Local Field Potential Biomarkers of Non-Motor Symptoms in Parkinson's Disease: Insights From the Subthalamic Nucleus in Deep Brain Stimulation

Non-motor symptoms can severely affect the quality of life of Parkinson's disease-afflicted patients, with the most common ones being pain, sleep impairments, and neuropsychiatric manifestations. In advanced cases, complex fluctuations of motor and non-motor symptoms can occur despite optimal medication. Research on deep brain stimulation of the subthalamic nucleus suggests that it may provide benefits for treating non-motor symptoms in addition to improving motor symptoms. With recent advancements in deep brain stimulation technology, simultaneous recording of local field potentials and delivery of therapeutic stimulation is possible. This opens new possibilities for better understanding the pathophysiology of non-motor symptoms in Parkinson's disease and for identifying potential electrophysiological biomarkers that accurately represent these symptoms. Specifically, this review aims to highlight potential local field potential biomarkers of non-motor symptoms in the subthalamic nucleus. The main findings indicate that activities in the beta frequency band are associated with nociception and sleep impairments such as insomnia and rapid eye movement sleep behavior disorders. Additionally, activities in the theta and alpha frequency bands seem to reflect neurocognitive manifestations, including depression and impulse control disorders. A better understanding of these biomarkers could improve the clinical management of non-motor symptoms in Parkinson's disease. They hold promise for adjusting deep brain stimulation parameters in open-loop settings and might eventually be applied in closed-loop deep brain stimulation systems, though their true impact remains uncertain.