Adaptive, personalized closed-loop therapy for Parkinson's disease: biochemical, neurophysiological, and wearable sensing systems

Introduction Motor complication management is one of the main unmet needs in Parkinson's disease patients. Areas covered Among the most promising emerging approaches for handling motor complications in Parkinson's disease, adaptive deep brain stimulation strategies operating in closed-loop have emerged as pivotal to deliver sustained, near-to-physiological inputs to dysfunctional basal ganglia-cortical circuits over time. Existing sensing systems that can provide feedback signals to close the loop include biochemical-, neurophysiological- or wearable-sensors. Biochemical sensing allows to directly monitor the pharmacokinetic and pharmacodynamic of antiparkinsonian drugs and metabolites. Neurophysiological sensing relies on neurotechnologies to sense cortical or subcortical brain activity and extract real-time correlates of symptom intensity or symptom control during DBS. A more direct representation of the symptom state, particularly the phenomenological differentiation and quantification of motor symptoms, can be realized via wearable sensor technology. Expert opinion Biochemical, neurophysiologic, and wearable-based biomarkers are promising technological tools that either individually or in combination could guide adaptive therapy for Parkinson's disease motor symptoms in the future.