Skin Conductance Responses and Neural Activations During Fear Conditioning and Extinction Recall Across Anxiety Disorders
Authors: Marie-France Marin, Rachel G. Zsido, Huijin Song, Natasha B. Lasko, William D. S. Killgore, Scott L. Rauch, Naomi M. Simon, Mohammed R. Milad
Journal: JAMA Psychiatry (2017)

<h3>Importance</h3> 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. <h3>Objectives</h3> 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. <h3>Design, Setting, and Participants</h3> 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. <h3>Exposures</h3> Two-day fear conditioning and extinction paradigm. <h3>Main Outcomes and Measures</h3> Skin conductance responses, blood oxygenation level–dependent responses, trait anxiety scores from the State Trait Anxiety Inventory–Trait Form, and functional connectivity. <h3>Results</h3> This study included 21 healthy controls (10 women) and 61 individuals with anxiety disorders (36 women).<i>P</i>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 (ηp<sup>2</sup> = 0.001,<i>P</i> = .79), where ηp<sup>2</sup>is partial eta squared. The anxiety group had lower activation of the ventromedial prefrontal cortex (vmPFC) during extinction recall (ηp<sup>2</sup> = 0.178,<i>P</i> = .02). A similar hypoactive pattern was found during early conditioning (ηp<sup>2</sup> = 0.106,<i>P</i> = .009). The vmPFC hypoactivation was associated with anxiety symptom severity (<i>r</i> = −0.420,<i>P</i> = .01 for conditioning and<i>r</i> = −0.464,<i>P</i> = .004 for extinction recall) and the number of co-occuring anxiety disorders diagnosed (ηp<sup>2</sup> = 0.137,<i>P</i> = .009 for conditioning and ηp<sup>2</sup> = 0.227,<i>P</i> = .004 for extinction recall). Psychophysiological interaction analyses revealed that the fear network connectivity differed between healthy controls and the anxiety group during fear learning (ηp<sup>2</sup>range between 0.088 and 0.176 and<i>P</i>range between 0.02 and 0.003) and extinction recall (ηp<sup>2</sup>range between 0.111 and 0.235 and<i>P</i>range between 0.02 and 0.002). <h3>Conclusions and Relevance</h3> 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.