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Reduction of spontaneous cortical beta bursts in Parkinson's disease is linked to symptom severity.

ABSTRACT: Parkinson's disease is characterized by a gradual loss of dopaminergic neurons, which is associated with altered neuronal activity in the beta-band (13-30?Hz). Assessing beta-band activity typically involves transforming the time-series to get the power of the signal in the frequency domain. Such transformation assumes that the time-series can be reduced to a combination of steady-state sine- and cosine waves. However, recent studies have suggested that this approach masks relevant biophysical features in the beta-band-for example, that the beta-band exhibits transient bursts of high-amplitude activity. In an exploratory study, we used magnetoencephalography to record beta-band activity from the sensorimotor cortex, to characterize how spontaneous cortical beta bursts manifest in Parkinson's patients on and off dopaminergic medication, and compare this to matched healthy controls. We extracted the time-course of beta-band activity from the sensorimotor cortex and characterized bursts in the signal. We then compared the burst rate, duration, inter-burst interval and peak amplitude between the Parkinson's patients and healthy controls. Our results show that Parkinson's patients off medication had a 5-17% lower beta bursts rate compared to healthy controls, while both the duration and the amplitude of the bursts were the same for healthy controls and medicated state of the Parkinson's patients. These data thus support the view that beta bursts are fundamental underlying features of beta-band activity, and show that changes in cortical beta-band power in Parkinson's disease can be explained-primarily by changes in the underlying burst rate. Importantly, our results also revealed a relationship between beta burst rate and motor symptom severity in Parkinson's disease: a lower burst rate scaled with increased severity of bradykinesia and postural/kinetic tremor. Beta burst rate might thus serve as a neuromarker for Parkinson's disease that can help in the assessment of symptom severity in Parkinson's disease or in the evaluation of treatment effectiveness.

SUBMITTER: Vinding MC

PROVIDER: S-EPMC7425382 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Reduction of spontaneous cortical beta bursts in Parkinson's disease is linked to symptom severity.

Vinding Mikkel C MC Tsitsi Panagiota P Waldthaler Josefine J Oostenveld Robert R Ingvar Martin M Svenningsson Per P Lundqvist Daniel D

Brain communications 20200428 1

Parkinson's disease is characterized by a gradual loss of dopaminergic neurons, which is associated with altered neuronal activity in the beta-band (13-30 Hz). Assessing beta-band activity typically involves transforming the time-series to get the power of the signal in the frequency domain. Such transformation assumes that the time-series can be reduced to a combination of steady-state sine- and cosine waves. However, recent studies have suggested that this approach masks relevant biophysical f ...[more]

PMID: 32954303

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Project description:Freezing of gait (FOG) is a devastating axial motor symptom in Parkinson's disease (PD) leading to falls, institutionalization, and even death. The response of FOG to dopaminergic medication and deep brain stimulation (DBS) is complex, variable, and yet to be optimized. Fundamental gaps in the knowledge of the underlying neurobiomechanical mechanisms of FOG render this symptom one of the unsolved challenges in the treatment of PD. Subcortical neural mechanisms of gait impairment and FOG in PD are largely unknown due to the challenge of accessing deep brain circuitry and measuring neural signals in real time in freely-moving subjects. Additionally, there is a lack of gait tasks that reliably elicit FOG. Since FOG is episodic, we hypothesized that dynamic features of subthalamic (STN) beta oscillations, or beta bursts, may contribute to the Freezer phenotype in PD during gait tasks that elicit FOG. We also investigated whether STN DBS at 60 Hz or 140 Hz affected beta burst dynamics and gait impairment differently in Freezers and Non-Freezers. Synchronized STN local field potentials, from an implanted, sensing neurostimulator (Activa® PC + S, Medtronic, Inc.), and gait kinematics were recorded in 12 PD subjects, off-medication during forward walking and stepping-in-place tasks under the following randomly presented conditions: NO, 60 Hz, and 140 Hz DBS. Prolonged movement band beta burst durations differentiated Freezers from Non-Freezers, were a pathological neural feature of FOG and were shortened during DBS which improved gait. Normal gait parameters, accompanied by shorter bursts in Non-Freezers, were unchanged during DBS. The difference between the mean burst duration between hemispheres (STNs) of all individuals strongly correlated with the difference in stride time between their legs but there was no correlation between mean burst duration of each STN and stride time of the contralateral leg, suggesting an interaction between hemispheres influences gait. These results suggest that prolonged STN beta burst durations measured during gait is an important biomarker for FOG and that STN DBS modulated long not short burst durations, thereby acting to restore physiological sensorimotor information processing, while improving gait.

Project description:Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could be more efficacious than conventional continuous deep brain stimulation in the treatment of Parkinson's disease, and helps inform how adaptive deep brain stimulation might best be delivered.

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Dataset Information

Reduction of spontaneous cortical beta bursts in Parkinson's disease is linked to symptom severity.

Publications

Reduction of spontaneous cortical beta bursts in Parkinson's disease is linked to symptom severity.

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