Slowing of oscillatory brain activity is a stable characteristic of Parkinson's disease without dementia

Abstract

Extensive changes in resting-state oscillatory brain activity have recently been demonstrated using magnetoencephalography (MEG) in moderately advanced, non-demented Parkinson's disease patients relative to age-matched controls. The aim of the present study was to determine the onset and evolution of these changes over the disease course and their relationship with clinical parameters. In addition, we evaluated the effects of dopaminomimetics on resting-state oscillatory brain activity in levodopa-treated patients. MEG background oscillatory activity was studied in a group of 70 Parkinson's disease patients with varying disease duration and severity (including 18 de novo patients) as well as in 21 controls that were age-matched to the de novo patients. Whole head 151-channel MEG recordings were obtained in an eyes-closed resting-state condition. Levodopa-treated patients (N = 37) were examined both in a practically defined 'OFF' as well as in the 'ON' state. Relative spectral power was calculated for delta, theta, low alpha, high alpha, beta and gamma frequency bands and averaged for 10 cortical regions of interest (ROIs). Additionally, extensive clinical and neuropsychological testing was performed in all subjects. De novo Parkinson's disease patients showed widespread slowing of background MEG activity relative to controls. Changes included a widespread increase in theta and low alpha power, as well as a loss of beta power over all but the frontal ROIs and a loss of gamma power over all but the right occipital ROI. Neuropsychological assessment revealed abnormal perseveration in de novo patients, which was associated with increased low alpha power in centroparietal ROIs. In the whole group of Parkinson's disease patients, longer disease duration was associated with reduced low alpha power in the right temporal and right occipital ROI, but not with any other spectral power measure. No association was found between spectral power and disease stage, disease severity or dose of dopaminomimetics. In patients on levodopa therapy, a change from the 'OFF' to the 'ON' state was associated with decreases in right frontal theta, left occipital beta and left temporal gamma power and an increase in right parietal gamma power. Widespread slowing of oscillatory brain activity is a characteristic of non-demented Parkinson's disease patients from the earliest clinical stages onwards that is (largely) independent of disease duration, stage and severity and hardly influenced by dopaminomimetic treatment. Some early cognitive deficits in Parkinson's disease appear to be associated with increased low alpha power. We postulate a role for hypofunctional non-dopaminergic ascending neurotransmitter systems in spectral power changes in non-demented Parkinson's disease patients.

Complexity of resting-state EEG activity in the patients with early-stage Parkinson’s disease

“…Then, the changes of PE or OI at C3 or C4 channels may be developed into a potential marker of the dyskinesia caused by PD. However, it should be noted that our complexity analysis of cortical activity is performed by a sensor-based approach, which makes the PE or OI results from different EEG channels highly correlated (Stoffers et al 2007;Olde Dubbelink et al 2013;Gómez et al 2011). Then, the changes observed in the regions of sensor space may not directly reflect the physiological changes in relevant regions underlying the sensor.…”

“…Then, the changes observed in the regions of sensor space may not directly reflect the physiological changes in relevant regions underlying the sensor. One alternative method for this issue is the source modeling technique (Stoffers et al 2007;Olde Dubbelink et al 2013), which allows one to analyze the distribution of reconstructed sources over the cortical areas.…”

“…However, several spectral studies with EEG/MEG (Olde Dubbelink et al 2013;Stoffers et al 2007;Neufeld et al 1994;Han et al 2013) have observed an increase in theta or delta powers for PD patients compared to controls. Our results of relative power in Fig.…”

“…Further, a number of studies concluded that the most common abnormality of EEG in PD patients was the generalized slowing of brain activity. For instance, Serizawa et al (2008) showed that PD patients exhibited a diffuse slowing in their quantitative EEG in comparison to age-adjusted normal controls; Bosboom et al (2006) found that the PD was characterized by a slowing of resting-state brain activity involving theta, beta and gamma bands, and dementia in PD was associated with a further slowing of resting-state brain activity; Stoffers et al (2007) further confirmed that the slowing of oscillatory brain activity was a stable characteristic of PD without dementia. They also made clear that the widespread slowing of brain activity already occurred in the earliest clinical stages of untreated PD patients (Stoffers et al 2007).…”

“…By characterizing the local field potentials (LFPs) recorded in the subthalamic nucleus (STN) or globus pallidus internus (GPi), it was shown that the motor symptoms in PD patients were related to an increased activity in alpha band and more importantly in beta band (Beuter et al 2014;Brown et al 2004). By analyzing the resting EEG signals, it was found that there was a decrease of resting beta power (Stam et al 1994;Pezard et al 2001) and a remarkable increase in theta and low alpha powers in non-demented PD patients relative to controls (Stoffers et al 2007;Tanaka et al 2000). Our previous study found that such abnormalities in EEG sub-bands already occurred in the early stages of the disease.…”