A three dimensional anatomical view of oscillatory resting-state activity and functional connectivity in Parkinson's disease related dementia: An MEG study using atlas-based beamforming

Abstract

Parkinson's disease (PD) related dementia (PDD) develops in up to 80% of PD patients. The present study was performed to further unravel the underlying pathophysiological mechanisms by applying a new analysis approach that uses an atlas-based MEG beamformer to provide a detailed anatomical mapping of cortical rhythms and functional interactions. Importantly, we used the phase lag index (PLI) as a measure of functional connectivity to avoid any biases due to effects of volume conduction.MEG recordings were obtained in 13 PDD and 13 non-demented PD patients. Beamforming was used to estimate spectral power and PLI in delta, theta, alpha, beta and gamma frequency bands. Compared to PD patients, PDD patients had more delta and theta power in parieto-occipital and fronto-parietal areas, respectively. The PDD patients had less alpha and beta power in parieto-temporo-occipital and frontal areas, respectively. Compared to PD patients, PDD patients had lower mean PLI values in the delta and alpha bands in fronto-temporal and parieto-temporo-occipital areas, respectively. In addition, in PDD patients connectivity between pairs of regions of interest (Brodmann areas) was stronger in the theta band and weaker in the delta, alpha and beta bands.The added value of the present results over previous studies analysing frequency-specific changes in neuronal activity in PD patients, is the anatomical framework in which we demonstrated a slowing in neuronal activity and a reduction in functional connectivity in PD related dementia. Moreover, this study shows a widespread reduction in functional connectivity between different regions in PDD.

A systematic review of MEG‐based studies in Parkinson's disease: The motor system and beyond

“…The effect of DRT on whole‐brain power was inconclusive for both EEG (e.g., (Mostile et al, ) and MEG studies (Stoffers, Bosboom, Wolters, et al, )), as well as the relationship between EEG/MEG‐findings and UPDRS‐III scores. Although EEG‐based longitudinal functional connectivity studies are missing, a few cross‐sectional studies hint at lower functional connectivity and network disruptions in cognitively disturbed PD patients (Hassan et al, ; Utianski et al, ), in accordance with the results of MEG studies (Olde Dubbelink et al, ; Olde Dubbelink, Hillebrand, Stoffers, et al, ; Ponsen et al, ).…”

“…The spectral slowing correlated with clinical progression of motor symptoms as well as global cognitive decline (Olde Dubbelink et al, ). In a cross‐sectional analysis involving Parkinson's disease dementia (PDD) patients, spectral power had progressed toward diffuse slowing, independent of motor and cognitive scores (Bosboom et al, ; Ponsen, Stam, Bosboom, Berendse, & Hillebrand, ). The spectral slowing in PDD patients could at least partly be reversed by treatment with the cholinesterase inhibitor rivastigmine (Bosboom, Stoffers, Stam, Berendse, & Wolters, ).…”

“…Comparison of a cohort of PDD patients with nondemented PD patients using two different processing pipelines led to conflicting outcomes that could at least partly be explained by differences in methodology (Bosboom, Stoffers, Wolters, Stam, & Berendse, ; Ponsen et al, ): in the first study, analysis was based on (ten) clusters of extracranial sensors and SL was used as FC measure. Compared to PD, PDD was characterized by lower fronto‐temporal SL in lower frequency bands (delta, theta and alpha1), and higher left‐sided parieto‐occipital SL in the higher frequency bands (alpha2 and beta; Bosboom, Stoffers, Wolters, et al, ).…”

Systems-Based Analyses of Brain Regions Functionally Impacted in Parkinson's Disease Reveals Underlying Causal Mechanisms

“…More recently, functional connectivity has been studied by means of electro- (EEG) and magnetoencephalography (MEG) and patients with advanced PD demonstrate decreased functional connectivity [11], [12]. The results of these cross-sectional studies suggest that changes in functional connectivity evolve over the course of the disease and may suggest that the observed loss of functional connectivity and neuronal network alterations reflect clinically relevant changes.…”

Neuroimaging of Parkinson's disease: Expanding views

“…MEG has been used to study cortico-muscular coherence (Airaksinen et al, 2015) and predict dementia in PD (Olde Dubbelink et al, 2014b). MEG has also been used to study functional connectivity alterations in PD (Olde Dubbelink et al, 2013, 2014a; Ponsen et al, 2013). …”