Brain Stimulation (DBS) is an invasive treatment to restore function to Parkinson’s Disease (PD) patients in the advanced stages of their condition. Despite the clinical improvement of DBS, its physiological basis is not fully understood. DBS provides a unique window into the human brain as, under certain conditions, one can record from the electrodes implanted in target brain nuclei, most commonly, the subthalamic nucleus (STN) in the basal ganglia (BG). Local field potentials (LFP) in the STN revealed synchronized neural oscillations in different frequency bands, mostly the beta-band. Beta-oscillations are modulated by dopaminergic drugs and DBS, and considered to play a role in generating bradykinesia. Nonetheless, the exact mechanism behind this is unclear. While previous models have mainly focused on the cortico-BG-thalamo-cortical circuitry, there is contradictory evidence as to whether beta-oscillations in the cortex are modulated by the BG. An insufficiently explored aspect is the connection of BG to several key structures in the brainstem, such as the pedunculopontine nucleus (PPN) that modulate locomotion, and are damaged in PD. However, investigating the oscillatory dynamics of the brainstem is challenging, due to technical limitations in recording human electrophysiology from subcortical structures in vivo. In this project, I will combine cutting-edge neuroimaging techniques with the latest advances in DBS technology to test the hypothesis that pathological beta oscillations of the BG are propagated to the brainstem. A clarification of the role of the brainstem in PD will lead to a better understanding of how pathological beta-oscillations are linked to the condition. Consequently, surgical targeting and stimulation programming can be optimised by focusing on the most relevant fibre tracts and new targets for DBS can be identified.

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