Differentiating tic electrophysiology from voluntary movement in the human thalamocortical circuit

Abstract

ObjectivesTourette syndrome is a neurodevelopmental disorder commonly associated with involuntary movements, or tics. We currently lack an ideal animal model for Tourette syndrome. In humans, clinical manifestation of tics cannot be captured via functional imaging due to motion artefacts and limited temporal resolution, and electrophysiological studies have been limited to the intraoperative environment. The goal of this study was to identify electrophysiological signals in the centromedian (CM) thalamic nucleus and primary motor (M1) cortex that differentiate tics from voluntary movements.MethodsThe data were collected as part of a larger National Institutes of Health-sponsored clinical trial. Four participants (two males, two females) underwent monthly clinical visits for collection of physiology for a total of 6 months. Participants were implanted with bilateral CM thalamic macroelectrodes and M1 subdural electrodes that were connected to two neurostimulators, both with sensing capabilities. MRI scans were performed preoperatively and CT scans postoperatively for localisation of electrodes. Electrophysiological recordings were collected at each visit from both the cortical and subcortical implants.ResultsRecordings collected from the CM thalamic nucleus revealed a low-frequency power (3–10 Hz) increase that was time-locked to the onset of involuntary tics but was not present during voluntary movements. Cortical recordings revealed beta power decrease in M1 that was present during tics and voluntary movements.ConclusionWe conclude that a human physiological signal was detected from the CM thalamus that differentiated tic from voluntary movement, and this physiological feature could potentially guide the development of neuromodulation therapies for Tourette syndrome that could use a closed-loop-based approach.

Non-invasive Brain Stimulation for the Treatment of Gilles de la Tourette Syndrome

“…No such systems have been tested in GTS, mainly because no unequivocal neural signal as a marker of tics has been identified. Recently, though, recordings of oscillatory activity from the centro-median nucleus of the thalamus in patients receiving DBS revealed a low-frequency power (3-10 Hz) increase time-locked to the onset of tics but not during voluntary movements in GTS patients (172). Such activity might guide the development of "closed-loop" neuromodulation.…”

Thalamic Local Field Potentials Are Related to Long-Term DBS Effects in Tourette Syndrome

“…DBS also provided the unique opportunity to record signals directly from the brain structures involved in TS pathophysiology, thus supporting both the study of the neurophysiological signatures of this complex pathology ( 13 – 17 ) and the improvement of DBS therapy per se ( 18 – 20 ). In particular, DBS electrodes allow recording the compound presynaptic and postsynaptic activity of neuronal populations in the area surrounding the lead, known as local field potentials (LFPs).…”

“…This “theta” power was shown to be correlated with tic severity, and especially with preoperative YGTSS scores ( 16 ), and was observed as a consistent signature of tic onset, but not of voluntary movement ( 17 ).…”

“…LFPs are signals characterized by oscillations, mostly studied in the 2–45-Hz range. Following the large experience gained with DBS in Parkinson's disease, LFP analysis in TS led to interesting results, especially for the characterization of abnormal oscillations in the thalamus at rest ( 13 , 14 , 17 , 19 , 21 ), during tics ( 14 , 17 , 22 ), and during voluntary movements ( 17 ).…”

A neural noise account of Gilles de la Tourette syndrome

“…Importantly, in this study, theta power and theta burst length correlated significantly with preoperative motor tic severity suggesting that longer theta bursts may be related to tics ( Neumann et al, 2018 ). In addition, recordings of oscillatory activity from the centro-median nucleus of the thalamus in GTS patients revealed power increases in the theta band time-locked to the onset of tics but not during voluntary movements in these patients ( Cagle et al, 2020 ). Collectively, these data suggest that pallido-thalamic oscillations in the theta range are relevant in the pathophysiology of GTS.…”