Efficacy and safety of novel high-frequency multi-train stimulation for recording transcranial motor evoked potentials in a rat model

Recently, low-frequency multi-train stimulation (MTS) was shown to effectively enhance transcranial motor-evoked potentials (TcMEPs). In contrast, high- frequency double-train stimulation was reported to elicit a marked facilitation. The aim of this study was to evaluate the efficacy of high-frequency MTS in the augmentation of potentials. In addition, we investigated the safety of high-frequency MTS, behaviorally and histologically. TcMEPs were recorded from the triceps surae muscle in 38 rats. A multipulse stimulus was delivered repeatedly at different rates (2, 5, 10, 20, and 50 Hz), and was defined as MTS. A conditioned taste aversion method was used to investigate the effect of high-frequency MTS on learning and memory function. Subsequently, animals were sacrificed, and the brains were removed and examined using the standard hematoxylin-eosin method. Compared with conventional single train stimulation, TcMEP amplitudes increased 1.3, 2.1, 1.9, and 2.0 times on average with 5, 10, 20, and 50 Hz stimulation, respectively. The aversion index was >0.8 in all animals after they received 100 high-frequency MTSs. Histologically, no pathological changes were evident in the rat brains. High-frequency MTS shows potential to effectively enhance TcMEP responses, and to be used safely in transcranial brain stimulation.