Cortical Network Modulation by Subthalamic Nucleus Deep Brain Stimulation

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Deep brain stimulation of the subthalamic nucleus (STN DBS) can provide substantial motor benefit yet occasional mood and cognitive side effects in Parkinson disease (PD). Current literature hypothesizes that downstream network level effects are a critical mechanism of STN DBS’s influence on motor and non-motor behavior, however our ability to test this hypothesis has been limited. Common imaging modalities either do not have the temporal resolution necessary to discern resting state functional connectivity of cortical networks or are not suitable or safe for patients with implanted DBS. We have developed a novel high-density diffuse optical tomography (HD-DOT) system for measuring brain hemodynamics which can accurately map the functional connectivity of cortical resting state networks (RSN) or task-evoked responses within the first ~1cm of cortex. HD-DOT has comparable temporal and spatial resolution to fMRI, greater comfort than MRI or PET, no radiation exposure, no electrical artifacts, no metal artifacts and no contraindications or safety concerns for DBS patients. We have strong preliminary data showing the validity and feasibility of assessing cortical RSNs and task-induced responses in STN DBS patients. With our novel HD-DOT system, careful experimental design and rigorous analyses, this study will determine the nature of cortical RSN-level modulation induced by STN DBS and its relationship to DBS-induced motor and cognitive change. Controls and individuals with PD will be enrolled pre-surgically and scanned with HD-DOT and MRI (resting state BOLD, structural]). After implantation and optimization of DBS, PD individuals will be scanned with HD-DOT in several conditions. With these data, we will test hypotheses about networks that are responsive to important characteristics of STN DBS (e.g.location) and their relationship to motor and non-motor function. This information ultimately could provide methods for faster optimization of DBS parameters and help identify cortical nodes or networks involved in STN DBS-induced benefits or side effects that would provide future targets for less invasive neuromodulation. Finally, this work could reveal fundamental properties of cortical network physiology such as the capacity for plasticity in response to up-stream perturbations.