Cognitive outcomes in multiple sclerosis are shaped by divergent functional connectivity trajectories

Area of Science:

• Neuroscience
• Medical Imaging
• Cognitive Science

Background:

• Cognitive impairment in people with multiple sclerosis (pwMS) is heterogeneous, necessitating research into pathophysiological processes and adaptive brain mechanisms.
• Understanding functional connectivity (FC) changes and their relationship with cognitive trajectories is crucial for pwMS.

Purpose of the Study:

• To investigate longitudinal changes in functional connectivity (FC) over seven years in pwMS.
• To determine if distinct FC patterns differentiate individuals with cognitive decline from those with stable cognitive performance.
• To explore the association between FC alterations, grey matter (GM) volume, and cognitive trajectories in pwMS.

Main Methods:

• Longitudinal analysis of 58 pwMS using cognitive assessments (Rao's battery) and functional MRI over seven years.
• Calculation of graph-based network metrics (global/node strength, efficiency, clustering coefficient) and regional normalized grey matter (GM) volumes.
• Application of mixed-effect regression models to analyze FC and GM volume differences and their link to cognition.

Main Results:

• Patients with cognitive decline showed reduced node strength, local efficiency, and clustering coefficient, particularly in deep GM and parietal cortex.
• The cognitively stable group exhibited increased node strength and local efficiency in temporal and prefrontal cortices.
• Both groups experienced reduced GM volume; distinct FC trajectories were associated with cognitive outcomes, suggesting compensatory network reorganization in stable patients.

Conclusions:

• Distinct functional connectivity (FC) trajectories are associated with cognitive outcomes in people with multiple sclerosis (pwMS) over a seven-year period.
• Cognitively stable pwMS may utilize compensatory network reorganization to mitigate the impact of structural damage on cognitive function.
• Findings highlight the brain's adaptive capacity and its role in shaping cognitive trajectories in MS.