IntroductionSitting activities involve trunk leaning, which requires precise coordination of the head, trunk, and pelvis to maintain the center of pressure (COP) within limits of stability. However, how the movement in each segment is associated with COP displacement remains unclear.MethodsTwenty-eight healthy volunteers performed seated trunk leaning twice in left, right, forward, and backward directions. COP displacements and angular changes were measured in head, trunk, and pelvic tilt in all directions, and additionally in the hip during forward-backward leaning. Within-session reliability of measured indices was assessed using intraclass correlation coefficients (ICCs) and Bland-Altman analyses, and relationships between segment angle changes and COP displacements were examined using mixed-effects models.ResultsICCs between two trials showed substantial to very high correlations (ICC = 0.84-0.95), and Bland-Altman analyses showed neither fixed nor proportional bias, suggesting sufficient reliability. Pelvic tilt angle changes were significantly associated with COP displacements during left-right and forward-backward leaning (p < 0.001). Head, trunk, and hip angle changes were also significantly associated with COP displacement during forward-backward leaning (all p < 0.01).ConclusionsPelvic tilt was associated with COP displacement during leaning, regardless of direction, indicating the importance of pelvic shifts in strategies for maintaining sitting balance in healthy adults.

Spinal cord injury disrupts corticospinal transmission and impairs voluntary motor control. While epidural spinal cord stimulation (ESCS) can augment residual motor output, its capacity to drive long-term neuroplasticity remains unoptimized. Here, we present a first-in-human case study showing that an implantable brain-computer interface (BCI) paired with cervical ESCS can potentiate corticospinal connectivity, leading to immediate and sustained improvements in upper-limb motor function in an individual with chronic, motor-complete cervical SCI. The BCI decoded motor intent from electrocorticography signals to trigger stimulation at intent onset, coupling ESCS to volitional movement attempts. This BCI-ESCS paradigm enhanced grip strength and object manipulation immediately and produced greater increases in corticospinal excitability after a single session compared to tonic ESCS. Notably, a four-week BCI-ESCS therapy led to clinically meaningful improvements in voluntary hand function even without system assistance, with some gains persisting one-month post-therapy. These proof-of-concept findings suggest that intention-driven neuromodulation may induce corticospinal plasticity, offering a mechanistically driven neuromotor recovery approach. Overall, BCI-ESCS reveals enhanced volitional control even in an individual with severe paralysis deemed at the recovery plateau. ### Competing Interest Statement M.E.I. is a consultant to Medtronic, and J.D.G. is a consultant to ONWARD Medical; Neither of these consulting roles are directly related to the work presented in this study. M.R.P. is a co-founder, director, and shareholder in MyndTec Inc., and is also a co-founder and consultant for NovaKonexus. W.D.D. is a co-founder and managing member of InflamaCORE, LLC, and has licensed patents on inflammasome proteins as biomarkers of injury and disease, as well as on targeting inflammasome proteins for therapeutic purposes. W.D.D. is also a Scientific Advisory Board Member of ZyVersa Therapeutics. M.C. holds several patents on spinal cord stimulation for motor recovery and is a shareholder of Reach Neuro Inc., a company developing spinal cord stimulation for post-stroke motor recovery. The remaining authors have no conflicts of interest, financial or otherwise. ### Clinical Trial NCT06533969 ### Funding Statement This study was supported by The Miami Project to Cure Paralysis, the Buoniconti Foundation, and the Morton Cure Paralysis Fund. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Miami Institutional Review Board (IRB) (IRB 20190536) and conducted in accordance with the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

Objectives: To investigate the feasibility of robot-assisted hand movement training using a novel end-effector robot in individuals after stroke. Methods: Eleven individuals with subacute stroke with hand motor impairment underwent robot-assisted repetitive finger flexion/extension for 20 min daily and repeated this training on 7 non-consecutive days. The robot was designed to allow the flexion and extension of the metacarpophalangeal and proximal interphalangeal joints of the index to the little fingers, and to provide assistive torque if the movement did not reach the target angle within a limited time. We assessed the co-contraction index (CCI) of the flexor digitorum superficialis and extensor digitorum muscles and assessed the active range of motion (AROM) of the index finger before and after training each day (intra-day effect). We performed clinical assessments of motor function and spasticity and evaluated the CCI and AROM before and immediately after the 7-day training (inter-day effect). Results: Ten participants completed the 7-day training. For the intra-day effect, the CCI was significantly decreased immediately after training, particularly during active finger flexion, and the AROM tended to improve from the middle of the training days. For the inter-day effect, there were no significant changes in the Stroke Impairment Assessment Set for Finger Function, modified Ashworth scale, CCI, or AROM after the 7-day training. Conclusions: Repetitive finger movement training with the assistance of the novel robot improves muscle activation patterns, reducing co-activation between the agonist and antagonist muscles immediately after training.

Exposure to millimeter waves potentially causes pain and tissue damage at the exposed body sites. However, the threshold temperature, especially the pain threshold, remains unclear. In this study, we investigated the perception thresholds of four different types of sensations-warmth, heat, tingling, and pain-and individual physical characteristics associated with the pain perception induced by millimeter-wave exposure. Thirty-five healthy adults were exposed to a 28-GHz millimeter wave on their left middle fingertip at an input power of 8.5 W (incident power density averaged over a 1 cm2 area: 1.00 W/cm2) for up to 10 min. The temperature at which the initial subjective perception of each of the four sensation types occurred was determined as the perception threshold for that sensation. When the skin surface temperature exceeded 44°C or when the participant felt pain, the exposure was terminated. The association between participants' physical characteristics and the presence of pain was investigated using logistic regression analysis. Consequently, the perception thresholds increased in the following order: warmth < heat < tingling < pain. A total of 18 (51%) participants perceived pain, and the average pain threshold was 41.9°C. Females were more likely than males to perceive pain (odds ratio, 4.80 [1.15-20.09]), which may be partially explained by sex-related differences in hydration levels and finger circumference. Our results demonstrated that exposure to millimeter waves can induce pain at approximately 42°C and revealed clear sex differences in sensitivity to pain perception under millimeter-wave exposure.NEW & NOTEWORTHY This study investigated the perception thresholds of four types of sensations-warmth, heat, tingling, and pain-when the fingertip was exposed to 28 GHz millimeter waves. The results showed that the perception thresholds followed the order of warmth, heat, tingling, and pain, with the threshold skin temperature for pain at 41.9°C. Notably, females exhibited significantly higher sensitivity to pain than males. These findings provide further evidence supporting the need for protection from millimeter-wave exposure.

Objective To investigate the feasibility and immediate effects of dynamic exercise using mixed reality (MR), a technology that allows real-time interaction between physical surroundings and computer-generated virtual objects, in older adults and individuals with Parkinson’s disease and stroke. Design Prospective single-arm intervention study. Setting Rehabilitation ward in the hospital. Participants Thirty-one participants, including 10 community-dwelling older adults without neurological or neuromuscular disorders [4 women; mean age: 70.4 years; standard deviation (SD): 3.0], 11 outpatients with Parkinson’s disease (4 women; mean age: 68.4 years, SD: 7.6), and 10 with a stroke (3 women; mean age, 62.8 years; SD, 16.2) in a subacute rehabilitation ward were recruited. Interventions Participants performed MR-based exercise for approximately 20 min. Main Outcome Measures After exercise, participants rated their level of simulator sickness using the simulator sickness questionnaire (SSQ). They further rated their enjoyment, continuation, exercise effectiveness, and fatigue using a numerical rating scale (NRS). The timed up and go test (TUG) and functional reach test (FRT) were performed both before and after the exercise. Results The median SSQ-nausea, SSQ-oculomotor, SSQ-disorientation, and SSQ-total scores were 9.5, 7.6, 0.0, and 7.5, respectively, indicating a low likelihood of simulator sickness. The median NRS scores for enjoyment, continuation, effectiveness, and fatigue were 8.0, 8.0, 7.5, and 2.0, respectively. The TUG in individuals with stroke and FRT in older adults showed significant improvement after exercise (p < 0.05). Conclusions Dynamic exercises with MR may be sufficiently feasible to perform balance exercises with less risk of simulator sickness, offering the potential to improve balance ability.

Stroke severity is associated with the presence or absence of motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS). However, there is limited evidence regarding the relationship between MEP waveforms, post-stroke motor impairment, and functional performance. This study aimed to evaluate the predictive value of inter-trial correlation (ITC), a novel metric reflecting waveform consistency, along with MEP amplitude and resting motor threshold (rMT), in estimating post-stroke motor outcomes. Thirty-eight stroke participants were enrolled, and TMS was applied to the hotspot of the first dorsal interosseous muscle in the ipsilesional or contralesional hemisphere to elicit MEPs. MEP amplitude, ITC, and rMT were analyzed in 20 participants with detectable MEPs. Pearson correlation coefficient (PCC) analysis assessed the relationships between MEP features and motor outcomes, including the Stroke Impairment Assessment Set (SIAS), Fugl-Meyer Assessment (FMA), and Action Research Arm Test (ARAT). A linear support vector machine (SVM) was trained using leave-one-subject-out cross-validation to predict the motor outcomes. Participants without detectable MEPs (n = 18) had significantly lower motor scores than those with detectable MEPs did. MEP amplitude from the contralesional side was positively correlated with SIAS, FMA, and ARAT (PCC = 0.51, 0.47, and 0.55, respectively), whereas LICI amplitude and ITC from the ipsilesional side were negatively correlated with motor scores. The SVM model predicted motor outcomes with an R2 of 0.42 and a normalized root mean square error of 0.26. A Gaussian classifier achieved 75 % accuracy in classifying motor outcome improvements. These findings suggest that bilateral MEP features, particularly those from the contralesional hemisphere, offer valuable prognostic information. This study proposes a practical framework for post-stroke motor outcome prediction based on MEP analysis with potential utility in individualized rehabilitation planning.

The motor system continuously receives sensory inputs and uses this information to perform purposeful movements in a process known as sensorimotor integration. As a biomarker of sensorimotor integration efficacy, short-latency afferent inhibition (SAI), the phenomenon whereby afferent sensory inputs inhibit cortical motor outputs in a given muscle, has been widely studied in humans. However, it remains unclear how the (sensory) nerve-muscle relationship, that is, anatomical proximity and homotopy (nerve supply to muscles), affects SAI magnitude. To address this question, we assessed SAI magnitudes in cortical motor excitability by examining the size of the motor representations of two intrinsic hand muscles when afferent inputs were provided to the nerves either innervating or noninnervating the muscles. In 16 healthy adults, we measured the effect of conditioning electrical stimuli to the median nerve (MN) or ulnar nerve (UN) at the wrist on motor evoked potentials induced by transcranial magnetic stimulation in the first dorsal interosseous (innervated by UN) and abductor pollicis brevis (innervated by MN) muscles, both of which are anatomically located closer to MN than to UN. Conditioning MN stimulation resulted in a significant SAI in both muscles, with no significant difference in SAI between the muscles. No clear SAI was found in either muscle with the UN stimulation. These results suggest that SAI magnitude may depend on anatomical proximity rather than on homotopy. Given the inhibition of the motor representation size of both muscles, the specific nature of such SAI may contribute to the synergistic coordination between muscles.NEW & NOTEWORTHY We found the significant SAI in both cortical broad (motor map) and local (hotspot) areas of the FDI and APB hand muscles only when a conditioning stimulus was delivered to the MN not to the UN. These results suggest that the SAI magnitude may depend on anatomical proximity rather than homotopic interactions between the nerve-muscle relationship, which may contribute to the synergistic coordination of muscles in response to afferent sensory inputs.

Radiofrequency contact current occurs when a human touches objects with different electrical potentials. For emerging wireless power transfer systems, this type of exposure is potentially more restrictive than direct exposure. The limits for contact current are prescribed in the international guidelines for human protection from electromagnetic fields, but its rationale is limited compared with that for direct field exposure. In this article, the perceptional threshold for electrostimulation and heating was evaluated based on computational dosimetry from 10 kHz to 10 MHz. First, the time course of the temperature rise was calculated until each subject perceived the contact current. Second, the perception of current was estimated considering the nerve activation modeling. The computationally estimated current threshold for nerve activation was consistent with the measured data at 100 kHz and increased linearly with increasing frequency, which was contrary to the measured threshold for perception above 300 kHz. By contrast, the estimated perceptual temperature increase was smaller at 100 kHz than at 300 kHz and above. These results indicate that the transient frequency of the threshold for stimulation and heating lies between 100 and 300 kHz, supporting the transition frequency of contact current in the international guidelines.

Introduction:Smiling during conversation occurs interactively between people and is known to build good interpersonal relationships. However, whether and how much the amount that an individual smiles is influenced by the other person's smile has remained unclear. This study aimed to quantify the amount of two individuals' smiles during conversations and investigate the dependency of one's smile amount (i.e., intensity and frequency) on that of the other. Method:Forty participants (20 females) engaged in three-minute face-to-face conversations as speakers with a listener (male or female), under three conditions, where the amount of smiling response by listeners was controlled as "less," "moderate," and "greater." The amount of the smiles was quantified based on their facial movements through automated facial expression analysis. Results:The results showed that the amount of smiling by the speaker changed significantly depending on the listener's smile amount; when the listeners smiled to a greater extent, the speakers tended to smile more, especially when they were of the same gender (i.e., male-male and female-female pairs). Further analysis revealed that the smiling intensities of the two individuals changed in a temporally synchronized manner. Discussion:These results provide quantitative evidence for the dependence of one's smile on the other's smile, and the differential effect between gender pairs.

BACKGROUND:Meta-learning is a metacognitive function for successful, efficient learning in various tasks. While it is possible that meta-learning is linked to functional recovery in stroke, it has not been investigated in previous clinical research on metacognition. AIM:Examine if individual meta-learning ability is associated with functional outcomes. DESIGN:Cohort study. SETTINGS:Rehabilitation ward in Fujita Health University Hospital. POPULATION:Twenty-nine hemiparetic people after stroke. METHODS:The study measured individual sensorimotor adaptation rate, meta-learning (acceleration of adaptation through training), and Functional Independence Measure (FIM) motor effectiveness, an index of functional outcome measuring improvement in proficiency of activity of daily living (ADL). Participants performed visuomotor adaptation training sessions with their less-affected arm. They made arm-reaching movements to hit a target with cursor feedback, which was occasionally rotated with regard to their hand positions, requiring them to change the movement direction accordingly. Initial adaptation rate and meta-learning were quantified from pre- and post-training tests. The relationship between these indices of adaptation ability and FIM motor effectiveness was examined by multiple linear regression analyses. RESULTS:One participant was excluded before data collection in the motor task. In the remaining 28 individuals, the regression analyses revealed that FIM motor effectiveness positively correlated with meta-learning (µ=0.90, P=0.008), which was attenuated by age (µ=-0.015, P=0.005), but not with initial adaptation rate (P=0.08). Control analyses suggested that this observed association between FIM motor effectiveness and meta-learning was not mediated by patients' demographics or stroke characteristics. CONCLUSIONS:This study demonstrates that those who can accelerate adaptation through training are likely to improve ADL, suggesting that meta-learning may be linked with functional outcomes in some stroke individuals. Meta-learning may enable the brain to keep (re-)learning motor skills when motor functions change abruptly due to stroke and neural recovery, thereby associated with improvement in ADL. CLINICAL REHABILITATION IMPACT:Meta-learning is part of metacognitive functions that is positively associated with functional outcomes.

The application of 28 GHz millimeter-wave is prevalent owing to the global spread of fifth-generation wireless communication systems. Its thermal effect is a dominant factor which potentially causes pain and tissue damage to the body parts exposed to the millimeter waves. However, the threshold of this thermal sensation, that is, the degree of change in skin temperature from the baseline at which the first subjective response to the thermal effects of the millimeter waves occurs, remains unclear. Here, we investigated the thermal sensation threshold and assessed its reliability when exposed to millimeter waves. Twenty healthy adults were exposed to 28 GHz millimeter-wave on their left middle fingertip at five levels of antenna input power: 0.2, 1.1, 1.6, 2.1, and 3.4 W (incident power density: 27–399 mW/cm2). This measurement session was repeated twice on the same day to evaluate the threshold reliability. The intraclass correlation coefficient (ICC) and Bland–Altman analysis were used as proxies for the relative and absolute reliability, respectively. The number of participants who perceived a sensation during the two sessions at each exposure level was also counted as the perception rate. Mean thermal sensation thresholds were within 0.9°C–1.0°C for the 126–399 mW/cm2 conditions, while that was 0.2°C for the 27 mW/cm2 condition. The ICCs for the threshold at 27 and 126 mW/cm2 were interpreted as poor and fair, respectively, while those at higher exposure levels were moderate to substantial. Apart from a proportional bias in the 191 mW/cm2 condition, there was no fixed bias. All participants perceived a thermal sensation at 399 mW/cm2 in both sessions, and the perception rate gradually decreased with lower exposure levels. Importantly, two-thirds of the participants answered that they felt a thermal sensation in both or one of the sessions at 27 mW/cm2, despite the low-temperature increase. These results suggest that the thermal sensation threshold is around 1.0°C, consistent across exposure levels, while its reliability increases with higher exposure levels. Furthermore, the perception of thermal sensation may be inherently ambiguous owing to the nature of human perception.

INTRODUCTION:Dose (number of repetitions) has been suggested as a key element in the effectiveness of rehabilitation exercises to promote motor recovery of the hemiparetic upper limb. However, rehabilitation exercises tend to be monotonous and require significant motivation to continue, making it difficult to increase the exercise dose. To address this issue, gamification technology has been implemented in exercises to promote self-engagement for people with hemiparesis in continuing monotonous repetitive movements. This study aimed to investigate how subjective perspectives, specifically enjoyability, motivation to continue, and expectancy of effectiveness, change through continuous daily exercise using a developed gamified exercise system. MATERIALS AND METHOD:Ten people with stroke suffering upper limb dysfunction underwent daily gamified exercise for seven days. The gamified exercise consisted of an electromyography (EMG)-controlled operating system that enabled users to play virtual games using repetitive finger movements. The participants performed conventional self-exercise on the same day as the control exercise, and rated their subjective perspectives on both exercises on a numerical rating scale on each exercise day. RESULTS:Ratings for enjoyability and motivation to continue consistently showed significantly higher scores for the gamified exercise than for conventional self-exercise on all exercise days. A similar trend was observed in the ratings for the expectancy of effectiveness. No changes over time were found in any of the ratings throughout the exercise period. CONCLUSIONS:Exercise using the developed EMG-controlled gamified system may have the potential to maintain motivation and enjoyment in people with stroke to continue monotonous repetitive finger movements.

IntroductionContact electrical currents in humans stimulate peripheral nerves at frequencies of <100 kHz, producing sensations such as tingling. At frequencies above 100 kHz, heating becomes dominant, resulting in a sensation of warmth. When the current amplitude exceeds the threshold, the sensation results in discomfort or pain. In international guidelines and standards for human protection from electromagnetic fields, the limit for the contact current amplitude has been prescribed. Although the types of sensations produced by contact current at low frequencies, i.e., approximately 50–60 Hz, and the corresponding perception thresholds have been investigated, there is a lack of knowledge about those in the intermediate-frequency band—particularly from 100 kHz to 10 MHz.MethodsIn this study, we investigated the current-perception threshold and types of sensations for 88 healthy adults (range: 20–79 years old) with a fingertip exposed to contact currents at 100 kHz, 300 kHz, 1 MHz, 3 MHz, and 10 MHz.ResultsThe current perception thresholds at frequencies ranging from 300 kHz to 10 MHz were 20–30% higher than those at 100 kHz (p < 0.001). In addition, a statistical analysis revealed that the perception thresholds were correlated with the age or finger circumference: older participants and those with larger finger circumferences exhibited higher thresholds. At frequencies of ≥300 kHz, the contact current mainly produced a warmth sensation, which differed from the tingling/pricking sensation produced by the current at 100 kHz.DiscussionThese results indicate that there exists a transition of the produced sensations and their perception threshold between 100 kHz and 300 kHz. The findings of this study are useful for revising the international guidelines and standards for contact currents at intermediate frequencies.Clinical trial registrationhttps://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000045660, identifier UMIN 000045213.

Arm reaching, a fundamental function required for the upper extremities, is often impaired after stroke due to muscle weakness and abnormal synergies. Nonetheless, how aiming directions influence performance remains unclear. Here, we report that direction-dependent differences in the quality and quantity of reaching performance exist, surprisingly regardless of the presence or severity of hemiparesis. This result highlights the need to consider the task work area when designing rehabilitative training.

Upper- and lower-limb neuromuscular electrical stimulation (NMES) is known to modulate the excitability of the neural motor circuits. However, it remains unclear whether short-duration trunk muscle NMES could achieve similar neuromodulation effects. We assessed motor evoked potentials (MEPs) elicited through transcranial magnetic stimulation of the primary motor cortex representation of the trunk extensor muscles to evaluate corticospinal excitability. Moreover, cervicomedullary motor evoked potentials (CMEPs) were assessed through cervicomedullary junction magnetic stimulation to evaluate subcortical excitability. Twelve able-bodied individuals participated in the MEP study, and another twelve in the CMEP study. During the interventions, NMES was applied bilaterally to activate the erector spinae muscle and produce intermittent contractions (20 s ON/20 s OFF) for a total of 20 min while participants remained seated. Assessments were performed: (i) before; (ii) during (in brief periods when NMES was OFF); and (iii) immediately after the interventions to compare MEP or CMEP excitability. Our results showed that MEP responses were not affected by trunk NMES, while CMEP responses were facilitated for approximately 8 min during the intervention, and returned to baseline before the end of the 20 min stimulating period. Our findings therefore suggest that short-duration NMES of the trunk extensor muscles likely does not affect the corticospinal excitability, but it has a potential to facilitate subcortical neural circuits immediately after starting the intervention. These findings indicate that short-duration application of NEMS may be helpful in rehabilitation to enhance neuromodulation of the trunk subcortical neural motor circuits.

Neural interactions between upper and lower limbs underlie motor coordination in humans. Specifically, upper limb voluntary muscle contraction can facilitate spinal and corticospinal excitability of the lower limb muscles. However, little remains known on the involvement of somatosensory information in arm-leg neural interactions. Here, we investigated effects of voluntary and electrically induced wrist flexion on corticospinal excitability and somatosensory information processing of the lower limbs. In Experiment 1, we measured transcranial magnetic stimulation (TMS)-evoked motor evoked potentials (MEPs) of the resting soleus (SOL) muscle at rest or during voluntary or neuromuscular electrical stimulation (NMES)-induced wrist flexion. The wrist flexion force was matched to 10% of the maximum voluntary contraction (MVC). We found that SOL MEPs were significantly increased during voluntary, but not NMES-induced, wrist flexion, compared to the rest (P < .001). In Experiment 2, we examined somatosensory evoked potentials (SEPs) following tibial nerve stimulation under the same conditions. The results showed that SEPs were unchanged during both voluntary and NMES-induced wrist flexion. In Experiment 3, we examined the modulation of SEPs during 10%, 20% and 30% MVC voluntary wrist flexion. During 30% MVC voluntary wrist flexion, P50-N70 SEP component was significantly attenuated compared to the rest (P = .003). Our results propose that the somatosensory information generated by NMES-induced upper limb muscle contractions may have a limited effect on corticospinal excitability and somatosensory information processing of the lower limbs. However, voluntary wrist flexion modulated corticospinal excitability and somatosensory information processing of the lower limbs via motor areas.

Non-invasive theta burst stimulation (TBS) can elicit facilitatory or inhibitory changes in the central nervous system when applied intermittently (iTBS) or continuously (cTBS). Conversely, neuromuscular electrical stimulation (NMES) can activate the muscles to send a sensory volley, which is also known to affect the excitability of the central nervous system. We investigated whether cortical iTBS (facilitatory) or cTBS (inhibitory) priming can affect subsequent NMES-induced corticospinal excitability. A total of six interventions were tested, each with 11 able-bodied participants: cortical priming followed by NMES (iTBS + NMES and cTBS + NMES), NMES only (iTBSsham + NMES and cTBSsham + NMES), and cortical priming only (iTBS + rest and cTBS + rest). After iTBS or cTBS priming, NMES was used to activate right extensor capri radialis (ECR) muscle intermittently for 10 min (5 s ON/5 s OFF). Single-pulse transcranial magnetic stimulation motor evoked potentials (MEPs) and maximum motor response (Mmax) elicited by radial nerve stimulation were compared before and after each intervention for 30 min. Our results showed that associative facilitatory iTBS + NMES intervention elicited greater MEP facilitation that lasted for at least 30 min after the intervention, while none of the interventions alone were effective to produce effects. We conclude that facilitatory iTBS priming can make the central nervous system more susceptible to changes elicited by NMES through sensory recruitment to enhance facilitation of corticospinal plasticity, while cTBS inhibitory priming efficacy could not be confirmed.

Transcranial magnetic stimulation has been used to assess plastic changes in the cortical motor representations of targeted muscles. The present study explored the optimal settings and stimulation intensity for simultaneous motor mapping of multiple upper-limb muscles across segments. In 15 healthy volunteers, we evaluated cortical representations simultaneously from one muscle in the shoulder, two in the upper arm, two in the forearm, and two intrinsic hand muscles, using five stimulation intensities, ranging from 40% to 100% of the maximum stimulator output. We represented the motor map area acquired at each intensity as a percentage of the maximum for each muscle. We defined a motor map area between 25% and 75% of the maximum as the optimal area size with sufficient scope for both up- and down-regulation, and stimulation intensities producing the map area size within this range as the optimal intensities. We found that motor maps with optimal area sizes could be produced simultaneously for the four distal muscles of the forearm and hand in most participants when the stimulation intensity was set at 120-140% of the resting motor threshold (RMT) of the first dorsal interosseous. For the remaining three proximal muscles, motor maps with optimal area sizes were produced only in a few participants, even when using a higher intensity (180-220% RMT). These findings suggest that cortical representations can be assessed simultaneously in a group of distal muscles using a relatively low stimulation intensity, while a separate operation is required to assess that of the proximal muscles.

Optimal parameters of combined repetitive associative transcranial magnetic stimulation (rTMS) and neuromuscular electrical stimulation (NMES) for neuromodulation of central nervous system (CNS) excitability are not well understood. We examined corticospinal excitability after short-duration concurrent and synchronized associative stimulation applied using primary motor cortex rTMS and upper-limb NMES. Intermittent theta burst stimulation (iTBS) was delivered with burst at 50 Hz and repeated at 5 Hz over the course of 192 s as an established cortical facilitation rTMS protocol. NMES was applied to activate the extensor carpi radialis muscle over the same 192 s duration. Four interventions were compared: (1) iTBS with concurrent and synchronized 50 Hz NMES; (2) iTBS with concurrent and synchronized 5 Hz NMES; (3) iTBS with concurrent and asynchronized 41 Hz NMES; (4) iTBS with 5 s delayed and synchronized 50 Hz NMES. Single-pulse motor evoked potential (MEP) responses elicited by transcranial magnetic stimulation of the primary motor cortex and maximum motor responses (Mmax) elicited by radial nerve stimulation were compared before and for 30 min after each intervention. Our results showed that corticospinal excitability (MEP/Mmax) was only facilitated after the iTBS and concurrent 50 Hz NMES intervention, but the responses returned to baseline within 10 min of completing the intervention. This result demonstrates that short-duration concurrent and synchronized stimulation could be applied to effectively neuromodulate corticospinal excitability. Therefore, repetitive synchronized associative stimulation of the primary motor cortical networks and sensorimotor peripheral circuits may be enhanced using synchronized 50 Hz frequency of activation during concurrent stimulation.