Biomarkers for closed-loop deep brain stimulation in Parkinson disease and beyond

Subthalamic deep brain stimulation (DBS) for Parkinson disease (PD) currently requires laborious open-loop programming, which can mitigate the benefits of this treatment. Experimental closed-loop DBS systems are emerging that can sense the electrophysiological surrogates of PD motor signs and respond with delivery of an automatically adapted stimulation. Such biomarker-based neural interfaces constitute a major advance towards improving the outcomes of patients treated with DBS and enhancing our understanding of the pathophysiological mechanisms underlying PD. In this Perspectives article, we argue that closed-loop DBS, in addition to offering advantages in patients with PD, might extend the current indications for DBS to include selected psychiatric disorders in which the symptoms are similarly driven by pathological brain circuit activity. The success of closed-loop DBS in such settings will depend on the identification of symptom-specific biomarkers, which ideally should reflect causal mechanisms of the underlying pathology