Closed-Loop Neuromodulation for Parkinson's Disease: Current State and Future Directions

Deep brain stimulation (DBS) refers to a neurosurgical process in which electrical stimulation is delivered via electrodes implanted within deep brain regions. DBS has become the most established clinical therapy for patients with movement disorders, although recent studies have investigated its application in a broad range of neurological and psychiatric disorders as well. Moreover, DBS has proven effective in controlling symptoms in patients with Parkinson's disease (PD). While early DBS systems were capable of stimulation only, technological advancements have allowed for the direct assessment of dysfunctional brain activity and subsequent stimulation of the pathological circuitry. DBS can also be combined with neurochemical stimulation to address decreased concentrations of dopamine in the brain. Given that both electrical and neurochemical treatments for PD aim to rectify abnormalities in neural activity, the general term 'neuromodulation' is considered more accurate and comprehensive. Recent improvements in signal detection and information processing techniques have provided further insight into PD mechanisms, which may aid in the development of personalized biomarkers and in the prediction of symptoms. In this comprehensive review, we discuss various aspects of neuromodulation in patients with PD, including basic theories, stimulation paradigms, and current challenges in the field.