Parkinsonian Beta Dynamics during Rest and Movement in the Dorsal Pallidum and Subthalamic Nucleus

Abstract

In Parkinson's disease (PD), pathologically high levels of beta activity (12-30 Hz) reflect specific symptomatology and normalize with pharmacological or surgical intervention. Although beta characterization in the subthalamic nucleus (STN) of PD patients undergoing deep brain stimulation (DBS) has now been translated into adaptive DBS paradigms, a limited number of studies have characterized beta power in the globus pallidus internus (GPi), an equally effective DBS target. Our objective was to compare beta power in the STN and GPi during rest and movement in people with PD undergoing DBS. Thirty-seven human female and male participants completed a simple behavioral experiment consisting of periods of rest and button presses, leading to local field potential recordings from 19 (15 participants) STN and 26 (22 participants) GPi nuclei. We examined overall beta power as well as beta time-domain dynamics (i.e., beta bursts). We found higher beta power during rest and movement in the GPi, which also had more beta desynchronization during movement. Beta power was positively associated with bradykinesia and rigidity severity; however, these clinical associations were present only in the GPi cohort. With regards to beta dynamics, bursts were similar in duration and frequency in the GPi and STN, but GPi bursts were stronger and correlated to bradykinesia-rigidity severity. Beta dynamics therefore differ across basal ganglia nuclei. Relative to the STN, beta power in the GPi may be readily detected, modulates more with movement, and relates more to clinical impairment. Together, this could point to the GPi as a potentially effective target for beta-based adaptive DBS.

Perturbation ofin vivoneural activity following α-Synuclein seeding in the olfactory bulb

“…We propose that the changes we uncovered in beta activity are particularly relevant to PD pathophysiology. Striatal and cortical beta band activity is elevated in persons with PD and deep brain stimulation, levodopa, and anti-cholinergic treatment may act by means of suppressing elevated beta power in the cortico-basal ganglia loop (Brown, 2006;Brown et al, 2001;Eisinger et al, 2020;Giannicola et al, 2010;Little and Brown, 2014;McCarthy et al, 2011). Additionally, deep brain stimulation of the subthalamic nucleus was shown in one study to improve cortical function in PD and reduce the excessive beta phase coupling of motor cortex neurons (De Hemptinne et al, 2015).…”

Revisiting the “Paradox of Stereotaxic Surgery”: Insights Into Basal Ganglia-Thalamic Interactions

“…Collectively, these data suggest that beta oscillations normally stabilize the current behavioral state (Engel and Fries, 2010;Shin et al, 2017). In PD, beta bursts are prolonged, increasing beta amplitude in power spectra averaged over long timescales (Tinkhauser et al, 2017(Tinkhauser et al, , 2018Deffains et al, 2018;Pina-Fuentes et al, 2019;Eisinger et al, 2020;Yu et al, 2021). Dopamine loss may prolong "normal" beta events, preventing transitions to new behaviors.…”

Globus Pallidus Internus (GPi) Deep Brain Stimulation for Parkinson’s Disease: Expert Review and Commentary

“…Much work has since been done, ultimately demonstrating that an aberrant network oscillatory activity is related to the pathophysiology of PD [34]. Exaggerated pallidal oscillations in the beta range (12-30 Hz) have been associated with bradykinesia severity and have been observed to attenuate with levodopa administration and with therapeutic DBS [35][36][37][38][39]. Beta power in the GPi in PD has also been shown to decrease with increased volitional movement, a phenomenon not exclusive to PD patients [38][39][40][41][42][43].…”

“…Exaggerated pallidal oscillations in the beta range (12-30 Hz) have been associated with bradykinesia severity and have been observed to attenuate with levodopa administration and with therapeutic DBS [35][36][37][38][39]. Beta power in the GPi in PD has also been shown to decrease with increased volitional movement, a phenomenon not exclusive to PD patients [38][39][40][41][42][43]. The results of subsequent DBS studies have suggested that neuromodulation may affect the oscillatory activity at a network circuitry level rather than by simply increasing or decreasing the firing rate of a single basal ganglia structure [34].…”

“…In the first study of its kind in the GPi region, adaptive DBS was well-tolerated when applied to a single PD patient; however, long-term efficacy data was not assessed [37]. In a recent study, Eisinger et al [34] demonstrated that a greater beta power was present in PD GPi as compared to PD STN, suggesting GPi to be a candidate for closed-loop DBS systems of the future [39]. Although preliminary work for the safety, feasibility and effectiveness of closedloop systems in PD has been mostly restricted to targeting the STN [37,[117][118][119][120][121][122][123][124], more studies in the future will likely explore the GPi, especially given the robustness of the physiological signal [37].…”