Delayed P100-Like Latencies in Multiple Sclerosis: A Preliminary Investigation Using Visual Evoked Spread Spectrum Analysis.

Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis

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

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

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