Subthalamic beta dynamics mirror Parkinsonian bradykinesia months after neurostimulator implantation

Abstract

BackgroundExaggerated oscillatory activity in the beta frequency band in the subthalamic nucleus has been suggested to be related to bradykinesia in Parkinson’s disease (PD). However, studies seeking correlations between such activity in the local field potential and motor performance have been limited to the immediate postoperative period, which may be confounded by a stun effect that leads to the temporary alleviation of PD deficits.MethodsLocal field potentials were recorded simultaneously with motor performance in PD patients several months after neurostimulator implantation. This was enabled by the chronic implantation of a pulse generator with the capacity to record and transmit local field potentials from deep brain stimulation electrodes. Specifically, we investigated oscillatory beta power dynamics and objective measures of bradykinesia during an upper limb alternating pronation and supination task in 9 patients.ResultsAlthough beta power was suppressed during continuously repeated movements, this suppression progressively diminished over time in tandem with a progressive decrement in the frequency and amplitude of movements. The relationship between changes within local field potentials and movement parameters was significant across patients, and not present for theta/alpha frequencies (5-12 Hz). Change in movement frequency furthermore related to beta power dynamics within patients.ConclusionsChanges in beta power are linked to changes in movement performance and the sequence effect of bradykinesia months after neurostimulator implantation. These findings provide further evidence that beta power may serve as a biomarker for bradykinesia and provide a suitable substrate for feedback control in chronic adaptive deep brain stimulation.

Neuronal Activity and Synaptic Plasticity in a Reimplanted STN-DBS Patient with Parkinson’s Disease: Recordings from Two Surgeries

“…During the first surgery, STN activity during HFS (≥50 Hz) was in accordance with the previously reported group data (robustly suppressed); however, the neurons appeared to be more resistant to suppression at high stimulation frequencies in recordings obtained during the second surgery. Neuronal suppression during stimulation at high frequencies has been attributed to synaptic depression [9,[21][22][23][24]; a transient decrease in synaptic strength that is hypothesized to occur by way of vesicle depletion (caused by delivery of subsequent stimuli before replenishment of neurotransmitter vesicles) and/or decreased presynaptic Ca 2+ conductance [21,25]. Thus, an increased resistance to synaptic depression, perhaps in response to chronic stimulation, may be attributable to increased presynaptic Ca 2+ conductance or changes to intracellular Ca 2+ homeostasis [26] or perhaps to adaptation in the rate at which vesicles are replenished.…”

Neurophysiological correlates of bradykinesia in Parkinson’s disease

“…Although we detected a correlation between the sequence effect and M1 plasticity measures, we acknowledge that alternative mechanisms may also contribute to this abnormality in PD. For example, it has been suggested that altered activity in pre-motor areas, basal ganglia or cerebellum may be responsible for the sequence effect in PD (Kang et al, 2010;Little et al, 2012;Tan et al, 2013aTan et al, , 2013bTan et al, and 2015Lee et al, 2014;Steiner et al, 2017)…”

Connectivity and dynamics underlying synaptic control of the Subthalamic Nucleus

“…Under physiological conditions, neurons in the basal ganglia engage in brief transient synchronization at beta frequencies, and the dynamics of synchronization are instrumental to basal ganglia function (Feingold et al, 2015;Mirzaei et al, 2017;Tinkhauser et al, 2017a). Conversely, beta activity recorded in the STN is exaggerated in PD (Neumann et al, 2016;Steiner et al, 2017;Tinkhauser et al, 2017a), and clinically effective DBS reduces synchrony in this nucleus (Kühn et al, 2008). Nevertheless, little is known of the anatomical substrate underlying synchronization in the STN.…”