Probing the mechanistic role of beta oscillations in cognition by means of deep brain stimulation
Final Report Abstract
The basal ganglia are one of the most fascinating structures in the brain. Yet, despite decades of intensive research, their function remains a matter of debate. It is undoubted, however, that understanding the basal ganglia is only possible when considering them part of an extensive network. This network is organized in segregated, parallel loops connecting specialized areas in cortex, basal ganglia, and thalamus. Although we still do not know how exactly information is processed in these loops, knowledge about their neurophysiology is growing rapidly. One of the key concepts that have emerged in the recent past is that temporal activity patterns have an important role to play. Accordingly, neuronal oscillations synchronized within and between large neuronal ensembles have been a focus of intensive research. In the context of Parkinson’s disease (PD), research has focused on neural synchronization in the beta frequency range (12-30Hz). Beta oscillations correlate with the severity of Parkinsonian motor symptoms and are reduced by standard therapies, such as dopaminergic medication and deep brain stimulation (DBS). The current research project investigated whether beta oscillations might cause motor symptoms, rather than being a mere correlate. To this end, we performed two studies in PD patients implanted with a DBS device. DBS is usually applied at high frequencies for motor symptom reduction (>100Hz). Here, we reduced the stimulation frequency to about 20Hz to see whether beta-band stimulation would slow down movement. Meanwhile, we measured brain activity by means of magnetoencephalography (MEG). Study 1 assessed the effect of beta-band DBS on resting-state brain activity and finger tapping speed in 14 PD patients. We found that beta-band DBS increased the strength of motor cortical beta oscillations in the 8-26Hz range and slowed down finger tapping. Both effects were correlated, i.e. the stronger the boost of cortical beta oscillations, the stronger the slowing of movement. In contrast to the original hypothesis, beta-band DBS did not force cortical oscillations towards the stimulation frequency (no entrainment). The findings of study 1 are in line with a causal role of beta oscillations in controlling movement speed. They have been published in the Journal of Neuroscience recently. Study 2 is ongoing and investigates the effect of beta-band DBS on response inhibition, a motor-cognitive behavior that is believed to rely on beta-band synchrony in basal ganglia-cortex loops. Patients performed a Go-NoGo task, meaning that they had to react quickly to Go stimulus while withholding their response upon presentation of a NoGo stimulus. The likelihood of the upcoming stimulus being Go or NoGo was indicated by a cue. With this study, we hope to clarify the effect of beta-band DBS on response inhibition and the associated brain activity patterns. So far, we have measured 15 patients (target sample size: 20).
Publications
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Poster at Movement Disorders 2023 by Lucy M. Werner: “Subthalamic nucleus deep brain stimulation in the beta range modulates cortical beta oscillations in Parkinson’s disease patients”
Lucy M. Werner
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Poster at the annual meeting of the Society for Neuroscience 2023 by Lucy M. Werner: “The impact of subthalamic nucleus deep brain stimulation in the beta range on cortical beta oscillations in Parkinson's disease patients”
Lucy M. Werner
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Talk at MEG-UKI 2024 by Lucy M. Werner: “The impact of subthalamic nucleus deep brain stimulation in the beta range on cortical beta oscillations and motor performance”
Lucy M. Werner
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Subthalamic Nucleus Deep Brain Stimulation in the Beta Frequency Range Boosts Cortical Beta Oscillations and Slows Down Movement. The Journal of Neuroscience, 45(9), e1366242024.
Werner, Lucy M.; Schnitzler, Alfons & Hirschmann, Jan
