Subthalamic nucleus stimulation modulates audiospinal reactions in Parkinson disease

Background: Axial symptoms of Parkinson disease (PD) may result from dysfunctional basal ganglia-brainstem connections. In this study, we assessed whether modulation of basal ganglia activity by high-frequency stimulation of the subthalamic nucleus (STN-HFS) in PD had an impact on the brainstem-controlled startle system. Methods: We assessed auditory startle responses (recorded from right orbicularis oculi, masseter, sternocleidomastoid, biceps brachii, and soleus muscle) and audiospinal facilitation (startle conditioned soleus H-reflexes at interstimulus intervals of 0-250 msec) in 24 patients with PD with chronically implanted, bilateral STN electrodes in the stimulation on (STIM ON) and off condition (STIM OFF) and 20 healthy controls. Results: The mixed linear analysis of variance model revealed a significant effect for the startle onset latency in the orbicularis oculi muscle for the factors GROUP (patients with PD vs controls; p < 0.0001, F = 44.66) and STIM (nested within GROUP) (p = 0.0034, F = 8.79). Audiospinal facilitation was modulated by STN-HFS as shown by highly significant effects for STIM [GROUP] (p < 0.0001, F = 15.9), ISI [GROUP] (p < 0.0001, F = 3.5), and the interaction of ISI x STIM [GROUP] (p = 0.0085, F = 2.65) in the mixed linear model. Conclusion: High-frequency stimulation of the subthalamic nucleus alters the excitability of the brainstem startle system in Parkinson disease, most likely by releasing the reticular motor system from abnormal descending input of the basal ganglia via pallidotegmental pathways.