Monoaminergic network abnormalities are associated with fatigue in pediatric multiple sclerosis

Area of Science:

• Neuroscience
• Neurology
• Radiology

Background:

• Fatigue is a common yet poorly understood symptom in pediatric multiple sclerosis (pedMS).
• Investigating the neural underpinnings of fatigue in pedMS is crucial for developing effective treatments.

Purpose of the Study:

• To determine if resting-state functional connectivity (FC) abnormalities in monoaminergic networks contribute to fatigue in pedMS patients.

Main Methods:

• Fifty-five pedMS patients and 23 healthy controls (HC) underwent resting-state functional MRI (fMRI).
• Patients were classified as fatigued (F) or non-fatigued (NF) using the Fatigue Severity Scale (FSS).
• Dopamine-, noradrenaline-, and serotonin-related FC patterns were analyzed using constrained independent component analysis and PET atlases.

Main Results:

• Fatigued pedMS patients exhibited decreased dopamine-related FC in the right postcentral gyrus and left insula, and increased FC in the left middle temporal gyrus and cerebellum.
• Abnormalities in noradrenaline-related networks included decreased FC in the left superior parietal lobule and increased FC in the right thalamus.
• Serotonin-related networks showed decreased FC in the right angular gyrus and increased FC in the right postcentral gyrus in fatigued pedMS patients compared to non-fatigued counterparts.

Conclusions:

• Specific abnormalities in dopamine, noradrenaline, and serotonin networks are associated with fatigue in pedMS.
• These findings identify potential pathological markers for fatigue in pedMS.
• Monoaminergic network alterations may represent therapeutic targets for managing fatigue in pediatric MS.