Short interval intracortical inhibition as measured by TMS-EEG

Abstract

The diagnosis of amyotrophic lateral sclerosis (ALS) relies on involvement of both upper (UMN) lower motor neurons (LMN). Yet, there remains no objective marker of UMN involvement, limiting early diagnosis of ALS. This study establishes whether TMS combined with EEG can be used to measure short-interval intracortical inhibition (SICI) via TMS evoked potentials (TEP) in healthy volunteers -an essential first step in developing an independent marker of UMN involvement in ALS.We hypothesised that a SICI paradigm would result in characteristic changes in the TMSevoked EEG potentials that directly mirror the changes in MEP.TMS was delivered to the left motor cortex using single-pulse and three inhibitory stimulation paradigms. SICI was present in all three conditions. TEP peaks were reduced predominantly under the SICI 70 protocol but less so for SICI 80 and not at all for SICI 90. There was a significant negative correlation between MEPs and N45 TEP peak for SICI 70 (rho = -0.54 , p = 0.04). In other words, as MEPs becomes inhibited the N45 increases. The same trend was maintained across SICI 80 and 90 (SICI 80, rho = -0.5, p = 0.06; SICI 90, rho = -0.48, p = 0.07). Additional experiments suggest these results cannot be explained by artefact.We establish that motor cortical inhibition can be measured during a SICI 70 protocol expanding on previous work. We have carefully considered the role of artefact in TEPs and have taken a number of steps to show that artefact cannot explain these results and we suggesting the differences are cortical in origin. TMS-EEG has potential to aid early diagnosis and to further understand central and peripheral pathophysiology in MND.

Alterations in cortical excitability during pain: A combined TMS-EEG Study

“…SICI refers to the reduction in MEP amplitude to a TMS pulse that is preceded 1-5ms by a subthreshold pulse, due to activation of GABA A receptors (Kujirai et al, 1993). Some studies have reported associations between SICI and the TEP N45 (Leodori et al, 2019;Rawji, Kaczmarczyk, Rocchi, Rothwell, & Sharma, 2019), suggesting the two may share common neurophysiological mechanisms. However, we also found that a larger reduction in MEP amplitude during pain was associated with less pain, while a larger increase in N45 peak during pain was associated with stronger pain ratings, suggesting that inhibitory processes mediating corticomotor excitability and the N45 peak during pain are distinct.…”

Modern Developments in Transcranial Magnetic Stimulation (TMS) – Applications and Perspectives in Clinical Neuroscience

“…Particularly in patients with brain tumors, the rMT can be frequently high in the tumor-affected hemisphere, and accurate mapping with a lower SI related to a lower determined rMT could permit successful use of nTMS even in the most demanding cases. This may also be highly relevant for other applications of nTMS in patients with brain tumors, such as language mapping [197][198][199][200][201]. In such applications, a higher SI is often used and stimulation is more widespread and, thus, can entail discomfort that negatively interferes with the mapping outcome.…”

“…For instance, the information given by TEPs obtained from M1 TMS may not completely overlap with those provided by MEPs; indeed, the latter arise from excitation of PTN and associated circuitry, whereas the former probably reflect activity of a larger ensemble of cortical cells [89,100,195]. Therefore, caution should be used when comparing conclusions drawn by the two variables, especially for ppTMS protocols, which were devised for MEPs, and are still of uncertain interpretation in the TMS-EEG setting [112,196,197]. Another issue is related to the use of TEPs to measure brain connectivity.…”

Contribution of TMS and TMS-EEG to the Understanding of Mechanisms Underlying Physiological Brain Aging

“…For instance, the information given by TEPs obtained from M1 TMS may not completely overlap with those provided by MEPs; indeed, the latter arise from excitation of PTN and associated circuitry, whereas the former probably reflect activity of a larger ensemble of cortical cells [ 89 , 100 , 195 ]. Therefore, caution should be used when comparing conclusions drawn by the two variables, especially for ppTMS protocols, which were devised for MEPs, and are still of uncertain interpretation in the TMS-EEG setting [ 112 , 196 , 197 ]. Another issue is related to the use of TEPs to measure brain connectivity.…”