Objective: To (1) investigate the impact on thalamocortical network dynamics in response to low frequency and high frequency deep brain stimulation and (2) uncover the mechanisms involved in the therapeutic benefits associated with high frequency stimulation.

Background: Tourette Syndrome (TS) is a neurological disorder characterized by undesired motor and vocal tics. Treatment of TS varies depending on symptom severity and individual therapy effectiveness. Deep brain stimulation (DBS) is an emerging therapy for the treatment of many neurological disorders, including severe TS through the electrical stimulation of deep brain nuclei.

Methods: Two patients with Tourette’s Syndrome was implanted at University of Florida (UF) Shands Hospital with two bilateral subdural 4-contact cortical strip electrodes and two bilateral 4-contact subcortical depth electrodes with the aim of capturing tic-related physiology. All procedures were approved by the FDA and UF IRB. Depth electrodes were placed bilaterally within the centromedian nucleus of the thalamus (Cm) and the cortical subdural strips were placed bilaterally over the premotor (PM) and primary motor (M1) cortices. Low frequency (60 hz) and high frequency (160 hz) stimulation was delivered to Cm in 10-minute windows. LFPs were recorded during/after stimulation, and while no stimulation was delivered. Data was collected each month at follow up visits (a total of 8 recordings). Time series analysis, Spectral analysis, Phase amplitude coupling(PAC), and coherence between and across Cm and M1 were computed.

Results: PAC calculated from the M1 alpha phase and M1 gamma amplitude increased during and following high frequency stimulation. An increase between Cm alpha phase and M1 gamma amplitude was observed following high frequency stimulation. Baseline and low frequency stimulation LFP exhibited similar PAC measures. Spectral analysis comparing low frequency to high frequency stimulation LFP revealed no significant change in beta power. Coherence calculations are underway.

Conclusions: High frequency stimulation of Cm, associated with therapeutic benefit in Tourette patients, was shown to drive PAC in M1. The dynamics of the thalamocortical network in response to stimulation may assist in uncovered the mechanisms involved in TS, DBS efficacy, and may serve as useful biomarkers for the development of closed loop stimulation tuning.

Partially presented at SFN 2015.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/modulation-of-thalamocortical-network-dynamics-via-deep-brain-stimulation-in-humans-with-tourette-syndrome/