Graph theoretical analysis indicates cognitive impairment in MS stems from neural disconnection

Abstract

Background: The mechanisms underlying cognitive impairment in MS are still poorly understood. However, due to the specific pathology of MS, one can expect alterations in connectivity leading to physical and cognitive impairment. Aim: In this study we aimed at assessing connectivity differences in EEG between cognitively impaired (CI) and cognitively preserved (CP) MS patients. We also investigated the influence of the measures used to construct networks. Methods: We included 308 MS patients and divided them into two groups based on their cognitive score. Graph theoretical network analyses were conducted based on networks constructed using different connectivity measures, i.e. correlation, correlation in the frequency domain, coherence, partial correlation, the phase lag index and the imaginary part of coherency. The most commonly encountered network parameters were calculated and compared between the two groups using Wilcoxon's rank test. Clustering coefficients and path lengths were normalized to a randomized mean clustering coefficient and path length for each patient. False discovery rate was used to correct for the multiple comparisons and Cohen's d effect sizes are reported. Results: Coherence analysis suggests that theta and delta connectivity is significantly smaller in cognitively impaired patients. Small-worldness differences are found in networks based on correlation, theta and delta coherence and correlation in the frequency domain. Modularity was related to age but not to cognition. Conclusion: Cognitive deterioration in MS is a symptom that seems to be caused by neural disconnections, probably the white matter tracts connecting both hemispheres, and leads to a wide range in network differences which can be assessed by applying GTA to EEG data. In the future, these results may lead to cheaper and more objective assessments of cognitive impairment in MS.

Keywords

• Network analysis
• Cognitive impairment
• Graph theoretical analysis
• Connectome
• Multiple sclerosis