Objective: We aim to develop a closed-loop adaptive deep brain stimulation (aDBS) system that turns DBS off based on the real-time detection of sleep using local field potentials (LFPs) recorded from electrodes in the ventral intermediate nucleus (VIM) of the thalamus in patients with essential tremor (ET). The primary objectives are to evaluate the feasibility of identifying personalized LFP biomarkers of sleep and to assess the safety of turning DBS off during sleep in ET patients. The secondary objectives are to analyze the non-inferiority of adaptive DBS for tremor suppression and to determine if turning DBS off at night reduces overall stimulation-induced side effects (SIEE).

Background: Due to disease progression and/or habituation to stimulation, the long-term benefits of DBS often wane over time in a variable proportion of ET patients, leading to increasing DBS requirements and potential SIEE [1]. “Stimulation holidays” has been proposed as one of the strategies to prevent and treat the loss of DBS benefits [1]. The sleep period provides an opportunity to turn DBS off in ET patients with minimal functional impact.

Method: We recruited 18 ET patients treated with VIM DBS at the University of Florida and analyzed 27 chronic LFP recordings obtained from the implanted Medtronic DBS electrodes attached to the Medtronic Percept PC implantable pulse generators. LFPs were recorded in preselected frequency bands ranging from 7-44 Hz. For each band, we averaged the LFP powers during the night and the day respectively and calculated the percent change in power.

Results: A circadian rhythm was observed in most patients. The powers of frequencies above 18 Hz were consistently decreased whereas the powers of frequencies below 18 Hz were either decreased or increased at night. A statistically significant difference was found when comparing the lower versus higher powers. Simulation of a single-threshold aDBS paradigm based on the theta power suggested that DBS could be automatically turned off at night, thereby reducing the total stimulation delivered by 29%.

Conclusion: VIM LFP activities can be used to track sleep. As the next step, we will conduct a single-center, prospective, crossover pilot trial to further evaluate the feasibility, safety, and non-inferiority of aDBS strategy, utilizing LFP power to turn DBS off at night in ET patients with stable VIM DBS settings.

References: [1] Fasano, A., & Helmich, R. C. (2019). Tremor habituation to deep brain stimulation: Underlying mechanisms and solutions. Movement disorders: official journal of the Movement Disorder Society, 34(12), 1761–1773. https://doi.org/10.1002/mds.27821

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MDS Abstracts - https://www.mdsabstracts.org/abstract/circadian-rhythm-and-adaptive-deep-brain-stimulation-in-essential-tremor/