Modulation of subthalamic beta oscillations by movement, dopamine, and deep brain stimulation in Parkinson’s disease. 

Mathiopoulou V, Lofredi R, Feldmann LK, Habets J, Darcy N, Neumann WJ, Faust K, Schneider GH, Kühn AA.

NPJ Parkinsons Dis. 2024; 10(1): 77.
doi: 10.1038/s41531-024-00693-3.
Download summary: ReTune PoM 2024 Sep

Parkinson’s disease (PD) is the most common movement disorder with the most pronounced symptoms being bradykinesia and rigidity and is typically treated with dopaminergic medication and Deep Brain Stimulation (DBS) in the subthalamic nucleus (STN). Electrodes from the STN give us the opportunity not only to administer stimulation, but also to record Local Field Potentials (LFP). Subthalamic LFP recordings have revealed that beta band activity (13-35 Hz) is substantially exaggerated in patients with PD. Notably, this reduction correlates with alleviation of parkinsonian motor symptoms. On a similar note, beta band activity significantly decreases during movement. For this reason, subthalamic beta is a robust biomarker for parkinsonian symptoms, and is more recently employed as a feedback signal for closed-loop DBS.
Although beta band activity is a reliable predictor for parkinsonian symptoms, little is known about the different intertwined factors that modulate it. Here we studied the interaction of dopaminergic medication, DBS, and voluntary movement on subthalamic beta in seven PD patients (12 STNs) implanted with DBS 3-12 months after the implantation. Recordings were performed at rest, and during a repetitive finger tapping task in the following four conditions: on/off medication/DBS. A triaxial accelerometer was placed on the index finger of the patients, to quantify movement. LFPs were acquired via the PERCEPT PC IPG with a sampling frequency of 250 Hz.
We found the dopaminergic medication and DBS improved motor performance, as measured with tapping frequency, with a similar effect size, while the combination of both treatments resulted in the optimal motor effect. However, the two treatments suppressed different components of the beta band both during rest, and movement; dopaminergic medication primarily suppressed low beta (13-20 Hz), while DBS was associated with a broader decrease. Movement suppressed beta in all four conditions and this decrease was larger with simultaneous medication and DBS. Last, beta band activity during movement correlated with motor performance within patients across all four states.
The differential modulation of beta band activity by medication and DBS suggest that the different beta components are linked to distinct neurophysiological mechanisms; low beta is mainly linked to the hypodopaminergic status, while high beta might be part of a physiological mechanisms that promotes movement. Nevertheless, the two therapies have a complementary effect with therapeutic benefits. Importantly, we show that subthalamic beta activity during movement significantly correlated with motor performance across all conditions, an important finding for future closed-loop DBS paradigms, which should aim at targeting beta band activity during treatment, as well as during rest and movement.

 

Varvara Mathiopoulou

Varvara Mathiopoulou is a Doctoral Student in the Movement Disorders and Neuromodulation Unit at Charité – Universitätsmedizin Berlin. She has been working on chronic recordings of local field potentials from the STN in PD patients, with a focus on beta and gamma band activity as biomarkers for closed-loop DBS.

Prof. Andrea Kühn

Andrea Kühn is the director of the Movement Disorders and Neuromodulation Unit at Charité Berlin and the ReTune Spokesperson. Her research on basal ganglia electrophysiology has majorly contributed to the understanding of the pathophysiology of movement disorders and the mechanisms of action of DBS.

 

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