Ventral Attention Network Connectivity Differentiates Radiologically Isolated Syndrome from Multiple Sclerosis: A Longitudinal Resting-State fMRI Study
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND AND PURPOSE: Radiologically isolated syndrome (RIS) entails incidental MS-like MRI lesions. Longitudinal fMRI could clarify brain-symptom links; however, no longitudinal resting-state fMRI studies in RIS existed until now. The goal was to 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. MATERIALS AND METHODS: Nineteen patients with RIS, 20 with MS, and 22 HC completed baseline and 14-month assessments (fatigue, neuropsychology) and 3T MRI (resting-state fMRI, 3D T1, FLAIR). FC within canonical networks and VAN seed-to-voxel connectivity were tested in the CONN toolbox using repeated-measures ANOVA with family-wise error (FWE) correction for multiple comparisons. Regression analyses examined associations between longitudinal changes in FC and changes in fatigue; receiver operating characteristic curves evaluated the ability of longitudinal FC measures to distinguish between groups. RESULTS: < .05). Greater increases in within-VAN and VAN-thalamus/caudate connectivity over time were associated with reductions in fatigue. A composite VAN metric differentiated RIS from MS (area under the curve = 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.
DOI: 10.3174/ajnr.a9212
Authors: María Díez-Cirarda, Jordi A. Matías-Guiu, Mariano Ruiz-Ortiz, Yolanda Aladro, Constanza Cuevas, Ángela Domingo-Santos, Victoria Galán Sánchez-Seco, Andrés Labiano-Fontcuberta, Ana Gómez-López, Paula Salgado-Cámara, Lucienne Costa-Frossard, Enric Monreal, Susana Sainz de la Maza, Jorge Matías-Guiu, Lidia Gil-Martínez, Miguel Yus-Fuertes, Paloma Montero-Escribano, María Luisa Martínez-Ginés, Lucía Ayuso-Peralta, Helena Melero, Norberto Malpica, Julián Benito-León
Institutions: Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Universidad Complutense de Madrid, Research Institute Hospital 12 de Octubre, Hospital Universitario 12 De Octubre, Hospital Universitario de Getafe, Universidad Europea de Madrid, Spanish Multiple Sclerosis Network, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Hospital General Universitario Gregorio Marañón, Universidad Rey Juan Carlos, Biomedical Research Networking Center on Neurodegenerative Diseases
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7128423141