Search Results (329)

Background: Neuropathic pain remains difficult to treat because current analgesics often provide insufficient efficacy or dose-limiting adverse effects. Nav1.7 is genetically validated as a key regulator of human pain sensation, but the development of selective small-molecule Nav1.7 inhibitors has been limited by the high similarity among voltage-gated sodium channel subtypes. Methods: We generated monoclonal antibodies selectively targeting Nav1.7, humanized them for therapeutic development, and evaluated their binding, selectivity, functional channel inhibition, systemic analgesic efficacy, and effects on neuronal activity in a rat model of partial sciatic nerve ligation-induced neuropathic pain. Results: The humanized antibodies showed high-affinity and selective binding to Nav1.7 and functionally inhibited the channel in cellular assays. After systemic administration to neuropathic pain model rats, the lead antibody produced robust analgesia lasting at least 96 h. Electrophysiological analyses demonstrated reduced mechanically evoked and spontaneous neuronal activity, and immunohistochemistry showed decreased mechanical stimulus-induced phosphorylation of extracellular signal-regulated kinase in dorsal root ganglion neurons. The antibodies did not impair physiological nociception or motor function under the tested conditions. Conclusions: These findings provide preclinical proof of concept that humanized anti-Nav1.7 antibodies can act as systemically administered, long-acting biologic analgesics for neuropathic pain while preserving normal nociceptive and motor functions. The clinical advancement of S-151128 further supports the translational potential of this modality. Full article

Objective: Evaluate the test–retest reliability of quadriceps corticospinal excitability and intracortical excitability using transcranial magnetic stimulation (TMS). Design: A test–retest observational cohort study. Methods: Twelve healthy adults attended two laboratory sessions, seated with their knee at 90 degrees and fitted with electrodes on the rectus femoris (RF), vastus lateralis (VL) and vastus medialis (VM). TMS was used to assess the active motor threshold (AMT), motor evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Individual results were calculated as the mean and median of the 10 trials of each measure for MEP, SICI and ICF. Intraclass correlation coefficients were calculated. Results: All muscles showed good or excellent reliability for the mean and median measures of the MEP amplitude (ICC ≥ 0.820) as well as the AMT of the RF (ICC = 0.991). SICI showed good reliability in the mean and median measures of the RF and the mean measure of the VL (ICC ≥ 0.809), moderate reliability in both measures of the VM (ICC ≥ 0.655) and was not significant for the median measure of the VL (ICC = 0.513). ICF showed excellent reliability in the mean measure of each muscle and median measure of the RF (ICC ≥ 0.906), with good reliability in the median measure of the VL (ICC = 0.888) and moderate reliability in the median measure of the VM (ICC = 0.719). Conclusion: The mean of an individual’s quadriceps corticospinal excitability and intracortical excitability have good or excellent reliability for every TMS measure, in every muscle (except SICI of the VM). With the previous reliability of TMS measures mostly investigating the upper limbs, these results offer important context for neurophysiological research in the quadriceps. Full article

Introduction: Navigated transcranial magnetic stimulation (nTMS) is an advanced, noninvasive method for stimulation-based functional brain mapping. Its main clinical value in neurosurgery lies in preoperative identification of eloquent cortical areas and the integration of functional information into neuronavigation-based surgical planning. State of the Art: This narrative review with a structured literature search summarizes the historical and technical foundations of TMS/nTMS, but primarily focuses on neurosurgical applications, including motor and language mapping, comparison with functional MRI and direct cortical stimulation, safety considerations, and practical limitations. Broader neurological and therapeutic applications are discussed as contextual extensions rather than as a comprehensive disease-specific review. Clinical Implications: Current evidence is strongest for preoperative motor mapping in patients with tumors located in or near the motor–eloquent cortex. Language mapping, neurological diagnostics, and therapeutic repetitive TMS (rTMS) applications remain more heterogeneous and require careful interpretation according to the level of evidence, protocol standardization, and patient selection. Future Directions: Further multicenter studies, standardized mapping protocols, integration with advanced imaging and tractography, and health-system implementation strategies are needed to define the optimal role of nTMS in personalized neurosurgical and neurological care. Full article

Purpose: This study investigated whether an acute bout of submaximal unilateral arm cycling elicits sustained changes in corticospinal excitability (CSE) and short-interval intracortical inhibition (SICI) in the homologous muscles of the non-exercised, resting limb. A secondary aim was to determine whether prior exercise induces a preconditioning effect on subsequent motor output. Methods: Transcranial magnetic stimulation was used to assess motor evoked potential (MEP) amplitude (single-pulse) and SICI (paired-pulse) in the resting non-dominant flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles of healthy participants. Measures were obtained at rest, during a 10 min bout of unilateral arm cycling (30 W, 60 rpm), and throughout a 20 min recovery period. To assess potential preconditioning effects, measurements were repeated during a second 2 min cycling bout following a 20 min recovery. Rest and exercise conditions were analyzed separately due to differences in stimulation intensity (RMT vs. AMT). Results: Unilateral arm cycling did not produce sustained changes in CSE or SICI in the resting limb when both arms were at rest. Furthermore, unilateral arm cycling followed by a 20 min recovery period did not result in a preconditioning effect, as CSE in the resting limb was not enhanced during a subsequent unilateral arm cycling bout. Conclusions: Submaximal unilateral arm cycling induces a transient, state-dependent increase in CSE to the non-exercised limb without altering SICI. The absence of SICI modulation suggests that this facilitation is not mediated by GABA_A-dependent intracortical mechanisms, and may instead reflect modulation arising from spinal and interlimb locomotor circuitry. The lack of sustained post-exercise effects indicates that low-intensity arm cycling does not induce a plasticity-permissive cortical state, highlighting a distinction between transient, movement-dependent facilitation and longer-lasting exercise-induced neuroplasticity. Full article

Background/Objectives: Upper-limb motor dysfunction is common after stroke, and patients often have limited recovery during rehabilitation. In this study, we aimed to investigate the relationship between contralesional neurophysiological parameters and the effects of rehabilitation on upper-limb motor function in stroke patients with corticospinal tract damage. Methods: Forty patients with subacute stroke with an absent MEP response on the ipsilesional side before admission were included. Contralesional neurophysiological parameters, including resting motor threshold, contralesional MEP, contralesional short-interval intracortical inhibition (short-ICI), and contralesional long-interval intracortical inhibition (long-ICI), were assessed via transcranial magnetic stimulation (TMS) pre-admission. The coefficients of variation for MEP, short-ICI, and long-ICI were calculated to assess cortical stability. Rehabilitation effect was measured using changes in the Fugl–Meyer assessment score after 21 days of rehabilitation. Results: No single contralesional parameter significantly predicted rehabilitation effect. Further exploratory analysis revealed that a model combining contralesional neurophysiological parameters was associated with proximal limb motor function recovery. Short-ICI played a prominent role in this exploratory model. Conclusions: Contralesional neurophysiological markers demonstrated limited predictive value in patients with stroke with moderate-to-severe motor dysfunction and damaged corticospinal tract function on the ipsilesional side. However, a model combining multimodal contralesional TMS measures, particularly short-ICI, may offer incremental value in predicting proximal limb motor improvement following 21-day rehabilitation. Although this mechanism was not directly measured, the findings suggest a compensatory role of the cortico-reticulo-spinal pathway. These exploratory results should be interpreted with caution regarding their clinical applicability and are premature as a predictive tool, pending rigorous external validation. Full article

Transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) provides a powerful framework to probe and modulate human cortical and corticospinal excitability. In recent years, brain state-dependent EEG–TMS paradigms have gained increasing interest by synchronizing stimulation to ongoing neural activity. However, traditional approaches relying on single oscillatory features or fixed thresholds have yielded heterogeneous and often inconsistent results, motivating the adoption of machine learning (ML) and artificial intelligence (AI) methods to model brain state in a multivariate, data-driven manner. This review synthesizes current ML and deep learning (DL) approaches aimed at predicting cortical and corticospinal excitability from pre-stimulus EEG. We contextualize these methods within brain state-dependent EEG–TMS frameworks based on oscillatory phase, power, and network-level features, and within evolving definitions of brain state that move beyond local biomarkers toward distributed, large-scale, and dynamically evolving neural representations. The reviewed studies span feature-engineered models, data-driven decoding approaches, and emerging adaptive closed-loop frameworks. Finally, we discuss key methodological challenges, translational barriers, and future directions toward personalized, interpretable, and fully closed-loop neuromodulation systems. Full article

With population aging, motor vehicle accidents involving older drivers have increased. Age-related cognitive decline affects driving performance; however, the underlying neural mechanisms remain unclear. This scoping review explored neurophysiological characteristics associated with driving in older adults, including those at risk of dementia. Following PRISMA-ScR guidelines, we searched PubMed, Scopus, and CINAHL for studies examining driving-related neurophysiological measures in older adults aged ≥60 years. Twelve studies were included. Findings converge on load-dependent neural compensation failure: older adults maintain driving performance under low-to-moderate demands, but compensatory mechanisms break down under high cognitive load. Electroencephalography (EEG) studies revealed blunted midfrontal theta upregulation during high-load conditions, associated with reduced steering precision and delayed responses. Event-related potential studies demonstrated that reduced P3b amplitude was associated with missed braking responses and that abnormal visual evoked potentials in Alzheimer’s disease predicted unfit-to-drive classifications. fNIRS studies during driving-related tasks and an fMRI study using a laboratory-based visual task consistently showed prefrontal hyperactivation in older adults. Although some older adults maintained comparable performance to younger adults, the brain–behavior associations observed in younger adults were absent, suggesting that this hyperactivation does not necessarily serve a functional compensatory role. Combined with EEG evidence of impaired oscillatory modulation, these findings suggest that prefrontal hyperactivation does not necessarily compensate for diminished neural synchronization under high-load conditions. Neurophysiological markers hold promise for fitness-to-drive assessments. Future research should employ high-load scenarios and multimodal neuroimaging to verify prefrontal compensatory mechanisms. Full article

Background: The phase of electroencephalogram (EEG) signals critically influences cortical reactivity to external inputs. Phase-dependent effects and their sensitivity to stimulation intensity have been observed at suprathreshold levels, while subthreshold transcranial magnetic stimulation (TMS) cannot induce motor evoked potentials (MEPs), resulting in limited research on phase-dependent responses under subthreshold stimulation. In this study, we used a combined transcranial magnetic stimulation and electroencephalography (TMS–EEG) approach to examine how the ongoing EEG phase influences cortical responses at subthreshold intensity and to characterize these responses in terms of temporal, spatial, and spectral features. Methods: Thirty-four healthy adults received subthreshold single-pulse TMS at the motor hotspot during 64-channel EEG recording. The mu-phase at the time of TMS delivery was estimated using autoregression-based forward prediction and categorized into four bins (0°, 90°, 180°, and 270°). The cortical responses were assessed using inter-trial phase coherence (ITPC), TMS-evoked potentials (TEPs), global mean field power (GMFP), and event-related spectral perturbation (ERSP). Results: Phase estimation reliably distinguished four mu-phase bins. Subthreshold TMS–EEG responses showed clear phase dependence: early ITPC and several TEP components (N15, P30, N45, P60, and N100) differed significantly across phases, with 180° and 270° often eliciting stronger responses. GMFP revealed robust phase effects at mid-latency components, and TMS-induced mu-rhythms were the greatest at 180°. Conclusions: Our results showed that the EEG phase significantly modulates cortical reactivity at subthreshold stimulation levels, supporting mu-phase-based closed-loop TMS as a promising strategy for precise neuromodulation. Full article

Background/Objectives: This study investigates the relationship between Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), neurophysiological markers assessed via Visual Evoked Potentials (VEPs), and functional capacity. Methods: A total of 190 participants, comprising 95 patients and 95 healthy controls, underwent specialized assessments of VEP latencies and amplitudes (P100 and N145), as well as dominant and non-dominant grip strength. Statistical analyses using independent-samples t-tests and linear regression revealed that patients exhibited significantly prolonged P100 and N145 latencies and reduced P100 amplitudes compared with controls, reflecting impaired neural conduction and heterogeneous fiber involvement. Results: Patients also demonstrated markedly reduced bilateral grip strength, confirming the disease’s impact on gross motor skills and sensorimotor integration. Although gender did not broadly differentiate clinical expression, patients receiving intravenous immunoglobulin (IVIg) therapy showed significant improvements in P100 latency and bilateral grip strength, compared with those not receiving treatment. Conclusions: These findings underscore the utility of VEPs and grip strength as reliable biomarkers for monitoring demyelination and functional status, suggesting that their combined evaluation can enhance clinical management and the assessment of therapeutic response in CIDP. Full article

Background and Objectives: Essential tremor (ET) is the most prevalent movement disorder, yet its neurophysiological basis remains incompletely understood. Emerging evidence indicates that ET may involve non-motor manifestations, including auditory dysfunction. Given the anatomical convergence of tremor-related and auditory pathways at the brainstem level, electrophysiological assessment of the auditory system may provide insights into ET pathophysiology. This study aimed to evaluate auditory pathway function in patients with essential tremor using conventional audiometry, brainstem auditory evoked potentials (BAEP), and medium-latency auditory evoked potentials (MLAEP), and to examine their associations with tremor characteristics. Materials and Methods: Thirty patients with ET (mean age 56.6 ± 19.2 years; 15 women) and 30 healthy controls with similar age and sex distribution underwent pure-tone audiometry, BAEP, and MLAEP recordings. Tremor severity and distribution were assessed using a standardized evaluation based on the Fahn–Tolosa–Marin Tremor Rating Scale. Results: Conventional audiometry demonstrated normal hearing thresholds in 63.3% of ET patients and 83% of controls, while sensorineural hearing loss was observed in 36.6% and 16.6%, respectively (p > 0.05). High-frequency hearing loss (HFHL) was significantly more prevalent in the ET group (p = 0.003). BAEP analysis revealed significant prolongation of peak latencies in right-sided waves II and III and left-sided waves I and II in ET patients compared with controls (p < 0.05), whereas interpeak latencies (I–III, III–V, I–V) did not differ between groups. MLAEP latencies (Na, Pa, Nb) showed no significant differences between ET patients and controls (all p > 0.05) and were not associated with tremor severity, disease duration, or hearing asymmetry. Conclusions: High-frequency hearing loss is more prevalent in essential tremor, and selective BAEP latency changes observed in the context of preserved interpeak intervals suggest predominantly delayed peripheral auditory input rather than a primary brainstem conduction abnormality. Preserved MLAEP responses indicate relative sparing of thalamocortical auditory processing, supporting the concept of essential tremor as a multisystem network disorder in which altered auditory input may interact with broader network-level mechanisms. Full article

Introduction: Idiopathic adolescent scoliosis (IAS) is commonly managed non-surgically; however, patients with a Cobb angle >45° before skeletal maturity often require posterior spinal fusion. Because this procedure carries a risk of neurological complications, intraoperative neurophysiological monitoring (IONM) is essential for early detection of spinal cord compromise. Case report: We present a 13-year-old girl with rapidly progressing scoliosis (Cobb angle 78°) who developed intraoperative changes in motor evoked potentials (MEPs) during posterior fusion from L4 to Th2. Total intravenous anesthesia without muscle relaxants was used, and standard multimodal IONM with somatosensory evoked potentials (SSEPs), MEPs, and spontaneous/triggered electromyography was applied. After induction of general anesthesia and surgical exposure, pedicle preparation at Th8–Th9 was followed by increased bleeding from the vertebral bodies and an abrupt loss of MEPs in both lower limbs, most prominently in the tibialis anterior muscles, whilst SSEPs remained unchanged. Intraoperative radiography confirmed correct screw placement, and anesthetic variables were reassessed with no reversible cause identified. Because MEPs remained absent, a wake-up test was performed and demonstrated intact voluntary movement, allowing the surgery to continue. By the end of the procedure, MEPs recovered fully on the left side and partially on the right. The patient awoke without any postoperative motor deficit. Conclusion: It is well known that motor responses can show variability during surgery, including a gradual decrease due to prolonged anesthesia. After excluding anesthetic and mechanical factors, one of the hypothetical explanations for the transient MEP loss was temporary venous congestion and retrograde flow within the intravertebral and epidural/intraspinal venous networks, resulting in reversible spinal cord drainage impairment. Another hypothetical possibility was transient vasospasm from surgical manipulation without direct neural or vascular injury. This case highlights the critical role of continuous multimodal neuromonitoring in detecting reversible spinal cord dysfunction and guiding safe decision-making during complex scoliosis surgery. Full article

Background/Objectives: The impact of stroke on upper extremity function in the older adult population underscores the need for accurate recovery prediction. Motor evoked potential (MEP) has been explored as a predictor of upper extremity function recovery in patients with stroke. However, research specifically targeting the geriatric population remains limited. Therefore, this study focused specifically on patients aged 65 years and older to investigate correlations between MEP parameters and upper extremity function. This study investigates correlations between MEP parameters (amplitude and latency) and upper extremity function-related measures, including Medical Research Council (MRC) scale, the Korean version of the Modified Barthel Index (K-MBI), and the Hand Function Test (HFT), including grip strength, pinch strength, the Box and Block Test, and the 9-Hole Peg Test, in older adults with stroke. Methods: A multiple linear regression model predicts upper extremity outcomes using initial MEP parameters, time, and function. The dataset includes 90 patients with stroke categorized by timing of the first MEP assessment: ≤3 months (n = 42) or >3 months (n = 48). Results: MEP amplitude and latency were significantly correlated with upper extremity function in both groups. No significant correlations were found between MEP amplitude or latency and outcome measures. Regression analysis showed that initial MEP amplitude had a limited association with outcomes, whereas latency was significantly associated with grip strength (β: −10.205, 95% CI: −19.374~−1.036) and the Box and Block Test (β: −10.204, 95% CI: −20.254~−0.154). Initial upper extremity parameters were significantly associated with K-MBI and HFT follow-up results (p < 0.05). Conclusions: Larger MEP amplitude and faster initial MEP latency were associated with improved upper extremity function in patients with stroke. In older patients, MEP latency, rather than amplitude, demonstrated greater predictive value for upper extremity function recovery, possibly due to age-related muscle atrophy, a factor not fully addressed in existing prognostic frameworks such as PREP2. These findings support the integration of MEP latency assessment into geriatric stroke prognostication, complementing existing frameworks such as PREP2, and may guide personalized rehabilitation planning to optimize functional recovery and independence. Full article

Background: Following anterior cruciate ligament reconstruction (ACLR), ACLR patients often experience quadriceps dysfunction, potentially linked to increased corticospinal excitability. However, the role of motor cortex neuroadaptations in persistent quadriceps strength deficits remains unclear. Purpose: The purpose of this study is to investigate neural behavior during a force reproduction task using transcranial magnetic stimulation (TMS) in ACLR participants compared to healthy controls (CONT). Methods: Electrocortical activation of 16 ACLR (10F and 6M, 20.0 ± 1.2 years, 171.9 ± 7.2 cm, 75.8 ± 17.1 kg) and 16 CONT (10F and 6M, 20.6 ± 1.4 yrs, 168.0 ± 9.9 cm, 66.3 ± 11.0 kg) was measured using a 64-channel EEG system during an isometric force reproduction task. Sixty TMS pulses (≥120% active motor threshold) were delivered to the primary motor cortex while participants maintained 10% of quadriceps maximal voluntary isometric contraction (QMVIC10%). Motor-evoked torque (METnorm, %), normalized to 100% TMS intensity, was measured to assess neuroadaptation in the corticospinal tract. EEG data was processed to compute N100 (80–200 ms) and P200 (160–300 ms) TMS-evoked event-related potentials (TEPs, µV) at three regions of interest (ROI): the motor (ROI1), parietal (ROI2), and frontal (ROI3) cortices. MET and TEP comparisons were conducted using independent and unpaired two-sample permutation-based t-tests, respectively. Results: The ACLR group exhibited a significantly greater MET than CONT. Although exploratory, differences were found in P200 TEP at ROI1 with lower power in ACLR than CONT. Conclusions: Lower TEP amplitude at ROI1 implies neural inhibition in the motor cortex, while heightened MET in ACLR suggests greater corticospinal excitability. Neural adaptations in the corticospinal tract in ACLR patients may contribute to excessive quadriceps activation in response to unanticipated stimuli, potentially increasing the risk of re-injury. Full article

Transcranial Magnetic Stimulation (TMS) is a non-invasive technique for neurological research and therapy, but its effectiveness depends on accurate and stable coil placement. Manual localization based on anatomical landmarks is time-consuming and operator-dependent, while state-of-the-art robotic and neuronavigation systems achieve high accuracy using optical tracking with head-mounted markers and infrared cameras, at the cost of increased system complexity and setup burden. This study presents a cost-effective, markerless robotic-assisted TMS system that combines a 3D depth camera and textile capacitive sensors to assist coil localization and contact control. Facial landmarks detected by the depth camera are used to estimate the motor cortex (C3) location without external tracking markers, while a dual textile-sensor suspension provides compliant “soft-landing” behavior, contact confirmation, and coil-tilt estimation. Experimental evaluation with five participants showed reliable C3 targeting with valid motor evoked potentials (MEPs) obtained in most trials after initial calibration, and tilt-verification experiments revealed that peak MEP amplitudes occurred near balanced sensor readings in 12 of 15 trials (80%). The system employs a collaborative robot designed in accordance with international human–robot interaction safety standards, including force-limited actuation and monitored stopping. These results suggest that the proposed approach can improve the accessibility, safety, and consistency of TMS procedures while avoiding the complexity of conventional optical tracking systems. Full article

Background: Repetitive peripheral magnetic stimulation (rPMS) delivers magnetic pulses to peripheral nerves and muscles, producing afferent input that can modulate corticospinal excitability (CSE). While the effects of rPMS on upper-limb muscles have been explored, its short-term effects on lower-limb CSE remain less understood. This study aimed to investigate the short-term effects of rPMS on CSE in the tibialis anterior (TA) muscle among healthy individuals. Methods: Twenty participants completed a repeated- measure, pre-post study. rPMS was applied to the non-dominant TA muscle at 10% above motor threshold for 15 min. CSE was assessed using transcranial magnetic stimulation (TMS), with measurements of motor evoked potential (MEP) amplitude, latency, and duration recorded at baseline, immediately after, 30 min, and 60 min post-stimulation. All analyses were conducted on clean datasets following removal of artifact-related outliers. Results: MEP amplitude showed a significant main effect of Side (p = 0.005), with greater values on the stimulated compared to the non-stimulated side. No significant main effects were found for Time (p = 0.351) or for the Side × Time interaction (p = 0.900). Descriptively, the largest increase in amplitude on the stimulated side was observed at 30 min post-stimulation (12% above baseline). MEP latency and duration showed no significant main or interaction effects. Conclusions: In conclusion, a single rPMS session applied to the TA produced a modest, side-specific increase in CSE lasting up to 60 min, as reflected in MEP amplitude. However, the absence of a significant time effect and perhaps non-optimized stimulation parameters limit the interpretation of sustained neuromodulatory effects. Future studies should examine optimal stimulation parameters and explore underlying mechanisms using measures such as the cortical silent period and interhemispheric inhibition. Full article