Transcutaneous spinal cord stimulation phase-dependently modulates spinal reciprocal inhibition induced by pedaling in healthy individuals.

Reciprocal inhibition (RI) between leg muscles is crucial for smooth movement. Pedaling is a rhythmic movement that can increase RI in healthy individuals. Transcutaneous spinal cord stimulation (tSCS) stimulates spinal neural circuits by targeting the afferent fibers. Pedaling with simultaneous tSCS may modulate the plasticity of the spinal neural circuit and alter neural activity based on movement and muscle engagement. This study investigated the RI changes after pedaling and tSCS and determined the phase of pedaling in which tSCS should be applied for optimal RI modulation in healthy individuals. Eleven subjects underwent three interventions: pedaling combined with tSCS during the early phase of lower extension (phase 1), pedaling combined with tSCS during the late phase of lower flexion (phase 4) of the pedaling cycle, and pedaling combined with sham tSCS. The RI from the tibialis anterior to the soleus muscle was assessed before, immediately after, 15 min, and 30 min after the intervention. RI increased immediately after phase 4 and pedaling combined with sham tSCS, whereas no changes were observed after phase 1. These results demonstrate that tSCS modulates RI changes induced by pedaling in a stimulus phase-dependent manner in healthy individuals. However, the mechanism involved in this intervention needs to be explored to achieve higher efficacy.

Validity Verification of Human Pose-Tracking Algorithms for Gait Analysis Capability.

Two-dimensional (2D) clinical gait analysis systems are more affordable and portable than contemporary three-dimensional (3D) clinical models. Using the Vicon 3D motion capture system as the standard, we evaluated the internal statistics of the Imasen and open-source OpenPose gait measurement systems, both designed for 2D input, to validate their output based on the similarity of results and the legitimacy of their inner statistical processes. We measured time factors, distance factors, and joint angles of the hip and knee joints in the sagittal plane while varying speeds and gaits during level walking in three in-person walking experiments under normal, maximum-speed, and tandem scenarios. The intraclass correlation coefficients of the 2D models were greater than 0.769 for all gait parameters compared with those of Vicon, except for some knee joint angles. The relative agreement was excellent for the time-distance gait parameter and moderate-to-excellent for each gait motion contraction range, except for hip joint angles. The time-distance gait parameter was high for Cronbach's alpha coefficients of 0.899-0.993 but low for 0.298-0.971. Correlation coefficients were greater than 0.571 for time-distance gait parameters but lower for joint angle parameters, particularly hip joint angles. Our study elucidates areas in which to improve 2D models for their widespread clinical application.

Examination of Rehabilitation Intensity According to Severity of Acute Stroke: A Retrospective Study.

OBJECTIVES: To investigate the intensity and effectiveness of rehabilitation in acute stroke patients according to the severity of functional impairments in them. MATERIALS AND METHODS: This retrospective cohort study included 294 patients with acute hemispheric stroke admitted to three acute-care hospitals who subsequently underwent an inpatient rehabilitation program. Stroke severity was classified according to neurological deficits and trunk dysfunction. The following data were obtained from medical records: age, sex, stroke type, lesion side, hospitalization duration, initial functional status determined using the National Institutes of Health Stroke Scale, rehabilitation start date, first day out of bed after admission, total treatment duration, total number of treatment sessions, rehabilitation implementation rate between start of rehabilitation and discharge, trunk control test and Barthel Index score on the first day out of bed after admission and discharge, and post-discharge outcomes. Hierarchical cluster analysis was performed with clusters categorized using the National Institutes of Health Stroke Scale and trunk control test scores. Variables were compared using the Kruskal-Wallis test, and Dunn's nonparametric comparison test was performed for post-hoc analysis to determine differences between clusters. RESULTS: The National Institutes of Health Stroke Scale and trunk control test showed a significant correlation (r = -0.816, p < 0.01) using which cluster analysis identified three clusters. Rehabilitation showed a ceiling effect in patients with mild stroke and a floor effect in patients with severe stroke. CONCLUSION: These results may guide the determination of rehabilitation intensity with reference to the severity of neurological deficits and trunk dysfunction.

Factors related to instrumental activities of daily living in persons with chronic thromboembolic pulmonary hypertension.

Instrumental activities of daily living (IADL) are significantly related to quality of life and mortality among individuals with heart disease. However, few reports have examined IADL in persons with chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to clarify factors related to IADL in persons with CTEPH. This retrospective, observational study enrolled 163 persons with CTEPH (mean ± standard deviation age = 65 ± 13 years; 68% female) admitted to the Department of Cardiology at Keio University Hospital between January 2015 and July 2019. The Frenchay Activities Index (FAI) was used to assess IADL. Age, sex, body mass index, World Health Organization functional class (WHO-FC), cardiac function (mean pulmonary arterial pressure, mean right atrial pressure, pulmonary capillary wedge pressure, and cardiac index), pulmonary function (percentage vital capacity, percentage forced expiratory volume in 1 s, diffusion capacity of carbon monoxide (DLCO)/alveolar volume (VA)), physical function (knee extension strength and walking speed), and 6-min walking distance (6MWD) were assessed. Multiple regression analysis was performed to identify factors significantly associated with FAI. Mean FAI was 25 ± 8. Univariate analysis showed that sex, WHO-FC, DLCO/VA, walking speed, and 6MWD were correlated with FAI. Multiple regression analysis showed that 6MWD (sß = 0.338, 95% CI 0.014-0.034, p < .001), sex (sß = 0.268, 95% CI 2.238-7.165, p < .001), and DLCO/VA (sß = 0.257, 95% CI 1.011-3.528, p < .001) were significantly correlated with FAI (R2 = 0.261). IADL were associated with exercise tolerance, sex, and DLCO/VA in persons with CTEPH. In the future, more details of IADL are expected to be clarified by analyzing individual components of IADL and investigating social background characteristics, including living environment.

Correction to: The role of spinal reciprocal inhibition and intracortical inhibition in functional recovery from stroke.

In the original publication of the article, it was published under the title 'Mini-review article: the role of spinal reciprocal inhibition and intracortical inhibition in functional recovery from stroke'.

The role of spinal reciprocal inhibition and intracortical inhibition in functional recovery from stroke.

Spinal reciprocal inhibition (RI) and intracortical inhibition are important physiological mechanisms for voluntary movement control and functional recovery of voluntary movement in patients with stroke. Spasticity, which impairs motor performance, is one of the major manifestations of stroke. RI may be involved in reducing spasticity. This might allow finger extension, and, therefore, better hand function by reducing co-contraction with finger extensors. One potential mechanism of functional reorganization of the motor cortex is that pre-existing masking pathways are unmasked by decreased intracortical inhibition. The inhibitory neurotransmitter GABA plays an important role in this process. Changes in RI might be mediated through unmasking of cortical pathways through decreased inhibition, with the neurotransmitter GABA. These changes can be assessed using short-latency intracortical inhibition (SICI) and RI. Functional recovery in the chronic phase of stroke induced by rehabilitation was accompanied by SICI and spinal RI changes. Cortical reorganization and spinal plasticity might play important roles in functional recovery induced by rehabilitation, even in patients with chronic severe hemiparesis. This review aims to provide a focused overview of neuroplasticity of spinal RI and intracortical inhibition associated with functional motor recovery from stroke.

Changes in the Excitability of Corticobulbar Projections Due to Intraoral Cooling with Ice.

The aim of this study was to assess the effects of ice applied to the oral cavity on the excitability of corticobulbar projections to the swallowing muscles. The subjects were 8 healthy adult volunteers (mean age 29.0 ± 4.9 years). Motor-evoked potentials (MEPs) were recorded from the suprahyoid muscle complex using surface electrodes. Two blocks of 20 MEPs with a test stimulus intensity of 120% of the resting motor threshold were recorded at rest (baseline). Subjects then underwent 5-min thermal stimulation by either of 3 different types: (1) "ice-stick inside mouth," (2) "ice-stick on neck," and (3) "room temperature inside mouth." Blocks of 20 MEPs were then recorded immediately and at 5-min intervals for the following 15 min. There was a significant difference in the effects of the 3 interventions on the amplitude of the MEPs following stimulation (two-way ANOVA: INTERVENTION × TIME; F8,84 = 3.76, p < 0.01). One-way ANOVA was used to evaluate the changes over time for each intervention type. Only "ice-stick inside mouth" caused an increase in the MEPs (one-way ANOVA main effect of TIME: F4,28 = 4.04, p = 0.010) with significant differences between baseline and P10 (mean difference 0.050; confidence interval (CI) 95% 0.019-0.079; p = 0.004). There were no significant effects of either "ice-stick on neck" or "room temperature inside mouth" (F4,28 = 1.13, p = 0.36; F4,28 = 1.36, p = 0.27, respectively). Ice stimulation within the oral cavity increases the excitability of the cortical swallowing motor pathway.

Relationship between spasticity and spinal neural circuits in patients with chronic hemiparetic stroke.

Spasticity is a common problem in patients with stroke that contributes to motor dysfunction. However, the pathophysiological mechanisms underlying spasticity are not fully understood. The purpose of the present study was to explain the relationship between features of spinal neural circuits assessed using electrophysiological techniques and the clinical manifestations of stroke. The participants were 71 patients with chronic hemiparetic stroke. To assess spinal neural circuits, Hmax/Mmax of the forearm flexor muscles and reciprocal inhibition (RI) between forearm extensor and flexor muscles with the H reflex conditioning-test paradigm were measured. The relationships between electrophysiological parameters and clinical variables (age, time from stroke onset, upper extremity functional scores, and spasticity) were then analyzed. It was found that the third phase of RI (RI-3) correlated with the modified Ashworth scores of the wrist and finger flexors. No other correlations were found between electrophysiological and clinical measures. These results suggest that RI-3 is associated with spasticity and may be helpful to understand the basis of post-stroke spasticity.

Change in Reciprocal Inhibition of the Forearm with Motor Imagery among Patients with Chronic Stroke.

We investigated cortically mediated changes in reciprocal inhibition (RI) following motor imagery (MI) in short- and long(er)-term periods. The goals of this study were (1) to describe RI during MI in patients with chronic stroke and (2) to examine the change in RI after MI-based brain-machine interface (BMI) training. Twenty-four chronic stroke patients participated in study 1. All patients imagined wrist extension on the affected side. RI from the extensor carpi radialis to the flexor carpi radialis (FCR) was assessed using a FCR H reflex conditioning-test paradigm. We calculated the "MI effect score on RI" (RI value during MI divided by that at rest) and compared that score according to lesion location. RI during MI showed a significant enhancement compared with RI at rest. The MI effect score on RI in the subcortical lesion group was significantly greater than that in the cortical lesion group. Eleven stroke patients participated in study 2. All patients performed BMI training for 10 days. The MI effect score on RI at a 20 ms interstimulus interval was significantly increased after BMI compared with baseline. In conclusion, mental practice with MI may induce plastic change in spinal reciprocal inhibitory circuits in patients with stroke.

Hybrid Assistive Neuromuscular Dynamic Stimulation Therapy: A New Strategy for Improving Upper Extremity Function in Patients with Hemiparesis following Stroke.

Hybrid Assistive Neuromuscular Dynamic Stimulation (HANDS) therapy is one of the neurorehabilitation therapeutic approaches that facilitates the use of the paretic upper extremity (UE) in daily life by combining closed-loop electromyography- (EMG-) controlled neuromuscular electrical stimulation (NMES) with a wrist-hand splint. This closed-loop EMG-controlled NMES can change its stimulation intensity in direct proportion to the changes in voluntary generated EMG amplitudes recorded with surface electrodes placed on the target muscle. The stimulation was applied to the paretic finger extensors. Patients wore a wrist-hand splint and carried a portable stimulator in an arm holder for 8 hours during the daytime. The system was active for 8 hours, and patients were instructed to use their paretic hand as much as possible. HANDS therapy was conducted for 3 weeks. The patients were also instructed to practice bimanual activities in their daily lives. Paretic upper extremity motor function improved after 3 weeks of HANDS therapy. Functional improvement of upper extremity motor function and spasticity with HANDS therapy is based on the disinhibition of the affected hemisphere and modulation of reciprocal inhibition. HANDS therapy may offer a promising option for the management of the paretic UE in patients with stroke.

After-effects of pedaling exercise on spinal excitability and spinal reciprocal inhibition in patients with chronic stroke.

PURPOSE OF THE STUDY: To evaluate the after-effects of pedaling on spinal excitability and spinal reciprocal inhibition in patients with post-stroke spastic hemiparesis. MATERIALS AND METHODS: Twenty stroke patients with severe hemiparesis participated in this study and were instructed to perform 7 min of active pedaling and 7 min of passive pedaling with a recumbent ergometer at a comfortable speed. H reflexes and M waves of paretic soleus muscles were recorded at rest before, immediately after and 30 min after active and passive pedaling. The Hmax/Mmax ratio and H recruitment curve were measured. Reciprocal inhibition was assessed using the soleus H reflex conditioning test paradigm. RESULTS: The Hmax/Mmax ratio was significantly decreased after active and passive pedaling exercise. The decreased Hmax/Mmax ratio after active pedaling lasted at least for 30 min. The H recruitment curve and reciprocal inhibition did not change significantly after active or passive pedaling exercise. CONCLUSIONS: Pedaling exercise decreased spinal excitability in patients with severe hemiparesis. Pedaling may be effective in rehabilitation following stroke.

The effects of anodal transcranial direct current stimulation and patterned electrical stimulation on spinal inhibitory interneurons and motor function in patients with spinal cord injury.

Supraspinal excitability and sensory input may play an important role for the modulation of spinal inhibitory interneurons and functional recovery among patients with incomplete spinal cord injury (SCI). Here, we investigated the effects of anodal transcranial direct current stimulation (tDCS) combined with patterned electrical stimulation (PES) on spinal inhibitory interneurons in patients with chronic incomplete SCI and in healthy individuals. Eleven patients with incomplete SCI and ten healthy adults participated in a single-masked, sham-controlled crossover study. PES involved stimulating the common peroneal nerve with a train of ten 100 Hz pulses every 2 s for 20 min. Anodal tDCS (1 mA) was simultaneously applied to the primary motor cortex that controls the tibialis anterior muscle. We measured reciprocal inhibition and presynaptic inhibition of a soleus H-reflex by stimulating the common peroneal nerve prior to tibial nerve stimulation, which elicits the H-reflex. The inhibition was assessed before, immediately after, 10 min after and 20 min after the stimulation. Compared with baseline, simultaneous application of anodal tDCS with PES significantly increased changes in disynaptic reciprocal inhibition and long-latency presynaptic inhibition in both healthy and SCI groups for at least 20 min after the stimulation (all, p < 0.001). In patients with incomplete SCI, anodal tDCS with PES significantly increased the number of ankle movements in 10 s at 20 min after the stimulation (p = 0.004). In conclusion, anodal tDCS combined with PES could induce spinal plasticity and improve ankle movement in patients with incomplete SCI.

MytiLec, a Mussel R-Type Lectin, Interacts with Surface Glycan Gb3 on Burkitt's Lymphoma Cells to Trigger Apoptosis through Multiple Pathways.

MytiLec; a novel lectin isolated from the Mediterranean mussel (Mytilus galloprovincialis); shows strong binding affinity to globotriose (Gb3: Galα1-4Galß1-4Glc). MytiLec revealed ß-trefoil folding as also found in the ricin B-subunit type (R-type) lectin family, although the amino acid sequences were quite different. Classification of R-type lectin family members therefore needs to be based on conformation as well as on primary structure. MytiLec specifically killed Burkitt's lymphoma Ramos cells, which express Gb3. Fluorescein-labeling assay revealed that MytiLec was incorporated inside the cells. MytiLec treatment of Ramos cells resulted in activation of both classical MAPK/ extracellular signal-regulated kinase and extracellular signal-regulated kinase (MEK-ERK) and stress-activated (p38 kinase and JNK) Mitogen-activated protein kinases (MAPK) pathways. In the cells, MytiLec treatment triggered expression of tumor necrosis factor (TNF)-α (a ligand of death receptor-dependent apoptosis) and activation of mitochondria-controlling caspase-9 (initiator caspase) and caspase-3 (activator caspase). Experiments using the specific MEK inhibitor U0126 showed that MytiLec-induced phosphorylation of the MEK-ERK pathway up-regulated expression of the cyclin-dependent kinase inhibitor p21, leading to cell cycle arrest and TNF-α production. Activation of caspase-3 by MytiLec appeared to be regulated by multiple different pathways. Our findings, taken together, indicate that the novel R-type lectin MytiLec initiates programmed cell death of Burkitt's lymphoma cells through multiple pathways (MAPK cascade, death receptor signaling; caspase activation) based on interaction of the lectin with Gb3-containing glycosphingolipid-enriched microdomains on the cell surface.

Transcranial direct current stimulation enhances mu rhythm desynchronization during motor imagery that depends on handedness.

Transcranial direct current stimulation (tDCS) can modulate the amplitude of event-related desynchronization (ERD) that appears on the electroencephalogram (EEG) during motor imagery. To study the effect of handedness on the modulating effect of tDCS, we compared the difference in tDCS-boosted ERD during dominant and non-dominant hand motor imagery. EEGs were recorded over the left sensorimotor cortex of seven healthy right-handed volunteers, and we measured ERD induced either by dominant or non-dominant hand motor imagery. Ten minutes of anodal tDCS was then used to increase the cortical excitability of the contralateral primary motor cortex (M1), and ERD was measured again. With anodal tDCS, we observed only a small increase in ERD during non-dominant hand motor imagery, whereas the same stimulation induced a prominent increase in ERD during dominant hand motor imagery. This trend was most obvious in the participants who used their dominant hand more frequently. Although our study is preliminary because of a small sample size, these results suggest that the increase in ERD by applying anodal tDCS was stronger on the dominant side than on the non-dominant side. The background excitability of M1 may determine the strength of the effect of anodal tDCS on ERD by hand motor imagery.

Executive dysfunction is related with decreased frontal lobe blood flow in patients with subarachnoid haemorrhage.

OBJECTIVE: This study evaluated executive dysfunction in patients with subarachnoid haemorrhage (SAH) using the Behavioural Assessment of the Dysexecutive Syndrome (BADS) and correlated the occurrence of executive dysfunction with cerebral blood flow (CBF) reduction in the frontal lobe as assessed by single photon emission computed tomography (SPECT). DESIGN: Correlational study. SUBJECTS: Twenty-two patients who underwent microsurgical clipping at least 3 months after SAH. METHODS: This study evaluated the BADS and the Wechsler Adult Intelligence Scale-III (WAIS-III). In addition, it assessed activities of daily living (ADL). CBF was evaluated using SPECT. The patients were divided into the following groups according to the results of SPECT: (1) those with reduced CBF in the frontal lobe (reduced CBF group, n = 8) and (2) those with intact CBF (intact CBF group, n = 14). RESULTS: The BADS score was significantly lower in the reduced CBF group compared with that of the intact CBF group, while there was no significant difference in the WAIS-III scores and ADL scale between the two groups. CONCLUSION: Although this result was conducted with a small sample size, executive dysfunction correlates with reduced CBF in the frontal lobes of SAH patients. A detailed evaluation of executive function is suggested in SAH patients, even if the patient's intelligence test and ADL scale reveal no abnormalities.

Effects of Different Intensities of Repetitive Peripheral Magnetic Stimulation on Spinal Reciprocal Inhibition in Healthy Persons.

Objectives: This study aimed to assess the effect of the spinal circuit of repetitive magnetic stimulation (rPMS) on the soleus muscle among healthy subjects. Methods: Nineteen healthy adults were included in this study. Intermittent rPMS was applied to the left soleus muscle for 20 minutes. We applied different intensity rPMS (high-intensity, low-intensity, and non-stimulation) in different three days. RI (reciprocal inhibition) from the tibialis anterior to the soleus muscle with an inter-stimulus interval (ISI) of 2ms and 20ms was assessed before, immediately after and 30 minutes at each session. Results: Two factor repeated measure ANOVA test showed a significant interaction (F2,33 = 9.688, p < 0.001) between tasks and time in the RI ratio 2ms. Post-hoc analysis showed that RI ratio 2ms significantly differed from those immediately after, and 30 min after high-intensity rPMS (p = 0.001 and p = 0.003, respectively). A significant difference was observed between high-intensity rPMS and non-stimulation immediately after the stimulation (p = 0.003). However, no significant difference was found in the RI ratio 20ms between all the intensities (p > 0.05). Conclusion: This study demonstrates that high-intensity rPMS can effectively modulate spinal circuits, as evidenced by the decreased RI in healthy individuals. This suggests the potential use of rPMS as a therapeutic intervention for patients with muscle weakness. Disinhibition of the RI may lead to a more effective contraction of the target muscle. This effect could be expected to strengthen the muscles and alleviate paralysis, making it a promising avenue for future research and clinical applications in the field of rehabilitation. Further investigation is warranted to explore the precise mechanisms underlying the observed effects and to optimize the parameters of rPMS for specific clinical populations.

Home Based Exercise Rehabilitation Programs to Prevent Physical Frailty and Hospitalization-Associated Disability.

Daily health management and exercise are important for staying healthy and avoiding the need for long-term care. However, it is not easy to maintain regular exercise. Therefore, exercise needs to be done efficiently. In recent years, due to the aging population and increasing severity of illness, older patients often experience a significant decline in physical function, even with minimal rest, which often interferes with their daily life after discharge from the hospital. Frailty not only affects ADLs, but also strongly influences prognosis, including the development of atherosclerotic disease and rehospitalization. This perspective is a summary of the 51st Metropolitan Public Lecture held on June 17, 2023, and discusses exercise-based rehabilitation programs that can be delivered at home to prevent physical frailty and avoid hospitalization-related disability.

Decreased grip strength is associated with paraspinal muscular oxidative stress in female lumbar degenerative disease patients.

We aimed to investigate the relationship between superoxide dismutase 2-related oxidative stress in the paraspinal muscles and spinal alignment, clinical skeletal muscle parameters, and mitochondrial function. Multifidus muscle samples from patients who underwent posterior lumbar surgery were analyzed. Patients with diseases affecting oxidative stress and spinal alignment were excluded. The superoxide dismutase 2 redox index was defined as the ratio of reactive oxygen species (superoxide) to antioxidant enzymes (superoxide dismutase 2) and was used as an index of oxidative stress. Patients were divided into two groups based on the superoxide dismutase 2 redox index. Spinal alignment, clinical skeletal muscle parameters, and succinic dehydrogenase (SDH) mean grayscale value were compared between the groups, with analyzes for both sexes. Multiple regression analyzes were used to adjust for the confounding effect of age on variables showing a significant difference between the two groups. Thirty-five patients with lumbar degenerative diseases were included. No significant differences were observed between the two groups for any of the parameters in males; however, females with a higher superoxide dismutase 2 redox index had greater lumbar lordosis, lower grip strength, and higher SDH mean grayscale value than those with a lower index. Multiple regression analyzes revealed that the superoxide dismutase 2 redox index was an independent explanatory variable for lumbar lordosis, grip strength, and SDH mean grayscale value in female patients. In conclusion, superoxide dismutase 2-related oxidative stress in the paraspinal muscles was associated with mitochondrial dysfunction and decreased grip strength in female lumbar degenerative disease patients.

Novel characteristics of the temporal transition to maximum tongue pressure in Parkinson's disease: A pilot study.

Introduction: The reason why maximum tongue pressure (MTP) decreases in patients with Parkinson's disease (PD) remains unclear. Repeated measurements of isometric force and MTP may be useful for analyzing muscle wasting and force generation. The purpose of this pilot study was to evaluate the clinical characteristics and temporal transition of MTP in PD and normal control (NC) groups. Methods: There were 18 participants in this study: 10 with PD and 8 NCs. The MTP was measured 20 times at regular intervals. The area under the curve of MTP temporal transitions, time to reach MTP, and total transition time of the tongue pressure (time to return to baseline) were compared between the groups. Results: MTP decreased from baseline in PD subjects. Unlike NCs, PD subjects showed diverse and inconsistent temporal transitions. The decrease in MTP and delays in time to reach MTP and time to return to baseline were significantly greater in PD subjects (p < 0.05), while there was no group difference in area under the curve values. According to repeated-measures ANOVA, MTP was not different over time between PD subjects and NCs. Conclusion: In this study, muscle fatigue did not affect the decrease in MTP seen in PD subjects, or the diversity and inconsistency of the temporal transition in MTP in that group. These findings indicate that the motor control needed for the repeated, identical movements associated with MTP generation may be impaired in PD patients.