Optimizing deep brain stimulation to improve visuomotor function in Parkinson’s disease

SUMMARY Visual impairments in Parkinson's disease (PD) are more prevalent than acknowledged, affecting activities like reading and driving. Impairment in simultaneous movements of the eyes, vergence, and binocular alignment, strabismus, are frequently seen in PD. Conventional pharmacotherapy with L-dopa is not an ideal treatment for vergence impairments and strabismus. Progressive neurodegeneration and symptom fluctuations in PD makes patients unsuitable for interventions like orbital muscle surgery or prism therapy. Although subthalamic nucleus region (STN) deep brain stimulation (DBS) improves motor symptoms, its impact on binocular control, strabismus, and vergence, and related quality of life remains unknown. Our research aims to establish treatment options for vergence impairments and strabismus in PD patients with STN DBS while preserving its motor symptom benefits. We propose two specific aims geared towards answering following questions: 1) Can STN DBS improve vergence abnormality in PD? If so, which STN regions are associated with improvement in vergence while preserving the positive effects on PD motor symptoms such as tremor, bradykinesia, hypokinesia, and increased tone? 2) Can STN DBS alleviate strabismus in PD? If so, which STN regions and pathways are linked to strabismus improvement while maintaining favorable effects on PD motor symptoms? Specific Aim 1 will test specific hypothesis that is bilateral STN DBS will improve vergence gain and latency in PD, and the effects will be favorable when the active electrode contact is in vicinity of the dorsal STN and when it activates cerebello-thalamic pathway. Specific Aim 2 will test the hypothesis that is bilateral STN DBS improves strabismus in PD, and the effects are favorable when the active electrode contact is in vicinity of the dorsal STN and when it activates cerebello-thalamic pathway. The endpoints for both aims include determining whether STN DBS improves vergence/strabismus while preserving motor symptom benefits and identifying associated STN regions and fiber pathways. This interdisciplinary research holds transformative potential as it seamlessly combines neurology, visual neuroscience, and computational modeling. It has the capacity to yield impactful treatments for visual abnormalities in PD while safeguarding the positive effects on motor symptoms, ultimately enhancing the overall well-being of affected individuals. Project Number: 1I01RX005298-01A1 | Fiscal Year: 2026 | NIH Institute/Center: Veterans Affairs (VA) | Principal Investigator: Aasef Shaikh | Institution: LOUIS STOKES CLEVELAND VA MEDICAL CENTER, CLEVELAND, OH | Activity Code: I01 | Study Section: Sensory Systems & Communication Disorders[RRD3] View on NIH RePORTER: https://reporter.nih.gov/project-details/11110882