Wolf-Julian Neumann1, Julius Huebl1, Christof Brücke1, Roxanne Lofredi1, Andreas Horn1, Assel Saryyeva2, Kirsten Müller-Vahl3, Joachim K Krauss2, Andrea A Kühn1,4,5. 1. Department of Neurology, Movement Disorders and Neuromodulation Unit, Campus Charite Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany. 2. Department of Neurosurgery, Hannover Medical School, Hannover, Germany. 3. Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany. 4. Berlin School of Mind and Brain, Charité-Universitätsmedizin Berlin, Berlin, Germany. 5. NeuroCure, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Abstract
OBJECTIVE: Aberrant oscillatory activity has been hypothesized to play a role in the pathophysiology of Tourette's syndrome (TS). Deep brain stimulation (DBS) has recently been established as an effective treatment for severe TS. Modulation of symptom-specific oscillations may underlie the mechanism of action of DBS and could be used for adaptive neuromodulation to improve therapeutic efficacy. The objective of this study was to demonstrate a pathophysiological association of pallidal and thalamic local field potentials (LFPs) with TS. METHODS:Nine medication-refractory TS patients were included in the study. Intracerebral LFPs were recorded simultaneously from bilateral pallidal and thalamic DBS electrodes. Spectral and temporal dynamics of pallidal and thalamic oscillations were characterized and correlated with preoperative Yale Global Tic Severity Scale (YGTSS) scores. RESULTS: Peaks of activity in the theta (3-12Hz) and beta (13-35Hz) were present in pallidal and thalamic recordings from all patients (3 women/6 men; mean age, 29.8 years) and coupled through coherence across targets. Presence of prolonged theta bursts in both targets was associated with preoperative motor tic severity. Total preoperative YGTSS scores (mean, 38.1) were correlated with pallidal and thalamic LFP activity using multivariable linear regression (R² = 0.96; p = 0.02). INTERPRETATION: Our findings suggest that pallidothalamic oscillations may be implicated in the pathophysiology of TS. Furthermore, our results highlight the utility of multisite and -spectral oscillatory features in severely affected patients for future identification and clinical use of oscillatory physiomarkers for adaptive stimulation in TS. Ann Neurol 2018;84:505-514.
RCT Entities:
OBJECTIVE: Aberrant oscillatory activity has been hypothesized to play a role in the pathophysiology of Tourette's syndrome (TS). Deep brain stimulation (DBS) has recently been established as an effective treatment for severe TS. Modulation of symptom-specific oscillations may underlie the mechanism of action of DBS and could be used for adaptive neuromodulation to improve therapeutic efficacy. The objective of this study was to demonstrate a pathophysiological association of pallidal and thalamic local field potentials (LFPs) with TS. METHODS: Nine medication-refractory TS patients were included in the study. Intracerebral LFPs were recorded simultaneously from bilateral pallidal and thalamic DBS electrodes. Spectral and temporal dynamics of pallidal and thalamic oscillations were characterized and correlated with preoperative Yale Global Tic Severity Scale (YGTSS) scores. RESULTS: Peaks of activity in the theta (3-12Hz) and beta (13-35Hz) were present in pallidal and thalamic recordings from all patients (3 women/6 men; mean age, 29.8 years) and coupled through coherence across targets. Presence of prolonged theta bursts in both targets was associated with preoperative motor tic severity. Total preoperative YGTSS scores (mean, 38.1) were correlated with pallidal and thalamic LFP activity using multivariable linear regression (R² = 0.96; p = 0.02). INTERPRETATION: Our findings suggest that pallidothalamic oscillations may be implicated in the pathophysiology of TS. Furthermore, our results highlight the utility of multisite and -spectral oscillatory features in severely affected patients for future identification and clinical use of oscillatory physiomarkers for adaptive stimulation in TS. Ann Neurol 2018;84:505-514.
Authors: Jackson N Cagle; Michael S Okun; Enrico Opri; Stephanie Cernera; Rene Molina; Kelly D Foote; Aysegul Gunduz Journal: J Neurol Neurosurg Psychiatry Date: 2020-03-05 Impact factor: 10.154
Authors: Andrea A Kühn; R Mark Richardson; Wolf-Julian Neumann; Robert S Turner; Benjamin Blankertz; Tom Mitchell Journal: Neurotherapeutics Date: 2019-01 Impact factor: 7.620
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