To investigate the associations between clinical disability and cognitive status with thalamic nuclei volumes in multiple sclerosis (MS).

Reduced thalamic volume has frequently been reported in MS and related to deficits including clinical disability and cognitive dysfunction. Although comprised of many nuclei with distinct functional roles, the thalamus is often treated as a single structure. The assessment of its individual components may allow for a more precise characterization of the associations between clinical deficits and thalamic volume.

MS patients were prospectively enrolled and scanned using 3T MRI. Participants underwent clinical and neuropsychological evaluation including: Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test (9-HPT), and Timed 25-Foot Walk (T25-FW), Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R), and California Verbal Learning Test–2^nd edition (CVLT2), Anterior, intralaminar, lateral, medial, ventral, posterior nuclei (including the pulvinar), and total thalamus volumes were measured using FreeSurfer. Regression models assessed associations between thalamic volumes and clinical/neuropsychological outcomes, controlling for age, sex and education.

One hundred and eight MS patients were studied. Volumes of individual thalamic nuclei rather than total structural volume were retained in the final model for all regression analyses. Lateral nuclei volume explained incremental variance for EDSS (adjusted R2=.345, R2 change=.178, p<.0001) and SDMT (adjusted R2=.256, R2 change=.144, p<.0001). Anterior nuclei volume explained incremental variance for BVMT-R (adjusted R2=.191, R2 change=.089, p=.001) and CVLT2 (adjusted R2=.218, R2 change=.056, p=.007). Ventral nuclei volume explained incremental variance for T25-FW (adjusted R2=.132, R2 change=.107, p=.001). Posterior nuclei volume explained incremental variance for 9-HPT (adjusted R2=.071, R2 change=.062, p=.009). Results were similar, albeit with smaller R2 changes, when forcing total thalamic volume into the model except for 9-HPT where no nuclei were retained.

Our findings highlight the importance of individual thalamic nuclei volume in explaining disparate aspects of physical and cognitive impairment in MS.