Modulation of Finely Tuned Gamma in the Globus Pallidus Internus with Deep Brain Stimulation and Levodopa
Zachary LaJoie1, Jackson Cagle2, Jordan Bartfield1, Achyutha Madamangalam2, Dinesh Kumar Vuddandam2, Kara Johnson2, Joshua Wong2, Coralie De Hemptinne2
1College of Medicine, 2Department of Neurology, Fixel Institute for Neurological Diseases, University of Florida
Objective:
To characterize finely tuned gamma (FTG) in the globus pallidus internus (GPi) in patients with Parkinson’s disease (PD) and its response to deep brain stimulation (DBS) and levodopa, in comparison to FTG in the STN.
Background:
DBS is effective for PD and electrophysiology-guided DBS has emerged as a potential strategy that provides responsive neuromodulation for a dynamic disease. Narrowband gamma (between 60-90 Hz) has emerged as a potential biomarker for this approach. However, it has primarily been characterized in the STN as a marker of levodopa therapy and the presence and nature of FTG in the GPi is unknown.
Design/Methods:
We prospectively recruited PD patients with unilateral or bilateral STN or GPi sensing-enabled DBS system (Medtronic Percept). Local field potentials were recorded during monopolar review in the medication OFF and ON state on the same day, incrementing stimulation by 0.5mA. 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. We recorded native narrowband gamma activity (MED ON/DBS OFF) in 3 GPi leads (10% of leads); DBS-entrained FTG (MED OFF/DBS ON) in 13 GPi leads (45%) and 5 STN leads (45%); and medication-and-DBS-entrained FTG (MED ON/DBS ON) 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%).
Conclusions:
FTG activity is present in the GPi in response to both levodopa and DBS, indicating its potential as a biomarker for treatment response and adaptive DBS. Further analysis will explore how FTG amplitude varies with stimulation amplitude and motor exam scores.
10.1212/WNL.0000000000216019
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