Abstract
Demyelination can be assessed structurally by magnetic resonance imaging and functionally with transcranial magnetic stimulation. Here we combined these techniques to investigate demyelination of the corpus callosum in multiple sclerosis. Our objective was to determine if corpus callosal demyelination impacts transcallosal inhibition (TCI). TCI is a brief suppression of voluntary activity in the primary motor cortex elicited by stimulation of the homologous region of the contralateral hemisphere, which is assumed to be transmitted via the corpus callosum. Magnetic resonance imaging and transcranial magnetic stimulation were performed in 26 participants with MS and 10 controls. Myelin water fraction (MWF) was measured in five regions of the corpus callosum and compared with the onset latency, duration, and depth of TCI as measured by electromyography at the forearm. Callosal MWF was greatest posteriorly compared to other regions of the corpus callosum. Lower MWF in MS compared to controls was more pronounced in the posterior corpus callosum. MS participants had a prolonged TCI duration (p=0.016), which correlated with EDSS (p=0.020) and disease duration (p=0.045). In MS, TCI depth correlated negatively with the MWF of the posterior callosal midbody (p=0.039), a region thought to mediate TCI transmission. In summary, TCI duration was increased in MS and demyelination of the posterior corpus callosum midbody was associated with measurable functional changes. This work demonstrates the potential for combining magnetic resonance imaging and transcranial magnetic stimulation with electromyography to draw insights about structure-function relationships in MS pathophysiology.
Highlights
Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by demyelination in focal lesions and normal appearing white matter (NAWM)
Our study investigated the process of transcallosal inhibition (TCI), the distribution of CC myelin water fraction (MWF), and the effects of CC demyelination on transcallosal connectivity in relapsing remitting MS (RRMS)
Taken together with previous studies, our work further describes the diagnostic value of ipsilateral silent period (iSP) onset and duration, demonstrating that iSP duration is a sensitive MS biomarker
Summary
Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by demyelination in focal lesions and normal appearing white matter (NAWM). The principles of myelin water imaging are based on the fact that in CNS tissue the MR signal decay due to T2 relaxation follows a multi-exponential time course. Non-negative least squares methods can fit the T2 decay curve to a sum of exponential components [1], which arise from water in different environments. The myelin water fraction (MWF) is the signal fraction with short T2 times (10–40 ms) arising from water trapped between myelin bilayers and has been validated as a marker for myelin in CNS tissue [2,3,4,5,6,7]. Lesions demonstrate heterogeneously decreased MWF and NAWM MWF is ∼16% lower on average in individuals with MS than in controls [8]
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