Multimodal brain network disruption and structural-functional decoupling in overt hypothyroidism

Overt hypothyroidism (OH) is frequently associated with cognitive impairment and emotional disturbances, yet its impact on the fundamental relationship between brain structure and function remains unclear.

A total of 45 patients with OH and 55 healthy controls (HCs) were enrolled in this study. All participants underwent psychological scale assessments, as well as diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI) scans. Based on the AAL90 atlas, structural connectivity (SC) was constructed from DTI data using PANDA, while functional connectivity (FC) was derived from rs-fMRI data using DPABI. Global and nodal topological properties were calculated using GRETNA and compared between groups. Whole-brain SC-FC coupling was computed as the Pearson correlation between non-zero SC edges and their corresponding FC values. Cortical regions were divided into seven Yeo-7 networks, with subcortical structures as a separate group, to calculate SC-FC coupling within each subnetwork. All results were FDR-corrected for multiple comparisons.

Compared with HCs, the OH group showed reduced small-worldness and clustering coefficient in structural networks, alongside decreased global efficiency in both structural and functional networks. Nodal analyses revealed reduced efficiency and centrality in multiple key regions, including nodes within the default mode network, limbic system, and salience network. Notably, OH patients displayed significantly weakened SC-FC coupling within the limbic system and salience networks. The disruption of these brain networks was significantly associated with both poorer cognitive performance and emotional disturbances in OH.

This study demonstrates topological disruptions and impaired SC-FC coupling in specific brain networks in OH, providing new insights into the neurobiological mechanisms underlying cognitive and emotional deficits.