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Conectividad de la red de atención ventral diferencia el síndrome radiológicamente aislado de la esclerosis múltiple:

María Díez-Cirarda¹, Jordi A Matías-Guiu¹, Mariano Ruiz-Ortiz¹

¹From the Departments of Neurology (M.D.-C., J.A.M.-G.,C.C., J.M.-G., P.M.-E.), Radiology (L.G.-M., M.Y.-F.), Hospital Universitario Clínico San Carlos. Health Research Institute "San Carlos" (IdISCC), Madrid, Spain; Department of Medicine (J.A.M.-G., J.M.-G., P.M.-E., J.B.-L.), Departamento de Psicobiología y Metodología en Ciencias del Comportamiento (H.M.), Faculty of Psychology, Complutense University of Madrid, Madrid, Spain; Department of Neurology (M.R.-O.,A.D.-S., V.G.S.-S., A.L.-F., A.G.-L., P.S.-C., J.B.-L.), Hospital Universitario 12 de Octubre Research Institute (imas12) (M.R.-O., J.B.-L.), Madrid, Spain; Department of Neurology (Y.A.), Getafe University Hospital, Madrid, Spain; Faculty of Biomedical and Health Sciences (Y.A.), European University of Madrid, Villaciosa de Odón (Madrid), Spain; Department of Neurology (L.C.-F., E.M., S.S.M.), Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), Madrid, Spain; Department of Medicine (E.M.), University of Alcalá de Henares, Neurology (L.A.-P.), Príncipe de Asturias University, Alcalá de Henares (Madrid), Spain; Department of Neurology (M.L.M.-G.), Gregorio Marañón General University Hospital, Madrid, Spain; Medical Image Analysis Laboratory (LAIMBIO) (N.M.), Rey Juan Carlos University, Móstoles, Madrid, Spain; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) (J.B.-L.), Madrid, Spain.

AJNR. American journal of neuroradiology

|February 9, 2026

Abstracto

Background:

Radiologically Isolated Syndrome (RIS) entails incidental Multiple Sclerosis (MS)-like MRI lesions. Longitudinal fMRI could clarify brain-symptom links; however, no longitudinal resting-state fMRI studies in RIS existed until now.

Objectives:

Compare 14-month clinical, neuropsychological, and resting-state functional connectivity (FC) trajectories in RIS, MS, and healthy controls (HC), and relate FC change to fatigue.

Methods:

Nineteen RIS, 20 MS, and 22 HC completed baseline and 14-month assessments (fatigue, neuropsychology) and 3T MRI (rs-fMRI, 3D T1, FLAIR). FC within canonical networks and the ventral attention network (VAN) seed-to-voxel (CONN) connections were tested with a repeated-measures ANOVA (FWE-corrected). Regression analysis related to FC to fatigue; ROC curves evaluated discrimination.

Results:

Fatigue rose in MS but was stable in RIS. VAN connectivity showed opposing trajectories (group × time, p < 0.001): RIS increased within-VAN (and within-DAN vs. HC), whereas MS decreased within-VAN. In MS, VAN connectivity increased with orbitofrontal and striatal regions and decreased with thalamus/caudate (FWE p<0.05). Greater increases in within-VAN and VAN-thalamus/caudate connectivity were predicted to lead to fatigue reduction. A composite VAN metric differentiated RIS from MS (AUC=0.919). Lesion volumes were unchanged.

Conclusions:

RIS and MS exhibit divergent, VAN-centered FC trajectories paralleling fatigue evolution. VAN-based longitudinal FC metrics may provide sensitive, noninvasive biomarkers that complement lesion measures in early MS.

Palabras clave:

esclerosis múltiple síndrome radiológicamente aislado resonancia magnética funcional en reposo red de atención ventral biomarcadores fatiga conectividad funcional neuroimagen neurología

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