Objective: To compare adaptive deep brain stimulation (aDBS) using stimulation-entrained gamma oscillations as a feedback signal to conventional constant-amplitude deep brain stimulation (cDBS) using validated clinical metrics in a double-blind, randomized study design.

Background: aDBS is a novel neuromodulation paradigm that dynamically adjusts stimulation based on neural signal biomarkers of symptoms. While previous studies have focused on beta-band (13-30 Hz) power as a feedback signal for aDBS (1-3), recent findings have highlighted either subthalamic or cortical gamma oscillations entrained to half the stimulation rate is an alternative neural signal biomarker (4). Though promising initial studies demonstrated improved symptom control compared to cDBS using non-validated nightly questionnaires, gamma-driven aDBS has not yet been evaluated using clinically validated metrics of motor fluctuation severity.

Method: Two male subjects with Parkinson’s disease (ages 68 and 59) with investigational sensing neurostimulators connected to bilateral subthalamic nucleus (STN) DBS leads and subdural quadripolar cortical paddles participated. Subject 1 had an STN gamma oscillation-driven aDBS system programmed, and subject 2 had cortical gamma oscillations-driven system. Over an 8-week period, subjects were blindly randomized weekly to either aDBS or cDBS. Each week, the blinded DBS system was evaluated using daily and weekly metrics, including two days per week completing a Hauser motor diary (5).

Results: Subjects reported increased “on” time without troublesome dyskinesia (Subject 1: +2.2 h; Subject 2: +1.7 h) and reduced “off” time (Subject 1: -0.7 h; Subject 2: -1.8 h). Subject 1 had a slight reduction in “on” time with bothersome dyskinesia (-0.3 h), while Subject 2 experienced a minor increase (+0.4 h).

Conclusion: This double-blind, randomized assessment using standardized clinical metrics provides further evidence that aDBS driven by stimulation-entrained gamma oscillations improves motor fluctuation control compared to cDBS.

References: 1. Little S, Pogosyan A, Neal S, Zavala B, Zrinzo L, Hariz M, et al. Adaptive deep brain stimulation in advanced Parkinson disease. Ann Neurol. 2013;74(3):449–57.
2. Velisar A, Syrkin-Nikolau J, Blumenfeld Z, Trager MH, Afzal MF, Prabhakar V, et al. Dual threshold neural closed loop deep brain stimulation in Parkinson disease patients. Brain Stimulat. 2019 Jul 1;12(4):868–76.
3. Priori A, Foffani G, Rossi L, Marceglia S. Adaptive deep brain stimulation (aDBS) controlled by local field potential oscillations. Exp Neurol. 2013 Jul 1;245:77–86.
4. Oehrn CR, Cernera S, Hammer LH, Shcherbakova M, Yao J, Hahn A, et al. Chronic adaptive deep brain stimulation versus conventional stimulation in Parkinson’s disease: a blinded randomized feasibility trial. Nat Med. 2024 Aug 19;1–12.
5. Hauser RA, Friedlander J, Zesiewicz TA, Adler CH, Seeberger LC, O’Brien CF, et al. A Home Diary to Assess Functional Status in Patients with Parkinson’s Disease with Motor Fluctuations and Dyskinesia. Clin Neuropharmacol. 2000 Apr;23(2):75.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/stimulation-entrained-gamma-driven-adaptive-dbs-improves-motor-diary-reports-of-symptom-fluctuations-in-parkinsons-disease/