as joint first authors.
    Affiliations
    Department of Psychiatry, University of Texas at Austin Dell Medical School, Austin, Texas
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  • Author Footnotes
    1 GAF and MSG contributed equally to this work as joint first authors.
    Madeleine S. Goodkind
    Footnotes
    1 GAF and MSG contributed equally to this work as joint first authors.
    Affiliations
    New Mexico Veterans Affairs Healthcare System, Albuquerque, New Mexico
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  • Desmond J. Oathes
    Affiliations
    Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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  • Yevgeniya V. Zaiko
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California

    Wu Tsai Neurosciences Institute, Stanford University, Stanford, California

    Veterans Affairs Palo Alto Healthcare System and Sierra Pacific Mental Illness, Research, Education, and Clinical Center, Palo Alto, California
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  • Meredith Harvey
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California

    Wu Tsai Neurosciences Institute, Stanford University, Stanford, California

    Veterans Affairs Palo Alto Healthcare System and Sierra Pacific Mental Illness, Research, Education, and Clinical Center, Palo Alto, California
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  • Kathy K. Peng
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California

    Wu Tsai Neurosciences Institute, Stanford University, Stanford, California

    Veterans Affairs Palo Alto Healthcare System and Sierra Pacific Mental Illness, Research, Education, and Clinical Center, Palo Alto, California
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  • M. Elizabeth Weiss
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California

    Wu Tsai Neurosciences Institute, Stanford University, Stanford, California

    Veterans Affairs Palo Alto Healthcare System and Sierra Pacific Mental Illness, Research, Education, and Clinical Center, Palo Alto, California
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  • Allison L. Thompson
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
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  • Sanno E. Zack
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
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  • Steven E. Lindley
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California

    Veterans Affairs Palo Alto Healthcare System and Sierra Pacific Mental Illness, Research, Education, and Clinical Center, Palo Alto, California
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  • Bruce A. Arnow
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
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  • Booil Jo
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
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  • Barbara O. Rothbaum
    Affiliations
    Trauma and Anxiety Recovery Program, Department of Psychiatry, Emory University School of Medicine, Atlanta, Georgia
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  • Amit Etkin
    Correspondence
    Address correspondence to Amit Etkin, M.D., Ph.D.
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California

    Wu Tsai Neurosciences Institute, Stanford University, Stanford, California

    Alto Neuroscience, Los Altos, California
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  • Author Footnotes
    1 GAF and MSG contributed equally to this work as joint first authors.
Published:December 07, 2020DOI:https://doi.org/10.1016/j.biopsych.2020.11.021

      Abstract

      Background

      Exposure-based psychotherapy is a first-line treatment for posttraumatic stress disorder (PTSD), but its mechanisms are poorly understood. Functional brain connectivity is a promising metric for identifying treatment mechanisms and biosignatures of therapeutic response. To this end, we assessed amygdala and insula treatment–related connectivity changes and their relationship to PTSD symptom improvements.

      Methods

      Individuals with a primary PTSD diagnosis (N = 66) participated in a randomized clinical trial of prolonged exposure therapy (n = 36) versus treatment waiting list (n = 30). Task-free functional magnetic resonance imaging was completed prior to randomization and 1 month following cessation of treatment/waiting list. Whole-brain blood oxygenation level–dependent responses were acquired. Intrinsic connectivity was assessed by subregion in the amygdala and insula, limbic structures key to the disorder pathophysiology. Dynamic causal modeling assessed evidence for effective connectivity changes in select nodes informed by intrinsic connectivity findings.

      Results

      The amygdala and insula displayed widespread patterns of primarily subregion-uniform intrinsic connectivity change, including increased connectivity between the amygdala and insula; increased connectivity of both regions with the ventral prefrontal cortex and frontopolar and sensory cortices; and decreased connectivity of both regions with the left frontoparietal nodes of the executive control network. Larger decreases in amygdala–frontal connectivity and insula–parietal connectivity were associated with larger PTSD symptom reductions. Dynamic causal modeling evidence suggested that treatment decreased left frontal inhibition of the left amygdala, and larger decreases were associated with larger symptom reductions.

      Conclusions

      PTSD psychotherapy adaptively attenuates functional interactions between frontoparietal and limbic brain circuitry at rest, which may reflect a potential mechanism or biosignature of recovery.

      Keywords

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      References

        • Hoge C.W.
        • Riviere L.A.
        • Wilk J.E.
        • Herrell R.K.
        • Weathers F.W.
        The prevalence of post-traumatic stress disorder (PTSD) in US combat soldiers: A head-to-head comparison of DSM-5 versus DSM-IV-TR symptom criteria with the PTSD checklist.
        Lancet Psychiatry. 2014; 1: 269-277
        • Kessler R.C.
        • Aguilar-Gaxiola S.
        • Alonso J.
        • Benjet C.
        • Bromet E.J.
        • Cardoso G.
        • et al.
        Trauma and PTSD in the WHO World Mental Health Surveys.
        Eur J Psychotraumatol. 2017; 8: 1353383
        • Marmar C.R.
        • Schlenger W.
        • Henn-Haase C.
        • Qian M.
        • Purchia E.
        • Li M.
        • et al.
        Course of posttraumatic stress disorder 40 years after the Vietnam War: Findings from the National Vietnam Veterans Longitudinal Study.
        JAMA Psychiatry. 2015; 72: 875-881
        • Kessler R.C.
        • Sonnega A.
        • Bromet E.
        • Hughes M.
        • Nelson C.B.
        Posttraumatic stress disorder in the National Comorbidity Survey.
        Arch Gen Psychiatry. 1995; 52: 1048-1060
        • Schnurr P.P.
        • Lunney C.A.
        • Bovin M.J.
        • Marx B.P.
        Posttraumatic stress disorder and quality of life: Extension of findings to veterans of the wars in Iraq and Afghanistan.
        Clin Psychol Rev. 2009; 29: 727-735
        • Cusack K.
        • Jonas D.E.
        • Forneris C.A.
        • Wines C.
        • Sonis J.
        • Middleton J.C.
        • et al.
        Psychological treatments for adults with posttraumatic stress disorder: A systematic review and meta-analysis.
        Clin Psychol Rev. 2016; 43: 128-141
        • Foa E.B.
        • Gillihan S.J.
        • Bryant R.A.
        Challenges and successes in dissemination of evidence-based treatments for posttraumatic stress: Lessons learned from prolonged exposure therapy for PTSD.
        Psychol Sci Public Interest. 2013; 14: 65-111
        • Bradley R.
        • Greene J.
        • Russ E.
        • Dutra L.
        • Westen D.
        A multidimensional meta-analysis of psychotherapy for PTSD.
        Am J Psychiatry. 2005; 162: 214-227
        • Schottenbauer M.A.
        • Glass C.R.
        • Arnkoff D.B.
        • Tendick V.
        • Gray S.H.
        Nonresponse and dropout rates in outcome studies on PTSD: Review and methodological considerations.
        Psychiatry. 2008; 71: 134-168
        • Malejko K.
        • Abler B.
        • Plener P.L.
        • Straub J.
        Neural correlates of psychotherapeutic treatment of post-traumatic stress disorder: A systematic literature review.
        Front Psychiatry. 2017; 8: 85
        • Finn E.S.
        • Shen X.
        • Scheinost D.
        • Rosenberg M.D.
        • Huang J.
        • Chun M.M.
        • et al.
        Functional connectome fingerprinting: Identifying individuals using patterns of brain connectivity.
        Nat Neurosci. 2015; 18: 1664-1671
        • Shah L.M.
        • Cramer J.A.
        • Ferguson M.A.
        • Birn R.M.
        • Anderson J.S.
        Reliability and reproducibility of individual differences in functional connectivity acquired during task and resting state.
        Brain Behav. 2016; 6: e456
        • Fonzo G.A.
        • Goodkind M.S.
        • Oathes D.J.
        • Zaiko Y.V.
        • Harvey M.
        • Peng K.K.
        • et al.
        PTSD psychotherapy outcome predicted by brain activation during emotional reactivity and regulation.
        Am J Psychiatry. 2017; 174: 1163-1174
        • Fonzo G.A.
        • Goodkind M.S.
        • Oathes D.J.
        • Zaiko Y.V.
        • Harvey M.
        • Peng K.K.
        • et al.
        Selective effects of psychotherapy on frontopolar cortical function in PTSD.
        Am J Psychiatry. 2017; 174: 1175-1184
        • Felmingham K.
        • Kemp A.
        • Williams L.
        • Das P.
        • Hughes G.
        • Peduto A.
        • et al.
        Changes in anterior cingulate and amygdala after cognitive behavior therapy of posttraumatic stress disorder.
        Psychol Sci. 2007; 18: 127-129
        • Lindauer R.J.
        • Booij J.
        • Habraken J.B.
        • Meijel E.P.
        • Uylings H.B.
        • Olff M.
        • et al.
        Effects of psychotherapy on regional cerebral blood flow during trauma imagery in patients with post-traumatic stress disorder: A randomized clinical trial.
        Psychol Med. 2008; 38: 543-554
        • Thomaes K.
        • Dorrepaal E.
        • Draijer N.
        • de Ruiter M.B.
        • Elzinga B.M.
        • van Balkom A.J.
        • et al.
        Treatment effects on insular and anterior cingulate cortex activation during classic and emotional Stroop interference in child abuse-related complex post-traumatic stress disorder.
        Psychol Med. 2012; 42: 2337-2349
        • Aupperle R.L.
        • Allard C.B.
        • Simmons A.N.
        • Flagan T.
        • Thorp S.R.
        • Norman S.B.
        • et al.
        Neural responses during emotional processing before and after cognitive trauma therapy for battered women.
        Psychiatry Res. 2013; 214: 48-55
        • Simmons A.N.
        • Norman S.B.
        • Spadoni A.D.
        • Strigo I.A.
        Neurosubstrates of remission following prolonged exposure therapy in veterans with posttraumatic stress disorder.
        Psychother Psychosom. 2013; 82: 382-389
        • Brown V.M.
        • LaBar K.S.
        • Haswell C.C.
        • Gold A.L.
        • McCarthy G.
        • Morey R.A.
        Altered resting-state functional connectivity of basolateral and centromedial amygdala complexes in posttraumatic stress disorder.
        Neuropsychopharmacology. 2014; 39: 351-359
        • Sripada R.K.
        • King A.P.
        • Garfinkel S.N.
        • Wang X.
        • Sripada C.S.
        • Welsh R.C.
        • et al.
        Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder.
        J Psychiatry Neurosci. 2012; 37: 241-249
        • Jin C.
        • Qi R.
        • Yin Y.
        • Hu X.
        • Duan L.
        • Xu Q.
        • et al.
        Abnormalities in whole-brain functional connectivity observed in treatment-naive post-traumatic stress disorder patients following an earthquake.
        Psychol Med. 2014; 44: 1927-1936
        • Nicholson A.A.
        • Sapru I.
        • Densmore M.
        • Frewen P.A.
        • Neufeld R.W.
        • Theberge J.
        • et al.
        Unique insula subregion resting-state functional connectivity with amygdala complexes in posttraumatic stress disorder and its dissociative subtype.
        Psychiatry Res Neuroimaging. 2016; 250: 61-72
        • Ghaziri J.
        • Tucholka A.
        • Girard G.
        • Boucher O.
        • Houde J.-C.
        • Descoteaux M.
        • et al.
        Subcortical structural connectivity of insular subregions.
        Sci Rep. 2018; 8: 8596
        • Baur V.
        • Hänggi J.
        • Langer N.
        • Jäncke L.
        Resting-state functional and structural connectivity within an insula–amygdala route specifically index state and trait anxiety.
        Biol Psychiatry. 2013; 73: 85-92
        • Kober H.
        • Barrett L.F.
        • Joseph J.
        • Bliss-Moreau E.
        • Lindquist K.
        • Wager T.D.
        Functional grouping and cortical-subcortical interactions in emotion: A meta-analysis of neuroimaging studies.
        NeuroImage. 2008; 42: 998-1031
        • Berret E.
        • Kintscher M.
        • Palchaudhuri S.
        • Tang W.
        • Osypenko D.
        • Kochubey O.
        • et al.
        Insular cortex processes aversive somatosensory information and is crucial for threat learning.
        Science. 2019; 364eaaw0474
        • Sripada R.K.
        • King A.P.
        • Welsh R.C.
        • Garfinkel S.N.
        • Wang X.
        • Sripada C.S.
        • et al.
        Neural dysregulation in posttraumatic stress disorder: Evidence for disrupted equilibrium between salience and default mode brain networks.
        Psychosom Med. 2012; 74: 904-911
        • Zhang Y.
        • Liu F.
        • Chen H.
        • Li M.
        • Duan X.
        • Xie B.
        • et al.
        Intranetwork and internetwork functional connectivity alterations in post-traumatic stress disorder.
        J Affect Disord. 2015; 187: 114-121
        • Koch S.B.
        • van Zuiden M.
        • Nawijn L.
        • Frijling J.L.
        • Veltman D.J.
        • Olff M.
        Aberrant resting-state brain activity in posttraumatic stress disorder: A meta-analysis and systematic review.
        Depress Anxiety. 2016; 33: 592-605
        • Rabinak C.A.
        • Angstadt M.
        • Welsh R.C.
        • Kenndy A.E.
        • Lyubkin M.
        • Martis B.
        • et al.
        Altered amygdala resting-state functional connectivity in post-traumatic stress disorder.
        Front Psychiatry. 2011; 2: 62
        • Bluhm R.L.
        • Williamson P.C.
        • Osuch E.A.
        • Frewen P.A.
        • Stevens T.K.
        • Boksman K.
        • et al.
        Alterations in default network connectivity in posttraumatic stress disorder related to early-life trauma.
        J Psychiatry Neurosci. 2009; 34: 187-194
        • Zhu X.
        • Suarez-Jimenez B.
        • Lazarov A.
        • Helpman L.
        • Papini S.
        • Lowell A.
        • et al.
        Exposure-based therapy changes amygdala and hippocampus resting-state functional connectivity in patients with posttraumatic stress disorder.
        Depress Anxiety. 2018; 35: 974-984
        • King A.P.
        • Block S.R.
        • Sripada R.K.
        • Rauch S.
        • Giardino N.
        • Favorite T.
        • et al.
        Altered default mode network (DMN) resting state functional connectivity following a mindfulness-based exposure therapy for posttraumatic stress disorder (PTSD) in combat veterans of Afghanistan and Iraq.
        Depress Anxiety. 2016; 33: 289-299
        • Misaki M.
        • Phillips R.
        • Zotev V.
        • Wong C.K.
        • Wurfel B.E.
        • Krueger F.
        • et al.
        Real-time fMRI amygdala neurofeedback positive emotional training normalized resting-state functional connectivity in combat veterans with and without PTSD: A connectome-wide investigation.
        NeuroImage Clin. 2018; 20: 543-555
        • Shou H.
        • Yang Z.
        • Satterthwaite T.D.
        • Cook P.A.
        • Bruce S.E.
        • Shinohara R.T.
        • et al.
        Cognitive behavioral therapy increases amygdala connectivity with the cognitive control network in both MDD and PTSD.
        NeuroImage Clin. 2017; 14: 464-470
        • Yang Z.
        • Gu S.
        • Honnorat N.
        • Linn K.A.
        • Shinohara R.T.
        • Aselcioglu I.
        • et al.
        Network changes associated with transdiagnostic depressive symptom improvement following cognitive behavioral therapy in MDD and PTSD.
        Mol Psychiatry. 2018; 23: 2314-2323
        • Etkin A.
        • Wager T.D.
        Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia.
        Am J Psychiatry. 2007; 164: 1476-1488
        • Patel R.
        • Spreng R.N.
        • Shin L.M.
        • Girard T.A.
        Neurocircuitry models of posttraumatic stress disorder and beyond: A meta-analysis of functional neuroimaging studies.
        Neurosci Biobehav Rev. 2012; 36: 2130-2142
        • Fenster R.J.
        • Lebois L.A.M.
        • Ressler K.J.
        • Suh J.
        Brain circuit dysfunction in post-traumatic stress disorder: From mouse to man.
        Nat Rev Neurosci. 2018; 19: 535-551
        • Disner S.G.
        • Marquardt C.A.
        • Mueller B.A.
        • Burton P.C.
        • Sponheim S.R.
        Spontaneous neural activity differences in posttraumatic stress disorder: A quantitative resting-state meta-analysis and fMRI validation.
        Hum Brain Mapp. 2018; 39: 837-850
        • Hayes J.P.
        • Hayes S.M.
        • Mikedis A.M.
        Quantitative meta-analysis of neural activity in posttraumatic stress disorder.
        Biol Mood Anxiety Disord. 2012; 2: 9
        • Etkin A.
        • Maron-Katz A.
        • Wu W.
        • Fonzo G.A.
        • Huemer J.
        • Vertes P.E.
        • et al.
        Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder.
        Sci Transl Med. 2019; 11eaal3236
        • Friston K.J.
        • Harrison L.
        • Penny W.
        Dynamic causal modelling.
        NeuroImage. 2003; 19: 1273-1302
        • Friston K.J.
        • Kahan J.
        • Biswal B.
        • Razi A.
        A DCM for resting state fMRI.
        NeuroImage. 2014; 94: 396-407
        • Blake D.D.
        • Weathers F.W.
        • Nagy L.M.
        • Kaloupek D.G.
        • Gusman F.D.
        • Charney D.S.
        • et al.
        The development of a Clinician-Administered PTSD Scale.
        J Trauma Stress. 1995; 8: 75-90
        • First M.B.
        • Spitzer R.L.
        • Gibbon M.
        • Williams J.B.W.
        Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P).
        Biometrics Research, New York State Psychiatric Institute, New York2002
        • Foa E.B.
        • Hembree E.A.
        • Rothbaum B.O.
        • Rauch S.A.
        Prolonged Exposure Therapy for PTSD: Emotional Processing of Traumatic Experiences.
        2nd ed. Oxford University Press, Oxford, UK2019
        • Whitfield-Gabrieli S.
        • Nieto-Castanon A.
        Conn: A functional connectivity toolbox for correlated and anticorrelated brain networks.
        Brain Connect. 2012; 2: 125-141
        • Amunts K.
        • Kedo O.
        • Kindler M.
        • Pieperhoff P.
        • Mohlberg H.
        • Shah N.J.
        • et al.
        Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: Intersubject variability and probability maps.
        Anat Embryol. 2005; 210: 343-352
        • Chang L.J.
        • Yarkoni T.
        • Khaw M.W.
        • Sanfey A.G.
        Decoding the role of the insula in human cognition: Functional parcellation and large-scale reverse inference.
        Cereb Cortex. 2013; 23: 739-749
        • Chen G.
        • Saad Z.S.
        • Britton J.C.
        • Pine D.S.
        • Cox R.W.
        Linear mixed-effects modeling approach to FMRI group analysis.
        NeuroImage. 2013; 73: 176-190
        • Almgren H.
        • Van de Steen F.
        • Razi A.
        • Friston K.
        • Marinazzo D.
        The effect of global signal regression on DCM estimates of noise and effective connectivity from resting state fMRI.
        NeuroImage. 2020; 208: 116435
        • Zeidman P.
        • Jafarian A.
        • Seghier M.L.
        • Litvak V.
        • Cagnan H.
        • Price C.J.
        • et al.
        A guide to group effective connectivity analysis, part 2: Second level analysis with PEB.
        NeuroImage. 2019; 200: 12-25
        • Friston K.
        • Penny W.
        Post hoc Bayesian model selection.
        NeuroImage. 2011; 56: 2089-2099
        • Penny W.D.
        • Stephan K.E.
        • Daunizeau J.
        • Rosa M.J.
        • Friston K.J.
        • Schofield T.M.
        • et al.
        Comparing families of dynamic causal models.
        PLoS Comput Biol. 2010; 6e1000709
        • Friston K.J.
        • Litvak V.
        • Oswal A.
        • Razi A.
        • Stephan K.E.
        • van Wijk B.C.M.
        • et al.
        Bayesian model reduction and empirical Bayes for group (DCM) studies.
        NeuroImage. 2016; 128: 413-431
        • Schaefer A.
        • Kong R.
        • Gordon E.M.
        • Laumann T.O.
        • Zuo X.N.
        • Holmes A.J.
        • et al.
        Local-global parcellation of the human cerebral cortex from intrinsic functional connectivity MRI.
        Cereb Cortex. 2018; 28: 3095-3114
        • Morey R.A.
        • Petty C.M.
        • Cooper D.A.
        • Labar K.S.
        • McCarthy G.
        Neural systems for executive and emotional processing are modulated by symptoms of posttraumatic stress disorder in Iraq War veterans.
        Psychiatry Res. 2008; 162: 59-72
        • Morey R.A.
        • Dolcos F.
        • Petty C.M.
        • Cooper D.A.
        • Hayes J.P.
        • LaBar K.S.
        • et al.
        The role of trauma-related distractors on neural systems for working memory and emotion processing in posttraumatic stress disorder.
        J Psychiatr Res. 2009; 43: 809-817
        • Muhle-Karbe P.S.
        • Derrfuss J.
        • Lynn M.T.
        • Neubert F.X.
        • Fox P.T.
        • Brass M.
        • et al.
        Co-activation-based parcellation of the lateral prefrontal cortex delineates the inferior frontal junction area.
        Cereb Cortex. 2015; 26: 2225-2241
        • 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.
        J Neurophysiol. 2011; 106: 1125-1165
        • Frassle S.
        • Lomakina E.I.
        • Razi A.
        • Friston K.J.
        • Buhmann J.M.
        • Stephan K.E.
        Regression DCM for fMRI.
        NeuroImage. 2017; 155: 406-421
        • Razi A.
        • Seghier M.L.
        • Zhou Y.
        • McColgan P.
        • Zeidman P.
        • Park H.J.
        • et al.
        Large-scale DCMs for resting-state fMRI.
        Netw Neurosci. 2017; 1: 222-241
        • Stephan K.E.
        • Penny W.D.
        • Moran R.J.
        • den Ouden H.E.
        • Daunizeau J.
        • Friston K.J.
        Ten simple rules for dynamic causal modeling.
        NeuroImage. 2010; 49: 3099-3109
        • Stefanacci L.
        • Amaral D.G.
        Some observations on cortical inputs to the macaque monkey amygdala: An anterograde tracing study.
        J Comp Neurol. 2002; 451: 301-323
        • Ray R.D.
        • Zald D.H.
        Anatomical insights into the interaction of emotion and cognition in the prefrontal cortex.
        Neurosci Biobehav Rev. 2012; 36: 479-501
        • Gehrlach D.A.
        • Dolensek N.
        • Klein A.S.
        • Roy Chowdhury R.
        • Matthys A.
        • Junghänel M.
        • et al.
        Aversive state processing in the posterior insular cortex.
        Nat Neurosci. 2019; 22: 1424-1437
        • Saygin Z.M.
        • Osher D.E.
        • Koldewyn K.
        • Martin R.E.
        • Finn A.
        • Saxe R.
        • et al.
        Structural connectivity of the developing human amygdala.
        PLoS One. 2015; 10e125170
        • Mégevand P.
        • Groppe D.M.
        • Bickel S.
        • Mercier M.R.
        • Goldfinger M.S.
        • Keller C.J.
        • et al.
        The hippocampus and amygdala are integrators of neocortical influence: A corticocortical evoked potential study.
        Brain Connect. 2017; 7: 648-660
        • Aggleton J.P.
        • Burton M.J.
        • Passingham R.E.
        Cortical and subcortical afferents to the amygdala of the rhesus monkey (Macaca mulatta).
        Brain Res. 1980; 190: 347-368