Resting state activity and connectivity of the nucleus basalis of Meynert and globus pallidus in Lewy body dementia and Parkinson's disease dementia

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

doi:10.1016/j.neuroimage.2020.117184

Abstract

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are two related diseases which can be difficult to distinguish. There is no objective biomarker which can reliably differentiate between them. The synergistic combination of electrophysiological and neuroimaging approaches is a powerful method for interrogation of functional brain networks in vivo. We recorded bilateral local field potentials (LFPs) from the nucleus basalis of Meynert (NBM) and the internal globus pallidus (GPi) with simultaneous cortical magnetoencephalography (MEG) in six PDD and five DLB patients undergoing surgery for deep brain stimulation (DBS) to look for differences in underlying resting-state network pathophysiology. In both patient groups we observed spectral peaks in the theta (2–8 Hz) band in both the NBM and the GPi. Furthermore, both the NBM and the GPi exhibited similar spatial and spectral patterns of coupling with the cortex in the two disease states. Specifically, we report two distinct coherent networks between the NBM/GPi and cortical regions: (1) a theta band (2–8 Hz) network linking the NBM/GPi to temporal cortical regions, and (2) a beta band (13–22 Hz) network coupling the NBM/GPi to sensorimotor areas. We also found differences between the two disease groups: oscillatory power in the low beta (13–22Hz) band was significantly higher in the globus pallidus in PDD patients compared to DLB, and coherence in the high beta (22–35Hz) band between the globus pallidus and lateral sensorimotor cortex was significantly higher in DLB patients compared to PDD. Overall, our findings reveal coherent networks of the NBM/GPi region that are common to both DLB and PDD. Although the neurophysiological differences between the two conditions in this study are confounded by systematic differences in DBS lead trajectories and motor symptom severity, they lend support to the hypothesis that DLB and PDD, though closely related, are distinguishable from a neurophysiological perspective.

Highlights

Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) are two of the most common neurodegenerative dementias (Aarsland and Kurz, 2010; Jellinger, 2018)
Motor symptom severity was greater in the PDD patients than the DLB patients (Unified Parkinson’s Disease Rating Scale Part III motor score off medication 46.67 [13.50] points vs 27.40 [10.81] points respectively), and this was reflected in the fact that the PDD patients were being treated with higher doses of levodopa therapy compared to the DLB patients (646.88 [204.71] mg/day vs. 325.00 [403.60] mg/day respectively)
We identified three distinct coherent networks between the cortex and both the nucleus basalis of Meynert (NBM) and globus pallidus internus (GPi): (1) A theta (2–8 Hz) band network between the NBM/GPi and temporal lobe, (2) a low beta (13–22 Hz) band network between the NBM/GPi and mesial sensorimotor areas, and (3) a high beta (22–35 Hz) band network between the NBM/GPi and lateral sensorimotor areas

Summary

Introduction

Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) are two of the most common neurodegenerative dementias (Aarsland and Kurz, 2010; Jellinger, 2018). The NBM provides the main source of cholinergic innervation to the entire cortical mantle (‘corticopetal’ innervation) and is strongly implicated in arousal, attention, memory and perceptive functions (Gratwicke et al, 2013; Mesulam and Geula, 1988; Mufson et al, 2003) Degeneration of this nucleus has been shown to be key in the pathogenesis of both DLB and PDD (Choi et al, 2012; Grothe et al, 2014; Ray et al, 2018; Whitehouse et al, 1983) and neuromodulation of NBM and its residual connections has, been proposed as a potential treatment (Gratwicke et al, 2013; Hardenacke et al, 2012; Kuhn et al, 2015). GPi DBS is a well recognised treatment for parkinsonian motor symptoms such as bradykinesia and rigidity (Foltynie and Hariz, 2010; Odekerken et al, 2012)

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Results

Conclusion