Alterations of Thalamic Nuclei Volumes and the Intrinsic Thalamic Structural Network in Patients with Multiple Sclerosis-Related Fatigue

Fatigue is a debilitating and prevalent symptom of multiple sclerosis (MS). The thalamus is atrophied at an earlier stage of MS and although the role of the thalamus in the pathophysiology of MS-related fatigue has been reported, there have been few studies on intra-thalamic changes. We investigated the alterations of thalamic nuclei volumes and the intrinsic thalamic network in people with MS presenting fatigue (F-MS). The network metrics comprised the clustering coefficient (Cp), characteristic path length (Lp), small-world index (σ), local efficiency (E(loc)), global efficiency (E(glob)), and nodal metrics. Volumetric analysis revealed that the right anteroventral, right central lateral, right lateral geniculate, right pulvinar anterior, left pulvinar medial, and left pulvinar inferior nuclei were atrophied only in the F-MS group. Furthermore, the F-MS group had significantly increased Lp compared to people with MS not presenting fatigue (NF-MS) (2.9674 vs. 2.4411, P(AUC) = 0.038). The F-MS group had significantly decreased nodal efficiency and betweenness centrality of the right mediodorsal medial magnocellular nucleus than the NF-MS group (false discovery rate corrected p < 0.05). The F-MS patients exhibited more atrophied thalamic nuclei, poorer network global functional integration, and disrupted right mediodorsal medial magnocellular nuclei interconnectivity with other nuclei. These findings might aid the elucidation of the underlying pathogenesis of MS-related fatigue.