Subthalamic Nucleus Deep Brain Stimulation Modulates 2 Distinct Neurocircuits

Objective Current understanding of the neuromodulatory effects of deep brain stimulation (DBS) on large‐scale brain networks remains elusive, largely due to the lack of techniques that can reveal DBS‐induced activity at the whole‐brain level. Using a novel 3T magnetic resonance imaging (MRI)‐compatible stimulator, we investigated whole‐brain effects of subthalamic nucleus (STN) stimulation in patients with Parkinson disease. Methods Fourteen patients received STN‐DBS treatment and participated in a block‐design functional MRI (fMRI) experiment, wherein stimulations were delivered during “ON” blocks interleaved with “OFF” blocks. fMRI responses to low‐frequency (60Hz) and high‐frequency(130Hz) STN‐DBS were measured 1, 3, 6, and 12 months postsurgery. To ensure reliability, multiple runs (48 minutes) of fMRI data were acquired at each postsurgical visit. Presurgical resting‐state fMRI (30 minutes) data were also acquired. Results Two neurocircuits showed highly replicable, but distinct responses to STN‐DBS. A circuit involving the globus pallidus internus (GPi), thalamus, and deep cerebellar nuclei was significantly activated, whereas another circuit involving the primary motor cortex (M1), putamen, and cerebellum showed DBS‐induced deactivation. These 2 circuits were dissociable in terms of their DBS‐induced responses and resting‐state functional connectivity. The GPi circuit was frequency‐dependent, selectively responding to high‐frequency stimulation, whereas the M1 circuit was responsive in a time‐dependent manner, showing enhanced deactivation over time. Finally, activation of the GPi circuit was associated with overall motor improvement, whereas M1 circuit deactivation was related to reduced bradykinesia. Interpretation Concurrent DBS‐fMRI using 3T revealed 2 distinct circuits that responded differentially to STN‐DBS and were related to divergent symptoms, a finding that may provide novel insights into the neural mechanisms underlying DBS. ANN NEUROL 2020;88:1178–1193