Objective: To assess the safety, feasibility, neurophysiology and neuroimaging-driven targeting of the centromedian thalamus (CM) and anterior globus pallidus internus (aGPi) for deep brain stimulation (DBS) in Tourette Syndrome (TS). Our team is developing a connectivity-guided closed-loop DBS system for the improved treatment of TS.

Background: TS can be debilitating and stigmatizing for patients with severe motor and vocal tics that are resistant to medication and behavioral intervention. DBS has emerged as a promising treatment option for addressing medication-resistant tics. In this study, we address a knowledge gap in understanding basal ganglia and thalamic TS DBS brain targets possibly useful for the detection and suppression of tics.

Method: Study subjects will be enrolled and implanted in a NIH Funded Brain Initiative Study with bilateral CM, and aGPi directional DBS leads. The choice of targets and approach was guided by our prior publications in in circuit-based targeting for TS. A month later, we will implant a next-generation stimulator that can record brain activity and can be programmed to deliver closed-loop stimulation in response to pathological activity. Structural and diffusion imaging will be used to inform circuit-based targeting and construct connectivity-guided DBS parameter selection. Daily text message surveys are used to capture real time side effects and responses to stimulation in addition to weekly YGTSS assessments. Efficacy of closed-loop DBS will be assessed based on a >30% reduction in the Yale Global Tic Severity Score (YGTSS).

Results: To date, one subject has been implanted; we anticipate that 3 more subjects will be implanted by August, 2023. Diffusion tensor reconstructions and predictive modeling will be used to inform circuit-based targeting and to identify stimulation device parameters for programming. The first subject has been through the initial 3 months of recording and has now received closed-loop DBS for over two months using four recording/stimulation groups (sensing lead/stimulation lead): CM/CM; CM/aGPi; aGPi/CM; aGPi/aGPi.

Conclusion: Preliminary data suggests that circuit-based targeting of aGPi and CM for closed-loop DBS was safe and has informed targeting and device management. We will present preliminary data on targeting and device management.

Study Funding: NIH-UH3-NS119844

References: [1] K. A. Johnson et al., “Basal Ganglia Pathways Associated with Therapeutic Pallidal Deep Brain Stimulation for Tourette Syndrome,” Biol. Psychiatry Cogn. Neurosci. Neuroimaging, no. 18, pp. 1–12, 2020, doi: 10.1016/j.bpsc.2020.11.005.

[2] K. A. Johnson et al., “Structural connectivity predicts clinical outcomes of deep brain stimulation for Tourette syndrome,” Brain, vol. 143, no. 8, pp. 2607–2623, Aug. 2020, doi: 10.1093/brain/awaa188.

[3] K. A. Johnson et al., “Image-based analysis and long-term clinical outcomes of deep brain stimulation for Tourette syndrome: a multisite study,” J. Neurol. Neurosurg. Psychiatry, vol. 90, no. 10, pp. 1078–1090, Oct. 2019, doi: 10.1136/jnnp-2019-320379.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/circuit-based-targeting-for-closed-loop-deep-brain-stimulation-for-tourette-syndrome/