Background: Subthalamic nucleus deep brain stimulation (STN-DBS) improves motor symptoms but can be associated with subtle cognitive changes, including declines in verbal fluency (VF). Network-based mechanisms underlying stimulation-induced fluency declines are not fully understood. Objective: This study investigates how STN-DBS stimulation locations interact with brain connectivity patterns, and whether this differentially drives VF changes. Methods: 20 patients with Parkinson's disease and unilateral STN-DBS were analyzed. Electrodes were localized with estimates for volume of tissue activation (VTA). VTAs were seeded in normative functional and structural connectomes to identify connectivity profiles correlating with VF changes (R-maps). Additionally, amongst the fibers passing through VTAs, a two-sample t-test assigned fibers associated with VF improvement or decline. Results: VF declines occurred following unilateral left but not right STN-DBS. R-maps revealed that improvements correlated with greater connectivity to prefrontal structures in right hemisphere such as inferior and superior frontal gyrus, whereas declines localized to structures on the left. Fibers filtered from right VTAs were associated with VF improvements. Fibers from left VTAs were associated with declines, but the gradient of fiber t-scores were distributed across an anterior-posterior axis ranging from supplementary motor area to paracentral lobule. Conclusion: Unilateral STN-DBS interacts with distributed cognitive networks that display strong hemispheric lateralization. Beyond the effects of implant hemisphere, our findings suggest that connectivity between local STN subregions to larger whole-brain networks impacts VF performance, in a manner that could yield more tailored approaches to electrode targeting and clinical programming.

Financial Disclosure / Conflict of Interest: H.C.W participates in data safety monitoring boards for 2 DBS studies. K.A.M has received honoraria from the Parkinson's foundation. All remaining authors do not report potential conflicts of interest.

H.C.W received research funding from NIH BRAIN, and the Michael J. Fox Foundation. K.A.M received research funding from NIH/NINDS (5K23NS101096-01A1), Michael J. Fox Foundation, Parkinson Foundation, UCB, FDA (U01FD005942), and received honoraria from the Parkinson Study Group.

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The United States Food and Drug Administration and the Ethics committee/IRB of the University of Alabama at Birmingham Institutional Review Board gave ethical approval for this work.

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The data that support the findings of this study are available upon reasonable request to the corresponding author, KAM. The data are not publicly available due to information that could compromise the privacy of patient subjects.