Objective: To analyze the influence of circadian rhythmson local field potentials (LFPs) recorded in the Globus Pallidus Internal (GPi) of patients with Parkinson’s disease (PD).

Background: Recent advances in deep brain stimulation (DBS) technology have led adaptive DBS (aDBS) algorithms by using markers of disease state to adjust the stimulation parameters responsively. Beta band (13-30hz)has been suggested as potential feedback signal in basal ganglia for aDBS, given its clinical correlates with rigidity and bradykinesia. Although a beta power reductionsduring stages of sleep have been described in the subthalamic nucleus (STN), little is known about GPi. Further, the network effects of applied stimulation to LFPs and circadian rhythms also remain to be explored.

Method: We enrolled 77 PD subjects with implantedleads in either GPi (n=63) or STN (n=12), connected to a pulse generator capable of chronic brain sensing (Percept, Medtronic Inc®). The contact pairs and frequency bandswith the most power were selected and tracked for aminimum of 5 days for each implanted hemisphere (9.6 mean). The power was averaged over two time-windows:daytime (4pm-7pm) and nighttime (2am-4am), for a comparison using a t-test. Subsequent recordings were conducted at various stimulation settings in order to determine the effects of parameters on pallidal circadian fluctuations.

Results: The most commonly tracked frequenciesremained between the alpha (8-12hz) and beta (13-30hz) bands. There was a variability in power at night vs daytime across the majority of patients, with a reduction of observed in 65% (p<0.00065) of patients, versus an increase in 35 % (p<0.00065) of patients. Increments in the stimulation amplitudes seemed to have led to an augmentation of the ‘baseline’ noise resulting in a blurring/reduction in day-night power change.

Conclusion: These results suggest that circadian rhythms appear to strongly modulate pallidal activity. This phenomenon could have potential applications as a form of passively tracking sleep in individuals with chronically implanted neurostimulators. Further, it could be used to develop novel aDBS algorithms, or should be factored into the current aDBS algorithms under investigation. Finally,the implications of the masking effect of stimulation on the detection of the circadian rhythms should be considered in future studies when entertaining its use as a strategy for aDBS.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/modulation-of-pallidal-activity-by-circadian-rhythms-a-new-variable-to-be-accounted-for-closed-loop-dbs/