AJNR. American journal of neuroradiology · 2026
Ventral Attention Network Connectivity Differentiates Radiologically Isolated Syndrome from Multiple Sclerosis: A Longitudinal Resting-State fMRI Study.
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Díez-Cirarda María, Matías-Guiu Jordi A, Ruiz-Ortiz Mariano, Aladro Yolanda, Cuevas Constanza, Domingo-Santos Ángela, Galán Sánchez-Seco Victoria, Labiano-Fontcuberta Andrés, Gómez-López Ana, Salgado-Cámara Paula, Costa-Frossard Lucienne, Monreal Enric, Sainz de la Maza Susana, Matías-Guiu Jorge, Gil-Martínez Lidia, Yus-Fuertes Miguel, Montero-Escribano Paloma, Martínez-Ginés María Luisa, Ayuso-Peralta Lucía, Melero Helena, Malpica Norberto, Benito-León Julián
Аннотация
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: Fatigue increased in MS but was stable in RIS. VAN connectivity showed opposing trajectories (group × time; P < .001): RIS showed increased within-VAN connectivity and increased within-dorsal attention network connectivity versus HC, whereas MS showed decreased within-VAN connectivity. In MS, VAN connectivity increased with orbitofrontal and striatal regions and decreased with thalamus/caudate (FWE P < .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.
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: Fatigue increased in MS but was stable in RIS. VAN connectivity showed opposing trajectories (group × time; P < .001): RIS showed increased within-VAN connectivity and increased within-dorsal attention network connectivity versus HC, whereas MS showed decreased within-VAN connectivity. In MS, VAN connectivity increased with orbitofrontal and striatal regions and decreased with thalamus/caudate (FWE P < .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.