The Excitability of Ipsilateral Motor Evoked Potentials Is Not Task-specific and Spatially Distinct From the Contralateral Motor Hotspot

ObjectiveThe role of ipsilateral descending motor pathways in voluntary movement of humans is still a matter of debate. Few studies have examined the task dependent modulation of ipsilateral motor evoked potentials (iMEPs). Here, we determined the location of upper limb biceps brachii (BB) representation within the ipsilateral primary motor cortex. MethodsMR-navigated transcranial magnetic stimulation mapping of the dominant hemisphere was undertaken with twenty healthy participants who made tonic unilateral, bilateral homologous or bilateral antagonistic elbow flexion-extension voluntary contractions. Map center of gravity (CoG) and area for each BB were obtained. ResultsThe map CoG of the ipsilateral BB was located more anterior-laterally than those of the contralateral BB within the primary motor cortex. However different tasks had no effect on either the iMEP CoG location or the size. ConclusionOur data suggests that ipsilateral and contralateral MEP might originate in distinct adjacent neural populations in the primary motor cortex, independent of task dependence.

Evidence for Shared Neural Information Between Muscle Synergies and Corticospinal Efficacy

Stroke survivors often exhibit gait dysfunction which compromises self-efficacy and quality of life. Muscle Synergy Analysis (MSA), derived from electromyography (EMG), has been argued as a method to quantify the complexity of descending motor commands and serve as a direct correlate of neural function. However, controversy remains regarding this interpretation, specifically attribution of MSA as a neuromarker. Here we sought to determine the relationship between MSA and accepted neurophysiological parameters of motor efficacy in healthy controls, high (HFH) and low (LFH) functioning stroke survivors. Surface EMG was collected from twenty-four participants while walking at their self-selected speed. Concurrently, transcranial magnetic stimulation (TMS) was administered, during walking, to elicit motor evoked potentials (MEPs) in the plantarflexor muscles during the pre-swing phase of gait. MSA was able to differentiate control and LFH individuals. Conversely, motor neurophysiological parameters including soleus MEP area, revealed that MEP latency differentiated control and HFH individuals. Significant correlations were revealed between MSA and motor neurophysiological parameters adding evidence to our understanding of MSA as a correlate of neural function and highlighting the utility of combining MSA with other relevant outcomes to aid interpretation of this analysis technique.

Motor Cortical Plasticity Induced by Volitional Muscle Activity-Triggered Transcranial Magnetic Stimulation and Median Nerve Stimulation

Bilateral motor training is a useful method for modifying corticospinal excitability. The effects of bilateral movement that are caused by artificial stimulation on corticospinal excitability have not been reported. We compared motor-evoked potentials (MEPs) of the primary motor cortex (M1) after conventional bilateral motor training and artificial bilateral movements generated by electromyogram activity of abductor pollicis brevis (APB) muscle-triggered peripheral nerve stimulation (c-MNS) and transcranial magnetic stimulation of the ipsilateral M1 (i-TMS). A total of three protocols with different interventions—bilateral finger training, APB-triggered c-MNS, and APB-triggered i-TMS—were administered to 12 healthy participants. Each protocol consisted of 360 trials of 30 min for each trial. MEPs that were induced by single-pulse TMS, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) that were induced by paired-pulse TMS were assessed as outcome measures at baseline and at 0, 20, 40, and 60 min after intervention. MEP amplitude significantly increased up to 40 min post-intervention in all protocols compared to that at the baseline, although there were some differences in the changing pattern of ICF and SICI in each protocol. These findings suggest that artificial bilateral movement has the potential to increase the ipsilateral cortical excitability of the moving finger.

Effect of Low-dose Lidocaine on Motor Evoked Potentials in Patients Undergoing Intracranial Tumor Resection With Propofol Anesthesia

ObjectTo investigate the effect of low-dose lidocaine on motor evoked potentials (MEP) in patients undergoing intracranial tumor resection with propofol anesthesia.MethodsForty patients undergoing intracranial tumor resection and required MEP monitoring were selected.They were randomly divided into the lidocaine group (Group L, n=20) and control group (Group C, n=20) by computer generated randomization. All patients were given propofol anesthesia under the guidance of bispectral index (BIS).In Group L, lidocaine 1 mg/kg was injected intravenously during anesthesia induction. Then, lidocaine was continuously pumped at the speed of 1 mg/kg·h until the operation start. Group C was given the equal volume of normal saline. Heart rate (HR), mean artery pressure (MAP), and BIS were recorded before anesthesia induction (T0), 2 min after tracheal intubation (T1), 35 min (T2) and 50 min (T3) after anesthesia induction. The amplitude and latency of MEP at T2 and T3, the total dosage of propofol, and adverse events before T3 were recorded.ResultsCompared with Group C, HR and MAP were significantly decreased at T1 in Group L. No significant difference was observed in HR and MAP at T0, T2 and T3 between Group L and Group C. The total dosage of propofol and the incidence of adverse events were significantly lower in Group L than in Group C before T3. There was no significant difference in the amplitude and latency of MEP between the two groups at each time point.ConclusionLow-dose lidocaine has no effect on MEP in patients undergoing intracranial tumor resection. In addition, it increased hemodynamic stability, reduced propofol use, and decreased the incidence of adverse events.

Facilitation of Motor Evoked Potentials in Response to a Modified 30 Hz Intermittent Theta-Burst Stimulation Protocol in Healthy Adults

Theta-burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (rTMS) developed to induce neuroplasticity. TBS usually consists of 50 Hz bursts at 5 Hz intervals. It can facilitate motor evoked potentials (MEPs) when applied intermittently, although this effect can vary between individuals. Here, we sought to determine whether a modified version of intermittent TBS (iTBS) consisting of 30 Hz bursts repeated at 6 Hz intervals would lead to lasting MEP facilitation. We also investigated whether recruitment of early and late indirect waves (I-waves) would predict individual responses to 30 Hz iTBS. Participants (n = 19) underwent single-pulse TMS to assess MEP amplitude at baseline and variations in MEP latency in response to anterior-posterior, posterior-anterior, and latero-medial stimulation. Then, 30 Hz iTBS was administered, and MEP amplitude was reassessed at 5-, 20- and 45-min. Post iTBS, most participants (13/19) exhibited MEP facilitation, with significant effects detected at 20- and 45-min. Contrary to previous evidence, recruitment of early I-waves predicted facilitation to 30 Hz iTBS. These observations suggest that 30 Hz/6 Hz iTBS is effective in inducing lasting facilitation in corticospinal excitability and may offer an alternative to the standard 50 Hz/5 Hz protocol.

Detection of Motor-Evoked Potentials Below the Noise Floor: Rethinking the Motor Threshold

Background: Motor-evoked potentials (MEP) are one of the most prominent responses to brain stimulation, such as supra-threshold transcranial magnetic stimulation (TMS) and electrical stimulation. Understanding of the neurophysiology and the determination of the lowest stimulation strength that evokes responses requires the detection of even smaller responses, e.g., from single motor units. However, available detection and quantization methods suffer from a large noise floor. Objective: This paper develops a detection method that extracts MEPs hidden below the noise floor. With this method, we aim to estimate excitatory activations of the corticospinal pathways well below the conventional detection level. Methods: The presented MEP detection method presents a self-learning matched-filter approach for improved robustness against noise. The filter is adaptively generated per subject through iterative learning. For responses that are reliably detected by conventional detection, the new approach is fully compatible with established peak-to-peak readings and provides the same results but extends the dynamic range below the conventional noise floor. Results: In contrast to the conventional peak-to-peak measure, the proposed method increases the signal-to-noise ratio by more than a factor of 5. The first detectable responses appear to be substantially lower than the conventional threshold definition of 50 μV median peak-to-peak amplitude. Conclusion: The proposed method shows that stimuli well below the conventional 50 μV threshold definition can consistently and repeatably evoke muscular responses and thus activate excitable neuron populations in the brain. As a consequence, the IO curve is extended at the lower end, and the noise cut-off is shifted. Importantly, the IO curve extends so far that the 50 μV point turns out to be closer to the center of the logarithmic sigmoid curve rather than close to the first detectable responses. The underlying method is applicable to a wide range of evoked potentials and other biosignals, such as in electroencephalography.

Bilateral and Optimistic Warning Paradigms Improve the Predictive Power of Intraoperative Facial Motor Evoked Potentials during Vestibular Schwannoma Surgery

Facial muscle corticobulbar motor evoked potentials (FMcoMEPs) are used to monitor facial nerve integrity during vestibular schwannoma resections to increase maximal safe tumor resection. Established warning criteria, based on ipsilateral amplitude reduction, have the limitation that the rate of false positive alarms is high, in part because FMcoMEP changes occur on both sides, e.g., due to brain shift or pneumocephalus. We retrospectively compared the predictive value of ipsilateral-only warning criteria and actual intraoperative warnings with a novel candidate warning criterion, based on “ipsilateral versus contralateral difference in relative stimulation threshold increase, from baseline to end of resection” (BilatMT ≥ 20%), combined with an optimistic approach in which a warning would be triggered only if all facial muscles on the affected side deteriorated. We included 60 patients who underwent resection of vestibular schwannoma. The outcome variable was postoperative facial muscle function. Retrospectively applying BilatMT, with the optimistic approach, was found to have a significantly better false positive rate, which was much lower (9% at day 90) than the traditionally used ipsilateral warning criteria (>20%) and was also lower than actual intraoperative warnings. This is the first report combining the threshold method with an optimistic approach in a bilateral multi-facial muscle setup. This method could substantially reduce the rate of false positive alarms in FMcoMEP monitoring.

Relationship between high-frequency activity in the sensory and the motor hand areas, and regional myelin content

BackgroundThe human primary sensory (S1) and primary motor (M1) hand areas feature high-frequency neuronal responses. Electrical nerve stimulation evokes high-frequency oscillations (HFO) at around 650 Hz in the contralateral S1. Likewise, paired-pulse transcranial magnetic stimulation of M1 produces short interval intracortical facilitation (SICF) of motor evoked potentials in contralateral hand muscles. SICF features several peaks of facilitation which are separated by inter-peak intervals resembling HFO rhythmicity.HypothesisIn this study, we tested the hypothesis that the individual expressions of HFO and SICF are tightly related to each other and to the regional myelin content in the sensorimotor cortex.MethodsIn 24 healthy volunteers, we recorded HFO and SICF, and, in a subgroup of 20 participants, we mapped the cortical myelin content using the ratio between the T1- and T2-weighted MRI signal as read-out.ResultsThe individual frequencies and magnitudes of HFO and SICF were tightly correlated: the intervals between the first and second peak of cortical HFO and SICF showed a positive linear relationship (r= 0.703, p< 0.001), while their amplitudes were inversely related (r= −0.613, p= 0.001). The rhythmicity, but not the magnitude of the high-frequency responses, was related to the cortical myelin content: the higher the cortical myelin content, the shorter the inter-peak intervals of HFO and SICF.ConclusionThe results confirm a tight functional relationship between high-frequency responses in S1 (i.e., HFO) and M1 (i.e., SICF). They also establish a link between the degree of regional cortical myelination and the expression of high-frequency responses in the human cortex, giving further the opportunity to infer their possible generators.

NAIAD-2020: Characteristics of Motor Evoked Potentials After 3-Day Exposure to Dry Immersion in Women

As female astronauts participate in space flight more and more frequently, there is a demand for research on how the female body adapts to the microgravity environment. In particular, there is very little research on how the neuromuscular system reacts to gravitational unloading in women. We aimed to estimate changes in motor evoked potentials (MEPs) in the lower leg muscles in women after 3-day exposure to Dry Immersion (DI), which is one of the most widely used ground models of microgravity. Six healthy female volunteers (mean age 30.17 ± 5.5 years) with a natural menstrual cycle participated in this experiment. MEPs were recorded from the gastrocnemius and soleus muscles twice before DI, on the day of DI completion, and 3 days after DI, during the recovery period. To evoke motor responses, transcranial and trans-spinal magnetic stimulation was applied. We showed that changes in MEP characteristics after DI exposure were different depending on the stimulation site, but were similar for both muscles. For trans-spinal stimulation, MEP thresholds decreased compared to baseline values, and amplitudes, on the contrary, increased, resembling the phenomenon of hypogravitational hyperreflexia. This finding is in line with data observed in other experiments on both male and female participants. MEPs to transcranial stimulation had an opposing dynamic, which may have resulted from the small group size and large inter-subject variability, or from hormonal fluctuations during the menstrual cycle. Central motor conduction time remained unchanged, suggesting that pyramidal tract conductibility was not affected by DI exposure. More research is needed to explore the underlying mechanisms.

Offline low-frequency rTMS of the primary and premotor cortices does not impact motor sequence memory consolidation despite modulation of corticospinal excitability

Motor skills are acquired and refined across alternating phases of practice (online) and subsequent consolidation in the absence of further skill execution (offline). Both stages of learning are sustained by dynamic interactions within a widespread motor learning network including the premotor and primary motor cortices. Here, we aimed to investigate the role of the dorsal premotor cortex (dPMC) and its interaction with the primary motor cortex (M1) during motor memory consolidation. Forty-eight healthy human participants (age 22.1 ± 3.1 years) were assigned to three different groups corresponding to either low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of left dPMC, rTMS of left M1, or sham rTMS. rTMS was applied immediately after explicit motor sequence training with the right hand. Motor evoked potentials were recorded before training and after rTMS to assess potential stimulation-induced changes in corticospinal excitability (CSE). Participants were retested on motor sequence performance after eight hours to assess consolidation. While rTMS of dPMC significantly increased CSE and rTMS of M1 significantly decreased CSE, no CSE modulation was induced by sham rTMS. However, all groups demonstrated similar significant offline learning indicating that consolidation was not modulated by the post-training low-frequency rTMS intervention despite evidence of an interaction of dPMC and M1 at the level of CSE. Motor memory consolidation ensuing explicit motor sequence training seems to be a rather robust process that is not affected by low-frequency rTMS-induced perturbations of dPMC or M1. Findings further indicate that consolidation of explicitly acquired motor skills is neither mediated nor reflected by post-training CSE.