Debugging Adaptive Deep Brain Stimulation for Parkinson's Disease

Abstract

A BS TRACT: Deep brain stimulation (DBS) is a successful treatment for patients with Parkinson's disease. In adaptive DBS, stimulation is titrated according to feedback about clinical state and underlying pathophysiology. This contrasts with conventional stimulation, which is fixed and continuous. In acute trials, adaptive stimulation matches the efficacy of conventional stimulation while delivering about half the electrical energy. The latter means potentially fewer side-effects. The next step is to determine the long-term efficacy, efficiency, and side-effect profile of adaptive stimulation, and chronic trials are currently being considered by the medical devices industry. However, there are several different approaches to adaptive DBS, and several possible limitations have been highlighted.Here we review the findings to date to ascertain how and who to stimulate in chronic trials designed to establish the long-term utility of adaptive DBS. © 2020 International Parkinson and Movement Disorder Society Adaptive deep brain stimulation (DBS) uses feedback indicative of the clinical state and underlying pathophysiology to adjust stimulation, save energy, and limit side-effects. With several medical device companies considering trials of chronic adaptive DBS for Parkinson's disease (PD), it is time to take stock and consider the approaches most likely to be fruitful and the potential limitations that should be anticipated. Hitherto, most research has focused on the use of beta local field potential activity to provide feedback control of DBS of the subthalamic nucleus (STN), and several publications have contrasted acute adaptive DBS with either no stimulation or conventional fixed stimulation. Here we consider the motivation behind these trials, what they have highlighted, and what remains to be understood.

Acute effects of adaptive Deep Brain Stimulation in Parkinson’s disease

“…Several clinical trials [ 9 – 11 , 18 , 32 , 52 – 54 ], including the present study, have demonstrated that beta oscillations in the STN correlate with bradykinesia and rigidity in PD patients [ 59 ]. For that reason, beta oscillations are likely to play a central role in future aDBS trials [ 60 , 61 ]. With the advent of new stimulation devices that are able to perform chronic LFP-recordings, the next step towards implementing beta-based aDBS in the clinical practice will be to explore the clinical benefits and limitations of aDBS in real-life situations.…”

Local field potential activity dynamics in response to deep brain stimulation of the subthalamic nucleus in Parkinson's disease

“…An understanding of the mechanisms of action of DBS could enable development of DBS strategies that are more specific, causing fewer side-effects, and even more effective, should it prove possible to directly counter the key malfunctions in neural circuits. In particular, there has been much recent interest in the possibility of controlling DBS using feedback from electrophysiological signals ( Bouthour et al, 2019 ; Little and Brown, 2020 ; Lozano et al, 2019 ).…”

Subthalamic beta-targeted neurofeedback speeds up movement initiation but increases tremor in Parkinsonian patients

“…For example, reduced activities in the beta band and increases in power in the tremor frequency band, corresponding to the theta band (3–7 Hz), in the STN, as well as reduced basal ganglia-cortical coherence in the beta frequency band have been observed during the presence of resting tremor in Parkinson’s disease ( Hirschmann et al, 2013 ; Qasim et al, 2016 ; Asch et al, 2020 ). Moreover, one in five patients shows resurgence of tremor if DBS is only switched on when STN beta activity is high ( Little and Brown, 2020 ). These observations raise the possibility that neurofeedback training that suppresses beta oscillations in the STN may not improve, even worsen, resting tremor in Parkinsonian patients.…”