Modelling and modulating mechanisms of escape and avoidance in the anxiety disorder spectrum: A precision medicine rTMS approach

Abstract Repetitive transcranial magnetic stimulation (rTMS) is a longstanding FDA-approved treatment for chronic depression, but its efficacy with anxiety and related disorders is not well-established. A growing literature suggests that improving efficacy of rTMS for anxiety/ related disorders could depend on increasing the degree to which targeted rTMS is paired with behavioral challenges so that specific disorder-relevant behaviors can be modified. In this vein, the current poster presents a large-scale project in which rTMS targeting theoretically critical neural nodes is paired with careful laboratory-based assay of behaviors central to the etiology and maintenance of pathological anxiety – namely, escape and avoidance behaviors. To comprehensively model these behaviors in our target sample of 80 anxiety treatment seekers, the project deploys multiple laboratory tasks that have been shown to capture different dimensions of escape and avoidance such that: 1) one task measures fear (startle reflex) reactivity during preparation to execute simple escape or avoidance responses, and finds anxious exaggerations of reactivity in the escape but not the avoidance context; 2) another task allows participants to increase monetary reward or chance to avoid punishment by moving, respectively, closer to or further from a dynamic virtual predator, and in this task anxious individuals show a bias toward punishment avoidance specifically with slow-moving predators. To test modulation of potentially distinct neural mediators of each effect, participants complete each task before and after rTMS targeted to a distinct neural hub across separate sessions – these being ventromedial prefrontal cortex (which regulates the fear-mediating amygdala) and pre-supplementary motor area (which communicates with dorsal basal ganglia, a critical mediator of proactive avoidance). In addition to presenting the comprehensive methodology, then, the current poster will present initial results for each task and rTMS session – and consider implications of positive results from this project for the precision treatment of anxiety and related concerns. Research Category and Technology and Methods Translational Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: Anxiety, Escape/ Avoidance Behaviors, rTMS, Experimental Psychophysiology