Aberrant resting-state oscillatory brain activity in Parkinson's disease patients with visual hallucinations: An MEG source-space study

Abstract

To gain insight into possible underlying mechanism(s) of visual hallucinations (VH) in Parkinson's disease (PD), we explored changes in local oscillatory activity in different frequency bands with source-space magnetoencephalography (MEG). Eyes-closed resting-state MEG recordings were obtained from 20 PD patients with hallucinations (Hall+) and 20 PD patients without hallucinations (Hall-), matched for age, gender and disease severity. The Hall+ group was subdivided into 10 patients with VH only (unimodal Hall+) and 10 patients with multimodal hallucinations (multimodal Hall+). Subsequently, neuronal activity at source-level was reconstructed using an atlas-based beamforming approach resulting in source-space time series for 78 cortical and 12 subcortical regions of interest in the automated anatomical labeling (AAL) atlas. Peak frequency (PF) and relative power in six frequency bands (delta, theta, alpha1, alpha2, beta and gamma) were compared between Hall+ and Hall-, unimodal Hall+ and Hall-, multimodal Hall+ and Hall-, and unimodal Hall+ and multimodal Hall+ patients. PF and relative power per frequency band did not differ between Hall+ and Hall-, and multimodal Hall+ and Hall- patients. Compared to the Hall- group, unimodal Hall+ patients showed significantly higher relative power in the theta band (p = 0.005), and significantly lower relative power in the beta (p = 0.029) and gamma (p = 0.007) band, and lower PF (p = 0.011). Compared to the unimodal Hall+, multimodal Hall+ showed significantly higher PF (p = 0.007). In conclusion, a subset of PD patients with only VH showed slowing of MEG-based resting-state brain activity with an increase in theta activity, and a concomitant decrease in beta and gamma activity, which could indicate central cholinergic dysfunction as underlying mechanism of VH in PD. This signature was absent in PD patients with multimodal hallucinations.

Keywords: Cholinergic dysfunction; MEG; Multimodal hallucinations; Parkinson's disease; Visual hallucinations.

Fig. 1

Average power spectra over 90 AAL regions for Parkinson's disease patients with (Hall+: yellow) and without (Hall-: blue) hallucinations. Peak frequency (i.e. frequency with the most power in the 4–13 Hz range) is lower in Hall+ compared to Hall- patients. Filled area represents the standard error of the mean.

Fig. 2

Average power spectra over 90 AAL regions for Parkinson's disease patients with only VH (unimodal Hall+: red), with multimodal (multimodal Hall+: green) and without (Hall-: blue) hallucinations. Peak frequency (i.e. frequency with the most power in the 4–13 Hz range) is lowest in unimodal Hall+ patients. Filled area represents the standard error of the mean. VH: Visual Hallucinations.

Fig. 3

Mean relative power for each region of interest (ROI) in unimodal Hall+ (left) and Hall- (right) patients displayed as a color-coded map on a parcellated template brain viewed from, in clockwise order, the left, top, right, right-midline and left-midline. Panel A: relative power in the theta band. Panel B: relative power in the beta band. Panel C: relative power in the gamma band. Panel D: Peak frequency. Hot and cold colors indicate higher and lower relative power/peak frequency, respectively. See table S1-S4 for the subcortical regions per frequency band that showed significant difference between the groups and for all the relative power and peak frequency values in the two groups. Hall-: Parkinson's disease patients without hallucinations; unimodal Hall+: Parkinson's disease patients with only visual hallucinations.

Fig. 4

Distribution of the brain regions that showed significant difference between unimodal Hall+ and Hall- patients, displayed as in Fig. 3, for the theta (panel A), beta (panel B), and gamma (panel C) band, and for peak frequency (panel D). Red: higher relative power in unimodal Hall+ patients. Blue: lower relative power/peak frequency in unimodal Hall+ patients. Gray: brain regions that did not differ between the groups. Note: subcortical regions are not shown in this figure. See table S6 for the subcortical regions per frequency band that showed significant difference between the two groups and table S5 for the mean relative power/peak frequency values in the two groups. Hall-: Parkinson's disease patients without hallucinations; unimodal Hall+: Parkinson's disease patients with only visual hallucinations.

Fig. 5

Distribution of the brain regions that showed significant difference between unimodal Hall+ and multimodal Hall+ patients, displayed as in Fig. 3, for the theta (panel A), and gamma (panel B) band, and for peak frequency (panel C). Red: higher relative power in unimodal Hall+ patients. Blue: lower relative power/peak frequency in unimodal Hall+ patients. Gray: brain regions that did not differ between the groups. Note: subcortical regions are not shown in this figure. See table S6 for the subcortical regions per frequency band that showed significant difference between the two groups and table S5 for the mean relative power/peak frequency values in the two groups. Multimodal Hall+: Parkinson's disease patients with multimodal hallucinations; unimodal Hall+: Parkinson's disease patients with only visual hallucinations.