Abstract
Evoked potentials (EPs) are well established in clinical practice for diagnosis and prognosis in multiple sclerosis (MS). However, their value is limited to the assessment of their respective functional systems. Here, we used transcranial magnetic stimulation (TMS) coupled with electroencephalography (TMS-EEG) to investigate cortical excitability and spatiotemporal dynamics of TMS-evoked neural activity in MS patients. Thirteen patients with early relapsing–remitting MS (RRMS) with a median Expanded Disability Status Scale (EDSS) of 1.0 (range 0–2.5) and 16 age- and gender-matched healthy controls received single-pulse TMS of left and right primary motor cortex (L-M1 and R-M1), respectively. Resting motor threshold for L-M1 and R-M1 was increased in MS patients. Latencies and amplitudes of N45, P70, N100, P180, and N280 TMS-evoked EEG potentials (TEPs) were not different between groups, except a significantly increased amplitude of the N280 TEP in the MS group, both for L-M1 and R-M1 stimulation. Interhemispheric signal propagation (ISP), estimated from the area under the curve of TEPs in the non-stimulated vs. stimulated M1, also did not differ between groups. In summary, findings show that ISP and TEPs were preserved in early-stage RRMS, except for an exaggerated N280 amplitude. Our findings indicate that TMS-EEG is feasible in testing excitability and connectivity in cortical neural networks in MS patients, complementary to conventional EPs. However, relevance and pathophysiological correlates of the enhanced N280 will need further study.
Highlights
Multiple sclerosis (MS) is an inflammatory and secondary neurodegenerative disorder associated with disseminated cortical and white-matter lesions (Dendrou et al, 2015)
Results show that low motor EPs (MEPs) amplitudes and slow central motor conduction time (CMCT) reflect axonal loss or chronodispersion due to inhomogeneous conduction slowing in fibers of the corticospinal tract (Hess et al, 1986, 1987)
There was no difference of resting motor threshold (RMT) between L-M1 and R-M1 in multiple sclerosis (MS) [t(12) = −0.170, p = 0.868], whereas healthy control (HC) had a lower RMT in L-M1 vs. R-M1 [t(15) = −2.192, p = 0.045]
Summary
Multiple sclerosis (MS) is an inflammatory and secondary neurodegenerative disorder associated with disseminated cortical and white-matter lesions (Dendrou et al, 2015). Recording of motor EPs (MEPs) obtained with transcranial magnetic stimulation (TMS) can be used to measure the excitability of the human motor cortex as well as the functional integrity of the corticospinal tract and callosal fibers (Kobayashi and Pascual-Leone, 2003; Jung et al, 2006; Ziemann, 2011). Given these properties, TMS has been applied in the context of MS disease to assist diagnostic processes. Multimodal EPs have been demonstrated to predict disability progression in early relapsing– remitting MS (RRMS) (Jung et al, 2008)
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