Abstract
Exaggerated basal ganglia beta activity (13–35 Hz) is commonly found in patients with Parkinson’s disease and can be suppressed by dopaminergic medication, with the degree of suppression being correlated with the improvement in motor symptoms. Importantly, beta activity is not continuously elevated, but fluctuates to give beta bursts. The percentage number of longer beta bursts in a given interval is positively correlated with clinical impairment in Parkinson’s disease patients. Here we determine whether the characteristics of beta bursts are dependent on dopaminergic state. Local field potentials were recorded from the subthalamic nucleus of eight Parkinson’s disease patients during temporary lead externalization during surgery for deep brain stimulation. The recordings took place with the patient quietly seated following overnight withdrawal of levodopa and after administration of levodopa. Beta bursts were defined by applying a common amplitude threshold and burst characteristics were compared between the two drug conditions. The amplitude of beta bursts, indicative of the degree of local neural synchronization, progressively increased with burst duration. Treatment with levodopa limited this evolution leading to a relative increase of shorter, lower amplitude bursts. Synchronization, however, was not limited to local neural populations during bursts, but also, when such bursts were cotemporaneous across the hemispheres, was evidenced by bilateral phase synchronization. The probability of beta bursts and the proportion of cotemporaneous bursts were reduced by levodopa. The percentage number of longer beta bursts in a given interval was positively related to motor impairment, while the opposite was true for the percentage number of short duration beta bursts. Importantly, the decrease in burst duration was also correlated with the motor improvement. In conclusion, we demonstrate that long duration beta bursts are associated with an increase in local and interhemispheric synchronization. This may compromise information coding capacity and thereby motor processing. Dopaminergic activity limits this uncontrolled beta synchronization by terminating long duration beta bursts, with positive consequences on network state and motor symptoms.
Highlights
Basal ganglia beta activity (13–35 Hz) is well known to be exaggerated in patients with Parkinson’s disease, and the amplitude of such activity has been linked to motor impairment (Brown, 2003) and dopaminergic tone (Jenkinson and Brown, 2011)
We test the hypotheses that pathological beta activity consists of prolonged bursts in Parkinson’s disease, that these bursts are associated with excessive synchronization within and between basal ganglia circuits and that such bursts are abbreviated and made less frequent by treatment with the dopaminergic prodrug, levodopa, thereby contributing to improved motor function
In line with the presence of more distributed synchronization, we found that beta bursts are much more likely to occur simultaneously and to be phase coupled across hemispheres than by chance in Parkinson’s disease patients
Summary
Basal ganglia beta activity (13–35 Hz) is well known to be exaggerated in patients with Parkinson’s disease, and the amplitude of such activity has been linked to motor impairment (Brown, 2003) and dopaminergic tone (Jenkinson and Brown, 2011). Albeit acute, studies have suggested that this adaptive approach can be at least as effective as conventional, continuous DBS, while using less battery power and incurring fewer stimulation-induced side effects, such as speech impairment and dyskinesias (Little et al, 2013a, 2016a, b; Rosa et al, 2015, 2017; Pina-Fuentes et al, 2017). Evidence is beginning to accrue that physiological beta activity consists of short-lived phasic bursts in basal ganglia-cortical motor circuits (Murthy and Fetz, 1992, 1996; Feingold et al, 2015) and studies in Parkinson’s disease patients undergoing DBS suggest that pathological beta activity may tend to consist of longer duration, phasic bursts (Tinkhauser et al, 2017). We test the hypotheses that pathological beta activity consists of prolonged bursts in Parkinson’s disease, that these bursts are associated with excessive synchronization within and between basal ganglia circuits and that such bursts are abbreviated and made less frequent by treatment with the dopaminergic prodrug, levodopa, thereby contributing to improved motor function
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