Interventional study reveals improved cognitive accuracy with 4 Hz subthalamic stimulation in Parkinson disease, suggesting low-frequency brain stimulation aids cognitive control.
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.
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Cole et al. (2026) studied this question.
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