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Acute low frequency dorsal subthalamic nucleus stimulation improves verbal fluency in Parkinson's disease
Institution:1. Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 2S8, Canada;2. Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada;3. Department of Neurological Surgery, University of Southern California, 1200 North State Street, Suite 3300, Los Angeles, CA, 90033, USA;4. USC Neurorestoration Center, Keck School of Medicine of USC, 1333 San Pablo Street, McKibben Hall B51, Los Angeles, CA, 90033, USA;5. Department of Neurosurgery, University Hospitals Leuven – KU Leuven, Herestraat 49, 3000, Leuven, Vlaams-Brabant, Belgium;6. Joint Department of Medical Imaging, University of Toronto, Toronto, ON, Canada;7. Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada;8. Edmond J. Safra Program in Parkinson''s Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada;9. Department of Psychology, University of Toronto, Toronto, Canada
Abstract:BackgroundParkinson's disease (PD) is a common neurodegenerative disorder that results in movement-related dysfunction and has variable cognitive impairment. Deep brain stimulation (DBS) of the dorsal subthalamic nucleus (STN) has been shown to be effective in improving motor symptoms; however, cognitive impairment is often unchanged, and in some cases, worsened particularly on tasks of verbal fluency. Traditional DBS strategies use high frequency gamma stimulation for motor symptoms (~130 Hz), but there is evidence that low frequency theta oscillations (5–12 Hz) are important in cognition.MethodsWe tested the effects of stimulation frequency and location on verbal fluency among patients who underwent STN DBS implantation with externalized leads. During baseline cognitive testing, STN field potentials were recorded and the individual patients’ peak theta frequency power was identified during each cognitive task. Patients repeated cognitive testing at five different stimulation settings: no stimulation, dorsal contact gamma (130 Hz), ventral contact gamma, dorsal theta (peak baseline theta) and ventral theta (peak baseline theta) frequency stimulation.ResultsAcute left dorsal peak theta frequency STN stimulation improves overall verbal fluency compared to no stimulation and to either dorsal or ventral gamma stimulation. Stratifying by type of verbal fluency probes, verbal fluency in episodic categories was improved with dorsal theta stimulation compared to all other conditions, while there were no differences between stimulation conditions in non-episodic probe conditions.ConclusionHere, we provide evidence that dorsal STN theta stimulation may improve verbal fluency, suggesting a potential possibility of integrating theta stimulation into current DBS paradigms to improve cognitive outcomes.
Keywords:Parkinson's disease  Treatment  Deep brain stimulation  Subthalamic nucleus  Verbal fluency  Theta  Gamma
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