A localized pallidal physiomarker in cervical dystonia

Abstract

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.

Cognitive control involves theta power within trials and beta power across trials in the prefrontal-subthalamic network

“…However, more recent evidence has suggested that indeed most STN neurons increase, rather than decrease, spiking activity during movement (Nambu et al, 2002; Goldberg et al, 2013; Zavala et al, 2017a). Furthermore, increased STN theta activity has been implicated in pathologies that involve excess movement such as dystonia, dyskinesia, impulsivity, and OCD (Alonso-Frech et al, 2006; Rodriguez-Oroz et al, 2011; Neumann et al, 2012, 2017; Rappel et al, 2018). …”

Pallidal low‐frequency activity in dystonia after cessation of long‐term deep brain stimulation

“…Overall, 3 to 12 Hz peaks occurred in 168 of 240 analyzed individual recordings. Beta peaks (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) Hz) could be detected in every patient, but not at all timepoints (range 2-16 of 30 recordings per patient), adding up to a total of 94 of 240 analyzed recordings, with overall lower amplitude. No other distinct peaks were revealed in higher frequency bands.…”

“…This correlation was frequency specific to low frequency, but not beta band, and replicates previous work reporting an association between pallidal low-frequency power and motor sign severity in patients with cervical dystonia. 15 In Parkinson's disease, beta activity in the basal ganglia has been shown to: 1) be reduced by dopaminergic medication and DBS, 2) correlate with motor sign severity and 3) be preserved after long-term stimulation. 20,27 Because of this modulation and stability over time, recent studies used beta activity as a feedback signal for demand-dependent, adaptive closed-loop stimulation and have already achieved promising preliminary results.…”

“…20,27 Because of this modulation and stability over time, recent studies used beta activity as a feedback signal for demand-dependent, adaptive closed-loop stimulation and have already achieved promising preliminary results. 28 Similarly, it has been suggested that pallidal low-frequency activity may contribute to motor circuit dysfunction, resulting in involuntary motor output in dystonia patients and thus may be utilized as a biomarker signal for feedback-based adaptive DBS paradigms, 15 as recently described in a pilot case by Piña-Fuentes and colleagues. 19 Our work provides further evidence in favor of this approach.…”

“…8,[11][12][13] We have recently shown that pallidal low-frequency activity, but not beta band activity, (that is also present in dystonia 14 ) correlates with the severity of dystonic motor signs, and patients with electrode position close to the maximum low-frequency local field potential (LFP) peak within the pallidum had the best motor outcome with chronic stimulation. 15 Moreover, DBS could suppress low-frequency activity in the short term in patients with predominant phasic, but not tonic, dystonic movements. 16 However, in dystonia the main clinical effect manifests during a much longer time scale of several weeks or months of continuous stimulation, which has been related to plastic changes and cortico-subcortical reorganization induced by DBS.…”