Date & time: Monday, April 27^th at 2pm

Location (building/room for in-person): Singleton Auditorium

Zoom link (hybrid): https://mit.zoom.us/j/93995148181

Talk title: Neural and Neurochemical Mechanisms of Social Anxiety Disorder: Multimodal Neuroimaging Investigations of Pathophysiology and Cognitive Behavioral Therapy Response

Abstract: Social anxiety disorder (SAD) is a prevalent and significantly impairing condition characterized by the intense fear of negative evaluation in social situations. Despite the well-documented efficacy of cognitive behavioral therapy (CBT) clinically, the neural and neurochemical mechanisms underlying SAD pathophysiology and CBT-induced change remain poorly understood. My thesis work presents findings from an ongoing clinical trial examining adults with SAD and age-matched healthy control subjects across multimodal neuroimaging sessions before and after 12 weeks of group CBT, to characterize the neurobiological mechanisms of SAD and their malleability to psychosocial intervention.

First, we used magnetic resonance spectroscopy to measure in vivo neurochemistry. We found that individuals with SAD showed significantly elevated levels of excitatory neurotransmitters relative to controls and a significant inverse relationship between antioxidant levels and anxiety symptom severity. Together, these neurochemical findings are consistent with a model of SAD involving the linked processes of excitotoxicity and oxidative stress.

Second, we used a well-validated emotional face-matching task to probe implicit emotional processing during functional magnetic resonance imaging (fMRI). We did not observe hypothesized baseline hyperactivation of the amygdala and insula in response to negative emotional stimuli in the SAD group. However, significant reductions were observed in amygdala and insula activation to negative emotional stimuli following CBT within the SAD group, with significantly greater reduction in right amygdala reactivity relative to controls.

Third, we developed a novel naturalistic social feedback paradigm in which participants viewed video clips of actors delivering direct second-person statements of social rejection, social acceptance, or neutral content to probe emotional processing in SAD with more salient and ecologically valid stimuli. We did not observe hypothesized group differences in limbic system activation in response to the social rejection stimuli. Analyses examining the similarity of temporal dynamics of neural timecourses, rather than event-evoked activation magnitude, revealed greater synchrony in the SAD group during social rejection in brain regions associated with self-referential processing and somatosensory integration.

Overall, the work in this thesis leverages multimodal neuroimaging approaches to advance our characterization of the neurobiological substrates of SAD and their plasticity in response to CBT.