Objective.The transcranial magnetic stimulation (TMS) coil induces an electric field that diminishes rapidly upon entering the brain. This presents a challenge in achieving focal stimulation of a deep brain structure. Neuronal elements, including axons, dendrites, and cell bodies, exhibit specific time constants. When exposed to repetitive TMS pulses at a high frequency, there is a cumulative effect on neuronal membrane potentials, resulting in temporal summation. This study aims to determine whether TMS pulse train at high-frequency and subthreshold intensity could induce a suprathreshold response.Approach.As a proof of concept, we developed a TMS machine in-house that could consistently output pulses up to 250 Hz, and performed experiments on 22 awake rats to test whether temporal summation was detectable under pulse trains at 100, 166, or 250 Hz.Main results.Results revealed that TMS pulses at 55% maximum stimulator output (MSO, peak dI/dt= 68.5 A/μs at 100% MSO, pulse width = 48μs) did not induce motor responses with either single pulses or pulse trains. Similarly, a single TMS pulse at 65% MSO failed to evoke a motor response in rats; however, a train of TMS pulses at frequencies of 166 and 250 Hz, but not at 100 Hz, successfully triggered motor responses and MEP signals, suggesting a temporal summation effect dependent on both pulse intensities and pulse train frequencies.Significance.We propose that the temporal summation effect can be leveraged to design the next-generation focal TMS system: by sequentially driving multiple coils at high-frequency and subthreshold intensity, areas with the most significant overlapping E-fields undergo maximal temporal summation effects, resulting in a suprathreshold response.

UNASSIGNED: Chronic low back pain (CLBP) is a global burden with an unknown etiology. Reorganization of the cortical representation of paraspinal muscles in the primary motor cortex (M1) may be related to the pathology. Single-pulse transcranial magnetic stimulation (TMS), commonly used to map the functional organization of M1, is not potent enough to stimulate the cortical maps of paraspinal muscles in M1 in CLBP patients with reduced corticospinal excitability (CSE) with intensities even as high as maximum stimulator output (100% MSO). This makes TMS mapping impractical for these patients. The aim of this study was to increase the practicality of TMS mapping for people with CLBP.
UNASSIGNED: This study included eight men and ten women who had CLBP for over three months. A biphasic paired-pulse TMS paradigm, conjunct anticipatory postural adjustment (APA), and maximal voluntary activation of paraspinal muscles (MVC) were used to facilitate TMS mapping.
UNASSIGNED: TMS mapping was possible in all CLBP participants, with TMS intensities <50% of the MSO. Reorganization in terms of an anterior and lateral shift of the center of gravity (COG) of the cortical maps of paraspinal muscles was observed in all participants with CLBP, and a reduced number of discrete peaks was found in 33%.
UNASSIGNED: The facilitation of the CSE to paraspinal muscles makes TMS mapping more practical and tolerable in people with CLBP, lowering the risk of seizure and discomfort associated with high-intensity TMS pulses.
UNASSIGNED: Conventional transcranial magnetic stimulation (TMS) brain mapping is not optimal for patients with Chronic low back pain (CLBP).Paired-pulse TMS dramatically lessens the energy needed for brain mapping.Maximal voluntary contraction of back muscles facilitates TMS mapping.Anticipatory postural activity of back muscles enhances the efficacy of TMS mapping.
UNASSIGNED: Chronic low back pain (CLBP) is a social, emotional, and economic burden and the leading cause of disability worldwide. Yet the etiology of the CLBP is unknown. The persistence of aberrant or antalgic movement patterns observed in people with CLBP has been suggested as a possible cause of pain chronification by inducing continuous damage to sensitive structures of the lumbar spine. It is well known that the brain is in charge of the production and planning of movements, so it is likely that abnormal movement patterns also stem from the abnormalities in the brain. However, until recently, human knowledge about the structure and function of the brain has been very limited. The invention of noninvasive and painless brain imaging and stimulating techniques such as transcranial magnetic stimulation (TMS) during the last decades has augmented our knowledge about the structure and function of the brain. Modification in terms of shift, shrinkage, or expansion of areas of the brain devoted to movement control or sensation of the back muscles has been documented in CLBP via these techniques, which are argued to relate to pain chronification but need further clarification. Yet monitoring the course of CLBP via TMS, despite its many potentials, is challenging. This could be due to the reduced cortical drive to back muscles in CLBP patients and the small area devoted to control of back muscles in the brain in general that increases the brain threshold to TMS in people with CLBP. The aim of this study was to tailor an approach to make TMS more applicable for CLBP patients by reducing the threshold to TMS. This could be achieved by engaging back muscles in anticipatory postural activity in combination with maximal voluntary activation of these muscles, along with TMS paradigms that induce intracortical facilitation.

Short-interval intracortical inhibition (SICI) is a common paired-pulse transcranial magnetic stimulation (TMS) measure used to assess primary motor cortex (M1) interneuron activity in healthy populations and in neurological disorders. Many of the parameters of TMS stimulation to most accurately measure SICI have been determined. However, one TMS parameter that has not been investigated is the time between SICI trials (termed inter-trial interval; ITI). This is despite a series of single-pulse TMS studies which have reported that motor evoked potential (MEP) amplitude were suppressed for short, but not long ITIs in approximately the initial ten trials of a TMS block of 20-30 trials. The primary purpose was to examine the effects of ITI on the quantification of SICI at rest. A total of 23 healthy adults completed an experimental session that included four SICI trial blocks. Each block utilized a different ITI (4, 6, 8, and 10 s) and was comprised of a total of 26 SICI trials divided into three epochs. ANOVA revealed that the main effects for ITI and epoch as well as their interaction were all non-statistically significant for SICI. We conclude that the shorter (4-6 s) ITIs used in studies investigating SICI should not alter the interpretation of M1 activity, while having the advantages of being more comfortable to participants and reducing the experimental time needed to evaluate perform single and paired-pulse TMS experiments.

Transcranial direct current stimulation (tDCS) increases primary motor cortex (M1) excitability and improves motor performance when applied unilaterally to the dominant hemisphere. However, the influence of tDCS on contralateral M1 excitability both during and after application has not been quantified. The purpose was to determine the influence of tDCS applied to the dominant M1 on the excitability of the contralateral non-dominant M1. This study employed a double-blind, randomized, SHAM-controlled, within-subject crossover experimental design. Eighteen young adults performed two experimental sessions (tDCS, SHAM) in counterbalanced order separated by a one-week washout. Transcranial magnetic stimulation (TMS) was used to quantify the excitability of the contralateral M1 to which anodal tDCS was applied for 20 min with a current strength of 1 mA. Motor evoked potential (MEP) amplitudes were assessed in 5 TMS test blocks (Pre, D5, D10, D15, and Post). The Pre and Post TMS test blocks were performed immediately before and after tDCS application, whereas the TMS test blocks performed during tDCS were completed at the 5, 10, and 15 min stimulation timepoints. MEPs were analyzed with a 2 condition (tDCS, SHAM) × 5 test (Pre, D5, D10, D15, Post) within-subject ANOVA. The main effect for condition (p = 0.213), the main effect for test (p = 0.502), and the condition × test interaction (p = 0.860) were all not statistically significant. These results indicate that tDCS does not modulate contralateral M1 excitability during or immediately after application, at least under the current set of common tDCS parameters of stimulation.

[This corrects the article DOI: 10.3389/fnhum.2023.1286238.].

Objective  Intraoperative neuromonitoring (IONM) is an acknowledged tool for real-time neuraxis assessment during surgery. Somatosensory evoked potential (SSEP) and transcranial motor evoked potential (MEP) are commonest deployed modalities of IONM. Role of SSEP and MEP in intradural extramedullary spinal cord tumor (IDEMSCT) surgery is not well established. The aim of this study was to evaluate sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of SSEP and transcranial MEP, in detection of intraoperative neurological injury in IDEMSCT patients as well as their postoperative limb-specific neurological improvement assessment at fixed intervals till 30 days. Materials and Methods  Symptomatic patients with IDEMSCTs were selected according to the inclusion criteria of study protocol. On modified McCormick (mMC) scale, their sensory-motor deficit was assessed both preoperatively and postoperatively. Surgery was done under SSEP and MEP (transcranial) monitoring using appropriate anesthetic agents. Gross total/subtotal resection of tumor was achieved as per IONM warning alarms. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of SSEP and MEP were calculated considering postoperative neurological changes as \"reference standard.\" Patients were followed up at postoperative day (POD) 0, 1, 7, and 30 for convalescence. Statistical Analysis  With appropriate tests of significance, statistical analysis was carried out. Receiver-operating characteristic curve was used to find cutoff point of mMC for SSEP being recordable in patients with higher neurological deficit along with calculation of sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of SSEP and MEP for prediction of intraoperative neurological injury. Results  Study included 32 patients. Baseline mean mMC value was 2.59. Under neuromonitoring, gross total resection of IDEMSCT was achieved in 87.5% patients. SSEP was recordable in subset of patients with mMC value less than or equal to 2 with diagnostic accuracy of 100%. MEP was recordable in all patients and it had 96.88% diagnostic accuracy. Statistically significant neurological improvement was noted at POD-7 and POD-30 follow-up. Conclusion  SSEP and MEP individually carry high diagnostic accuracy in detection of intraoperative neurological injuries in patients undergoing IDEMSCT surgery. MEP continues to monitor the neuraxis, even in those subsets of patients where SSEP fails to record.

BACKGROUND: After spinal cord injury (SCI), a large number of survivors suffer from severe motor dysfunction (MD). Although the injury site is in the spinal cord, excitability significantly decreases in the primary motor cortex (M1), especially in the lower extremity (LE) area. Unfortunately, M1 LE area-targeted repetitive transcranial magnetic stimulation (rTMS) has not achieved significant motor improvement in individuals with SCI. A recent study reported that the M1 hand area in individuals with SCl contains a compositional code (the movement-coding component of neural activity) that links matching movements from the upper extremities (UE) and the LE. However, the correlation between bilateral M1 hand area excitability and overall functional recovery is unknown.
OBJECTIVE: To clarify the changes in the excitability of the bilateral M1 hand area after SCI and its correlation with motor recovery, we aim to specify the therapeutic parameters of rTMS for SCI motor rehabilitation.
METHODS: This study is a 12-month prospective cohort study. The neurophysiological and overall functional status of the participants will be assessed. The primary outcomes included single-pulse and paired-pulse TMS. The second outcome included functional near-infrared spectroscopy (fNIRS) measurements. Overall functional status included total motor score, modified Ashworth scale score, ASIA Impairment Scale grade, spinal cord independence measure and modified Barthel index. The data will be recorded for individuals with SCI at disease durations of 1 month, 2 months, 4 months, 6 months and 12 months. The matched healthy controls will be measured during the same period of time after recruitment.
CONCLUSIONS: The present study is the first to analyze the role of bilateral M1 hand area excitability changes in the evaluation and prediction of overall functional recovery (including motor function and activities of daily living) after SCI, which will further expand the traditional theory of the predominant role of M1, optimize the current rTMS treatment, and explore the brain-computer interface design for individuals with SCI.
BACKGROUND: ChiCTR2300068831.

BACKGROUND: Acupuncture as a traditional Chinese medicine therapy relies on unique theories to alleviate fatigue. The aim of this study is to evaluate the effect of acupuncture on exercise-induced fatigue utilizing transcranial magnetic stimulation (TMS).
METHODS: A total of 20 participants with regular exercise habits were recruited for this study. All participants were randomly assigned to receive either acupuncture or sham acupuncture intervention for exercise-induced fatigue. TMS and a heart rate monitor were used to measure the amplitude and latency of motor evoked potential (MEP) as well as heart rate every 5 min over a 30-min period. The blood lactic acid (BLA) levels were measured using Lactate Scout+ at baseline, 0 min, and 30 min after fatigue. Two-way repeated measures analysis of variance was utilized to compare the differences between the effects of acupuncture method and time. Bonferroni post hoc tests were conducted to compare specific differences. Statistical significance was set at p < .05.
RESULTS: Interaction effect was observed between acupuncture method and time effect in terms of amplitude (F(1, 38) = 5.40, p < .001, η2 = 0.12) and latency (F(1, 38) = 3.78, p = .008, η2 = .09) of MEP. The application of acupuncture can promote the recovery of heart rate especially at 30 min (p < .05), but which seem insufficient to generate significant difference in BLA (F(1, 38) = 0.067, p = .797, η2 = 0.002).
CONCLUSIONS: Acupuncture can promote the increase of MEP amplitude, shorten MEP latency, and restore heart rate. Preliminary findings provide novel insights for individuals with exercise habits to alleviate fatigue and enhance sports performance.

UNASSIGNED: The firing rate of the mirror neuron system in monkeys decreases systematically with more repetitions. The aim of this study is to investigate whether the activity of the mirror neuron system varies based on the observed movement and the contents of the action, as well as whether there is inhibition in the mirror neuron system when humans observe repeated actions. If inhibition is present, the second question of the study is whether it is related to the organization of the observed action.
UNASSIGNED: Fourteen healthy volunteers participated in the study. Transcranial magnetic stimulation was applied to the left primary motor cortex and motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous and abductor pollicis brevis muscles while the participants were watching videos specially prepared for the study.
UNASSIGNED: There were no significant changes in MEP amplitudes compared to baseline MEPs while observing aimless action. However, while participants watched the repeated action video, the mean MEP amplitude increased at the beginning of the movement, but neither facilitation nor inhibition was detected when the participants watched the phase of grasping the object of the action compared to the baseline MEP amplitude. On the other hand, while participants were watching different activities, an increased MEP amplitude was observed at the beginning of the movement and in the grasping of the object of the action. Additionally, there was no significant reduction in MEP amplitude during any movement stages while observing the repeated action video.
UNASSIGNED: The findings of this study suggest that the activation of the mirror neuron system in humans depends on the content and stages of the observed movement. Additionally, there was no inhibition or systematic reduction in MEP amplitudes while watching a repeated action.

METHODS: Development of a clinical practice guideline following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process.
OBJECTIVE: The objectives of this study were to develop guidelines that outline the utility of intraoperative neuromonitoring (IONM) to detect intraoperative spinal cord injury (ISCI) among patients undergoing spine surgery, to define a subset of patients undergoing spine surgery at higher risk for ISCI and to develop protocols to prevent, diagnose, and manage ISCI.
METHODS: All systematic reviews were performed according to PRISMA standards and registered on PROSPERO. A multidisciplinary, international Guidelines Development Group (GDG) reviewed and discussed the evidence using GRADE protocols. Consensus was defined by 80% agreement among GDG members. A systematic review and diagnostic test accuracy (DTA) meta-analysis was performed to synthesize pooled evidence on the diagnostic accuracy of IONM to detect ISCI among patients undergoing spinal surgery. The IONM modalities evaluated included somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), electromyography (EMG), and multimodal neuromonitoring. Utilizing this knowledge and their clinical experience, the multidisciplinary GDG created recommendations for the use of IONM to identify ISCI in patients undergoing spine surgery. The evidence related to existing care pathways to manage ISCI was summarized and based on this a novel AO Spine-PRAXIS care pathway was created.
RESULTS: Our recommendations are as follows: (1) We recommend that intraoperative neurophysiological monitoring be employed for high risk patients undergoing spine surgery, and (2) We suggest that patients at \"high risk\" for ISCI during spine surgery be proactively identified, that after identification of such patients, multi-disciplinary team discussions be undertaken to manage patients, and that an intraoperative protocol including the use of IONM be implemented. A care pathway for the prevention, diagnosis, and management of ISCI has been developed by the GDG.
CONCLUSIONS: We anticipate that these guidelines will promote the use of IONM to detect and manage ISCI, and promote the use of preoperative and intraoperative checklists by surgeons and other team members for high risk patients undergoing spine surgery. We welcome teams to implement and evaluate the care pathway created by our GDG.