Lesion-Independent Associations Between Thalamic Nuclei Volumes and Information Processing Speed in Multiple Sclerosis

Abstract

Background: Cognitive impairment in multiple sclerosis (MS) is driven by both focal inflammation and compartmentalized neurodegeneration, yet the relative effect of lesion-independent thalamic atrophy on information processing speed (IPS) remains unclear. Methods: This retrospective cohort study included 100 participants with MS. Automatic segmentation techniques quantified lesion load and delineated 26 thalamic regions of interest (ROIs). Linear models compared associations between ROI volumes and Symbol Digit Modalities Test (SDMT) performance in lesion-adjusted and unadjusted models. Results: Twenty-one of 26 ROIs showed significant SDMT associations before lesion adjustment; twelve remained significant after adjustment. Lesion-independent associations were observed in the global thalamus, sensory relay nuclei (ventral posterolateral, medial and lateral geniculate), and associative hubs (pulvinar and mediodorsal-parafascicular complex). These processing-associated ROIs exhibited significantly lower lesion-mediated effects (13.4%) than those losing significance after adjustment (34.2%, p < 0.001). Conclusion: Our findings suggest that IPS impairment reflects heterogeneous contributions from focal lesion-driven and chronic neurodegenerative pathology, with nucleus-specific phenotyping potentially informing identification of higher risk individuals.