Objective: To investigate the clinical relevance of entraining finely tuned gamma (FTG) oscillations via deep brain stimulation (DBS) in Parkinson’s disease (PD).

Background: Prior studies relate levodopa and DBS-induced FTG activity to a prokinetic state and implicate levodopa-induced FTG in the generation of dyskinesia [1]. Having previously shown that FTG entrainment by unilateral DBS at a subharmonic of the stimulation frequency occurs at select frequency-amplitude combinations and varies with medication and movement states, we postulate that DBS-induced FTG activity may have a modulatory effect on motor outcomes in PD.

Method: We collected multisite field potential recordings from basal ganglia and sensorimotor cortex in five hemispheres of four PD patients. Patients underwent bilateral implantation of quadripolar DBS leads into the subthalamic nucleus (STN) and quadripolar electrocorticography paddles over sensorimotor cortex, which were connected to a sensing-enabled investigational neurostimulator. We quantified entrained FTG amplitude in the pre- and postcentral gyri across a range of stimulation amplitude-frequency pairs using the FOOOF algorithm [2] during rest and movement, rated bradykinesia at each setting using the ReTap accelerometry-based assessment tool [3], and modeled the relationship between cortical FTG entrainment power and ReTap scores. In one hemisphere, we quantified FTG amplitude induced by stimulation at each electrode contact.

Results: Cortical FTG entrainment was present in all hemispheres, but the exact entrainment-inducing set of stimulation settings was specific to each hemisphere. Entrainment power was higher during movement than rest in all patients. Additionally, we show that the exact STN electrode contact where DBS is applied influences the power of entrained oscillations and dictates the set of entrainment-inducing frequency-amplitude pairs. In general, wearable-derived bradykinesia scores were improved in trials where FTG was detected than in those with no entrainment; mobility scores were worse in trials with entrainment in the beta frequency range.

Conclusion: Presence of cortical FTG entrainment by DBS was found to predict better mobility, which, in conjunction with its stimulation parameter and hemisphere specificity, may be a mechanism of individual stimulation treatment response.

References: [1] Olaru et al., Brain, 2024
[2] Donoghue et al., Nat. Neurosci., 2020
[3] Habets et al., Sensors, 2023

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-applications-of-cortical-finely-tuned-gamma-oscillations-induced-via-subthalamic-deep-brain-stimulation-in-parkinsons-disease/