Oscillatory beta dynamics inform biomarker-driven treatment optimization for Parkinson’s disease

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons and dysregulation of the basal ganglia. Cardinal motor symptoms include bradykinesia, rigidity, and tremor. Deep brain stimulation (DBS) of select subcortical nuclei is standard-of-care for medication-refractory PD. Conventional open-loop DBS delivers continuous stimulation with fixed parameters that do not account for a patient's dynamic activity state or medication cycle. In comparison, closed-loop, or adaptive DBS (aDBS) adjusts stimulation based on biomarker feedback that correlates with clinical state. Recent work has identified several neurophysiological biomarkers in local field potential recordings from PD patients, the most promising of which are: 1) elevated beta (~13-30 Hz) power in the subthalamic nucleus (STN), 2) increased beta synchrony throughout basal ganglia-thalamocortical circuits, notably, observed as coupling between the STN beta phase and cortical broadband gamma (~50-200 Hz) amplitude, and 3) prolonged beta bursts in the STN and cortex. In this review, we highlight relevant frequency and time domain features of STN beta measured in PD patients and summarize how spectral beta power, oscillatory beta synchrony, phase-amplitude coupling, and temporal beta bursting informs PD pathology, neurosurgical targeting, and DBS therapy. We then review how STN beta dynamics inform predictive, biomarker-driven aDBS approaches for optimizing PD treatment. We therefore provide clinically useful and actionable insight that can be applied towards aDBS implementation for PD.

Perspectives of Implementation of Closed-Loop Deep Brain Stimulation: From Neurological to Psychiatric Disorders

“…As mentioned earlier, targeting oscillatory responses in movement disorders, namely PD, is already making strides for CL-DBS [16,72], but similar oscillatory features are proving useful for other diseases, such as Tourette syndrome [73,74], and both neurologic and neuropsychiatric diseases often show increased oscillatory hypersynchrony [75][76][77]. Further, in psychiatric diseases different networks may need to be targeted for optimal clinical outcome [78].…”

“…In PD, the possibilities of CL-DBS for the management of clinical symptoms, mostly based on LFP measurements, have already been shown and recently reviewed [16]. These studies have evidenced that delivering highfrequency stimulation only when increased beta-band power is detected at a patient-specific threshold improved PD motor symptoms with higher clinical efficacy than continuous DBS [17][18][19][20].…”