Time-Varying Brain Functional Reconfiguration Patterns Associated With Fatigue in Multiple Sclerosis.

Area of Science:

• Neuroscience
• Medical Imaging
• Neurology

Background:

• Fatigue affects a significant portion of people with multiple sclerosis (pwMS), severely impacting daily life.
• The underlying neurobiological mechanisms of MS-related fatigue are not well understood.
• Aberrant time-varying brain network reconfigurations may play a role in MS fatigue.

Purpose of the Study:

• To investigate the association between time-varying brain network reconfigurations and fatigue in pwMS.
• To explore if specific patterns of network reconfiguration correlate with motor and cognitive fatigue.

Main Methods:

• Cross-sectional study involving 155 pwMS and 48 healthy controls (HC).
• Resting-state functional MRI was used to assess time-varying functional connectivity.
• Measures of network reconfiguration included promiscuity, flexibility, cohesion, and disjointedness.
• Fatigue was assessed using the Fatigue Scale for Motor and Cognitive Function.

Main Results:

• Higher total and motor fatigue in pwMS correlated with increased global brain network promiscuity and disjointedness.
• Motor fatigue was also associated with greater network flexibility.
• Increased limbic network promiscuity was linked to higher total and motor fatigue in pwMS.
• These associations remained significant after controlling for clinical factors and brain damage.

Conclusions:

• Elevated fatigue levels in pwMS are associated with more unstable and dispersed brain network reconfigurations.
• Limbic network instability may be particularly relevant, potentially reflecting reward processing dysfunction.
• The findings suggest that altered brain network dynamics contribute to the experience of fatigue in multiple sclerosis.