Cortical connectivity of the nucleus basalis of Meynert in Parkinson’s disease and Lewy body dementias

Author:

Oswal Ashwini123ORCID,Gratwicke James4,Akram Harith4,Jahanshahi Marjan4,Zaborszky Laszlo5,Brown Peter12,Hariz Marwan46,Zrinzo Ludvic4,Foltynie Tom4,Litvak Vladimir3

Affiliation:

1. Medical Research Council Brain Network Dynamics Unit, University of Oxford, Oxford, UK

2. Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK

3. Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology, London, UK

4. Department of Clinical and Movement Neurosciences, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK

5. Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, USA

6. Department of Clinical Neuroscience, Umeå University, Umeå, Sweden

Abstract

Abstract Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) are related conditions that are associated with cholinergic system dysfunction. Dysfunction of the nucleus basalis of Meynert (NBM), a basal forebrain structure that provides the dominant source of cortical cholinergic innervation, has been implicated in the pathogenesis of both PDD and DLB. Here we leverage the temporal resolution of magnetoencephalography with the spatial resolution of MRI tractography to explore the intersection of functional and structural connectivity of the NBM in a unique cohort of PDD and DLB patients undergoing deep brain stimulation of this structure. We observe that NBM-cortical structural and functional connectivity correlate within spatially and spectrally segregated networks including: (i) a beta band network to supplementary motor area, where activity in this region was found to drive activity in the NBM; (ii) a delta/theta band network to medial temporal lobe structures encompassing the parahippocampal gyrus; and (iii) a delta/theta band network to visual areas including lingual gyrus. These findings reveal functional networks of the NBM that are likely to subserve important roles in motor control, memory and visual function, respectively. Furthermore, they motivate future studies aimed at disentangling network contribution to disease phenotype.

Funder

NIHR Academic Clinical Lectureship

Academy of Medical Sciences Starter Grant

Wellcome Centre for Human Neuroimaging

Wellcome

Medical Research Council

NIH

NINDS

NIHR

Michael J Fox Foundation

Cure Parkinson’s Trust

Innovate UK

John Black Charitable Foundation

Janet Owens Fellowship & Defeat MSA

Brain Research Trust

National Institute for Health Research University College London Hospitals Biomedical Research Centre

The Unit of Functional Neurosurgery

Parkinson's Appeal and the Sainsbury Monument Trust

Publisher

Oxford University Press (OUP)

Subject

Clinical Neurology

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