Structure-Function Decoupling of the Sensorimotor and Default Mode Networks in Black Americans With MS.
Emilio Cipriano, Giacomo Boffa, Maria Petracca, Marta Ponzano, Nicole Graziano, Claire Wigley, Claire Riley, Jonathan Howard, Pietro Bontempi, Sylvia Klineova, Fred Lublin, Matilde Inglese
Annals of Clinical and Translational Neurology February 12, 2026 DOI: 10.1002/acn3.70331 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Cross-sectional observational neuroimaging study Peer reviewed |
|---|---|
| Sample size | 176 |
| Population | Adults with multiple sclerosis and healthy controls: 50 Black people with MS, 50 non-Hispanic White people with MS, 41 Black healthy controls, and 35 non-Hispanic White healthy controls |
| Measures | Expanded-Disability-Status-Scale (EDSS), Symbol-Digit-Modalities-Test (SDMT) |
| Topics | Default mode network |
| Keywords | Nerve net Humans Multiple sclerosis Magnetic resonance imaging Adult Middle aged Female Connectome Sensorimotor cortex Functional connectivity Structural connectivity Structure‐function coupling |
| Key findings | Despite similar disease duration, treatment exposure, lesion load, and brain volumes, Black people with MS showed higher EDSS and lower SDMT scores than non-Hispanic White people with MS, influenced by total income and body mass index. Black people with MS also showed greater structural and functional connectivity rearrangement and greater structure-function decoupling in the sensorimotor network, with trends toward associations between decoupling and higher physical disability and lower cognitive scores. |
Abstract
Background and
Objectives: 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.
Methods: 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.
Results: 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).
Discussion: 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.
Comparable studies
Other experimental studies on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Functional connectivity of default mode network components: Correlation, anticorrelation, and causality Healthy subjects | 2008 | Observational study using resting-state fMRI and seed correlation analysis | |
| Patterns of Brain Activity Supporting Autobiographical Memory, Prospection, and Theory of Mind, and Their Relationship to the Default Mode Network Healthy subjects | 2009 | Experimental study using fMRI | |
| Dynamic reconfiguration of the default mode network during narrative comprehension Human subjects | 2016 | Experimental study | |
| Broadband Cortical Desynchronization Underlies the Human Psychedelic State Healthy human participants | 2013 | Experimental study | |
| The brain on art: intense aesthetic experience activates the default mode network Human observers | 2012 | Observational study with fMRI and behavioral analysis |