• Annals of neurology · Dec 2020

    Clinical Trial

    Subthalamic Nucleus Deep Brain Stimulation Modulates 2 Distinct Neurocircuits.

    • Lunhao Shen, Changqing Jiang, Catherine S Hubbard, Jianxun Ren, Changgeng He, Danhong Wang, Louisa Dahmani, Yi Guo, Yiming Liu, Shujun Xu, Fangang Meng, Jianguo Zhang, Hesheng Liu, and Luming Li.
    • National Engineering Laboratory for Neuromodulation, School of Aerospace Engineering, Tsinghua University, Beijing, China.
    • Ann. Neurol. 2020 Dec 1; 88 (6): 1178-1193.

    ObjectiveCurrent 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.MethodsFourteen 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.ResultsTwo 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.InterpretationConcurrent 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.© 2020 American Neurological Association.

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