Date(s) - 01/28/2015
Tourette Syndrome (TS) is a complex neuropsychiatric disorder characterized by involuntary and urge–driven motor and vocal tics. The pathophysiology of the disease is poorly understood and treatment options (e.g., pharmacological, behavioral) vary from patient to patient. For intractable cases of the disorder, deep brain stimulation
(DBS) has emerged as a potential treatment option for addressing tics; however, continuous DBS in TS leads to undesired side effects. Our central hypothesis is that neurostimulators programmed to detect and respond to abnormal neural activity related to tics can bring about enhanced treatment opportunities for TS and alleviate the unwanted side effects of continuous DBS. The research project proposed herein is aimed at detecting tics directly from brain activity captured through chronic implantable neurostimulators, which can record brain activity and stimulate at the same time. These efforts are expected to have a significant impact on our understanding the pathophysiology of TS and to open the door for enhanced treatment options.
Tourette syndrome (TS) is a complex neuropsychiatric disorder characterized by the childhood onset of multiple motor and vocal tics.
These symptoms can be debilitating as they lead to social embarrassment, functional impairment, tic-related injuries, and self-injurious behavior . The underlying neural mechanisms and pathogenesis of TS are not well understood and the limited pharmacological and behavioral and treatments are of poor efficacy . Recently DBS has emerged as a promising treatment avenue for severe medication resistant patients, who failed all available therapies . Chronic implantation of electrodes can facilitate the recording of brain activity in TS patients, which could help elucidate the etiology of the disease.
The objective of this research project is to uncover neural markers of tic generation and expression in TS, to advance the methodologies and therapeutic benefit of deep brain stimulation. Our central hypothesis is that a systematic approach to couple stimulation and physiological recordings, we will achieve greater reduction in motor and vocal tics.
The rationale for the proposed research is that non-direct detection of tics from brain activity can be used to guide responsive deep brain stimulation (DBS) strategies to resolve the tics. In this proposed project, we will study local field potential (LFP) activity of patients with Tourette’s Syndrome (TS) undergoing deep brain stimulation of the centromedian (CM) thalamus. LFPs will be recorded from the CM thalamus and from subdural strips over the hand motor cortex. We have FDA and IRB approval to implant electrodes in the brains of 10 patients with TS. The data will be collected using Medtronic Activa PC+S chronic (subcutaneous) devices and will be accessed through telemetry. These devices are capable of sensing (recording) signals as well as stimulating. Our project will uncover the neuronal activity inherent to CM and cortex, and will reveal how DBS affects this activity in human TS.
Aim 1. To determine the electrophysiological markers of tics in TS.
Aim 2. To uncover the effects of acute and chronic DBS stimulation on thalamo-cortical circuits in TS.
Aim 3. To test the effectiveness of responsive stimulation in acute settings.
With respect to expected outcomes, this study will fill a critical knowledge gap as it will advance our understanding of the mechanisms of TS and contribute neurophysiological insights and essential therapeutic targets to the field. We expect these will have an important positive impact on the quality of life of TS patients.