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Objective: The pathophysiological mechanisms underlying Parkinson's disease (PD)-related cognitive decline and conversion to PD dementia are poorly understood. In the healthy human brain, stable patterns of posterior-to-anterior cortical information flow have recently been demonstrated in the higher frequency bands using magnetoencephalography (MEG). In this study we estimated PD-related changes in information flow patterns, as well as the contribution of subcortical regions., Methods: Resting-state MEG recordings were acquired in moderately advanced PD patients (n=34; mean Hoehn and Yahr-stage 2.5) and healthy controls (n=12). MEG signals were projected to both cortical and subcortical brain regions, following which we estimated the balance between incoming and outgoing information flow per region., Results: In PD patients, compared to controls, preferential beta band information outflow was significantly higher for the basal ganglia and frontotemporal cortical regions, and significantly lower for parieto-occipital regions. In addition, in patients, low preferential information outflow from occipital regions correlated with poor global cognitive performance., Conclusion: In the PD brain, a shift in balance towards more anterior-to-posterior beta band information flow takes place and is associated with poorer cognitive performance., Significance: Our results indicate that a reversal of the physiological posterior-to-anterior information flow may be an important mechanism in PD-related cognitive decline., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The assessment of resting-state functional connectivity has become an important tool in studying brain disease mechanisms. Here we use magnetoencephalography to longitudinally evaluate functional connectivity changes in relation to clinical measures of disease progression in Parkinson's disease (PD). Using a source-space based approach with detailed anatomical mapping, functional connectivity was assessed for temporal, prefrontal and high order sensory association areas known to show neuropathological changes in early clinical disease stages. At baseline, early stage, untreated PD patients (n = 12) had lower parahippocampal and temporal delta band connectivity and higher temporal alpha1 band connectivity compared to controls. Longitudinal analyses over a 4-year period in a larger patient group (n = 43) revealed decreases in alpha1 and alpha2 band connectivity for multiple seed regions that were associated with motor or cognitive deterioration. In the earliest clinical stages of PD, delta and alpha1 band resting-state functional connectivity is altered in temporal cortical regions. With disease progression, a reversal of the initial changes in alpha1 and additional decreases in alpha2 band connectivity evolving in a more widespread cortical pattern. These changes in functional connectivity appear to reflect clinically relevant phenomena and therefore hold promise as a marker of disease progression, with potential predictive value for clinical outcome.

The pathophysiological mechanisms of Parkinson's disease (PD)-related dementia (PDD) are still poorly understood. Previous studies using electroencephalography (EEG) and magnetoencephalography (MEG) have demonstrated widespread slowing of oscillatory brain activity as a neurophysiological characteristic of PD-related dementia. Here, we use MEG to longitudinally study early changes in oscillatory brain activity in initially nondemented PD patients that may be associated with cognitive decline. Using a longitudinal design, resting-state MEG recordings were performed twice at an approximate 4-year interval in 14 healthy controls and 49 PD patients. Changes in peak frequency and in relative spectral power for 10 brain regions were analyzed in relation to clinical measures of cognitive and motor function. In contrast to healthy controls, PD patients showed a slowing of the dominant peak frequency. Furthermore, analysis per frequency band revealed an increase in theta power over time, along with decreases in alpha1 and alpha2 power. In PD patients, decreasing cognitive performance was associated with increases in delta and theta power, as well as decreases in alpha1, alpha2, and gamma power, whereas increasing motor impairment was associated with a theta power increase only. The present longitudinal study revealed widespread progressive slowing of oscillatory brain activity in initially nondemented PD patients, independent of aging effects. The slowing of oscillatory brain activity strongly correlated with cognitive decline and therefore holds promise as an early marker for the development of dementia in PD., (Copyright © 2013 Elsevier Inc. All rights reserved.)