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Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: a functional MRI study

  • Scott L Rauch
    Correspondence
    Address reprint requests to Scott L. Rauch, M.D., Massachusetts General Hospital—East, Department of Psychiatry, 13th Street, Building 149, Room 9130, Charlestown MA 02129
    Affiliations
    Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA (SLR, PJW, LMS, SCM, NBL, SPO, RKP)

    Department of Radiology, Massachusetts General Hospital, Boston Massachusetts, USA (SLR)

    Harvard Medical School, Boston, Massachusetts, USA (SLR, PJW, LMS, NBL, SPO, RKP)
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  • Paul J Whalen
    Affiliations
    Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA (SLR, PJW, LMS, SCM, NBL, SPO, RKP)

    Harvard Medical School, Boston, Massachusetts, USA (SLR, PJW, LMS, NBL, SPO, RKP)
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  • Lisa M Shin
    Affiliations
    Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA (SLR, PJW, LMS, SCM, NBL, SPO, RKP)

    Harvard Medical School, Boston, Massachusetts, USA (SLR, PJW, LMS, NBL, SPO, RKP)

    Department of Psychology, Tufts University, Medford, MassachusettsUSA (LMS)
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  • Sean C McInerney
    Affiliations
    Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA (SLR, PJW, LMS, SCM, NBL, SPO, RKP)
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  • Michael L Macklin
    Affiliations
    VA Research Service, Manchester, New HampshireUSA (MLM, NBL, SPO, RKP)
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  • Natasha B Lasko
    Affiliations
    Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA (SLR, PJW, LMS, SCM, NBL, SPO, RKP)

    Harvard Medical School, Boston, Massachusetts, USA (SLR, PJW, LMS, NBL, SPO, RKP)

    VA Research Service, Manchester, New HampshireUSA (MLM, NBL, SPO, RKP)
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  • Scott P Orr
    Affiliations
    Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA (SLR, PJW, LMS, SCM, NBL, SPO, RKP)

    Harvard Medical School, Boston, Massachusetts, USA (SLR, PJW, LMS, NBL, SPO, RKP)

    VA Research Service, Manchester, New HampshireUSA (MLM, NBL, SPO, RKP)
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  • Roger K Pitman
    Affiliations
    Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA (SLR, PJW, LMS, SCM, NBL, SPO, RKP)

    Harvard Medical School, Boston, Massachusetts, USA (SLR, PJW, LMS, NBL, SPO, RKP)

    VA Research Service, Manchester, New HampshireUSA (MLM, NBL, SPO, RKP)
    Search for articles by this author

      Abstract

      Background: Converging lines of evidence have implicated the amygdala in the pathophysiology of posttraumatic stress disorder (PTSD). We previously developed a method for measuring automatic amygdala responses to general threat-related stimuli; in conjunction with functional magnetic resonance imaging, we used a passive viewing task involving masked presentations of human facial stimuli.
      Methods: We applied this method to study veterans with PTSD and a comparison cohort of combat-exposed veterans without PTSD.
      Results: The findings indicate that patients with PTSD exhibit exaggerated amygdala responses to masked-fearful versus masked-happy faces.
      Conclusions: Although some previous neuroimaging studies of PTSD have demonstrated amygdala recruitment in response to reminders of traumatic events, this represents the first evidence for exaggerated amygdala responses to general negative stimuli in PTSD. Furthermore, by using a probe that emphasizes automaticity, we provide initial evidence of amygdala hyperresponsivity dissociated from the “top-down” influences of medial frontal cortex.

      Keywords

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      References

        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders. 4th ed. American Psychiatric Association, Washington, DC1994
        • Beck A.T.
        • Ward C.H.
        • Mendelson M.
        An inventory for measuring depression.
        Arch Gen Psychiatry. 1961; 4: 561-571
        • 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
        • Breiter H.C.
        • Etcoff N.L.
        • Whalen P.J.
        • Kennedy W.A.
        • Rauch S.L.
        • Buckner R.L.
        • et al.
        Response and habituation of the human amygdala during visual processing of facial expression.
        Neuron. 1996; 17: 875-887
        • Bremner J.D.
        • Staib L.H.
        • Kaloupek D.
        • Southwick S.M.
        • Soufer R.
        • Charney D.S.
        Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder.
        Biol Psychiatry. 1999; 45: 806-816
        • Cahill L.
        • Weinberger N.M.
        • Roozendaal B.
        • McGaugh J.L.
        Is the amygdala a locus of “conditioned fear”? Some questions and caveats.
        Neuron. 1999; 23: 227-228
        • Cohen M.S.
        • Weisskoff R.M.
        Ultra-fast imaging.
        Magn Reson Imaging. 1991; 9: 1-37
        • Davis M.
        The neurobiology of fear responses.
        J Neuropsychiatry Clin Neurosci. 1997; 9: 382-402
        • Ekman P.
        • Friesen W.V.
        Pictures of Facial Affect. Consulting Psychologists Press, Palo Alto, CA1976
        • Esteves F.
        • Öhman A.
        Masking the face.
        Scand J Psychol. 1993; 34: 1-18
        • Filipek P.
        • Richelme C.
        • Kennedy D.
        • Caviness V.
        The young adult human brain.
        Cereb Cortex. 1994; 4: 344-360
        • First M.B.
        • Spitzer R.L.
        • Gibbon M.
        • Williams J.B.W.
        Structured Clinical Interview for DSM-IV. New York State Psychiatric Institute, Biometrics Research Department, New York1995
        • Jiang A.J.
        • Kennedy D.N.
        • Baker J.R.
        • Weisskoff R.M.
        • Tootell R.B.H.
        • Woods R.P.
        • et al.
        Motion detection and correction in functional MR imaging.
        Hum Brain Mapping. 1995; 3: 224-235
        • Kanwisher N.
        • McDermott J.
        • Chun M.M.
        The fusiform face area.
        J Neurosci. 1997; 17: 4302-4311
        • Kapp B.S.
        • Whalen P.J.
        • Supple W.F.
        • Pascoe J.
        Amygdaloid contributions to conditioned arousal and sensory information processing.
        in: Aggleton J.P. The Amygdala Neurobiological Aspects of Emotion, Memory and Mental Dysfunction. Wiley, New York1992: 229-254
        • Keane T.M.
        • Fairbank J.A.
        • Caddell J.M.
        • Zimering R.T.
        • Taylor K.L.
        • Mora C.A.
        Clinical evaluation of a measure to assess combat exposure.
        Psychol Assess J Consult Clin Psychol. 1989; 1: 53-55
        • Kulka R.A.
        • Schlenger W.E.
        • Fairbank J.A.
        • Hough R.L.
        • Jorda B.K.
        • Marmar C.R.
        • et al.
        Trauma and the Vietnam Generation. Brunner/Mazel, New York1990
        • Kwong K.K.
        Functional magnetic resonance imaging with echo planar imaging.
        Magn Reson Q. 1995; 11: 1-20
        • LeDoux J.E.
        The Emotional Brain. Simon & Schuster, New York1996
        • Liberzon I.
        • Taylor S.F.
        • Amdur R.
        • Jung T.D.
        • Chamberlain K.R.
        • Minoshima S.
        • et al.
        Brain activation in PTSD in response to trauma-related stimuli.
        Biol Psychiatry. 1999; 45: 817-826
        • Mai J.K.
        • Assheuer J.
        • Paxinos G.
        Atlas of the Human Brain. Academic Press, San Diego1997
        • Mansfield P.
        Multi-planar image formation using NMR spin echoes.
        J Physics. 1977; C10: L55-L58
        • Mathews A.
        • MacLeod C.
        Cognitive approaches to emotion and emotional disorders.
        Annu Rev Psychol. 1994; 45: 25-50
        • McNally R.J.
        Information-processing abnormalities in anxiety disorders; implications for cognitive neuroscience.
        Cogn Emotion. 1998; 12: 479-495
        • Morgan M.A.
        • LeDoux J.E.
        Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats.
        Behav Neurosci. 1995; 109: 681-688
        • Morris J.S.
        • Frith C.D.
        • Perrett D.I.
        • Rowland D.
        • Young A.W.
        • Calder A.J.
        • et al.
        A differential response in the human amygdala to fearful and happy facial expressions.
        Nature. 1996; 383: 812-815
        • Morris J.S.
        • Öhman A.
        • Dolan R.J.
        Conscious and unconscious emotional learning in the human amygdala.
        Nature. 1998; 393: 467-470
        • Oldfield R.C.
        The assessment and analysis of handedness.
        Neuropsychologia. 1971; 9: 97-113
      1. Orr SP, Metzger LJ, Lasko NB, Macklin ML, Peri T, Pitman RK (in press): De Novo conditioning in trauma-exposed individuals with and without post-traumatic stress disorder. J Abnorm Psychol.

      2. Orr SP, Roth WT (in press): Psychophysiological assessment: Clinical applications for PTSD. J Affect Disord.

      3. Peri T, Ben-Shakhar G, Orr SP, Ahalev AY (in press): Psychophysiologic assessment of aversive conditioning in posttraumatic stress disorder. Biol Psychiatry.

        • Pitman R.K.
        Overview of biological themes in PTSD.
        Ann N Y Acad Sci. 1997; 821: 1-9
        • Pitman R.K.
        • Shalev A.Y.
        • Orr S.P.
        Post-traumatic stress disorder.
        in: Gazzaniga M.S. The Cognitive Neurosciences. MIT Press, Cambridge, MA2000: 1133-1147
        • Rauch S.L.
        • van der Kolk B.A.
        • Fisler R.E.
        • Alpert N.M.
        • Orr S.P.
        • Savage C.R.
        • et al.
        A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery.
        Arch Gen Psychiatry. 1996; 53: 380-387
        • Reese T.G.
        • Davis T.L.
        • Weisskoff R.M.
        Automated shimming at 1.5 T using echo-planar image frequency maps.
        J Magn Reson Imaging. 1995; 5: 739-745
        • Shalev A.Y.
        • Rogel Fuchs Y.
        • Pitman R.K.
        Conditioned fear and psychological trauma.
        Biol Psychiatry. 1992; 31: 863-865
        • Shin L.M.
        • Kosslyn S.M.
        • McNally R.J.
        • Alpert N.M.
        • Thompson W.L.
        • Rauch S.L.
        • et al.
        Visual imagery and perception in posttraumatic stress disorder.
        Arch Gen Psychiatry. 1997; 54: 233-241
        • Shin L.M.
        • McNally R.J.
        • Kosslyn S.M.
        • Thompson W.L.
        • Rauch S.L.
        • Alpert N.M.
        • et al.
        Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related posttraumatic stress disorder.
        Am J Psychiatry. 1999; 156: 575-584
        • Talairach J.
        • Tournoux P.
        Co-Planar Stereotaxic Atlas of the Human Brain. Thieme, New York1988
        • Vogt B.A.
        • Finch D.M.
        • Olson C.R.
        Functional heterogeneity in cingulate cortex.
        Cereb Cortex. 1992; 2: 435-443
        • Whalen P.J.
        Fear, vigilance, and ambiguity.
        Curr Dir Psychol Sci. 1998; 7: 177-188
        • Whalen P.J.
        • Rauch S.L.
        • Etcoff N.L.
        • McInerney S.
        • Lee M.B.
        • Jenike M.A.
        Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge.
        J Neurosci. 1998; 18: 411-418
        • Woods R.P.
        • Cherry S.R.
        • Mazziotta J.C.
        Automated algorithm for aligning tomographic images. II. Cross-modality MRI-PET registration.
        J Comput Assist Tomogr. 1992; 16: 620-633
        • Yehuda R.
        • Antelman S.M.
        Criteria for rationally evaluating animal models of posttraumatic stress disorder.
        Biol Psychiatry. 1993; 33: 479-486