A localized pallidal physiomarker in cervical dystonia

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Deep brain stimulation (DBS) of the internal pallidum has been established as a highly effective treatment for severe idiopathic dystonia in patients that are refractory to medical therapy.1 Although the clinical benefit of DBS in cervical and other focal types of dystonia is well documented,3 the underlying therapeutic mechanism remains to be elucidated. Converging evidence points to a modulation of aberrant neural population activity in the basal ganglia through high‐frequency stimulation.4 However, the basal ganglia have been difficult to characterize electrophysiologically, because of their anatomical distance from the scalp and their complex interwoven functional pathways. In recent years, DBS has offered the unique opportunity to record oscillatory activity directly from the basal ganglia during surgery and in a postoperative interval in which the DBS electrodes are externalized. Here, oscillatory patterns of pallidal local field potentials (LFPs) were found to differ in a disease‐specific manner.5 This has inspired the concept of pathological oscillations in movement disorders, which is now best established in the form of increased beta‐synchronization (13–35Hz) in Parkinson disease (PD).6 A multitude of studies that explored beta activity in PD have fostered its current application/impact as a biomarker in PD that mirrors motor symptom severity and can be used for target localization8 and adaptive DBS.9 A recent study used beta power recorded from a large cohort to map out the subthalamic nucleus functionally, demonstrating higher activity in active versus inactive DBS contacts and in the sensorimotor part versus associative part of the nucleus.10 This mounting evidence demonstrates great clinical significance in using pathological oscillations to guide DBS surgery and programming, as well as adaptive closed‐loop applications.
In dystonia, such a physiomarker is missing. Low‐frequency activity in the theta–alpha range has been reported in the internal pallidum5 and was also shown in the subthalamic nucleus.11 Both beta band oscillations in PD14 and theta activity in dystonia patients with phasic movements are suppressed by high‐frequency DBS.16 However, no quantitative relationship between symptom severity and theta activity in dystonia could be shown to date. The aim of this study was to investigate the association of theta oscillations with clinical symptom severity recorded from dystonic patients, while taking electrode location into account. Specifically, recording sites across patients were mapped into standard stereotactic space to reveal relationships between recording sites, theta power, symptom severity, and DBS‐related long‐term clinical outcome in a large cohort of patients with idiopathic cervical dystonia. Here, we investigate 3 main questions. First, is theta activity correlated to symptom severity? Second, is theta activity spatially organized within the nucleus, that is, is it possible to define a hot spot of activity in the theta band? Finally, we ask whether proximity of the active DBS contact to such a hot spot is predictive of clinical improvement across patients and whether theta activity correlates to DBS‐mediated improvements.
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