Ventral Attention Network Connectivity Differentiates Radiologically Isolated Syndrome from Multiple Sclerosis: A
María Díez-Cirarda1, Jordi A Matías-Guiu1,2, Mariano Ruiz-Ortiz3,4
1From the Department of Neurology (M.D.-C., J.A.M.-G., C.C., J.M.-G., P.M.-E.), Hospital Universitario Clínico San Carlos, Health Research Institute "San Carlos" (IdISCC), Madrid, Spain.
AJNR. American Journal of Neuroradiology
|February 9, 2026
Summary
Radiologically Isolated Syndrome (RIS) and Multiple Sclerosis (MS) show different brain connectivity changes over time. These changes in the ventral attention network (VAN) correlate with fatigue levels, offering potential new biomarkers for early MS detection.
Area of Science:
- Neuroimaging
- Neurology
- Medical Research
Background:
- Radiologically Isolated Syndrome (RIS) presents with incidental Multiple Sclerosis (MS)-like MRI lesions.
- Longitudinal resting-state fMRI studies were lacking to understand brain-symptom links in RIS.
Purpose of the Study:
- To compare clinical, neuropsychological, and resting-state functional connectivity (FC) trajectories over 14 months in RIS, MS, and healthy controls (HC).
- To investigate the relationship between changes in FC and fatigue.
- To identify potential biomarkers for differentiating RIS and MS.
Main Methods:
- 19 RIS, 20 MS, and 22 HC underwent baseline and 14-month assessments including fatigue, neuropsychology, and 3T MRI (rs-fMRI, 3D T1, FLAIR).
- FC was analyzed within canonical networks and using seed-to-voxel analyses for the ventral attention network (VAN).
- Statistical analyses included repeated-measures ANOVA, regression for FC-fatigue relationships, and ROC curves for discrimination.
Main Results:
- Fatigue remained stable in RIS but increased in MS.
- Opposing VAN connectivity trajectories were observed: RIS showed increased within-VAN connectivity, while MS showed decreased within-VAN connectivity.
- Changes in VAN connectivity predicted fatigue reduction, and a composite VAN metric differentiated RIS from MS with high accuracy (AUC=0.919).
Conclusions:
- RIS and MS exhibit distinct, VAN-centric FC trajectories that parallel their differing fatigue evolution.
- Longitudinal FC metrics derived from the VAN may serve as sensitive, noninvasive biomarkers for early MS detection, complementing traditional lesion imaging.
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