Modulating prefrontal circuits underlying behavioral flexibility in OCD: a TMS study

点击翻译按钮获取中文摘要

PROJECT SUMMARY/ABSTRACT The primary goal of this proposed COBRE Center for Neuromodulation Project is to elucidate neural circuits underlying impairments in behavioral flexibility in OCD, using transcranial magnetic stimulation as a probe of the system and fMRI to measure functional changes within neural circuitry implicated in behavioral (in)flexibility in obsessive-compulsive disorder (OCD). OCD is a chronic and impairing neuropsychiatric disorders associated with impairments in behavioral flexibility – most notably, the compulsions which are a hallmark of the disorder. Patients with OCD also show impaired behavioral flexibility on a range of experimental tasks (e.g., set-shifting, task-switching, reversal learning). Moreover, neuroimaging findings in OCD routinely show abnormal patterns of activation during tasks probing behavioral flexibility. The proposed research project will use slow frequency (1-Hz) rTMS to probe dysfunctional circuitry, targeting frontal pole, an area involved in higher level cognitive control processes which likely plays a key role in coordination between multiple neural circuits involved in behavioral flexibility and which shares structural and functional connections to circuitry implicated in behavioral inflexibility in OCD. We aim to test whether (1) slow frequency (1-Hz) rTMS to frontal pole can affect functional changes within circuits showing abnormal functioning during behavioral flexibility in OCD, (2) whether rTMS targeting this circuitry can affect behavioral changes in a population with deficits in behavioral flexibility, and (3) whether circuit functioning relates to behavioral performance following rTMS. While a number of studies have shown abnormal neural circuit functioning during behavioral flexibility tasks in OCD, to our knowledge, this will be the first to move beyond correlational findings to directly examine changes to circuit functioning following a probe of the system using TMS. The long-term goal of this work is to inform target identification for development of neurocircuit-based interventions which may improve treatment outcomes for those with OCD.