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

BackgroundFinely-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 Parkinsons disease (PD), representing a potential biomarker for adaptive deep brain stimulation (DBS). However, the conditions in which FTG arises and its determinants remain unclear. MethodsLocal field potentials recorded in the subthalamic nucleus (STN) in PD patients with SenSightTM leads and PerceptTM neurostimulator were retrospectively analyzed. The analysis was guided by a comprehensive list of clinically relevant questions. ResultsAmong 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. ConclusionsThis 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.