Acute low frequency dorsal subthalamic nucleus stimulation improves verbal fluency in Parkinson's disease

Darrin J Lee; Neil M Drummond; Utpal Saha; Philippe De Vloo; Robert F Dallapiazza; Robert Gramer; Tameem M Al-Ozzi; Jordan Lam; Aaron Loh; Gavin J B Elias; Alexandre Boutet; Jurgen Germann; Mojgan Hodaie; Alfonso Fasano; Renato P Munhoz; William Hutchison; Melanie Cohn; Robert Chen; Suneil K Kalia; Andres M Lozano

doi:10.1016/j.brs.2021.04.016

Acute low frequency dorsal subthalamic nucleus stimulation improves verbal fluency in Parkinson's disease

Brain Stimul. 2021 Jul-Aug;14(4):754-760. doi: 10.1016/j.brs.2021.04.016. Epub 2021 Apr 30.

Authors

Darrin J Lee¹, Neil M Drummond², Utpal Saha³, Philippe De Vloo⁴, Robert F Dallapiazza⁵, Robert Gramer⁵, Tameem M Al-Ozzi⁵, Jordan Lam⁶, Aaron Loh², Gavin J B Elias², Alexandre Boutet⁷, Jurgen Germann², Mojgan Hodaie⁵, Alfonso Fasano⁸, Renato P Munhoz⁸, William Hutchison⁵, Melanie Cohn⁹, Robert Chen⁸, Suneil K Kalia⁵, Andres M Lozano⁵

Affiliations

¹ Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 2S8, Canada; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada; Department of Neurological Surgery, University of Southern California, 1200 North State Street, Suite 3300, Los Angeles, CA, 90033, USA; USC Neurorestoration Center, Keck School of Medicine of USC, 1333 San Pablo Street, McKibben Hall B51, Los Angeles, CA, 90033, USA. Electronic address: Darrin.lee@med.usc.edu.
² Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 2S8, Canada.
³ Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 2S8, Canada; USC Neurorestoration Center, Keck School of Medicine of USC, 1333 San Pablo Street, McKibben Hall B51, Los Angeles, CA, 90033, USA.
⁴ Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 2S8, Canada; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada; Department of Neurosurgery, University Hospitals Leuven - KU Leuven, Herestraat 49, 3000, Leuven, Vlaams-Brabant, Belgium.
⁵ Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 2S8, Canada; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.
⁶ Department of Neurological Surgery, University of Southern California, 1200 North State Street, Suite 3300, Los Angeles, CA, 90033, USA; USC Neurorestoration Center, Keck School of Medicine of USC, 1333 San Pablo Street, McKibben Hall B51, Los Angeles, CA, 90033, USA.
⁷ Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 2S8, Canada; Joint Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.
⁸ Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 2S8, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada; Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada.
⁹ Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 2S8, Canada; Department of Psychology, University of Toronto, Toronto, Canada.

PMID: 33940243
DOI: 10.1016/j.brs.2021.04.016

Abstract

Background: Parkinson'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.

Methods: We 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.

Results: Acute 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.

Conclusion: Here, 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: Deep brain stimulation; Gamma; Parkinson's disease; Subthalamic nucleus; Theta; Treatment; Verbal fluency.

MeSH terms

Cognition
Deep Brain Stimulation*
Humans
Neuropsychological Tests
Parkinson Disease* / therapy
Subthalamic Nucleus*