Nonmotor Symptoms in Parkinson’s Disease: Neurophysiology Biomarkers and Neuromodulation Approaches

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder, with increasing global incidence and prevalence. While PD is diagnosed based on the presence of classic motor symptoms including tremor, bradykinesia, and rigidity, non-motor symptoms also play an important role in disease pathogenesis. Increasing evidence has demonstrated that non-motor symptoms, including neuropsychiatric changes, cognitive impairment, sleep disturbances, autonomic dysfunction, and pain and sensory symptoms, significantly affect PD patients' disease burden, quality of life, and utilization of healthcare resources. SUMMARY: Deep brain stimulation (DBS) is an effective treatment for motor symptoms in advanced PD. The neurophysiology changes associated with PD motor symptoms are relatively well understood and have been used to inform closed-loop DBS approaches to improve motor symptom control. Unfortunately, effective treatments for many of the non-motor symptoms of advanced PD are lacking, and DBS to treat motor symptoms may worsen non-motor symptoms such as depression, cognitive impairment, and impulsive and compulsive behaviors in some patients. KEY MESSAGES: Recent work has provided some insight into neurophysiological changes underlying nonmotor symptoms, which may inform development of future therapeutic approaches. In this manuscript, we review neurophysiology biomarkers associated with non-motor symptoms and their application to developing novel neuromodulation treatments. We additionally review how existing DBS approaches may impact non-motor symptoms. We highlight the need for precise and individualized neuromodulation approaches.