Neuromodulation for Depression: Insights Gained from Neuroimaging and Computational Models

NEUROMODULATION FOR DEPRESSION: INSIGHTS GAINED FROM NEUROIMAGING AND COMPUTATIONAL MODELS Yagna Pathak, B.S., M.Eng. Marquette University, 2014 Major depressive disorder (MDD) is a public health concern worldwide, affecting a sixth of the American population. Neuromodulation therapies have been employed to treat severe cases of treatment resistant depression. These procedures attempt to modulate activity in cortical regions that represent nodes in brain circuits believed to be involved in MDD. One challenge in neuromodulation trials has been the difficulty in quantifying outcome variability. We sought to understand the effects of neuromodulation therapies and their sources of variability while adding an objective perspective to assess clinical improvement in neuropsychiatric disorders such as depression. The goal of my dissertation was to investigate the neuronal circuitry of MDD patients who were treated using neuromodulation. Our primary measures were behavior scores and results from functional neuroimaging. The specific aims of this study were to answer three fundamental questions: 1) What is the role of stimulation parameters in patient response to chronic epidural cortical stimulation (EpCS) for MDD? 2) What functional changes result from repetitive transcranial magnetic stimulation (rTMS) for MDD? 3) How does stimulation of different targets in the depressive circuit affect antidepressive response? Our results suggest that combining neuroimaging with computational tools can increase the predictive power to determine who is likely to respond to a specific neuromodulation treatment course. We demonstrated the significance of stimulation parameters (location, polarity, duration) and the engagement of crucial nodes of the depressive circuit in order to achieve a sustained clinical improvement. Additionally, we showed that it is possible to affect deeper brain regions by targeting superficial areas that are easier to access with noninvasive modalities. The approaches highlighted in this dissertation can provide valuable insights about patients evaluated for neuromodulation for depression.