Only Low Frequency Event-Related EEG Activity Is Compromised in Multiple Sclerosis: Insights from an Independent Component Clustering Analysis

<div><p>Cognitive impairment (CI), often examined with neuropsychological tests such as the Paced Auditory Serial Addition Test (PASAT), affects approximately 65% of multiple sclerosis (MS) patients. The P3b event-related potential (ERP), evoked when an infrequent target stimulus is presented, indexes cognitive function and is typically compared across subjects' scalp electroencephalography (EEG) data. However, the clustering of independent components (ICs) is superior to scalp-based EEG methods because it can accommodate the spatiotemporal overlap inherent in scalp EEG data. Event-related spectral perturbations (ERSPs; event-related mean power spectral changes) and inter-trial coherence (ITCs; event-related consistency of spectral phase) reveal a more comprehensive overview of EEG activity. Ninety-five subjects (56 MS patients, 39 controls) completed visual and auditory two-stimulus P3b event-related potential tasks and the PASAT. MS patients were also divided into CI and non-CI groups (n = 18 in each) based on PASAT scores. Data were recorded from 128-scalp EEG channels and 4 IC clusters in the visual, and 5 IC clusters in the auditory, modality were identified. In general, MS patients had significantly reduced ERSP theta power versus controls, and a similar pattern was observed for CI vs. non-CI MS patients. The ITC measures were also significantly different in the theta band for some clusters. The finding that MS patients had reduced P3b task-related theta power in both modalities is a reflection of compromised connectivity, likely due to demyelination, that may have disrupted early processes essential to P3b generation, such as orientating and signal detection. However, for posterior sources, MS patients had a greater decrease in alpha power, normally associated with enhanced cognitive function, which may reflect a compensatory mechanism in response to the compromised early cognitive processing.</p> </div

The ITC showing consistency between the trials and the degree of phase-locking to the target stimuli.

<p>Highest event-related phase consistencies for each condition are plotted in red, and lowest in green (range 0 to 1, no consistency to full consistency respectively). Statistical significance is illustrated by red/green frames, in which red areas signify statistically significant (p<0.0125 for visual condition and p<0.01 for auditory condition, controlled for multiple comparisons) differences between the CI MS patients and the non-CI MS patients in time and in log spectral power.</p

The ITC showing consistency between the trials and the degree of phase-locking to the target stimuli.

<p>Highest event-related phase consistencies for each condition are plotted in red, and lowest in green (range 0 to 1, no consistency to full consistency respectively). Statistical significance is illustrated by red/green frames, in which red areas signify statistically significant (p<0.0125 for visual condition and p<0.01 for auditory condition, controlled for multiple comparisons) differences between MS patients and controls in time and in log spectral power.</p

The mean ERSPs time-locked to the presentation of target stimuli in visual and auditory conditions are showing IC cluster mean differences in log spectral EEG power (dB) relative to log power in pre-stimulus EEG baseline.

<p>Red areas indicate an increase in power and blue areas a decrease in power. Statistical significance is illustrated by red/green frames beside ERSP activation frames, in which red areas signify statistically significant (p<0.0125 for visual condition and p<0.01, controlled for multiple comparisons) differences between the MS patients and controls in time and in log spectral power.</p

The scalp-based analysis of A) ERP, B) topography, C) ERSP, C) ITC of post-target activations at Pz in visual and auditory condition; comparison of MS patients and controls on the left side, and of CI and non-CI MS patients on the right side.

<p>Statistically significant (p<.05) differences in ERP indicated by red, and in the ERSP and ITC difference frames by non-green areas relative to time and log spectral power.</p

Number of subjects and components in each IC cluster, and Talairach coordinates with associated Brodmann areas and brain regions of each IC cluster centroid.

<p>Note. BA = Brodmann area, IC = independent component, MS = MS patients, C = controls, CI = CI MS patients, non-CI = non-CI MS patients.</p

The mean ERSPs time-locked to the presentation of target stimuli in visual and auditory conditions are showing IC cluster mean differences in log spectral EEG power (dB) relative to log power in pre-stimulus EEG baseline.

<p>Red areas indicate an increase in power and blue areas a decrease in power. Statistical significance is illustrated by red/green frames beside ERSP activation frames, in which red areas signify statistically significant (p<0.0125 for visual condition and p<0.01, controlled for multiple comparisons) differences between CI MS patients and the non-CI MS patients in time and in log spectral power.</p

Demographical and behavioural data of subjects.

<p>Note. Non-CI = MS patients with the highest PASAT Z-score, CI = MS patients with the lowest Z-score, PASAT = Paced Auditory Serial Addition Test, EDSS = Expanded Disability Status Scale, RT = reaction time, SD = standard deviation, IQR = interquartile range.</p