Potentiation of cortico-spinal output via targeted electrical stimulation of the motor thalamus.

Cerebral white matter lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to loss of motor control. However, in most cases, the damage to cortico-spinal axons is incomplete offering a potential target for therapies aimed at improving volitional muscle activation. Here we hypothesize that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby immediately potentiating motor output. To test this hypothesis, we identify optimal thalamic targets and stimulation parameters that enhance upper-limb motor-evoked potentials and grip forces in anesthetized monkeys. This potentiation persists after white matter lesions. We replicate these results in humans during intra-operative testing. We then design a stimulation protocol that immediately improves strength and force control in a patient with a chronic white matter lesion. Our results show that electrical stimulation targeting surviving neural pathways can improve motor control after white matter lesions.

A novel strategy for spinal cord reconstruction via vascularized allogeneic spinal cord transplantation combine spinal cord fusion.

AIMS: Spinal cord injuries (SCI) pose persistent challenges in clinical practice due to the secondary injury. Drawing from our experience in spinal cord fusion (SCF), we propose vascularized allogeneic spinal cord transplantation (vASCT) as a novel approach for SCI, much like organ transplantation has revolutionized organ failure treatment and vascularized composite-tissue allotransplantation has addressed limb defects. MATERIALS AND METHODS: In this study, 24 dogs were paired and underwent vASCT, with donor spinal cord grafts and polyethylene glycol (PEG) application for SCF. The experimental group (n = 8) received tacrolimus and methylprednisolone, while the control group (n = 4) received only methylprednisolone. Safety and efficacy of vASCT were evaluated through electrophysiology, imaging, and 6-month follow-up. RESULTS: The experimental group showed substantial recovery in hind limb motor function. Imaging revealed robust survival of spinal cord grafts and restoration of spinal cord continuity. In contrast, the control group maintained hind limb paralysis, with imaging confirming spinal cord graft necrosis and extensive defects. Electrophysiologically, the experimental group exhibited restored motor evoked potential signal conduction postoperatively, unlike the control group. Notably, PEG application during vASCT led to signal conduction recovery in intraoperative spinal cord evoked potential examinations for all dogs. CONCLUSION: In the vASCT surgical model, the combination of PEG with tacrolimus has demonstrated the ability to reconstruct spinal cord continuity and restore hind limb motor function in beagles. Notably, a low dose of tacrolimus has also exhibited an excellent anti-immune rejection effect. These findings highlight vASCT's potential promise as a therapeutic strategy for addressing irreversible SCI.

Transcranial Corticospinal Motor-Evoked Potentials in Cases of Ventral and Ventrolateral Intradural Extramedullary Cervical Spinal Cord Tumors.

Background and Objectives: We studied the clinical significance of an amplitude decrement and disappearance alarm criteria in transcranial motor-evoked potential (MEP) monitoring during surgeries on extramedullary tumors at the cervical spine with reference to postoperative morbidity. Material and Methods: We diagnosed and surgically treated fourteen patients with intradural extramedullary ventral or ventrolateral lesions to the cervical spinal cord in the Clinic of Neurosurgery at the University Hospital St Ivan Rilski from January 2018 to July 2022. Eight cases were diagnosed with schwannoma, and the remaining six had meningiomas. The follow-up period for neurological assessment was six months. Results: A decrease in the intraoperative transcranial MEPs of 50% or more compared to baseline in two cases (14.3%) resulted in an immediate postoperative motor deficit. One patient demonstrated full neurological recovery within six months, while the other exhibited only partial improvement. In six cases (42.9%) with preoperative motor deficits, tumor resection and decompression of the cervical spinal cord led directly to an increment of the transcranial MEPs by more than 20%. Postoperatively and at the 6-month follow-up, these patients showed recovery from the preoperative deficits. In the remaining cases, MEPs were stable during surgery with no clinical deterioration of the motor function. Conclusions: The decremented MEP criteria corresponded to postoperative motor deficit, whereas the improvement of the same parameters after decompression implied future recovery of preoperative motor deficits. The combination of different MEP criteria is likely to be helpful when tailored to a specific case of ventral or ventrolateral extramedullary lesions in the cervical spine.

Lasting effects of transcranial direct current stimulation on the inducibility of synaptic plasticity by paired-associative stimulation in humans.

BACKGROUND: Transcranial direct current stimulation (tDCS) is capable of eliciting changes in cortical neuroplasticity. Increasing duration or repetition of tDCS during the after-effects of a first stimulation has been hypothesized to enhance efficacy. Computational models suggest sequential stimulation patterns with changing polarities to further enhance effects. Lasting tDCS effects on neural plasticity are of great importance for clinical applications. OBJECTIVE: The study systematically examined the influence of different tDCS paradigms on long term potentiation (LTP)-like plasticity in humans, focusing on stimulation duration, repetition frequency and sequential combinations of changing polarities as the underlying characteristics. METHODS: Amplitude changes of motor evoked potentials (MEP) were measured in response to paired associative stimulation (PAS) 6 h after application of different tDCS protocols. In total, 36 healthy participants completed the study, randomised into three groups with different stimulation protocols (N = 12 each). RESULTS: tDCS was able to display lasting modulatory effects on the inducibility of LTP-like plasticity in the human motor cortex 6 h after stimulation. TDCS with the anode on primary motor cortex significantly increased MEP amplitudes following PAS induction. Further analyses highlighted single stimulation block duration to be of higher importance than repetitive protocols for efficacy of effects. CONCLUSIONS: tDCS is capable of inducing lasting changes in the brain's capability to interact with future stimuli. Especially, effects on the inducibility of LTP-like plasticity might only be detectable with specific tests such as PAS and might otherwise be overlooked. Refined tDCS protocols should focus on higher current and duration of single stimulations instead of implementing complex repetitive schedules.

TMS-EEG signatures of the effects of transcranial static magnetic field stimulation (tSMS) on cortical excitability.

In transcranial static magnetic field stimulation (tSMS), a strong and small magnet placed over the head can modulate cortical functions below the magnet as well as those in the region remote from the magnet. We studied the neuromodulation induced by tSMS using transcranial magnetic stimulation (TMS) combined with simultaneous electroencephalography (EEG) to clarify the neurophysiological underpinnings of tSMS. tSMS or sham stimulation was applied over the left primary motor cortex (M1) for 20 min in 15 healthy subjects. Single pulse TMS was delivered over the left M1 before and after the intervention, while recording EEG. The amplitude around the P30 of the TMS-evoked potentials (TEPs) in the left primary sensorimotor area (SM1) significantly decreased after the real tSMS, and that around the N60 of the TEPs in the right SM1 significantly increased after the real tSMS. In addition, the alpha power of the TMS-induced oscillatory responses (IORs) in the left and right SM1 significantly decreased after the real tSMS. TMS-EEG is a powerful tool for studying local and global cortical reactivity to external stimuli at high temporal resolution. tSMS altered TEPs and IORs both at the stimulated cortex and at the contralateral cortex. These findings would be related to the neurophysiological mechanisms underlying the neuromodulation induced by tSMS.

Intraoperative neuromonitoring in Chiari I malformation surgery: a systematic review and meta-analysis.

Chiari Malformation Type I (CMI) is a prevalent neurosurgical condition characterized by the descent of cerebellar tonsils below the foramen magnum. Surgery, aimed at reducing symptomatology and syrinx size, presents risks, making intraoperative neuromonitoring (IONM) a potentially vital tool. Despite its widespread use in cervical spine surgery, the utility of IONM in CMI surgery remains controversial, with concerns over increased operative time, cost, restricted anesthetic techniques and tongue lacerations. This systematic review and meta-analysis followed the Cochrane Group standards and PRISMA framework. It encompassed an extensive search through PubMed, Embase, and Web of Science up to December 2023, focusing on clinical and surgical outcomes of IONM in CMI surgery. Primary outcomes included the use of various IONM techniques, complication rates, clinical improvement, reoperation, and mortality. The review, registered at PROSPERO (CRD42024498996), included both prospective and retrospective studies, with rigorous selection and data extraction processes. Statistical analysis was conducted using R software. The review included 16 studies, comprising 1358 patients. It revealed that IONM techniques predominantly involved somatosensory evoked potentials (SSEPs), followed by motor evoked potentials (MEPs) and Brainstem auditory evoked potentials (BAEPs). The estimated risk of complications with IONM was 6% (95% CI: 2-11%; I2 = 89%), lower than previously reported rates without IONM. Notably, the clinical improvement rate post-surgery was high at 99% (95% CI: 98-100%; I2 = 56%). The analysis also showed lower reoperation rates in surgeries with IONM compared to those without. Interestingly, no mortality was observed in the included studies. This systematic review and meta-analysis indicate that intraoperative neuromonitoring in Chiari I malformation surgery is associated with favorable clinical outcomes, including lower complication and reoperation rates, and high rates of clinical improvement.

Modulation of motor cortex inhibition during manual dexterity tasks: an adaptive threshold hunting study.

The ability to perform intricate movements is crucial for human motor function. The neural mechanisms underlying precision and power grips are incompletely understood. Corticospinal output from M1 is thought to be modulated by GABAA-ergic intracortical networks within M1. The objective of our study was to investigate the contribution of M1 intracortical inhibition to fine motor control using adaptive threshold hunting (ATH) with paired-pulse TMS during pinch and grasp. We hypothesized that short-interval intracortical inhibition (SICI) could be assessed during voluntary activation and that corticomotor excitability and SICI modulation would be greater during pinch than grasp, reflecting corticospinal control. Seventeen healthy participants performed gradual pinch and grasp tasks. Using ATH, paired-pulse TMS was applied in the anterior-posterior current direction to measure MEP latencies, corticomotor excitability, and SICI. MEP latencies indicated that the procedure preferentially targeted late I-waves. In terms of corticomotor excitability, there was no difference in the TMS intensity required to reach the MEP target during pinch and grasp. Greater inhibition was found during pinch than during grasp. ATH with paired-pulse TMS permits investigation of intracortical inhibitory networks and their modulation during the performance of dexterous motor tasks revealing a greater modulation of GABAA-ergic inhibition contributing to SICI during pinch compared with grasp. NEW & NOTEWORTHY Primary motor cortex intracortical inhibition was investigated during dexterous manual task performance using adaptive threshold hunting. Motor cortex intracortical inhibition was uniquely modulated during pinching versus grasping tasks.

Shaping corticospinal pathways in virtual reality: effects of task complexity and sensory feedback during mirror therapy in neurologically intact individuals.

BACKGROUND: Restoration of limb function for individuals with unilateral weakness typically requires volitional muscle control, which is often not present for individuals with severe impairment. Mirror therapy-interventions using a mirror box to reflect the less-impaired limb onto the more-impaired limb-can facilitate corticospinal excitability, leading to enhanced recovery in severely impaired clinical populations. However, the mirror box applies limitations on mirror therapy, namely that all movements appear bilateral and are confined to a small area, impeding integration of complex activities and multisensory feedback (e.g., visuo-tactile stimulation). These limitations can be addressed with virtual reality, but the resulting effect on corticospinal excitability is unclear. OBJECTIVE: Examine how virtual reality-based unilateral mirroring, complex activities during mirroring, and visuo-tactile stimulation prior to mirroring affect corticospinal excitability. MATERIALS AND METHODS: Participants with no known neurological conditions (n = 17) donned a virtual reality system (NeuRRoVR) that displayed a first-person perspective of a virtual avatar that matched their motions. Transcranial magnetic stimulation-induced motor evoked potentials in the nondominant hand muscles were used to evaluate corticospinal excitability in four conditions: resting, mirroring, mirroring with prior visuo-tactile stimulation (mirroring + TACT), and control. During mirroring, the movements of each participant's dominant limb were reflected onto the nondominant limb of the virtual avatar, and the avatar's dominant limb was kept immobile (i.e., unilateral mirroring). The mirroring + TACT condition was the same as the mirroring condition, except that mirroring was preceded by visuo-tactile stimulation of the nondominant limb. During the control condition, unilateral mirroring was disabled. During all conditions, participants performed simple (flex/extend fingers) and complex (stack virtual blocks) activities. RESULTS: We found that unilateral mirroring increased corticospinal excitability compared to no mirroring (p < 0.001), complex activities increased excitability compared to simple activities during mirroring (p < 0.001), and visuo-tactile stimulation prior to mirroring decreased excitability (p = 0.032). We also found that these features did not interact with each other. DISCUSSIONS: The findings of this study shed light onto the neurological mechanisms of mirror therapy and demonstrate the unique ways in which virtual reality can augment mirror therapy. The findings have important implications for rehabilitation for design of virtual reality systems for clinical populations.

Effects of transcranial magnetic stimulation on axonal regeneration in the corticospinal tract of female rats with spinal cord injury.

BACKGROUND: This study investigates the potential of transcranial magnetic stimulation (TMS) to enhance spinal cord axon regeneration by modulating corticospinal pathways and improving motor nerve function recovery in rats with spinal cord injury (SCI). NEW METHOD: TMS is a non-invasive neuromodulation technique that generates a magnetic field to activate neurons in the brain, leading to depolarization and modulation of cortical activity. Initially utilized for brain physiology research, TMS has evolved into a diagnostic and prognostic tool in clinical settings, with increasing interest in its therapeutic applications. However, its potential for treating motor dysfunction in SCI has been underexplored. RESULTS: The TMS intervention group exhibited significant improvements compared to the control group across behavioral assessments, neurophysiological measurements, pathological analysis, and immunological markers. COMPARISON WITH EXISTING METHODS: Unlike most studies that focus on localized spinal cord injury or muscle treatments, this study leverages the non-invasive, painless, and highly penetrating nature of TMS to focus on the corticospinal tracts, exploring its therapeutic potential for SCI. CONCLUSIONS: TMS enhances motor function recovery in rats with SCI by restoring corticospinal pathway integrity and promoting axonal regeneration. These findings highlight TMS as a promising therapeutic option for SCI patients with currently limited treatment alternatives.

No effects of cerebellar transcranial random noise stimulation on cerebellar brain inhibition, visuomotor learning, and pupil diameter.

Cerebellar brain inhibition (CBI) is an inhibitory output from the cerebellum to the primary motor cortex, which is decreased in early motor learning. Transcranial random noise stimulation (tRNS) is a noninvasive brain stimulation to induce brain plastic changes; however, the effects of cerebellar tRNS on CBI and motor learning have not been investigated yet to our knowledge. In this study, whether cerebellar tRNS decreases CBI and improves motor learning was examined, and pupil diameter was measured to examine physiological changes due to the effect of tRNS on motor learning. Thirty-four healthy subjects were assigned to either the cerebellar tRNS group or the Sham group. The subjects performed visuomotor tracking task with ten trials each in the early and late learning stages while receiving the stimulus intervention. CBI and motor evoked potentials were measured before the learning task, after the early learning stage, and after the late learning stage, and pupil diameter was measured during the task. There was no change in CBI in both groups. No group differences in motor learning rates were observed at any learning stages. Pupil diameter was smaller in the late learning stage than in the early learning stage in both groups. The cerebellar tRNS was suggested not to induce changes in CBI and improvement in motor learning, and it did not affect pupil diameter.

Effects of cerebellar transcranial direct current stimulation on the excitability of spinal motor neurons and vestibulospinal tract in healthy individuals.

Cerebellar transcranial direct current stimulation (ctDCS) modulates cerebellar cortical excitability in a polarity-dependent manner and affects inhibitory pathways from the cerebellum. The cerebellum modulates spinal reflex excitability via the vestibulospinal tract and other pathways projecting to the spinal motor neurons; however, the effects of ctDCS on the excitability of spinal motor neurons and vestibulospinal tract remain unclear. The experiment involved 13 healthy individuals. ctDCS (sham-ctDCS, anodal-ctDCS, and cathodal-ctDCS) was applied to the cerebellar vermis at 2 mA with an interval of at least 3 days between each condition. We measured the maximal M-wave (Mmax) and maximal H-reflex (Hmax) in the right soleus muscle to assess the excitability of spinal motor neurons. We applied galvanic vestibular stimulation (GVS) for 200 ms at 100 ms before tibial nerve stimulation to measure Hmax conditioned by GVS (GVS-Hmax) and calculated the change rate of Hmax by GVS as the excitability of vestibulospinal tract. We measured the Mmax, Hmax, and GVS-Hmax before, during, and after ctDCS in the sitting posture. No main effects of tDCS condition, main effects of time, or interaction effects were observed in Hmax/Mmax or the change rate of Hmax by GVS. It has been suggested that ctDCS does not affect the excitability of spinal motor neurons and vestibulospinal tract, as measured by neurophysiological methods, such as the H-reflex, in healthy individuals in a sitting posture. Effect of ctDCS on other descending pathways to spinal motor neurons, the neurological mechanism of tDCS and the cerebellar activity during the experiment may have contributed to these results. Therefore, we need to investigate the involvement of the cerebellum in Hmax/Mmax and the change rate of Hmax by GVS under different neuromodulation techniques and postural conditions.

Machine learning allows expert level classification of intraoperative motor evoked potentials during neurosurgical procedures.

OBJECTIVE: To develop and evaluate machine learning (ML) approaches for muscle identification using intraoperative motor evoked potentials (MEPs), and to compare their performance to human experts. BACKGROUND: There is an unseized opportunity to apply ML analytic techniques to the world of intraoperative neuromonitoring (IOM). MEPs are the ideal candidates given the importance of their correct interpretation during a surgical operation to the brain or the spine. In this work, we develop and test a set of different ML models for muscle identification using intraoperative MEPs and compare their performance to human experts. In addition, we provide a review of the available literature on current ML applications to IOM data in neurosurgery. METHODS: We trained and tested five different ML classifiers on a MEP database developed from six different muscles in patients who underwent brain or spinal cord surgery. MEPs were obtained by both transcranial (TES) and direct cortical stimulation (DCS) protocols. The models were evaluated within a single patient and on previously unseen patients, considering signals from TES and DCS both independently and mixed. Ten expert neurophysiologists classified a set of 50 randomly selected MEPs, and their performance was compared to the best performing model. RESULTS: A total of 25.423 MEPs were included in the study. Random Forest proved to be the best performing model with 99 % accuracy in the single patient dataset task and a 78 %-94 % accuracy range on previously unseen patients. The model performance was maximized by representing MEPs as a set of features typically employed in signal processing compared to traditional neurophysiological parameters. The classification ability of the Random Forest model between six different muscles and across different MEP acquisition modalities (79 %) significantly exceeded that of human experts (mean 48 %). CONCLUSIONS: Carefully selected ML models proved to have reliable capacity of extracting meaningful information to classify intraoperative MEPs using a limited number of features, proving robustness across patients and signal acquisition modalities, outperforming human experts, and with the potential to act as decision support systems to the IOM team. Such encouraging results lay the path to further explore the underlying nature of clinically important signals, with the aim to continue to produce useful applications to make surgeries safer and more efficient.

Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans.

Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition in humans (Fomenko et al., 2020). At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from TUS pulsing at audible frequencies. In this study, we disentangle direct neuromodulatory and indirect auditory contributions to motor inhibitory effects of TUS. To this end, we include tightly matched control conditions across four experiments, one preregistered, conducted independently at three institutions. We employed a combined transcranial ultrasonic and magnetic stimulation paradigm, where TMS-elicited motor-evoked potentials (MEPs) served as an index of corticospinal excitability. First, we replicated motor inhibitory effects of TUS but showed through both tight controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation, not direct neuromodulation. Furthermore, we consider neuromodulation beyond driving overall excitation/inhibition and show preliminary evidence of how TUS might interact with ongoing neural dynamics instead. Primarily, this study highlights the substantial shortcomings in accounting for the auditory confound in prior TUS-TMS work where only a flip-over sham and no active control was used. The field must critically reevaluate previous findings given the demonstrated impact of peripheral confounds. Furthermore, rigorous experimental design via (in)active control conditions is required to make substantiated claims in future TUS studies. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for research and clinical applications.

Multisensory integration and motor resonance in the primary motor cortex.

Humans are endowed with a motor system that resonates to speech sounds, but whether concurrent visual information from lip movements can improve speech perception at a motor level through multisensory integration mechanisms remains unknown. Therefore, the aim of the study was to explore behavioral and neurophysiological correlates of multisensory influences on motor resonance in speech perception. Motor-evoked potentials (MEPs), by single pulse transcranial magnetic stimulation (TMS) applied over the left lip muscle (orbicularis oris) representation in the primary motor cortex, were recorded in healthy participants during the presentation of syllables in unimodal (visual or auditory) or multisensory (audio-visual) congruent or incongruent conditions. At the behavioral level, subjects showed better syllable identification in the congruent audio-visual condition as compared to the unimodal conditions, hence showing a multisensory enhancement effect. Accordingly, at the neurophysiological level, increased MEPs amplitudes were found in the congruent audio-visual condition, as compared to the unimodal ones. Incongruent audio-visual syllables resulting in illusory percepts did not increase corticospinal excitability, which in fact was comparable to that induced by the real perception of the same syllable. In conclusion, seeing and hearing congruent bilabial syllables increases the excitability of the lip representation in the primary motor cortex, hence documenting that multisensory integration can facilitate speech processing by influencing motor resonance. These findings highlight the modulation role of multisensory processing showing that it can boost speech perception and that multisensory interactions occur not only within higher-order regions, but also within primary motor areas, as shown by corticospinal excitability changes.

Context, transparency and culture in motor resonance phenomena: Causal evidence of the motor cortex.

A connection between language and movement information in metaphorical and literal expressions activates the motor system. Despite numerous studies exploring distinctions between idioms and metaphors, a notable research gap remains in the specific effect of idioms with different transparency levels concerning motor resonance. Our primary focus was analysing the functional role of the primary motor cortex (M1) in processing hand motor verbs both in literal expressions and in two idiomatic contexts, i.e., opaque and transparent idioms. Additionally, we explored a potential language and cultural effect by comparing Turkish and Spanish speakers. An overt priming task with self-paced reading was used to judge the relatedness of a primer and a target sentence. We implemented a repetitive transcranial magnetic stimulation (TMS) protocol using continuous theta-burst stimulation (cTBS) compared to sham stimulation over the M1 in both Turkish and Spanish native speakers prior to the experimental task. Our findings reveal that the performance of Turkish and Spanish participants in processing hand motor actions was facilitated after the application of cTBS over the left M1. Moreover, brain stimulation specifically facilitated the processing of only transparent-but not opaque-idioms in both Spanish and Turkish participants. Our study reports distinct motor resonance results between different types of idioms with a parallel cross-cultural effect.

The influence of menstrual phase on synaptic plasticity induced via intermittent theta-burst stimulation.

BACKGROUND: Ovarian hormones influence the propensity for short-term plasticity induced by repetitive transcranial magnetic stimulation (rTMS). Estradiol appears to enhance the propensity for neural plasticity. It is currently unknown how progesterone influences short-term plasticity induced by rTMS. OBJECTIVE: The present research investigates whether the luteal versus follicular phase of the menstrual cycle influence short-term plasticity induced by intermittent theta-burst stimulation (iTBS). We tested the hypothesis that iTBS would increase motor evoked potentials (MEPs) during the follicular phase. Further, we explored the effects of the luteal phase on iTBS-induced neural plasticity. METHOD: Twenty-nine adult females participated in a placebo-controlled study that delivered real and sham iTBS to the left primary motor cortex in separate sessions corresponding to the follicular phase (real iTBS), luteal phase (real iTBS), and a randomly selected day (sham iTBS). Outcomes included corticospinal excitability as measured by the amplitude of MEPs and short-interval intracortical inhibition (SICI) recorded from the right first dorsal interosseous muscle before and following iTBS (612 pulses). RESULTS: MEP amplitude was increased following real iTBS during the follicular condition. No significant changes in MEP amplitude were observed during the luteal or sham visits. SICI was unchanged by iTBS irrespective of menstrual phase. CONCLUSION: These findings suggest women experience a variable propensity for iTBS-induced short-term plasticity across the menstrual cycle. This information is important for designing studies aiming to induce plasticity via rTMS in women.

Spatial sensorimotor mismatch between the motor command and somatosensory feedback decreases motor cortical excitability. A transcranial magnetic stimulation-virtual reality study.

Effective control of movement predominantly depends on the exchange and integration between sensory feedback received by our body and motor command. However, the precise mechanisms governing the adaptation of the motor system's response to altered somatosensory signals (i.e., discrepancies between an action performed and feedback received) following movement execution remain largely unclear. In order to address these questions, we developed a unique paradigm using virtual reality (VR) technology. This paradigm can induce spatial incongruence between the motor commands executed by a body district (i.e., moving the right hand) and the resulting somatosensory feedback received (i.e., feeling touch on the left ankle). We measured functional sensorimotor plasticity in 17 participants by assessing the effector's motor cortical excitability (right hand) before and after a 10-min VR task. The results revealed a decrease in motor cortical excitability of the movement effector following exposure to a 10-min conflict between the motor output and the somatosensory input, in comparison to the control condition where spatial congruence between the moved body part and the area of the body that received the feedback was maintained. This finding provides valuable insights into the functional plasticity resulting from spatial sensorimotor conflict arising from the discrepancy between the anticipated and received somatosensory feedback following movement execution. The cortical reorganization observed can be attributed to functional plasticity mechanisms within the sensorimotor cortex that are related to establishing a new connection between somatosensory input and motor output, guided by temporal binding and the Hebbian plasticity rule.

The predictive value of intraoperative facial motor evoked potentials in cerebellopontine angle tumor surgery.

OBJECTIVE: Our aim is to explore the value of intraoperative facial motor evoked potentials (FMEP) for facial outcomes in cerebellopontine angle (CPA) tumor surgery to provide an evidence-based consensus standard for future clinical practice and prospective studies. METHODS: Electronic databases were searched from inception to June 2023. Study quality was assessed with the QUADAS-2 tool. Bivariate and random-effects models for meta-analysis and meta-regression generated summary receiver operating characteristic curves (ROC) and forest plots for estimates of sensitivity and specificity. RESULTS: We included 17 studies (1,206 participants). Sensitivity was lower in the immediate (IM) post-operative (0.76, 95% CI 0.65-0.84) compared to follow-up (FU) period (0.82, 95% CI 0.74-0.88) while specificity was similar in both groups (IM, 0.94, 95% CI 0.89-0.97; FU, 0.93, 95% CI 0.87-0.96). Data driven estimates improved FMEP performance but require confirmation from future studies. Amplitude cutoff criteria and studies that scored new deficits as worse than House-Brackmann (HB) grade 2 yielded best sensitivities. CONCLUSIONS: FMEP demonstrated statistically significant accuracy for facial function monitoring. Implementation of FMEPs varied widely across studies. SIGNIFICANCE: Our study is the first systematic review with meta-analysis to demonstrate that intraoperative FMEP is valuable in CPA tumor surgery for facial outcomes. Meta-regression identified the methods that were most useful in the application of FMEPs.

'Remote inhibition' of motor cortex in Epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS): A TMS based cortical excitability study.

OBJECTIVES: The study compared real-time motor cortex excitability using transcranial magnetic stimulation (TMS)-derived parameters between children with epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS) and age-matched neurotypical controls. The EE-SWAS group received steroids as standard of care and were longitudinally followed for three months. MATERIALS & METHODS: Children aged 5-12 years with immunotherapy-naive EE-SWAS (spike-wave-index≥50 %) and neurotypical controls were enrolled. Cognitive and behavioral assessments were performed using valid psychometric tools. Real-time motor cortex excitability was assessed by measuring resting motor threshold (RMT), short intra-cortical inhibition (SICI) and long intra-cortical inhibition (LICI) in both groups. In EE-SWAS group, a follow up evaluation with TMS at 4- and 12-week intervals, EEG, and neurobehavioral assessments at 12-weeks were performed to assess the effect of steroids on cortical excitability and to determine electroclinical outcome. RESULTS: Forty-eight children with suspected EE-SWAS and 26 neurotypical controls were screened; 20 were enrolled in each group. Children with EE-SWAS (mean age: 8.05 ± 1.76 years) had cognitive and behavioral problems (20/20), and ongoing seizures (12/20). At baseline, the dominant motor cortex was significantly inhibited in the EE-SWAS group compared to neurotypical children{RMT(%)[86.3 ± 6.96 vs 58.05 ± 4.71(p < 0.0001)]; LICI(%)[55.05 ± 4.39 vs 73.9 ± 3.75(p < 0.0001)]; SICI(%)[39.2 ± 4.36 vs 55.45 ± 4.78(p < 0.0001)]}. Reversal of motor cortex inhibition was sequentially observed in EE-SWAS group at 4- and 12-week follow-ups{(RMT[4, 12 weeks]: 71.45 ± 9.83, 63.45 ± 8.48); (LICI[4, 12 weeks]: 66.00 ± 6.26, 74.50 ± 5.36); (SICI[4, 12 weeks]: 49.35 ± 6.24, 56.05 ± 5.57)}[repeated-measures ANOVA: p < 0.0001]. CONCLUSION: Motor cortex is remotely inhibited in EE-SWAS, which may contribute to neurobehavioral impairment. Steroids can disinhibit/reverse the epilepsy-induced motor cortex inhibition leading to improvement in neurobehavior.