Network Localization of Fatigue in Multiple Sclerosis

Area of Science:

• Neuroscience
• Neurology
• Medical Imaging

Background:

• Fatigue is a prevalent symptom in multiple sclerosis (MS), significantly impacting patient quality of life.
• The precise neurobiological underpinnings of MS-related fatigue remain incompletely understood.
• This study investigates brain networks associated with fatigue in MS patients by examining lesion locations and their connectivity patterns.

Purpose of the Study:

• To identify specific brain networks and neural substrates linked to fatigue in multiple sclerosis (MS).
• To explore the relationship between lesion connectivity and fatigue severity in MS patients.
• To determine if the identified MS fatigue network is reproducible in other neurological conditions like stroke.

Main Methods:

• Voxel-lesion symptom mapping and lesion network mapping were employed to analyze lesion-symptom associations.
• The study included 38 MS patients with fatigue and 21 without, with findings validated in two independent datasets (199 MS patients, 85 stroke patients).
• Resting-state functional connectivity MRI (rs-fcMRI) was utilized in one validation dataset.

Main Results:

• No specific anatomical lesion locations were directly associated with fatigue in MS.
• Lesions linked to fatigue showed connectivity to a network peaking in the right premotor cortex and negatively with the left temporal pole.
• Connectivity from the premotor cortex to other brain regions correlated with MS fatigue severity and was reproducible in post-stroke fatigue.

Conclusions:

• Fatigue in multiple sclerosis (MS) localizes to a specific brain network, rather than isolated lesion sites.
• Lesion connectivity, particularly involving the premotor cortex, is a key neural substrate for MS fatigue.
• The findings provide crucial insights into the neurobiological mechanisms driving fatigue in MS and related conditions.