Disruption of the Atrophy-based Functional Network in Multiple Sclerosis Is Associated with Clinical Disability:
Florence L Chiang1, Max Feng1, Rebecca S Romero1
1From the Department of Radiology (F.L.C., B.T., P.T.F.), Research Imaging Institute (F.L.C., C.G.F., S.D., J.P.G., P.T.F.), Joe R. and Teresa Lozano Long School of Medicine (F.L.C., M.F., R.S.R., B.T., P.T.F.), and Department of Neurology (R.S.R., P.T.F.), The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, MC7800, San Antonio, TX 78229-3900; Division of Methodology, Measurement and Statistical Analysis, Texas State University, San Marcos, Tex (L.P.); Department of Radiology, Division of Neuroradiology, The University of Texas Southwestern Medical Center, Dallas, Tex (F.F.Y.); Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Mass (S.Y.H.); Department of Radiology, Division of Neuroradiology, Massachusetts General Hospital, Boston, Mass (S.Y.H.); and South Texas Veteran Health Care System, Research Service, San Antonio, Tex (P.T.F.).
The network degeneration hypothesis explains gray matter atrophy in multiple sclerosis (MS) by showing how functional networks are affected. This study confirms that disrupted brain networks in MS correlate with clinical disability.
Area of Science:
- Neuroimaging
- Neurology
- Systems Neuroscience
Background:
- Gray matter (GM) atrophy in multiple sclerosis (MS) follows a specific pattern linked to clinical disability.
- The underlying mechanisms for regional GM atrophy specificity in MS are not well understood.
- The network degeneration hypothesis (NDH) proposes that localized GM atrophy in MS is mediated by functional brain networks.
Purpose of the Study:
- To test the NDH in MS using a data-driven approach with the atrophy-based functional network (AFN) model.
- To validate the AFN model in an independent sample of individuals with MS.
Main Methods:
- Structural equation modeling was used for model fit testing, calculating semipartial correlations.
- Model verification utilized coordinate-based data from healthy controls (n=9035 experiments) from the BrainMap database.
- Model validation involved prospectively acquired resting-state functional MRI data from individuals with relapsing-remitting MS (n=20).
Main Results:
- The AFN model demonstrated excellent fit in healthy control data (RMSEA=0.037).
- In individuals with MS, the model showed deviation from optimal fit (RMSEA=0.071), correlating significantly with Expanded Disability Status Scale (EDSS) scores (r=0.68, P=.002).
- Reduced functional network integrity in MS positively correlated with clinical disability.
Conclusions:
- The atrophy-based functional network model supports the network degeneration hypothesis in multiple sclerosis.
- Functional network disruption is a key factor in the regional specificity of gray matter atrophy in MS.
- Resting-state functional MRI reveals that impaired functional network integrity in MS is strongly associated with clinical disability.
