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Tactile Imagery (TI) remains a fairly understudied phenomenon despite growing attention to this topic in recent years. Here, we investigated the effects of TI on corticospinal excitability by measuring motor evoked potentials (MEPs) induced by single-pulse transcranial magnetic stimulation (TMS). The effects of TI were compared with those of tactile stimulation (TS) and kinesthetic motor imagery (kMI). Twenty-two participants performed three tasks in randomly assigned order: imagine finger tapping (kMI); experience vibratory sensations in the middle finger (TS); and mentally reproduce the sensation of vibration (TI). MEPs increased during both kMI and TI, with a stronger increase for kMI. No statistically significant change in MEP was observed during TS. The demonstrated differential effects of kMI, TI and TS on corticospinal excitability have practical implications for devising the imagery-based and TS-based brain-computer interfaces (BCIs), particularly the ones intended to improve neurorehabilitation by evoking plasticity changes in sensorimotor circuitry.

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Introduction: Ipsilateral motor evoked potentials (iMEPs) are difficult to obtain in distal upper limb muscles of healthy participants but give a direct insight into the role of ipsilateral motor control. Methods: We tested a new high-intensity double pulse transcranial magnetic stimulation (TMS) protocol to elicit iMEPs in wrist extensor and flexor muscles during four different bimanual movements (cooperative-asymmetric, cooperative-symmetric, non-cooperative-asymmetric and non-cooperative-symmetric) in 16 participants. Results: Nine participants showed an iMEP in the wrist extensor in at least 20% of the trials in each of the conditions and were classified as iMEP+ participants. iMEP persistence was greater for cooperative (50.5 ± 28.8%) compared to non-cooperative (31.6 ± 22.1%) tasks but did not differ between asymmetric and symmetric tasks. Area and amplitude of iMEPs were also increased during cooperative (area = 5.41 ± 3.4 mV × ms; amplitude = 1.60 ± 1.09 mV) compared to non-cooperative (area = 3.89 ± 2.0 mV × ms; amplitude = 1.12 ± 0.56 mV) tasks and unaffected by task-symmetry. Discussion: The upregulation of iMEPs during common-goal cooperative tasks shows a functional relevance of ipsilateral motor control in bimanual movements. The paired-pulse TMS protocol is a reliable method to elicit iMEPs in healthy participants and can give new information about neural control of upper limb movements. With this work we contribute to the research field in two main aspects. First, we describe a reliable method to elicit ipsilateral motor evoked potentials in healthy participants which will be useful in further advancing research in the area of upper limb movements. Second, we add new insight into the motor control of bimanual movements. We were able to show an upregulation of bilateral control represented by increased ipsilateral motor evoked potentials in cooperative, object-oriented movements compared to separate bimanual tasks. This result might also have an impact on neurorehabilitation after stroke.

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OBJECTIVE: Multimodal intraoperative neuromonitoring (IOM) using somatosensory-evoked potentials and motor-evoked potentials is a sensitive and specific tool for detecting intraoperative neurologic injury during spine surgery. This study aimed to evaluate the use of multimodal IOM in a lower-middle-income country (LMIC) during cervical and thoracic spine surgery in order to prevent and predict new postoperative neurologic deficits early on. This is the first report of multimodal IOM application in LMICs. METHODS: The neurophysiologist raised the cutoff warning criteria of 50 patients who underwent surgery for different cervical and thoracic pathologies to decrease postoperative neurologic deficits. We retrospectively reviewed the medical charts and neuromonitoring traces of these patients followed by calculating the sensitivity, specificity, positive predictive value, and negative predictive value of combined IOM for postoperative neurologic deficit occurrence. RESULTS: A significant relationship was found between the reversibility of alerts and the development of new postoperative deficits (P < 0.001). There was no relationship between the cause of alerts and the reversibility of those alerts after corrective measures were carried out (P = 0.455), or the frequency of alerts and the development of new deficits postoperatively (P = 0.578). Sensitivity, specificity, positive predictive value, and negative predictive value of combined somatosensory-evoked potential and motor-evoked potential monitoring were 100%, 80%, 62.5%, and 100%, respectively. CONCLUSION: Because of the limited experience and the many technical difficulties faced in LMICs, we found that this cutoff limit resulted in more false-positive warnings but helped to avoid any false-negative results, thus enhancing the safety of surgery.

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Muscle motor-evoked potentials are commonly monitored during brain tumour surgery in motor areas, as these are assumed to reflect the integrity of descending motor pathways, including the corticospinal tract. However, while the loss of muscle motor-evoked potentials at the end of surgery is associated with long-term motor deficits (muscle motor-evoked potential-related deficits), there is increasing evidence that motor deficit can occur despite no change in muscle motor-evoked potentials (muscle motor-evoked potential-unrelated deficits), particularly after surgery of non-primary regions involved in motor control. In this study, we aimed to investigate the incidence of muscle motor-evoked potential-unrelated deficits and to identify the associated brain regions. We retrospectively reviewed 125 consecutive patients who underwent surgery for peri-Rolandic lesions using intra-operative neurophysiological monitoring. Intraoperative changes in muscle motor-evoked potentials were correlated with motor outcome, assessed by the Medical Research Council scale. We performed voxel-lesion-symptom mapping to identify which resected regions were associated with short- and long-term muscle motor-evoked potential-associated motor deficits. Muscle motor-evoked potentials reductions significantly predicted long-term motor deficits. However, in more than half of the patients who experienced long-term deficits (12/22 patients), no muscle motor-evoked potential reduction was reported during surgery. Lesion analysis showed that muscle motor-evoked potential-related long-term motor deficits were associated with direct or ischaemic damage to the corticospinal tract, whereas muscle motor-evoked potential-unrelated deficits occurred when supplementary motor areas were resected in conjunction with dorsal premotor regions and the anterior cingulate. Our results indicate that long-term motor deficits unrelated to the corticospinal tract can occur more often than currently reported. As these deficits cannot be predicted by muscle motor-evoked potentials, a combination of awake and/or novel asleep techniques other than muscle motor-evoked potentials monitoring should be implemented.

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To offer engaging neurorehabilitation training to neurologic patients, motor tasks are often visualized in virtual reality (VR). Recently introduced head-mounted displays (HMDs) allow to realistically mimic the body of the user from a first-person perspective (i.e., avatar) in a highly immersive VR environment. In this immersive environment, users may embody avatars with different body characteristics. Importantly, body characteristics impact how people perform actions. Therefore, alternating body perceptions using immersive VR may be a powerful tool to promote motor activity in neurologic patients. However, the ability of the brain to adapt motor commands based on a perceived modified reality has not yet been fully explored. To fill this gap, we "tricked the brain" using immersive VR and investigated if multisensory feedback modulating the physical properties of an embodied avatar influences motor brain networks and control. Ten healthy participants were immersed in a virtual environment using an HMD, where they saw an avatar from first-person perspective. We slowly transformed the surface of the avatar (i.e., the "skin material") from human to stone. We enforced this visual change by repetitively touching the real arm of the participant and the arm of the avatar with a (virtual) hammer, while progressively replacing the sound of the hammer against skin with stone hitting sound via loudspeaker. We applied single-pulse transcranial magnetic simulation (TMS) to evaluate changes in motor cortical excitability associated with the illusion. Further, to investigate if the "stone illusion" affected motor control, participants performed a reaching task with the human and stone avatar. Questionnaires assessed the subjectively reported strength of embodiment and illusion. Our results show that participants experienced the "stone arm illusion." Particularly, they rated their arm as heavier, colder, stiffer, and more insensitive when immersed with the stone than human avatar, without the illusion affecting their experienced feeling of body ownership. Further, the reported illusion strength was associated with enhanced motor cortical excitability and faster movement initiations, indicating that participants may have physically mirrored and compensated for the embodied body characteristics of the stone avatar. Together, immersive VR has the potential to influence motor brain networks by subtly modifying the perception of reality, opening new perspectives for the motor recovery of patients.

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Control of muscles about the ankle joint is an important component of locomotion and balance that is negatively impacted by spinal cord injury (SCI). Volitional control of the ankle dorsiflexors (DF) is impaired by damage to pathways descending from supraspinal centers. Concurrently, spasticity arising from disrupted organization of spinal reflex circuits, further erodes control. The association between neurophysiological changes (corticospinal and spinal) with volitional ankle control (VAC) and spasticity remains unclear. The goal of this scoping review was to synthesize what is known about how changes in corticospinal transmission and spinal reflex excitability contribute to disrupted ankle control after SCI. We followed published guidelines for conducting a scoping review, appraising studies that contained a measure of corticospinal transmission and/or spinal reflex excitability paired with a measure of VAC and/or spasticity. We examined studies for evidence of a relationship between neurophysiological measures (either corticospinal tract transmission or spinal reflex excitability) with VAC and/or spasticity. Of 1,538 records identified, 17 studies were included in the review. Ten of 17 studies investigated spinal reflex excitability, while 7/17 assessed corticospinal tract transmission. Four of the 10 spinal reflex studies examined VAC, while 9/10 examined ankle spasticity. The corticospinal tract transmission studies examined only VAC. While current evidence suggests there is a relationship between neurophysiological measures and ankle function after SCI, more studies are needed. Understanding the relationship between neurophysiology and ankle function is important for advancing therapeutic outcomes after SCI. Future studies to capture an array of corticospinal, spinal, and functional measures are warranted.

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Craniovertebral junction (CVJ) surgery encompasses a wide spectrum of neurosurgical procedures ranging from transoral approaches for CVJ bone anomalies to surgery for intramedullary tumours. Intraoperative neurophysiological monitoring (IONM) has been increasingly used in recent years because of its ability to prevent neurological complications during surgery. In CVJ surgery the risk of neurological injuries is related first to the positioning of the patient and then to the surgical procedure. Application of IONM during the positioning of the patient permits fast recognition of impending causes of neurological injury. During surgery, continuous IONM permits real-time assessment of the functional integrity of the spinal tracts and provides useful feedback during surgical manoeuvres. The applications of IONM are mainly related to intradural procedures, but wider application of these techniques during surgery for CVJ instability and degenerative disorders has recently been described, leading also to better understanding of the pathophysiology of spinal cord injuries. In this paper we review and discuss the principal IONM techniques used during surgery around the CVJ.

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Continuous theta-burst stimulation (cTBS) is a repetitive transcranial magnetic stimulation paradigm reported to decrease the excitability of the stimulated cortical area and which is thought to reflect a form of inhibitory synaptic plasticity. However, since its introduction, the effect of cTBS has shown a remarkable variability in its effects, which are often quantified by measuring the amplitude of motor evoked potentials (MEPs). Part of this inconsistency in experimental results might be due to an intrinsic variability of TMS effects caused by genetic or neurophysiologic factors. However, it is also possible that MEP only reflect the excitability of a sub-population of output neurons; resting EEG power and measures combining TMS and electroencephalography (TMS-EEG) might represent a more thorough reflection of cortical excitability. The aim of the present study was to verify the robustness of several predictors of cTBS response, such as I wave recruitment and baseline MEP amplitude, and to test cTBS after-effects on multiple neurophysiologic measurements such as MEP, resting EEG power, local mean field power (LMFP), TMS-related spectral perturbation (TRSP), and inter-trial phase clustering (ITPC). As a result, we were not able to confirm either the expected decrease of MEP amplitude after cTBS or the ability of I wave recruitment and MEP amplitude to predict the response to cTBS. Resting EEG power, LMFP, TRSP, and ITPC showed a more consistent trend toward a decrease after cTBS. Overall, our data suggest that the effect of cTBS on corticospinal excitability is variable and difficult to predict with common electrophysiologic markers, while its effect might be clearer when probed with combined TMS and EEG.

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Influential theories suggest that a defensive behavioral inhibition system (BIS) supports the inhibition of action tendencies when facing potential threats. However, little is known about threat-related inhibitory mechanisms in humans and their relations to inter-individual differences in BIS sensitivity. To address this issue, we used paired-pulse TMS to investigate early human motor cortex (M1) responses to social signals of potential threats, like another's fearful body posture. In two experiments, participants observed pictures of fearful and happy postures, and neutral postures that were either dynamic (in Exp1) or static (in Exp2). To test suppression of M1 excitatory activity, we assessed intracortical facilitation (ICF) in an early phase of threat monitoring by administering TMS pulses at 100-125 ms from picture onset. We investigated the motor representation of hand and arm muscles that are differentially involved in flexion, extension, and abduction. As a control, we also assessed corticospinal excitability and short intracortical inhibition. In both experiments, and independently of the muscle, watching fearful bodies suppressed ICF relative to watching happy and non-emotional (dynamic or static) body expressions. Remarkably, greater fear-related ICF suppression was found in participants who scored higher on a self-report questionnaire assessing BIS sensitivity. These findings suggest that observing fearful body language activates a defensive suppression of M1 excitatory activity that is influenced by the personality disposition to experience fear and anxiety when facing potential threats. This BIS-related motor suppression may have the functional role of transiently suppressing action tendencies to promote threat monitoring and, ultimately, survival.

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The aim of the present study was to investigate the neurophysiological triggers underlying muscle relaxation from the contracted state, and to examine the mechanisms involved in this process and their subsequent modification by neuromuscular electrical stimulation (NMES). Single-pulse transcranial magnetic stimulation (TMS) was used to produce motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) in 23 healthy participants, wherein motor cortex excitability was examined at the onset of voluntary muscle relaxation following a period of voluntary tonic muscle contraction. In addition, the effects of afferent input on motor cortex excitability, as produced by NMES during muscle contraction, were examined. In particular, two NMES intensities were used for analysis: 1.2 times the sensory threshold and 1.2 times the motor threshold (MT). Participants were directed to execute constant wrist extensions and to release muscle contraction in response to an auditory "GO" signal. MEPs were recorded from the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, and TMS was applied at three different time intervals (30, 60, and 90 ms) after the "GO" signal. Motor cortex excitability was greater during voluntary ECR and FCR relaxation using high-intensity NMES, and relaxation time was decreased. Each parameter differed significantly between 30 and 60 ms. Moreover, in both muscles, SICI was larger in the presence than in the absence of NMES. Therefore, the present findings suggest that terminating a muscle contraction triggers transient neurophysiological mechanisms that facilitate the NMES-induced modulation of cortical motor excitability in the period prior to muscle relaxation. High-intensity NMES might facilitate motor cortical excitability as a function of increased inhibitory intracortical activity, and therefore serve as a transient trigger for the relaxation of prime mover muscles in a therapeutic context.

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Transcranial direct current stimulation (tDCS) uses a weak electric current to modulate neuronal activity. A neurophysiologic outcome measure to demonstrate reliable tDCS modulation at the group level is transcranial magnetic stimulation engendered motor evoked potentials (MEPs). Here, we conduct a study testing the reliability of individual MEP response patterns following a common tDCS protocol. Fourteen participants (7m/7f) each underwent nine randomized sessions of 1 mA, 10 min tDCS (3 anode; 3 cathode; 3 sham) delivered using an M1/orbito-frontal electrode montage (sessions separated by an average of ~5.5 days). Fifteen MEPs were obtained prior to, immediately following and in 5 min intervals for 30 min following tDCS. TMS was delivered at 130 % resting motor threshold using neuronavigation to ensure consistent coil localization. A number of non-experimental variables were collected during each session. At the individual level, considerable variability was seen among different testing sessions. No participant demonstrated an excitatory response ≥20 % to all three anodal sessions, and no participant demonstrated an inhibitory response ≥20 % to all three cathodal sessions. Intra-class correlation revealed poor anodal and cathodal test-retest reliability [anode: ICC(2,1) = 0.062; cathode: ICC(2,1) = 0.055] and moderate sham test-retest reliability [ICC(2,1) = 0.433]. Results also revealed no significant effect of tDCS at the group level. Using this common protocol, we found the effects of tDCS on MEP amplitudes to be highly variable at the individual level. In addition, no significant effects of tDCS on MEP amplitude were found at the group level. Future studies should consider utilizing a more strict experimental protocol to potentially account for intra-individual response variations.

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Noninvasive brain stimulation has been demonstrated to modulate cortical activity in humans. In particular, theta burst stimulation (TBS) has gained notable attention due to its ability to induce lasting physiological changes after short stimulation durations. The present study aimed to provide a comprehensive meta-analytic review of the efficacy of two TBS paradigms; intermittent (iTBS) and continuous (cTBS), on corticospinal excitability in healthy individuals. Literature searches yielded a total of 87 studies adhering to the inclusion criteria. iTBS yielded moderately large MEP increases lasting up to 30 min with a pooled SMD of 0.71 (p<0.00001). cTBS produced a reduction in MEP amplitudes lasting up to 60 min, with the largest effect size seen at 5 min post stimulation (SMD=-0.9, P<0.00001). The collected studies were of heterogeneous nature, and a series of tests conducted indicated a degree of publication bias. No significant change in SICI and ICF was observed, with exception to decrease in SICI with cTBS at the early time point (SMD=0.42, P=0.00036). The results also highlight several factors contributing to TBS efficacy, including the number of pulses, frequency of stimulation and BDNF polymorphisms. Further research investigating optimal TBS stimulation parameters, particularly for iTBS, is needed in order for these paradigms to be successfully translated into clinical settings.

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OBJECTIVE: This randomized, sham-controlled, double-blind study was conducted to investigate the effects of high-frequency versus low-frequency repetitive transcranial magnetic stimulation (rTMS) on patients with poststroke dysphagia during early rehabilitation. METHODS: Forty patients with poststroke dysphagia were randomized to receive five daily sessions of sham, 3-Hz ipsilesional, or 1-Hz contralesional rTMS. Swallowing function, the severity of stroke and functional disability, and cortical excitability were examined before, immediately after five daily sessions, as well as the first, second, and third month after the last session. RESULTS: At baseline, no significant differences between groups were observed in terms of demographic and clinical rating scales. However, a significantly greater improvement in swallowing function as well as functional disability was observed after real rTMS when compared with sham rTMS, which remained 3 months after the end of the treatment sessions. In addition, 1-Hz rTMS increased cortical excitability of the affected hemisphere and decreased that of the non-affected hemisphere; however, 3-Hz rTMS only increased cortical excitability of the affected hemisphere. CONCLUSION: rTMS (both high and low frequency) improved swallowing recovery in patients with poststroke dysphagia, and the effects lasted for at least 3 months. SIGNIFICANCE: rTMS appears to be a beneficial therapeutic modality for patients with dysphagia during the early phase of stroke.

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We postulated that gradual muscle relaxation during motor learning would dynamically change activity in the primary motor cortex (M1) and modify short-interval intracortical inhibition (SICI). Thus, we compared changes in M1 excitability both pre and post motor learning during gradual muscle relaxation. Thirteen healthy participants were asked to gradually relax their muscles from an isometric right wrist extension (30% maximum voluntary contraction; MVC) using a tracking task for motor learning. Single or paired transcranial magnetic stimulation (TMS) was applied at either 20% or 80% of the downward force output during muscle release from 30% MVC, and we compared the effects of motor learning immediately after the 1st and 10th blocks. Motor-evoked potentials (MEPs) from the extensor and flexor carpi radialis (ECR and FCR) were then measured and compared to evaluate their relationship before and after motor learning. In both muscles and each downward force output, motor cortex excitability during muscle relaxation was significantly increased following motor learning. In the ECR, the SICI in the 10th block was significantly increased during the 80% waveform decline compared to the SICI in the 1st block. In the FCR, the SICI also exhibited a greater inhibitory effect when muscle relaxation was terminated following motor learning. During motor training, acquisition of the ability to control muscle relaxation increased the SICI in both the ECR and FCR during motor termination. This finding aids in our understanding of the cortical mechanisms that underlie muscle relaxation during motor learning.

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The perception of movements is associated with increased activity in the human motor cortex, which in turn may underlie our ability to understand actions, as it may be implicated in the recognition, understanding and imitation of actions. Here, we investigated the involvement and lateralization of the primary motor cortex (M1) in the perception of singing and speech. Transcranial magnetic stimulation (TMS) was applied independently for both hemispheres over the mouth representation of the motor cortex in healthy participants while they watched 4-s audiovisual excerpts of singers producing a 2-note ascending interval (singing condition) or 4-s audiovisual excerpts of a person explaining a proverb (speech condition). Subjects were instructed to determine whether a sung interval/written proverb, matched a written interval/proverb. During both tasks, motor evoked potentials (MEPs) were recorded from the contralateral mouth muscle (orbicularis oris) of the stimulated motor cortex compared to a control task. Moreover, to investigate the time course of motor activation, TMS pulses were randomly delivered at 7 different time points (ranging from 500 to 3500 ms after stimulus onset). Results show that stimulation of the right hemisphere had a similar effect on the MEPs for both the singing and speech perception tasks, whereas stimulation of the left hemisphere significantly differed in the speech perception task compared to the singing perception task. Furthermore, analysis of the MEPs in the singing task revealed that they decreased for small musical intervals, but increased for large musical intervals, regardless of which hemisphere was stimulated. Overall, these results suggest a dissociation between the lateralization of M1 activity for speech perception and for singing perception, and that in the latter case its activity can be modulated by musical parameters such as the size of a musical interval.

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INTRODUCTION: Vitamin B12 deficiency causes neurologic and psychiatric disease, especially in older adults. Subacute combined degeneration is characterized by damage to the posterior and lateral spinal cord affecting the corticospinal tract. OBJECTIVE: To test corticospinal tract projections using motor evoked potentials (MEPs) by transcranial magnetic stimulation (TMS) in asymptomatic older adults with low vitamin B12 (B12) levels. METHODS: Cross-sectional study of 53 healthy older adults (>70 years). MEPs were recorded in the abductor pollicis brevis and tibialis anterior muscles, at rest and during slight tonic contraction. Central motor conduction time (CMCT) was derived from the latency of MEPs and peripheral motor conduction time (PMCT). Neurophysiological variables were analyzed statistically according to B12 status. RESULTS: Median age was 74.3 ± 3.6 years (58.5% women). Twenty-six out of the 53 subjects had low vitamin B12 levels (B12 < 221 pmol/l). MEPs were recorded for all subjects in upper and lower extremities. There were no significant differences in either latency or amplitude of MEPs and CMCT between low and normal B12 groups. There was a significant PMCT delay in the lower extremities in the low B12 group (p = 0.014). CONCLUSIONS: No subclinical abnormality of the corticospinal tract is detected in asymptomatic B12-deficient older adults. The peripheral nervous system appears to be more vulnerable to damage attributable to this vitamin deficit. The neurophysiological evaluation of asymptomatic older adults with lower B12 levels should be focused mainly in peripheral nervous system evaluation.

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@#Objective To investigate the effects of muscle relaxants on motor evoked potentials (MEPs) monitoring during intracranial surgery. Methods 62 patients with neurological tumor were divided into 2 groups: muscle relaxant group (n=21) and non-muscle relaxant group (n=41). The incidence of successful MEPs monitoring was investigated. Results The incidence of successful MEPs monitoring was 76.2% in the muscle relaxant group and 41.5% in the non-muscle relaxant group (P<0.05). Conclusion Muscle relaxants can affect the MEP monitoring, which would not be administered as possible during anesthesia for intracranial surgery in functional area.