The Cumulative Effect of Transient Synchrony States on Motor Performance in Parkinson's Disease

Abstract

Bursts of beta frequency band activity in the basal ganglia of patients with Parkinson's disease (PD) are associated with impaired motor performance. Here we test in human adults whether small variations in the timing of movement relative to beta bursts have a critical effect on movement velocity and whether the cumulative effects of multiple beta bursts, both locally and across networks, matter. We recorded local field potentials from the subthalamic nucleus (STN) in 15 PD patients of both genders OFF-medication, during temporary lead externalization after deep brain stimulation surgery. Beta bursts were defined as periods exceeding the 75th percentile amplitude threshold. Subjects performed a visual cued joystick reaching task, with the visual cue being triggered in real time with different temporal relationships to bursts of STN beta activity. The velocity of actions made in response to cues prospectively triggered by STN beta bursts was slower than when responses were not time-locked to recent beta bursts. Importantly, slow movements were those that followed multiple bursts close to each other within a trial. In contrast, small differences in the delay between the last burst and movement onset had no significant impact on velocity. Moreover, when the overlap of bursts between the two STN was high, slowing was more pronounced. Our findings suggest that the cumulative, but recent, history of beta bursting, both locally and across basal ganglia networks, may impact on motor performance.

Neurofeedback-Linked Suppression of Cortical β Bursts Speeds Up Movement Initiation in Healthy Motor Control: A Double-Blind Sham-Controlled Study

“…Such movement-related beta power reduction has been suggested to reflect changes in the probability of beta bursts rather than a smooth modulation of sustained beta activity (Feingold et al, 2015), and more recently, it has been emphasized that the beta bursts in the cortical-basal ganglia motor network predict sensorimotor behavior (Feingold et al, 2015;Sherman et al, 2016;Shin et al, 2017;Torrecillos et al, 2018;Little et al, 2019;Wessel 2019) and correlate with motor impairment in patients with Parkinson's disease (Tinkhauser et al, 2017a, b). Indeed, beta bursts in the subthalamic nucleus, a key relay in basal ganglia-cortical circuits, are more predictive of motor impairment than average beta power in patients with Parkinson's disease (Torrecillos et al, 2018;Tinkhauser et al, 2020), and similar observations have been made regarding cortical beta bursts and trialaveraged beta power. Little et al (2019) showed that the timing of beta bursts was a stronger predictor of single trial behaviour than single trial-averaged beta amplitude.…”

Local field potential activity dynamics in response to deep brain stimulation of the subthalamic nucleus in Parkinson's disease

“…Specifically, the rapid response of beta activity to the onset and offset of stimulation means that it can be used to target beta bursts in the STN ( Little et al, 2013 , Little et al, 2016b , Little et al, 2016a ; Tinkhauser et al, 2017a ; Velisar et al, 2019 ). These are increasingly reported to play a key role in the mechanism of bradykinesia and rigidity in PD ( Deffains et al, 2018 ; Tinkhauser et al, 2020 , Tinkhauser et al, 2017a , Tinkhauser et al, 2017b ; Torrecillos et al, 2018 ). The ERNA does not provide direct feedback relevant to beta bursts and undergoes relatively slow changes with respect to the duration of stimulation.…”

Simulation of Closed-Loop Deep Brain Stimulation Control Schemes for Suppression of Pathological Beta Oscillations in Parkinson’s Disease

“…The probability of pathological burst occurrence in the model was a simplified representation of beta burst activity observed in PD. Research has observed that the probability of pathological burst occurrence is modulated in PD patients by factors such as medication and motor tasks (Tinkhauser et al, 2017a(Tinkhauser et al, , 2020. Although not considered in this study, future studies may incorporate modulation of the burst probabilities to emulate variations in burst probabilities induced by these factors.…”