Finely Tuned γ Tracks Medication Cycles in Parkinson's Disease: An Ambulatory Brain‐Sense Study
Aaron Colombo, Elena Bernasconi, Laura Alva, Mário Sousa, Ines Debove, Andreas Nowacki, Camille Serquet, Katrin Petermann, T. A. Khoa Nguyen, Andreia D. Magalhães, M. Lenard Lachenmayer, Julia Waskönig, Tobias Nef, Michael Schuepbach, Claudio Pollo, Paul Krack, Alberto Averna, Gerd Tinkhauser
Abstract
BACKGROUND: Novel commercial brain-sense neurostimulators enable us to contextualize brain activity with symptom and medication states in real-life ambulatory settings in Parkinson's disease (PD). Although various candidate biomarkers have been proposed for adaptive deep brain stimulation (DBS), a comprehensive comparison of their ambulatory profiles is lacking. OBJECTIVES: To systematically compare the ambulatory neurophysiological dynamics and clinical properties of three candidate biomarkers-low-frequency, beta (β), and finely tuned γ (FTG) activity. METHODS: We investigated 14 PD patients implanted with the Medtronic Percept PC, who underwent up to two 4-week ambulatory multimodal recording periods on their regular medication and stimulation. Subthalamic nucleus local field potentials (LFPs) of low-frequency, β, and FTG activity were recorded. Additionally, objective motor symptom states, physical activity and heart rate using wearables, as well as medication-intake times, sleep-awake times, and subjective symptom states using diaries were co-registered. LFP dynamics were also compared to high-resolution in-hospital recordings under off/on dopaminergic medication and stimulation conditions. RESULTS: FTG reliably indexed off to on medication states in the ambulatory setting at the group and individual levels, and these spectral dynamics could be anticipated by high-resolution in-hospital recordings. Both FTG and low-frequency correlated with wearable-based dyskinesia scores, whereas diary-based dyskinesia events were only linked to FTG. Importantly, FTG indicated on-medication states regardless of the presence of dyskinesia and despite potential motion and heart rate artifacts. The 24-hour profile revealed large circadian power shifts that may overdrive medication-intake dynamics. CONCLUSION: Despite the limitations of low-temporal resolution recordings, this work provides valuable insights into the real-life dynamics of biomarkers. Specifically, it highlights the utility of FTG as a primary and reliable indicator of medication states for adaptive DBS. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.