Probing and Modulating Neural Circuitry Relevant to Affective Illness (R01)

The choice of TMS targets has been determined from imaging data supporting deficits in prefrontal cortical connectivity. Both resting state fMRI and task-based fMRI reveal dimensional components of pathophysiology across major depression (MDD) and post-traumatic stress disorder (PTSD), which fall within the negative valence construct of the RDoC framework; both disorders are treated with TMS. A principal barrier to understanding the mechanisms of repetitive TMS (rTMS) treatment for depression is a limitation common to neuroimaging methods that utilize correlational approaches to understand brain/ behavior relationships. TMS without concurrent measurement of neural activity cannot measure in vivo processes that give rise to behavior. Combining traditional resting state fMRI measures of connectivity with evoked fMRI connectivity with TMS allows novel insights into how traditional connectivity measures can be confirmed by causally manipulating particular brain areas while monitoring downstream effects in deeper brain targets.