Objective: To characterize the role of oscillatory neural changes and inter-regional synchronization in the pathophysiology of Parkinson’s disease (PD), and in response to pharmacological- and neurostimulation-based therapies.

Background: Increasing attention has been geared towards optimizing DBS paradigms for treatment of PD such as coordinated reset-DBS, which is hypothesized to have long-lasting therapeutic benefits derived from targeted disruption of abnormal neuronal synchrony. Here, we used local field potentials (LFP) to characterize changes in local and inter-regional neural activity between sensorimotor cortex and the subthalamic nucleus (STN) across the naïve and parkinsonian-state and in response to dopamine replacement therapy (DRT) and DBS-based therapy.

Method: A rhesus macaque was instrumented with a scaled, six-contact, directional STN DBS lead as well as bilateral, twelve-channel subdural, ECoG paddle electrodes spanning anterior parietal to prefrontal cortical regions. LFPs were recorded in multiple states (naïve, parkinsonian, and following DRT, traditional tr-DBS, or cr-DBS). We analyzed the oscillations recorded with LFP in a cued touchscreen task. Data were re-referenced using bipolar montage and segmented to obtain trials relevant to motor planning and execution. LFPs were bandpass filtered into the low frequency bands, and the power spectral densities (PSD) were calculated. Moreover, magnitude squared coherence was used to establish the inter-cortical connectivity in the different states.

Results: Analyses of LFPs revealed that 1) after induction of parkinsonism using MPTP, beta band power increased in the motor and STN brain areas; there was also an increase in inter-cortical coherence in the theta (4-9 Hz) and beta bands (13-20 Hz) in parkinsonism; and 2) during tr-DBS therapy there was acute drop in PSD power and inter-cortical coherence but this increased when stimulation was turned off. Notably, the drop in PSD power and inter-cortical coherence following cr-DBS was sustained even after stimulation was turned off, consistent with the behavioral carry-over effects observed in response to cr-DBS therapy.

Conclusion: These results support the hypothesis that changes in frequency oscillatory activity and coherence are biomakers of parkinsonian pathophysiology and reveal that cr-DBS is a potential optimal therapy with long-lasting effects for PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/unraveling-neural-oscillatory-changes-due-to-stn-coordinated-reset-deep-brain-stimulation-in-the-mptp-non-human-primate-model-of-parkinsonism/