Objective: To characterize narrow band gamma and finely tuned gamma (FTG) in the globus pallidus internus (GPi) in patients with Parkinson’s disease (PD) and the influence of deep brain stimulation (DBS) and levodopa on these signals, in comparison to FTG in the STN.

Background: DBS can be effective for alleviating PD motor symptoms and electrophysiology-guided DBS has emerged as a potential strategy that provides responsive neuromodulation for this heterogeneous disease. Finely tuned gamma is a narrowband (~1-2 Hz) increase in power in the gamma frequency range (60-90 Hz) that emerges at half the stimulation frequency. It has been shown as a marker of the ON state of levodopa and DBS therapy. However, it has primarily been characterized in the STN and the presence and nature of FTG in the GPi is unknown.

Method: We prospectively recruited PD patients with unilateral or bilateral STN or GPi sensing-enabled DBS systems (Medtronic Percept). Local field potentials were recorded in the medication OFF and ON state on the same day during a monopolar review where the  stimulation amplitude is increased by 0.5mA intervals [figure1]. Presence of FTG was defined as 30sec of narrowband gamma that is 25% greater than the background gamma.

Results: 26 patients (19 GPi, 7 STN) representing 40 DBS leads (29 GPi,11 STN) were included for analysis. The LFPs revealed distinct patterns across different treatment conditions and targets. In the baseline state (Medication ON/DBS OFF), native narrowband gamma activity was observed in 3 GPi leads (10%). Under the DBS-entrained condition (Medication OFF/DBS ON), finely tuned gamma (FTG) oscillations were identified in 13 GPi leads (45%) and 5 STN leads (45%). Finally, the combination of medication and DBS stimulation (Medication ON/DBS ON) yielded FTG in 14 GPi leads (48%) and 8 STN leads (72%). The center frequency of the FTG response was within 2.5 Hz of half of the stimulation frequency in 6 STN leads (75% of observed FTG responses) and 11 GPi leads (65%). A representative FTG response to variation in stimulation amplitude is shown in [figure2].

Conclusion: FTG activity is present in the GPi and can be elicited from both levodopa and DBS, indicating its potential as a biomarker for treatment response and adaptive DBS. Further analysis will explore how stimulation frequency and amplitude influence FTG amplitude and how FTG correlates with motor exam scores.

FTG activity at half of stim frequency in the GPi

FTG occurs in narrow band of stim amplitudes

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MDS Abstracts - https://www.mdsabstracts.org/abstract/modulation-of-finely-tuned-gamma-in-the-globus-pallidus-internus-with-deep-brain-stimulation-and-levodopa/