Clinically Meaningful Cognitive Improvement from Intermittent Neurostimulation of the Nucleus Basalis of Meynert in Parkinson's Disease
- 1Stanford University
Abstract
Cognitive decline begins in early stages of Parkinson's disease (PD) for many individuals and remains largely untreated. The nucleus basalis of Meynert (NBM), the brain's cortical cholinergic hub, and its lateral efferent fiber bundle degenerate early in PD and are linked to cognitive and cognitive-motor impairment. Pre-clinical evidence indicates intermittent stimulation of the NBM improves cognition. The objective of this study is to establish the feasibility of combined continuous subthalamic nucleus (STN) and intermittent NBM DBS for cognitive impairment in people with PD. Five patients with PD and cognitive impairment approved for STN DBS were enrolled as part of an ongoing clinical trial for combined STN and NBM DBS under an Investigational Device Exemption. Three participants received a 'vertical' trajectory in which two leads were placed in the STN, and two additional leads were placed in the anterior portion of the NBM, both using the same burr hole for each hemisphere. The two other participants received a novel 'lateral trajectory' in which the NBM leads were placed along the NBM lateral efferent bundle via a small twist craniostomy behind the ear. An automated programming algorithm DBS Illumina 3D (Boston Scientific) was used to program the NBM leads based on volume of tissue activated modeling. The investigational Chronos software (Boston Scientific) was used to deliver continuous high frequency DBS to the STN 24 hours/day and intermittent patterned DBS to the NBM for 1 hour/day. The two leads placed in the NBM ('Vertical' target) or its lateral efferent bundle ('Lateral' target) were successfully and accurately placed as part of the usual STN DBS procedure. All participants were successfully programmed using the Illumina 3D algorithm without adverse effects. Following 6 months of combined continuous STN and intermittent NBM DBS, all five participants saw clinically meaningful improvements in cognition as part of a neuropsychological assessment battery, as well as the expected motoric benefit from STN DBS. The current study demonstrated that intermittent stimulation of the NBM to target cortical cholinergic deficits may provide clinically meaningful improvements in cognitive symptoms in Parkinson's disease.
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BibTeX
@misc{wilkins2026clinically,
title = {{Clinically Meaningful Cognitive Improvement from Intermittent Neurostimulation of the Nucleus Basalis of Meynert in Parkinson's Disease}},
author = {K. B. Wilkins and P. Acharyya and C. Casselton and A. K. Abay and R. A. Crockett and G. K. Deutsch and M. Malekmohammadi and H. Bokil and V. Cina and B. Reid and A. G. Ramayya and M. Zeineh and G. Seo and T. M. Howard and M. Papworth Burrel and D. T. Blake and J. M. Henderson and V. P. Buch and H. M. Bronte-Stewart},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.02.26366824},
url = {https://www.medrxiv.org/content/10.64898/2026.11.02.26366824v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Clinically Meaningful Cognitive Improvement from Intermittent Neurostimulation of the Nucleus Basalis of Meynert in Parkinson's Disease
AU - K. B. Wilkins
AU - P. Acharyya
AU - C. Casselton
AU - A. K. Abay
AU - R. A. Crockett
AU - G. K. Deutsch
AU - M. Malekmohammadi
AU - H. Bokil
AU - V. Cina
AU - B. Reid
AU - A. G. Ramayya
AU - M. Zeineh
AU - G. Seo
AU - T. M. Howard
AU - M. Papworth Burrel
AU - D. T. Blake
AU - J. M. Henderson
AU - V. P. Buch
AU - H. M. Bronte-Stewart
PY - 2026
DA - 2026/11/02
PB - medRxiv
DO - 10.64898/2026.11.02.26366824
UR - https://www.medrxiv.org/content/10.64898/2026.11.02.26366824v1
AB - Cognitive decline begins in early stages of Parkinson's disease (PD) for many individuals and remains largely untreated. The nucleus basalis of Meynert (NBM), the brain's cortical cholinergic hub, and its lateral efferent fiber bundle degenerate early in PD and are linked to cognitive and cognitive-motor impairment. Pre-clinical evidence indicates intermittent stimulation of the NBM improves cognition. The objective of this study is to establish the feasibility of combined continuous subthalamic nucleus (STN) and intermittent NBM DBS for cognitive impairment in people with PD. Five patients with PD and cognitive impairment approved for STN DBS were enrolled as part of an ongoing clinical trial for combined STN and NBM DBS under an Investigational Device Exemption. Three participants received a 'vertical' trajectory in which two leads were placed in the STN, and two additional leads were placed in the anterior portion of the NBM, both using the same burr hole for each hemisphere. The two other participants received a novel 'lateral trajectory' in which the NBM leads were placed along the NBM lateral efferent bundle via a small twist craniostomy behind the ear. An automated programming algorithm DBS Illumina 3D (Boston Scientific) was used to program the NBM leads based on volume of tissue activated modeling. The investigational Chronos software (Boston Scientific) was used to deliver continuous high frequency DBS to the STN 24 hours/day and intermittent patterned DBS to the NBM for 1 hour/day. The two leads placed in the NBM ('Vertical' target) or its lateral efferent bundle ('Lateral' target) were successfully and accurately placed as part of the usual STN DBS procedure. All participants were successfully programmed using the Illumina 3D algorithm without adverse effects. Following 6 months of combined continuous STN and intermittent NBM DBS, all five participants saw clinically meaningful improvements in cognition as part of a neuropsychological assessment battery, as well as the expected motoric benefit from STN DBS. The current study demonstrated that intermittent stimulation of the NBM to target cortical cholinergic deficits may provide clinically meaningful improvements in cognitive symptoms in Parkinson's disease.
ER -