Wolf-Julian Neumann1, Andreas Horn1, Siobhan Ewert1, Julius Huebl1, Christof Brücke1, Colleen Slentz1, Gerd-Helge Schneider2, Andrea A Kühn1,3,4. 1. Department of Neurology, Movement Disorders and Neuromodulation Unit, Campus Charite Mitté, Charité-Universitätsmedizin Berlin. 2. Department of Neurosurgery, Campus Charite Mitté, Charité-Universitätsmedizin Berlin. 3. Berlin School of Mind and Brain, Charité-Universitätsmedizin Berlin. 4. NeuroCure, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Abstract
OBJECTIVE: Deep brain stimulation (DBS) allows for direct recordings of neuronal activity from the human basal ganglia. In Parkinson's disease, a disease-specific physiomarker was identified that is now used to investigate adaptive closed-loop stimulation in first studies. In dystonia, such a physiomarker is missing. METHODS: Pallidal oscillations were recorded from 153 contact pairs in 27 patients. We investigated whether power amplitudes in theta and beta bands correlate with dystonic symptom severity across patients. We then projected theta power from each contact pair onto standard subcortical anatomy. In this way, we defined a theta hot spot on a group level and investigated whether proximity of the active DBS contacts to it correlated with clinical improvement. RESULTS: Dystonic symptom severity significantly correlated with theta but not beta oscillatory amplitudes (ρ = 0.4, p = 0.009) and interhemispheric coherence (ρ = 0.5, p = 0.002). The sweet spot of theta activity localized to the posterior third of the internal pallidum and theta power correlated with proximity to this location (ρ = 0.23, p = 0.002), which coincided with 3 previously published coordinates describing optimal stimulation targets. Finally, motor improvement through pallidal long-term DBS correlated with theta peak amplitude (ρ = 0.38, p = 0.018). INTERPRETATION: Our findings suggest that theta oscillations in the internal pallidum are robustly associated with dystonic symptoms in cervical dystonia and may be a useful biomarker for adaptive closed-loop stimulation. Furthermore, theta oscillatory activity may have a predictive value for the clinical benefit after chronic DBS that could be used to improve intraoperative neurophysiological target mapping during electrode implantation. Ann Neurol 2017;82:912-924.
OBJECTIVE: Deep brain stimulation (DBS) allows for direct recordings of neuronal activity from the human basal ganglia. In Parkinson's disease, a disease-specific physiomarker was identified that is now used to investigate adaptive closed-loop stimulation in first studies. In dystonia, such a physiomarker is missing. METHODS: Pallidal oscillations were recorded from 153 contact pairs in 27 patients. We investigated whether power amplitudes in theta and beta bands correlate with dystonic symptom severity across patients. We then projected theta power from each contact pair onto standard subcortical anatomy. In this way, we defined a theta hot spot on a group level and investigated whether proximity of the active DBS contacts to it correlated with clinical improvement. RESULTS:Dystonic symptom severity significantly correlated with theta but not beta oscillatory amplitudes (ρ = 0.4, p = 0.009) and interhemispheric coherence (ρ = 0.5, p = 0.002). The sweet spot of theta activity localized to the posterior third of the internal pallidum and theta power correlated with proximity to this location (ρ = 0.23, p = 0.002), which coincided with 3 previously published coordinates describing optimal stimulation targets. Finally, motor improvement through pallidal long-term DBS correlated with theta peak amplitude (ρ = 0.38, p = 0.018). INTERPRETATION: Our findings suggest that theta oscillations in the internal pallidum are robustly associated with dystonic symptoms in cervical dystonia and may be a useful biomarker for adaptive closed-loop stimulation. Furthermore, theta oscillatory activity may have a predictive value for the clinical benefit after chronic DBS that could be used to improve intraoperative neurophysiological target mapping during electrode implantation. Ann Neurol 2017;82:912-924.
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