title: Skin Conductance Responses and Neural Activations During Fear Conditioning and Extinction Recall Across Anxiety Disorders.
abstract: The fear conditioning and extinction neurocircuitry has been extensively studied in healthy and clinical populations, with a particular focus on posttraumatic stress disorder. Despite significant overlap of symptoms between posttraumatic stress disorder and anxiety disorders, the latter has received less attention. Given that dysregulated fear levels characterize anxiety disorders, examining the neural correlates of fear and extinction learning may shed light on the pathogenesis of underlying anxiety disorders.
  
  
  
  To investigate the psychophysiological and neural correlates of fear conditioning and extinction recall in anxiety disorders and to document how these features differ as a function of multiple diagnoses or anxiety severity.
  
  
  
  This investigation was a cross-sectional, case-control, functional magnetic resonance imaging study at an academic medical center. Participants were healthy controls and individuals with at least 1 of the following anxiety disorders: generalized anxiety disorder, social anxiety disorder, specific phobia, and panic disorder. The study dates were between March 2013 and May 2015.
  
  
  
  Two-day fear conditioning and extinction paradigm.
  
  
  
  Skin conductance responses, blood oxygenation level-dependent responses, trait anxiety scores from the State Trait Anxiety Inventory-Trait Form, and functional connectivity.
  
  
  
  This study included 21 healthy controls (10 women) and 61 individuals with anxiety disorders (36 women). P values reported for the neuroimaging results are all familywise error corrected. Skin conductance responses during extinction recall did not differ between individuals with anxiety disorders and healthy controls (ηp2 = 0.001, P = .79), where ηp2 is partial eta squared. The anxiety group had lower activation of the ventromedial prefrontal cortex (vmPFC) during extinction recall (ηp2 = 0.178, P = .02). A similar hypoactive pattern was found during early conditioning (ηp2 = 0.106, P = .009). The vmPFC hypoactivation was associated with anxiety symptom severity (r = -0.420, P = .01 for conditioning and r = -0.464, P = .004 for extinction recall) and the number of co-occuring anxiety disorders diagnosed (ηp2 = 0.137, P = .009 for conditioning and ηp2 = 0.227, P = .004 for extinction recall). Psychophysiological interaction analyses revealed that the fear network connectivity differed between healthy controls and the anxiety group during fear learning (ηp2 range between 0.088 and 0.176 and P range between 0.02 and 0.003) and extinction recall (ηp2 range between 0.111 and 0.235 and P range between 0.02 and 0.002).
  
  
  
  Despite no skin conductance response group differences during extinction recall, brain activation patterns between anxious and healthy individuals differed. These findings encourage future studies to examine the conditions longitudinally and in the context of treatment trials to improve and guide therapeutics via advanced neurobiological understanding of each disorder.
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston2Department of Psychiatry, Harvard Medical School, Boston, Massachusetts3currently with the Research Center of the Montreal Mental Health University Institute, Department of Psychiatry, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Marin
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Zsido
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston2Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
authors.forename: Huijin
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston2Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Lasko
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, Massachusetts4Department of Psychiatry, McLean Hospital, Belmont, Massachusetts5currently with the Social, Cognitive, and Affective Neuroscience Laboratory, University of Arizona College of Medicine, Tucson.
authors.forename: William D S
authors.initials: WDS
authors.lastname: Killgore
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, Massachusetts4Department of Psychiatry, McLean Hospital, Belmont, Massachusetts.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Rauch
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston2Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
authors.forename: Naomi M
authors.initials: NM
authors.lastname: Simon
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston2Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Milad
mesh_terms: D000328:Adult; D001008:Anxiety Disorders / Q000503:physiopathology* / Q000523:psychology*; D001143:Arousal / Q000502:physiology*; D001921:Brain / Q000503:physiopathology; D001931:Brain Mapping; D016022:Case-Control Studies; D003214:Conditioning, Classical / Q000502:physiology*; D003430:Cross-Sectional Studies; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D005712:Galvanic Skin Response / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011939:Mental Recall / Q000502:physiology*; D009415:Nerve Net / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D016584:Panic Disorder / Q000503:physiopathology / Q000523:psychology; D000072861:Phobia, Social / Q000503:physiopathology / Q000523:psychology; D010698:Phobic Disorders / Q000503:physiopathology / Q000523:psychology; D013223:Statistics as Topic
chemical_list: D010100:Oxygen