John R Younce1, Meghan C Campbell1,2, Tamara Hershey2,3, Aaron B Tanenbaum1, Mikhail Milchenko2, Mwiza Ushe1, Morvarid Karimi1, Samer D Tabbal4, Albert E Kim1, Abraham Z Snyder1,2, Joel S Perlmutter1,2,3,5,6,7, Scott A Norris1,2. 1. Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA. 2. Department of Radiology, Washington University in St. Louis, St. Louis, Missouri, USA. 3. Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri, USA. 4. Department of Neurology, American University of Beirut, Beirut, Lebanon. 5. Department of Neuroscience, Washington University in St. Louis, St. Louis, Missouri, USA. 6. Program in Physical Therapy, Washington University in St. Louis, St. Louis, Missouri, USA. 7. Program in Occupational Therapy, Washington University in St. Louis, St. Louis, Missouri, USA.
Abstract
BACKGROUND: Deep brain stimulation of the subthalamic nucleus is a widely used adjunctive therapy for motor symptoms of Parkinson's disease, but with variable motor response. Predicting motor response remains difficult, and novel approaches may improve surgical outcomes as well as the understanding of pathophysiological mechanisms. The objective of this study was to determine whether preoperative resting-state functional connectivity MRI predicts motor response from deep brain stimulation of the subthalamic nucleus. METHODS: We collected preoperative resting-state functional MRI from 70 participants undergoing subthalamic nucleus deep brain stimulation. For this cohort, we analyzed the strength of STN functional connectivity with seeds determined by stimulation-induced (ON/OFF) 15 O H2 O PET regional cerebral blood flow differences in a partially overlapping group (n = 42). We correlated STN-seed functional connectivity strength with postoperative motor outcomes and applied linear regression to predict motor outcomes. RESULTS: Preoperative functional connectivity between the left subthalamic nucleus and the ipsilateral internal globus pallidus correlated with postsurgical motor outcomes (r = -0.39, P = 0.0007), with stronger preoperative functional connectivity relating to greater improvement. Left pallidal-subthalamic nucleus connectivity also predicted motor response to DBS after controlling for covariates. DISCUSSION: Preoperative pallidal-subthalamic nucleus resting-state functional connectivity predicts motor benefit from deep brain stimulation, although this should be validated prospectively before clinical application. These observations suggest that integrity of pallidal-subthalamic nucleus circuits may be critical to motor benefits from deep brain stimulation.
BACKGROUND: Deep brain stimulation of the subthalamic nucleus is a widely used adjunctive therapy for motor symptoms of Parkinson's disease, but with variable motor response. Predicting motor response remains difficult, and novel approaches may improve surgical outcomes as well as the understanding of pathophysiological mechanisms. The objective of this study was to determine whether preoperative resting-state functional connectivity MRI predicts motor response from deep brain stimulation of the subthalamic nucleus. METHODS: We collected preoperative resting-state functional MRI from 70 participants undergoing subthalamic nucleus deep brain stimulation. For this cohort, we analyzed the strength of STN functional connectivity with seeds determined by stimulation-induced (ON/OFF) 15 O H2 O PET regional cerebral blood flow differences in a partially overlapping group (n = 42). We correlated STN-seed functional connectivity strength with postoperative motor outcomes and applied linear regression to predict motor outcomes. RESULTS: Preoperative functional connectivity between the left subthalamic nucleus and the ipsilateral internal globus pallidus correlated with postsurgical motor outcomes (r = -0.39, P = 0.0007), with stronger preoperative functional connectivity relating to greater improvement. Left pallidal-subthalamic nucleus connectivity also predicted motor response to DBS after controlling for covariates. DISCUSSION: Preoperative pallidal-subthalamic nucleus resting-state functional connectivity predicts motor benefit from deep brain stimulation, although this should be validated prospectively before clinical application. These observations suggest that integrity of pallidal-subthalamic nucleus circuits may be critical to motor benefits from deep brain stimulation.
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