On-Off and Proportional Closed-Loop Adaptive Deep Brain Stimulation Reduces Motor Symptoms in Freely Moving Hemiparkinsonian Rats

Objectives: Closed-loop adaptive deep brain stimulation (aDBS) continuously adjusts stimulation parameters, with the potential to improve efficacy and reduce side effects of deep brain stimulation (DBS) for Parkinson's disease (PD). Rodent models can provide an effective platform for testing aDBS algorithms and establishing efficacy before clinical investigation. In this study, we compare two aDBS algorithms, on-off and proportional modulation of DBS amplitude, with conventional DBS in hemiparkinsonian rats.

Materials and methods: DBS of the subthalamic nucleus (STN) was delivered wirelessly in freely moving male and female hemiparkinsonian (N = 7) and sham (N = 3) Wistar rats. On-off and proportional aDBS, based on STN local field potential beta power, were compared with conventional DBS and three control stimulation algorithms. Behavior was assessed during cylinder tests (CT) and stepping tests (ST). Successful model creation was confirmed via apomorphine-induced rotation test and Tyrosine Hydroxylase-immunocytochemistry. Electrode location was histologically confirmed. Data were analyzed using linear mixed models.

Results: Contralateral paw use in parkinsonian rats was reduced to 20% and 25% in CT and ST, respectively. Conventional, on-off, and proportional aDBS significantly improved motor function, restoring contralateral paw use to approximately 45% in both tests. No improvement in motor behavior was observed with either randomly applied on-off or low-amplitude continuous stimulation. Relative STN beta power was suppressed during DBS. Relative power in the alpha and gamma bands decreased and increased, respectively. Therapeutically effective adaptive DBS used approximately 40% less energy than did conventional DBS.

Conclusions: Adaptive DBS, using both on-off and proportional control schemes, is as effective as conventional DBS in reducing motor symptoms of PD in parkinsonian rats. Both aDBS algorithms yield substantial reductions in stimulation power. These findings support using hemiparkinsonian rats as a viable model for testing aDBS based on beta power and provide a path to investigate more complex closed-loop algorithms in freely behaving animals.