Structure-Function Decoupling of the Sensorimotor and Default Mode Networks in Black Americans With MS

Multiple sclerosis (MS) exhibits racially disparate rates of disease progression. Black people with MS (B-PwMS) experience a more severe disease course than non-Hispanic White people with MS (NHW-PwMS). Here we investigated structural and functional connectivity as well as structure-function decoupling in the sensorimotor and default mode networks (SMN and DMN, respectively), which play a key role in determining physical and cognitive disability in people with MS.

A total of 176 participants (50 B-PwMS, 50 NHW-PwMS, 41 Black healthy controls (B-HCs), and 35 NHW-HCs) underwent 3T-MRI with T1, resting-state functional, & diffusion imaging, and clinical assessment with Expanded-Disability-Status-Scale (EDSS) & Symbol-Digit-Modalities-Test (SDMT). T1-weighted images were lesion-filled and segmented to obtain cortical, subcortical, and cerebellar structures. Diffusion and functional MRI datasets were preprocessed, and structural and functional connectivity were extracted between regions defined by the AAL3 atlas. Global and local network measures were extracted for both structural and functional connectivity, and structure-function decoupling was quantified by calculating the correlation between the strengths of the two networks, considering only edges with non-zero structural connectivity. Network measures were compared between subgroups, accounting for the impact of demographics and social determinants of health, with correction for multiple comparisons.

Despite similar disease duration, treatment exposure, lesion load and brain volumes, B-PwMS exhibited higher EDSS and lower SDMT scores compared to NHW-PwMS, which were influenced by total income and body mass index. In both B- and NHW-PwMS, structural global efficiency and streamline density were lower in the SMN and DMN compared to their respective HCs. Structural characteristic path length in SMN was significantly higher in B-PwMS versus B-HCs, whereas no significant differences were observed in NHW groups. Extensive local rearrangements of structural and functional hubs were observed in the SMN and DMN of B-PwMS compared to B-HCs and NHW-PwMS. B-PwMS showed greater structure-function decoupling in the SMN as compared to the other groups. There was a trend towards a higher decoupling in the DMN with lower SDMT scores (ρ = -0.20, p = 0.05), and higher decoupling in the SMN with higher EDSS scores (ρ = 0.20, p = 0.06).

Despite similar brain volumes and lesion load, B-PwMS showed a greater rearrangement of brain structural and functional connectivity within the SMN and DMN when compared with NHW-PwMS. Moreover, B-PwMS showed a higher degree of structure-function decoupling in the SMN, with a trend towards association with increased physical disability.