Targeting salience network dysfunction in depression with individualized brain network mapping and TMS

摘要

Abstract The goals of the proposed F32 Career Development Award are to provide the PI with a technical skillset and knowledge of mood disorder psychopathology that will facilitate his developing into an independent investigator using individualized neuroimaging and non-invasive brain stimulation technologies to 1) precisely understand brain network dysfunction in mood disorders and 2) develop methods for enhancing engagement of potential treatment targets in single patients. The PI has assembled a team of experts on mood disorders, human neuroimaging, and non-invasive brain stimulation to help him complete the aims of this proposal and a training plan that will provide experience essential to his long-term career goals. The proposed project will be conducted at Weill Cornell Medicine (WCM) and leverage the intellectual environment at Brain Mind Research Institute (BMRI) and access to the core facilities of WCM, including Sackler Institute and Citigroup Biomedical Imaging Center. This proposal is focused on Major Depressive Disorder (MDD), one of the leading causes of disability worldwide. Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for medication-resistant MDD but its antidepressant mechanisms are incompletely understood, especially at the level of neural circuits and large-scale brain networks, complicating efforts to enhance its treatment potential in single patients. The central hypothesis of this proposal is that 10 Hz rTMS administered to a brain network implicated in valence processing deficits in patients with MDD, termed the salience network, decreases circuit responsivity to aversive stimuli. The PI will use state-of-the-art technologies for individualized functional brain network mapping and measure engagement of the salience network using concurrent TMS-fMRI. The PI will also evaluate if rTMS administered to the salience network rescues circuit dysfunction and valence processing deficits. The proposed training plan complements the research aims of this proposal with formal didactics, hands-on workshops run by leading experts on non-invasive brain stimulation, research collaborations, that will provide the PI with knowledge and skills in five areas: 1) mood disorder psychopathology; 2) new statistical and computational methods; 3) new investigational tools; 4) mentorship; 5) scientific communication. Completing this proposal will generate preliminary data necessary for pursuing a K funding mechanism and will set-the-stage for developing neurobiologically informed, personalized rTMS interventions for mood disorders later in the PI’s career. !