Single-Trajectory Multiple-Target Deep Brain Stimulation for Parkinsonian Mobility and Cognition

Sanskriti Sasikumar; Melanie Cohn; Irene E Harmsen; Aaron Loh; Sang Soo Cho; Michel Sáenz-Farret; Ricardo Maciel; Derrick Soh; Alexandre Boutet; Jürgen Germann; Gavin Elias; Ariana Youm; Katherine Duncan; Nathan C Rowland; Antonio P Strafella; Suneil K Kalia; Andres M Lozano; Alfonso Fasano

doi:10.1002/mds.28870

Single-Trajectory Multiple-Target Deep Brain Stimulation for Parkinsonian Mobility and Cognition

Mov Disord. 2022 Mar;37(3):635-640. doi: 10.1002/mds.28870. Epub 2021 Nov 22.

Authors

Sanskriti Sasikumar¹, Melanie Cohn^{2

3}, Irene E Harmsen^{4

5}, Aaron Loh⁵, Sang Soo Cho^{6

7}, Michel Sáenz-Farret⁸, Ricardo Maciel⁹, Derrick Soh¹⁰, Alexandre Boutet^{5

11}, Jürgen Germann⁵, Gavin Elias⁵, Ariana Youm², Katherine Duncan², Nathan C Rowland¹², Antonio P Strafella^{1

6

8

13}, Suneil K Kalia^{3

5

14}, Andres M Lozano^{3

5

14}, Alfonso Fasano^{1

3

8

14}

Affiliations

¹ Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
² Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
³ Krembil Brain Institute, Toronto, Ontario, Canada.
⁴ Mitchell Goldhar MEG Unit, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
⁵ Toronto Western Hospital, Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada.
⁶ Division of Brain, Imaging and Behaviour-Systems Neuroscience, Krembil Brain Institute, UHN, University of Toronto, Toronto, Ontario, Canada.
⁷ Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Republic of Korea.
⁸ Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, UHN, Toronto, Ontario, Canada.
⁹ Movement Disorders Unit, Hospital das Clínicas, Federal University of Minas Gerais, Belo Horizonte, Brazil.
¹⁰ Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia.
¹¹ Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada.
¹² Department of Neurosurgery, Medical University of South Carolina, Charleston, South Carolina, USA.
¹³ Brain Health Imaging Centre, Campbell Family Mental Health Research Institute, CAMH, University of Toronto, Toronto, Ontario, Canada.
¹⁴ Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Ontario, Canada.

PMID: 34806782
DOI: 10.1002/mds.28870

Abstract

Background: Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) is an emerging target to potentially treat cognitive dysfunction.

Objectives: The aim of this study is to achieve feasibility and safety of globus pallidus pars interna (GPi) and NBM DBS in advanced PD with cognitive impairment.

Methods: We performed a phase-II double-blind crossover pilot trial in six participants to assess safety and cognitive measures, the acute effect of NBM stimulation on attention, motor and neuropsychological data at one year, and neuroimaging biomarkers of NBM stimulation.

Results: NBM DBS was well tolerated but did not improve cognition. GPi DBS improved dyskinesia and motor fluctuations (P = 0.04) at one year. NBM stimulation was associated with reduced right frontal and parietal glucose metabolism (P < 0.01) and increased low- and high-frequency power and functional connectivity. Volume of tissue activated in the left NBM was associated with stable cognition (P < 0.05).

Conclusions: Simultaneous GPi and NBM stimulation is safe and improves motor complications. NBM stimulation altered neuroimaging biomarkers but without lasting cognitive improvement. © 2021 International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; cognitive impairment; controlled trial; deep brain stimulation; globus pallidus pars interna; nucleus basalis of Meynert.

Publication types

Clinical Trial, Phase II
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Basal Nucleus of Meynert
Cognition
Deep Brain Stimulation* / methods
Globus Pallidus
Humans
Parkinson Disease* / complications

Grants and funding

PJ8-1699695/CIHR/Canada