9 research outputs found
Basal Ganglia Pathways Associated With Therapeutic Pallidal Deep Brain Stimulation for Tourette Syndrome
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
Structural connectivity predicts clinical outcomes of deep brain stimulation for Tourette syndrome
Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate 'reverse' tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P 0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome