BACKGROUND: Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) can improve tics and
comorbid obsessive-compulsive behavior (OCB) in patients with treatment-refractory Tourette syndrome (TS).
However, some patients’ symptoms remain unresponsive, the stimulation applied across patients is variable, and
the mechanisms underlying improvement are unclear. Identifying the fiber pathways surrounding the GPi that are
associated with improvement could provide mechanistic insight and refine targeting strategies to improve outcomes.
METHODS: Retrospective data were collected for 35 patients who underwent bilateral GPi DBS for TS. Computational models of fiber tract activation were constructed using patient-specific lead locations and stimulation settings
to evaluate the effects of DBS on basal ganglia pathways and the internal capsule. We first evaluated the relationship
between activation of individual pathways and symptom improvement. Next, linear mixed-effects models with
combinations of pathways and clinical variables were compared in order to identify the best-fit predictive models
of tic and OCB improvement.
RESULTS: The best-fit model of tic improvement included baseline severity and the associative pallido-subthalamic
pathway. The best-fit model of OCB improvement included baseline severity and the sensorimotor pallidosubthalamic pathway, with substantial evidence also supporting the involvement of the prefrontal, motor, and
premotor internal capsule pathways. The best-fit models of tic and OCB improvement predicted outcomes across
the cohort and in cross-validation.
CONCLUSIONS: Differences in fiber pathway activation likely contribute to variable outcomes of DBS for TS.
Computational models of pathway activation could be used to develop novel approaches for preoperative targeting
and selecting stimulation parameters to improve patient outcomes