Decoding Finely-Tuned Gamma Oscillations in Chronic Deep Brain Stimulation for Parkinson’s Disease

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Abstract

Background

Finely-tuned gamma (FTG) activity—spontaneous narrowband oscillations within the low-gamma range or entrained to half the stimulation frequency—is traditionally associated with ON medication states and dyskinesia in Parkinson’s disease (PD), representing a potential biomarker for adaptive deep brain stimulation (DBS). However, the conditions in which FTG arises and its determinants remain unclear.

Methods

Local field potentials recorded in the subthalamic nucleus (STN) in PD patients with SenSight TM leads and Percept TM neurostimulator were retrospectively analyzed. The analysis was guided by a comprehensive list of clinically relevant questions.

Results

Among 67 patients (134 STN), spontaneous FTG was observed in 11% of STNs, and entrained FTG—including both 1:2 and the novel 1:1 entrainment— in 33%. FTG types never appeared simultaneously and were mostly ON-related but independent of dyskinesia. Beta-activity was inversely related with 1:2 entrainment during stimulation state transitions. Notably, as previously hypothesized, 1:2 entrainment diminished with higher stimulation amplitudes and was inversely related to 1:1 entrainment.

Conclusions

This study provides clinical evidence of 1:1 entrainment. FTG expression – spontaneous, 1:2, or 1:1 entrained – is modulated by DBS and clinical state, but can occur independent of dyskinesia. We confirm that FTG is prokinetic and is inversely related with akinetic beta activity.

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