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BACKGROUND AND OBJECTIVES: Fear activation and reduction have traditionally been considered important mechanisms of exposure therapy. Evidence to date is mixed and impeded by inadequate methodology. This study examined the extent to which fear activation and reduction within and across exposures predicted treatment outcomes for social anxiety disorder within a paradigm suitable for their measurement. METHODS: Sixty-eight adults with social anxiety disorder and fear of public speaking completed seven exposure sessions, each consisting of seven speeches conducted in virtual reality. Exposures were identical in duration, task requirements, and virtual public speaking situation. Fear was measured with skin conductance and subjective distress ratings. At baseline and post-treatment, participants completed a public speaking behavioral approach test with a panel of confederate judges; subjective fear was measured. A standardized questionnaire of anxiety symptoms was administered at baseline, post-treatment, and one-month follow-up. RESULTS: No indices of within- or between-session fear reduction, measured by subjective distress and skin conductance response, predicted treatment outcome. One measure of fear activation was associated with outcomes such that less activation predicted greater symptom reduction; remaining indices did not predict outcomes. LIMITATIONS: Data were collected in the context of a randomized controlled trial of scopolamine; drug group was included in analytic models to account for drug influence. VR exposures elicited mild levels of distress that may underestimate levels of distress in clinical settings. CONCLUSIONS: Findings failed to support fear activation or reduction within or across exposure sessions as significant predictors of treatment outcome for social anxiety. Treatment implications are discussed.

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Background: Specific phobias represent the largest category of anxiety disorders. Previous work demonstrated that stimulating the ventromedial prefrontal cortex (vmPFC) with repetitive Transcranial Magnetic Stimulation (rTMS) may improve response to exposure therapy for acrophobia. Objective: To examine feasibility of accelerating extinction learning in subjects with spider phobia using intermittent Theta Burst Stimulation (iTBS) rTMS of vmPFC. Methods: In total, 17 subjects with spider phobia determined by spider phobia questionnaires [Spider Phobia Questionnaire (SPQ) and Fear of Spiders questionnaire (FSQ)] underwent ratings of fear of spiders as well as behavioral and skin conductance data during a behavioral avoidance test (BAT). Subjects then received a sequential protocol of in vivo spider exposure followed by iTBS for three sessions administered to either active or control treatment sites (vmPFC [n = 8] or vertex [n = 9], respectively), followed 1 week later by repetition of questionnaires and BAT. Results: All subjects improved significantly regardless of group across both questionnaires (FSQ η2 = 0.43, p = 0.004; SPQ η2 = 0.39, p = 0.008) and skin conductance levels during BAT (Wald χ2 = 30.9, p < 0.001). Subjects in the vmPFC group tolerated lower treatment intensity than in the control group, and there was a significant correlation between treatment intensity, BAT subjective distress improvement, and physiologic measures (all ρ > 0.5). Conclusion: This proof-of-concept study provides preliminary evidence that a sequential exposure and iTBS over vmPFC is feasible and may have rTMS intensity-dependent effects on treatment outcomes, providing evidence for future areas of study in the use of rTMS for phobias.

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Exposure therapy is widely empirically supported as a treatment for anxiety disorders, but clinically significant response rates hover around 50%. This study explores strategies for consolidating the exposure memory as a way of improving efficacy. Between-session mental rehearsal of exposure learning was examined as a way of enhancing the effects of exposure therapy. Sixty-two spider-fearful individuals completed baseline questionnaires and a behavioral approach test with a live tarantula, followed by two sessions of in vivo exposures, and a post-assessment one-week later that repeated the baseline questionnaires and behavioral approach test. Skin conductance, subjective distress, and number of steps completed were recorded at each behavioral approach test. Participants were randomized to mental rehearsal or control (non-specific) rehearsal that was prompted on three occasions after each exposure session. Participants in both conditions improved from baseline to post-assessment, but mental rehearsal participants showed significantly greater improvement than control participants across questionnaire measurements of spider fear, subjective distress, and number of steps completed during the behavioral approach test. Findings suggest that between-session mental rehearsal is an effective supplement to exposure therapy. As such, mental rehearsal may be a promising avenue toward increasing treatment response rates across many psychiatric disorders that benefit from exposure therapy.

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BACKGROUND AND OBJECTIVES: Difficulty disengaging attention from threat has been observed in some anxious samples, but the evidence to date is mixed. The current study examines temporal trends in attention disengagement and compares this construct across multiple forms of social threat. METHODS: Participants (85 adults with a principal diagnosis of social anxiety disorder) completed a spatial cueing task with four image categories (angry faces, disapproving faces, neutral faces, neutral objects). Attention disengagement was assessed via reaction time (RT) over 256 trials. RESULTS: Participants with greater social anxiety exhibited an initial delay in attention disengagement from disapproving faces that habituated over the course of the task. RTs to angry and neutral stimuli did not differ as a function of social anxiety. LIMITATIONS: The current task only allowed for examining speed of attention disengagement, and thus we were unable to compare our results to trajectories of speed at which participants orient towards threat. Additionally, disapproving facial images were created for this paradigm and may benefit from further validation. CONCLUSIONS: Findings suggest that social anxiety is associated with an initial delay in attention disengagement from social threat that resolves over the course of repeated exposures to such stimuli. Treatment implications are discussed.

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OBJECTIVE: Although behaviorally inhibited (BI) temperament predicts risk for anxiety, anxiety in BI may involve distinct neural responses to errors. The current study examines the relations between anxiety and neural correlates of error processing both in youths identified as BI in early childhood and in youths seeking treatment for an anxiety disorder. METHOD: All participants underwent functional magnetic resonance imaging using a flanker task to assess responses to errors. A study in healthy subjects assessed test-retest reliability to inform analyses in two other samples. For one sample, a cohort of BI youths (Low BI, n = 28; High BI, n = 27) was followed into adolescence. For the other, participants were recruited based on the presence or absence of an anxiety disorder. Using identical methods in medication-free subjects, analyses compared relations between anxiety and error processing across the two samples. RESULTS: Error-processing exhibited acceptable reliability. Within a ventromedial-prefrontal-cortex (vmPFC) cluster, anxiety related to error processing only in youths whose early-life BI status was known. In the high BI group, anxiety related to reduced neural response to errors. No such associations manifested in treatment-seeking youths. Other analyses mapped relations between error-processing and anxiety in each sample on its own. However, only the vmPFC cluster statistically differentiated the neural correlates of anxiety in BI. CONCLUSION: BI temperament may define a unique pathway into anxiety involving perturbed neural responding to errors. Although BI is a risk factor for later anxiety, the neural and associated features of anxiety in BI youths may differ from those in treatment-seeking youths.

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BACKGROUND AND OBJECTIVES: Following an aversive experience, fears often generalize across contexts. Contextual fear generalization is modeled in a laboratory paradigm in which one context (CTX+) is paired with an aversive unconditional stimulus (US), while the other context (CTX-) is not. The current study sought to validate a novel paradigm assessing contextual fear generalization, and to determine the extent to which stress and anxiety symptoms enhanced contextual fear generalization. METHODS: Fifty-nine participants were randomized to a stress induction or control arithmetic test, followed by a differential context fear conditioning paradigm. One to three days later, participants completed a generalization gradient test with CTX+, CTX, and four generalization contexts. RESULTS: We found successful contextual fear conditioning on measures of US expectancy, self-report fear and valence, and startle reflex, and linear generalization across the contextual gradient on expectancies and self-report measures. Acute stress induction impaired learning of the US-CTX + association during context fear acquisition. Anxiety significantly predicted greater contextual fear generalization as measured by US expectancy. LIMITATIONS: Our study provides pilot data introducing a novel fear conditioning paradigm to assess contextual generalization of fear. There is a need for further replication to validate its utility. CONCLUSIONS: Findings suggest that individuals high in anxiety show greater contextual fear generalization as measured by US expectancy. Results are discussed in terms of potential mechanisms that contribute to pervasive anxiety.

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