Bradykinesia and Its Progression Are Related to Interhemispheric Beta Coherence

Abstract

Objective Bradykinesia is the major cardinal motor sign of Parkinson disease (PD), but its neural underpinnings are unclear. The goal of this study was to examine whether changes in bradykinesia following long‐term subthalamic nucleus (STN) deep brain stimulation (DBS) are linked to local STN beta (13–30 Hz) dynamics or a wider bilateral network dysfunction. Methods Twenty‐one individuals with PD implanted with sensing neurostimulators (Activa® PC + S, Medtronic, PLC) in the STN participated in a longitudinal ‘washout’ therapy study every three to 6 months for an average of 3 years. At each visit, participants were withdrawn from medication (12/24/48 hours) and had DBS turned off (>60 minutes) before completing a repetitive wrist‐flexion extension task, a validated quantitative assessment of bradykinesia, while local field potentials were recorded. Local STN beta dynamics were investigated via beta power and burst duration, while interhemispheric beta synchrony was assessed with STN‐STN beta coherence. Results Higher interhemispheric STN beta coherence, but not contralateral beta power or burst duration, was significantly associated with worse bradykinesia. Bradykinesia worsened off therapy over time. Interhemispheric STN‐STN beta coherence also increased over time, whereas beta power and burst duration remained stable. The observed change in bradykinesia was related to the change in interhemispheric beta coherence, with greater increases in synchrony associated with further worsening of bradykinesia. Interpretation Together, these findings implicate interhemispheric beta synchrony as a neural correlate of the progression of bradykinesia following chronic STN DBS. This could imply the existence of a pathological bilateral network contributing to bradykinesia in PD. ANN NEUROL 2023;93:1029–1039

Shared pathway-specific network mechanisms of dopamine and deep brain stimulation for the treatment of Parkinson's disease

“…Accordingly, recorded activity in the STN and other components of the cortex -basal ganglia network may not reflect the typical Parkinsonian state. However, STN-LFP recordings months and years after implantation have repeatedly revealed similar profiles of activity to seen in the immediate post-operative state 46,[80][81][82][83] . Second, only a preliminary clinical review of stimulation parameters could be conducted to determine those used in the ON STN-DBS recordings.…”

Asymmetries of the subthalamic activity in Parkinson’s disease: phase-amplitude coupling among local field potentials

“…For instance, inter-hemispheric coupling in the beta range, but not power spectrum or burst dynamics, seems to correlate with progressive worsening in bradykinesia over time. 29 , 58 …”

“… 28 Recently, one study revealed that the degree of STN–STN synchronization in the beta range (13–30 Hz) is associated with worse bradykinesia but not with tremor or rigidity. 29 …”

Translating Pathological Brain Activity Primers in Parkinson’s Disease Research

“…Aberrant beta band activity is robust over time [ 33 , 34 ]. Recently, there has been an interest into the effect of the state of dopamine and movement on the long-range beta functional connections between the basal ganglia and lower motor neurons, utilizing both STN LFP and electromyogram recordings [ 35 ].…”