Resting-State Functional Connectivity Predicts STN DBS Clinical Response

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. © 2020 International Parkinson and Movement Disorder Society.

Keywords: DBS; Parkinson's disease; functional connectivity.

Figure 1:

Study flowchart. Each imaging modality (rs-fcMRI and PET) occurred as independent components of a larger DBS outcome study focused on clinical outcomes (322 participants enrolled between 2007–2017). The PET component was performed only between 2009 and 2015. 19 participants received both rs-fcMRI and PET and passed all quality-control criteria for study inclusion.

Figure 2:

PET rCBF responses to unilateral STN stimulation in whole-brain analysis. Responses shown are significant at cluster-wise FWE p<0.05. Side ipsilateral to stimulation is displayed as standard radiological left (figure right). Reference atlas is in Talairach space. A: STN stimulation produced negative rCBF response centered in ipsilateral dorsal sensorimotor regions, including primary motor, primary sensory, and SMA cortex. B: STN stimulation produced positive rCBF response centered in ipsilateral thalamus, including ventrolateral and mediodorsal regions. Scale is in t-statistic for paired T-test between stimulation condition and OFF condition. Voxels displayed are thresholded to cluster-wise FWE-corrected significance at p<0.05.

Figure 3:

Resting state fcMRI connectivity matrices. A: Z-transformed correlation matrix of all regions of PET defined DBS response, mirrored in contralateral hemisphere and inclusive of bilateral STN, for all DBS subjects. B: Matrix in (A) correlated with percent change UPDRS-III. C. Scatterplot of left STN – left GPI FC versus percent change UPDRS-III (r = −0.385, p = 0.001).