Theta deep-brain stimulation improves cognitive performance in Parkinson’s patients with cognitive impairments

ABSTRACT Background Patients with Parkinson’s disease (PD) almost inevitably experience cognitive impairments. These deficits have been linked to low frequency “theta” cortical activity ∼4 Hz, previously associated with cognitive control. Objective Our study investigated effects of 4 Hz subthalamic nucleus (STN) deep brain stimulation (DBS) on cognitive performance in PD patients with cognitive impairments. Methods We recruited 17 PD participants with (n=10) and without (n=7) cognitive impairment. In these patients, we compared motor and cognitive performance during 4 Hz STN DBS, typical DBS for motor symptoms of PD (∼130Hz) and DBS OFF. Motor performance was tested by Part III of the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-III). Cognitive performance was tested during performance of the Multi-Source Interference Task (MSIT), which requires conflict resolution to respond accurately. Results Motor function improved with 4 Hz STN DBS and further improved with ∼130 Hz STN DBS. Compared to DBS OFF, reaction times were decreased during 4 Hz STN DBS and were further decreased at ∼130 Hz. Strikingly, 4 Hz DBS alone improved accuracy compared to both DBS OFF and compared to ∼130 Hz STN DBS. Conclusions These data suggest that theta-frequency 4 Hz STN stimulation is effective in PD patients with cognitive impairments. Our findings will help guide new therapies targeted at improving cognitive dysfunction in PD and could broaden applications for low-frequency brain stimulation.