Pallidal Connectivity Profiling of Stimulation-Induced Dyskinesia in Parkinson's Disease

Takashi Tsuboi, Marc Charbel, David T. Peterside, Mohit Rana, Ahmad Elkouzi, Wissam Deeb, Adolfo Ramirez-Zamora, Janine Lemos Melo Lobo Jofili Lopes, Leonardo Almeida, Pamela R. Zeilman, Robert S. Eisinger, Kelly D. Foote, Lela Okromelidze, Sanjeet S. Grewal, Michael S. Okun, Erik H. Middlebrooks

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Objectives: The aim of this study is to identify anatomical regions related to stimulation-induced dyskinesia (SID) after pallidal deep brain stimulation (DBS) in Parkinson's disease (PD) patients and to analyze connectivity associated with SID. Methods: This retrospective study analyzed the clinical and imaging data of PD patients who experienced SID during the monopolar review after pallidal DBS. We analyzed structural and functional connectivity using normative connectivity data with the volume of tissue activated (VTA) modeling. Each contact was assigned to either that producing SID (SID VTA) or that without SID (non-SID VTA). Structural and functional connectivity was compared between SID and non-SID VTAs. “Optimized VTAs” were also estimated using the DBS settings at 6 months after implantation. Results: Of the 68 consecutive PD patients who underwent pallidal implantation, 20 patients (29%) experienced SID. SID VTAs were located more dorsally and anteriorly compared with non-SID and optimized VTAs and were primarily in the dorsal globus pallidus internus (GPi) and dorsal globus pallidus externus (GPe). SID VTAs showed significantly higher structural connectivity than non-SID VTAs to the associative cortex and supplementary motor area/premotor cortex (P < 0.0001). Simultaneously, non-SID VTAs showed greater connectivity to the primary sensory cortex, cerebellum, subthalamic nucleus, and motor thalamus (all P < 0.0004). Functional connectivity analysis showed significant differences between SID and non-SID VTAs in multiple regions, including the primary motor, premotor, and prefrontal cortices and cerebellum. Conclusion: SID VTAs were primarily in the dorsal GPi/GPe. The connectivity difference between the motor-related cortices and subcortical regions may explain the presence and absence of SID.

Original languageEnglish (US)
Pages (from-to)380-388
Number of pages9
JournalMovement Disorders
Issue number2
StatePublished - Feb 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 International Parkinson and Movement Disorder Society


  • Parkinson's disease
  • deep brain stimulation
  • dyskinesia
  • globus pallidus internus
  • pallidum


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