Title: Personalized target selection for TMS therapy using functional vs. structural connectivity MRI Transcranial magnetic stimulation (TMS) is an FDA-approved treatment for major depressive disorder (MDD). Remission rates are estimated to be around 30%, similar to other antidepressant therapies yet still suboptimal. A key reason for the variability in response is the lack of an individualized approach that identifies the cortical therapeutic target for each patient. A proposed strategy is to use functional connectivity MRI to identify the topography of functional networks relevant to MDD. In this project, we propose a novel strategy to personalized identification of TMS targets by using diffusion MRI (dMRI) to identify the white matter bundles that connect two critical nodes affected by MDD: the left prefrontal cortex (PFC) and the subgenual cingulate (SGC). We will study 500 subjects from the Human Connectome Project (HCP) and 20 patients with MDD who were treated with TMS. We will use state-of-the-art functional connectivity and diffusion MRI data and analyses. Our goal is to quantify and compare, for the first time, the reliability of these methods to identify cortical targets for TMS therapy. In addition we will study the clinical efficacy of dMRI-guided TMS by retrospectively analyzing the relationship between therapeutic response and location of the stimulated TMS target in relation to the optimal dMRI node. Last, we will use sophisticated dMRI metrics to assess the changes in white matter microstructure induced by TMS and how they relate to clinical efficacy (therefore defining anatomical mechanisms of action and therapeutic targets). Results from this project will support future prospective trials aiming to confirm target engagement and therapeutic response using individualized dMRI-guided TMS in MDD and other neuropsychiatric conditions.

Public Health Relevance

! This project aims to develop individualized image-guided strategies for therapeutic Transcranial Magnetic Stimulation (TMS) based on state-of-the art diffusion MRI (dMRI) tractography. We will retrospectively analyze both functional connectivity and diffusion tractography scans from 500 subjects in the Human Connectome Project database and 20 patients with depression treated with TMS in our center. Results will establish the comparative reliability of these imaging modalities to define therapeutic cortical targets in individual patients, in addition to estimating the clinical efficacy of dMRI-guided TMS and proposing its mechanisms of action based on white matter microstructural changes.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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Mcmullen, David
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Brigham and Women's Hospital
United States
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Ning, Lipeng; Nilsson, Markus; Lasi?, Samo et al. (2018) Cumulant expansions for measuring water exchange using diffusion MRI. J Chem Phys 148:074109
Ning, Lipeng; Rathi, Yogesh (2018) A Dynamic Regression Approach for Frequency-Domain Partial Coherence and Causality Analysis of Functional Brain Networks. IEEE Trans Med Imaging 37:1957-1969
Ellard, Kristen K; Zimmerman, Jared P; Kaur, Navneet et al. (2018) Functional Connectivity Between Anterior Insula and Key Nodes of Frontoparietal Executive Control and Salience Networks Distinguish Bipolar Depression From Unipolar Depression and Healthy Control Subjects. Biol Psychiatry Cogn Neurosci Neuroimaging 3:473-484