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Theta deep-brain stimulation improves 1 cognitive performance in Parkinson's patients with cognitive impairments

Cole, R.; Cavanagh, J.; Zhang, Q.; Groth, C.; Vivanco-Suarez, J.; Espinoza, A. I.; Greenlee, J.; Narayanan, N.

2026-03-13 neurology
10.64898/2026.03.12.26348246 medRxiv
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BackgroundPatients with Parkinsons 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. ObjectiveOur study investigated effects of 4 Hz subthalamic nucleus (STN) deep brain stimulation (DBS) on cognitive performance in PD patients with cognitive impairments. MethodsWe 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 Parkinsons 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. ResultsMotor 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. ConclusionsThese 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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