Abstract
Background: Deep brain stimulation (DBS) is an emerging treatment strategy for severe, medication-refractory Tourette syndrome (TS). Thalamic (Cm-Pf) and pallidal (including globus pallidus interna, GPi) targets have been the most investigated. While the neurophysiological correlates of Parkinson's disease (PD) in the GPi and subthalamic nucleus (STN) are increasingly recognized, these patterns are not well characterized in other disease states. Recent findings indicate that the cross-frequency coupling (CFC) between beta band and high frequency oscillations (HFOs) within the STN in PD patients is pathologic.Methods: We recorded intraoperative local field potentials (LFPs) from the postero-ventrolateral GPi in three adult patients with TS at rest, during voluntary movements, and during tic activity and compared them to the intraoperative GPi-LFP activity recorded from four unmedicated PD patients at rest.Results: In all PD patients, we noted excessive beta band activity (13–30 Hz) at rest which consistently modulated the amplitude of the co-existent HFOs observed between 200 and 400 Hz, indicating the presence of beta-HFO CFC. In all 3TS patients at rest, we observed theta band activity (4–7 Hz) and HFOs. Two patients had beta band activity, though at lower power than theta oscillations. Tic activity was associated with increased high frequency (200–400 Hz) and gamma band (35–200 Hz) activity. There was no beta-HFO CFC in TS patients at rest. However, CFC between the phase of 5–10 Hz band activity and the amplitude of HFOs was found in two TS patients. During tics, this shifted to CFC between the phase of beta band activity and the amplitude of HFOs in all subjects.Conclusions: To our knowledge this is the first study that shows that beta-HFO CFC exists in the GPi of TS patients during tics and at rest in PD patients, and suggests that this pattern might be specific to pathologic/involuntary movements. Furthermore, our findings suggest that during tics, resting state 5–10 Hz-HFO CFC shifts to beta-HFO CFC which can be used to trigger stimulation in a closed loop system when tics are present.
Highlights
Tourette syndrome (TS) is a neuropsychiatric disorder defined by the presence of vocal and motor tics, but characterized by frequent co-morbidities such as attention deficit disorder and obsessive compulsive disorder (Jankovic, 2001)
We did find a substantial difference in cross-frequency coupling (CFC) between tic periods compared to the resting state, which was not seen during voluntary movements
In TS subjects at rest, we found coupling between the phase of theta-low alpha oscillations to the amplitude of high frequency oscillations (HFOs) in 2 subjects, and during tic activity we found coupling between the phase of beta oscillations to the amplitude of HFOs in all 3 subjects
Summary
Tourette syndrome (TS) is a neuropsychiatric disorder defined by the presence of vocal and motor tics, but characterized by frequent co-morbidities such as attention deficit disorder and obsessive compulsive disorder (Jankovic, 2001). While the worst-ever time period for tics is often 10–12 years of age (Bloch et al, 2006a; Shprecher et al, 2014), 5–10% of patients will continue to experience significant or worsening symptoms into adulthood (Freeman and Tourette Syndrome International Database, 2007). Predictors of severity or the course of TS are not well understood, though contributing factors may include presence of fine motor skills deficits (Bloch et al, 2006b), reduced caudate volumes (Bloch et al, 2005) or greater tic severity at a younger age (Bloch et al, 2006a). Recent findings indicate that the cross-frequency coupling (CFC) between beta band and high frequency oscillations (HFOs) within the STN in PD patients is pathologic
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