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

Ashwini Oswal,Vladimir Litvak,Marwan Hariz,Peter Brown,Harith Akram,Ludvic Zrinzo,Marjan Jahanshahi,James Gratwicke,Laszlo Zaborszky,Tom Foltynie

doi:10.1093/brain/awaa411

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.

Highlights

Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) are two of the commonest neurodegenerative dementias (Aarsland and Kurz, 2010; Jellinger, 2018)
By combining recordings of nucleus basalis of Meynert (NBM) local field potentials (LFP) from deep brain stimulation (DBS) electrodes with magnetoencephalography (MEG), we have been able to identify NBM-cortical networks that are common to both diseases (Gratwicke et al, 2020a) including: (i) a delta/theta band (2–8 Hz) network between the NBM and temporal cortex; and (ii) a low beta band (13–22 Hz) network between the NBM and mesial motor areas
The correlation of structural and functional connectivity was specific to the NBM rather than to the GP region, which we hypothesize may be reflective of a monosynaptic input-output relationship between the NBM and cortical structures (Saper, 1984; Gielow and Zaborszky, 2017; Zaborszky et al, 2018)

Summary

Introduction

Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) are two of the commonest neurodegenerative dementias (Aarsland and Kurz, 2010; Jellinger, 2018). They are both characterized by the neuropathological hallmark of cortical Lewy bodies composed of alpha-synuclein (Hurtig et al, 2000; Horvath et al, 2013) and are associated with marked cholinergic neurotransmitter system dysfunction (Shimada et al, 2009) They share a common phenotype including prominent executive, attentional and visual processing dysfunction, memory deficits, cognitive fluctuations, visual hallucinations and parkinsonism (Emre et al, 2007; McKeith et al, 2017). By combining recordings of NBM local field potentials (LFP) from DBS electrodes with magnetoencephalography (MEG), we have been able to identify NBM-cortical networks that are common to both diseases (Gratwicke et al, 2020a) including: (i) a delta/theta band (2–8 Hz) network between the NBM and temporal cortex; and (ii) a low beta band (13–22 Hz) network between the NBM and mesial motor areas It remains unclear how the functional connectivity of the NBM relates to its structural connectivity

Methods

Results

Conclusion