Investigating the Effects of Deep Brain Stimulation on Functional and Effective Connectivity in Humans using Functional Magnetic Resonance Imaging

Deep Brain Stimulation (DBS) is an established treatment for movement disorders including Parkinson's disease, essential tremor, and dystonia. The utility of DBS is quickly expanding into the neuropsychiatric arena, where it has been used to treat patients suffering from major depressive disorder, obsessive-compulsive disorder, and Tourette syndrome. While DBS was originally thought to work by silencing pathological neuronal activity, more recent studies suggest that DBS achieves its effects by a more complex mechanism that involves neuronal excitation and inhibition, both proximal and distal to the site of stimulation. Functional magnetic resonance imaging (FMRI) can be combined with DBS to assess the impact of stimulation on neural activity at the network level. In addition, the application of effective connectivity analysis methods, including dynamic causal modeling (DCM), to FMRI data allow us to evaluate neural state models that can shed light on DBS-evoked changes in effective connectivity. In this work, we applied intraoperative fMRI and clinical evaluations in patients receiving DBS for the treatment of movement disorders as well as psychiatric conditions. We combined these methods to test the hypothesis that measures of functional and effective connectivity might correlate with the therapeutic and adverse effects of DBS. In patients suffering from psychiatric and neurological disorders, we identified BOLD activation patterns that correlated with acute DBS-evoked effects and the clinical effects of stimulation, respectively. These results provide novel insights into the network-level mechanisms that mediate the clinical effects of DBS. In addition, they indicate that intraoperative fMRI holds untapped potential as a clinical tool that could help clinicians arrive at optimal stimulation parameters.