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Altered functional and structural connectivities in patients with MS

A 3-T study

From the Neuroimaging Research Unit (M.A.R., E.P., M.A., P.V., M.F.), Department of Neurology (M.A.R., M.A., G.C., M.F.), CERMAC (M.A.R., A.F., G.S., M.F.), and Department of Neuroradiology (A.F., G.S.), Scientific Institute and University Ospedale San Raffaele, Milan Italy.

Address correspondence and reprint requests to Dr. Massimo Filippi, Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Via Olgettina, 60, 20132 Milan, Italy m.filippi{at}hsr.it

Objective: To determine the functional and structural substrates of motor network dysfunction in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: Using a 3-T scanner, in 12 right-handed RRMS patients and 14 matched controls, we acquired diffusion tensor (DT) MRI and functional MRI during the performance of a simple motor task with the right (R) hand. Using DT MRI tractography, we calculated DT-derived metrics from several motor and nonmotor white matter (WM) fiber bundles. Functional connectivity analysis was performed using SPM2.

Results: Compared with control, MS patients had abnormal DT MRI metrics of all the WM bundles studied. Compared with controls, MS patients had more significant activations of the left (L) supplementary motor area (SMA), the L primary sensorimotor cortex (SMC), and the R cerebellum. They also had increased functional connectivity between the R primary SMC and the R cerebellum (p = 0.01) and the L SMA and the L primary SMC (p = 0.04). Coefficients of altered connectivity were correlated with structural MRI metrics of tissue damage of the corticospinal and the dentatorubrothalamic tract (r values ranging from –0.73 to 0.85).

Conclusions: The correlations found between measures of functional connectivity and structural damage to some of the major brain motor white matter bundles suggest an adaptive role of functional connectivity changes in limiting the clinical consequences of structural damage in patients with relapsing-remitting multiple sclerosis. Combining measures of altered functional and structural connectivities of specific brain networks is a promising tool to elucidate the mechanisms responsible for clinical manifestations of CNS damage.

Abbreviations: 9-HPT = nine-hole peg test; CC = corpus callosum; CST = corticospinal tract; DCM = dynamic causal model; DRT = dentatorubrothalamic; DT = diffusion tensor; EDSS = Expanded Disability Status Scale; FA = fractional anisotropy; fMRI = functional MRI; FOV = field of view; LL = lesion load; MD = mean diffusivity; MS = multiple sclerosis; OR = optic radiation; ROI = region of interest; RRMS = relapsing-remitting MS; SFOF = superior fronto-occipital fasciculus; SLF = superior longitudinal fasciculus; SMA = supplementary motor area; SMC = sensorimotor cortex; TE = echo time; TR = repetition time; WM = white matter.

Supported by a grant from FISM (2004/R/7).

Disclosure: The authors report no conflicts of interest.

Received April 17, 2007. Accepted in final form June 1, 2007.