湯浅 明子

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.

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.

Arm reaching is often impaired in individuals with stroke. Nonetheless, how aiming directions influence reaching performance and how such differences change with motor recovery over time remain unclear. Here, we elucidated kinematic parameters of reaching toward various directions in people with post-stroke hemiparesis in the sub-acute phase. A total of 13 and 15 participants with mild and moderate-to-severe hemiparesis, respectively, performed horizontal reaching in eight directions with their affected and unaffected sides using an exoskeleton robotic device at admission and discharge. The movement time, path length, and number of velocity peaks were computed for the mild group (participants able to reach toward all eight directions). Additionally, the total amount of displacement (i.e., movement quantity) toward two simplified directions (mediolateral or anteroposterior) was evaluated for the moderate-to-severe group (participants who showed difficulty in completing the reaching task). Motor recovery was evaluated using the Fugl-Meyer Assessment.The mild group exhibited decreases in movement parameters when reaching in the anteroposterior direction, irrespective of the side of the arm or motor recovery achieved. The moderate-to-severe group exhibited less movement toward the anteroposterior direction than toward the mediolateral direction at admission; however, this direction-dependent bias in movement quantity decreased, with the movement expanding toward the anteroposterior direction with motor recovery at discharge. These results suggest that direction-dependent differences in the quality and quantity of reaching performance exist in people after stroke, regardless of the presence or severity of hemiparesis. This highlights the need to consider the task work area when designing rehabilitative training.

<jats:sec><jats:title>Introduction</jats:title><jats:p>Contact electrical currents in humans stimulate peripheral nerves at frequencies of &amp;lt;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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In 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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The current perception thresholds at frequencies ranging from 300 kHz to 10 MHz were 20–30% higher than those at 100 kHz (<jats:italic>p</jats:italic> &amp;lt; 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.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>These 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.</jats:p></jats:sec><jats:sec><jats:title>Clinical trial registration</jats:title><jats:p><jats:ext-link>https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000045660</jats:ext-link>, identifier UMIN 000045213.</jats:p></jats:sec>

Abstract 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.

Previous evidence indicated that interventions with combined neuromuscular electrical stimulation (NMES) and voluntary muscle contractions could have superior effects on corticospinal excitability when the produced total force is larger than each single intervention. However, it is unclear whether the superior effects exist when the produced force is matched between the interventions. Ten able-bodied individuals performed three intervention sessions on separate days: (i) NMES–tibialis anterior (TA) stimulation; (ii) NMES+VOL–TA stimulation combined with voluntary ankle dorsiflexion; (iii) VOL–voluntary ankle dorsiflexion. Each intervention was exerted at the same total output of 20% of maximal force and applied intermittently (5 s ON / 19 s OFF) for 16 min. Motor evoked potentials (MEP) of the right TA and soleus muscles and maximum motor response (M_max) of the common peroneal nerve were assessed: before, during, and for 30 min after each intervention. Additionally, the ankle dorsiflexion force-matching task was evaluated before and after each intervention. Consequently, the TA MEP/M_max during NMES+VOL and VOL sessions were significantly facilitated immediately after the interventions started until the interventions were over. Compared to NMES, larger facilitation was observed during NMES+VOL and VOL sessions, but no difference was found between them. Motor control was not affected by any interventions. Although superior combined effects were not shown compared to voluntary contractions alone, low-level voluntary contractions combined with NMES resulted in facilitated corticospinal excitability compared to NMES alone. This suggests that the voluntary drive could improve the effects of NMES even during low-level contractions, even if motor control is not affected.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a technique that can noninvasively modulate neural states in a targeted brain region. As cerebellar activity levels are associated with upper limb motor improvement after stroke, the cerebellum is a plausible target of tDCS. However, the effect of tDCS remains unclear. Here, we designed a pilot study to assess: (1) the feasibility of a study that aims to examine the effects of cerebellar tDCS combined with an intensive rehabilitation approach based on the concept of constraint-induced movement therapy (CIMT) and (2) the preliminary outcome of the combined approach on upper limb motor function in patients with stroke in the chronic stage. METHODS: This pilot study has a double-blind randomized controlled design. Twenty-four chronic stroke patients with mild to moderate levels of upper limb motor impairment will be randomly assigned to an active or sham tDCS group. The participants will receive 20 min of active or sham tDCS to the contralesional cerebellum at the commencement of 4 h of daily intensive training, repeatedly for 5 days per week for 2 weeks. The primary outcomes are recruitment, enrollment, protocol adherence, and retention rates and measures to evaluate the feasibility of the study. The secondary outcome is upper limb motor function which will be evaluated using the Action Research Arm Test, Fugl-Meyer Assessment, for the upper extremity and the Motor Activity Log. Additionally, neurophysiological and neuroanatomical assessments of the cerebellum will be performed using transcranial magnetic stimulation and magnetic resonance imaging. These assessments will be conducted before, at the middle, and after the 2-week intervention, and finally, 1 month after the intervention. Any adverse events that occur during the study will be recorded. DISCUSSION: Cerebellar tDCS combined with intensive upper limb training may increase the gains of motor improvement when compared to the sham condition. The present study should provide valuable evidence regarding the feasibility of the design and the efficacy of cerebellar tDCS for upper limb motor function in patients with stroke before a future large trial is conducted. TRIAL REGISTRATION: This study has been registered at the Japan Registry of Clinical Trials ( jRCTs042200078 ). Registered 17 December 2020.

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.

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.

<jats:p>Functional electrical stimulation therapy (FEST) can improve motor function after neurological injuries. However, little is known about cortical changes after FEST and weather it can improve motor function after traumatic brain injury (TBI). Our study examined cortical changes and motor improvements in one male participant with chronic TBI suffering from mild motor impairment affecting the right upper-limb during 3-months of FEST and during 3-months follow-up. In total, 36 sessions of FEST were applied to enable upper-limb grasping and reaching movements. Short-term assessments carried out using transcranial magnetic stimulation (TMS) showed reduced cortical silent period (CSP), indicating cortical and/or subcortical inhibition after each intervention. At the same time, no changes in motor evoked potentials (MEPs) were observed. Long-term assessments showed increased MEP corticospinal excitability after 12-weeks of FEST, which seemed to remain during both follow-ups, while no changes in CSP were observed. Similarly, long-term assessments using TMS mapping showed larger hand MEP area in the primary motor cortex (M1) after 12-weeks of FEST as well as during both follow-ups. Corroborating TMS results, functional magnetic resonance imaging (fMRI) data showed M1 activations increased during hand grip and finger pinch tasks after 12-weeks of FEST, while gradual reduction of activity compared to after the intervention was seen during follow-ups. Widespread changes were seen not only in the M1, but also sensory, parietal rostroventral, supplementary motor, and premotor areas in both contralateral and ipsilateral hemispheres, especially during the finger pinch task. Drawing test performance showed improvements after the intervention and during follow-ups. Our findings suggest that task-specific and repetitive FEST can effectively increase cortical activations by integrating voluntary motor commands and sensorimotor network through functional electrical stimulation (FES). Overall, our results demonstrated cortical re-organization in an individual with chronic TBI after FEST.</jats:p>

Ankle dorsiflexion force control is essential for performing daily living activities. However, the involvement of the corticospinal pathway during different ankle dorsiflexion tasks is not well understood. The objective of this study was to compare the corticospinal excitability during: (1) unilateral and bilateral; and (2) ballistic and tonic ankle dorsiflexion force control. Fifteen healthy young adults (age: 25.2 ± 2.8 years) participated in this study. Participants performed unilateral and bilateral isometric ankle dorsiflexion force-control tasks, which required matching a visual target (10% of maximal effort) as quickly and precisely as possible during ballistic and tonic contractions. Transcranial magnetic stimulation (TMS) was applied over the primary motor cortex to elicit motor-evoked potentials (MEPs) from the right tibialis anterior during: (i) pre-contraction phase; (ii) ascending contraction phase; (iii) plateau phase (tonic tasks only); and (iv) resting phase (control). Peak-to-peak MEP amplitude was computed to compare the corticospinal excitability during each experimental condition. MEP amplitudes significantly increased during unilateral contraction compared to bilateral contraction in the pre-contraction phase. There were no significant differences in the MEP amplitudes between the ballistic tasks and tonic tasks in any parts of the contraction phase. Although different strategies are required during ballistic and tonic contractions, the extent of corticospinal involvement appears to be similar. This could be because both tasks enhance the preparation for precise force control. Furthermore, our results suggest that unilateral muscle contractions may largely facilitate the central nervous system during movement preparation for unilateral force control compared to bilateral muscle contractions.

We investigated whether bilateral lower-limb control and leg dominance affect force control ability in 15 healthy young adults (9 males and 6 females, age =26.8 ± 4.1 years). Participants performed isometric ankle dorsiflexion force control tasks, matching a visual target (10% of maximal effort) as quickly and precisely as possible in ballistic and tonic tasks. Performance was evaluated using force error, force steadiness, amount of muscle activity of the tibialis anterior, and response time characteristics. Results showed no significant effects of leg dominance during both ballistic and tonic tasks, while bilateral condition resulted in significantly larger error, less force steadiness, compared to unilateral condition, and only during the tonic task. Consequently, bilateral control, specifically in tasks utilizing feedback control (i.e., tonic task) might affect force control ability, possibly because of the interhemispheric inhibition to meet bilateral task complexity and integrate afferent bilateral sensory information from both right and left legs.