The Neurorehabilitation of Neurological Movement Disorders Requires Rigorous and Sustained Research.

Movement disorders that stem from neurological conditions such as stroke, cerebral palsy, multiple sclerosis (MS), Parkinson's disease (PD), and spinocerebellar degeneration (SCD) can significantly impair a person's activities of daily living (ADL) [...].

The Influence of Physical, Mental, and Cognitive Factors on Health-Related Quality of Life among Community-Dwelling Older Adults: A Focus on Central Sensitization-Related Symptoms.

Most older adults wish to maintain independence in their familiar communities. However, many experience pain and pain-related disabilities which reduce their health-related quality of life (HRQOL), leading to increased hospitalizations and mortality. This study aimed to determine the impact of physical, mental, and cognitive factors, particularly central sensitization-related symptoms (CSS), on the HRQOL of community-dwelling older adults. A total of 206 participants were included in the analysis, which measured HRQOL, basic attributes, physical functions and body pain, mental factors, cognitive factors, and CSS severity using validated tools. A correlation analysis was used to examine the association between HRQOL and each measure. Furthermore, multiple regression analysis (forced entry method) was performed to identify the factors influencing the HRQOL. The study found that pain intensity and CSS severity significantly influenced the HRQOL among community-dwelling older adults. The higher the pain intensity and CSS severity, the lower their HRQOL. The participants had mild pain and CSS, demonstrating the need to monitor, address, and treat even non-severe issues in community-dwelling older adults. This association, revealed for the first time in this study, suggests that approaches to reduce pain and CSS are important for maintaining and improving the HRQOL of community-dwelling older adults.

Chemokine CCL19 promotes type 2 T-cell differentiation and allergic airway inflammation.

BACKGROUND: Allergic asthma is driven largely by allergen-specific TH2 cells, which develop in regional lymph nodes on the interaction of naive CD4+ T cells with allergen-bearing dendritic cells that migrate from the lung. This migration event is dependent on CCR7 and its chemokine ligand, CCL21. However, is has been unclear whether the other CCR7 ligand, CCL19, has a role in allergic airway disease. OBJECTIVE: This study sought to define the role of CCL19 in TH2 differentiation and allergic airway disease. METHODS: Ccl19-deficient mice were studied in an animal model of allergic asthma. Dendritic cells or fibroblastic reticular cells from wild-type and Ccl19-deficient mice were cultured with naive CD4+ T cells, and cytokine production was measured by ELISA. Recombinant CCL19 was added to CD4+ T-cell cultures, and gene expression was assessed by RNA-sequencing and quantitative PCR. Transcription factor activation was assessed by flow cytometry. RESULTS: Lungs of Ccl19-deficient mice had less allergic airway inflammation, reduced airway hyperresponsiveness, and less IL-4 and IL-13 production compared with lungs of Ccl19-sufficient animals. Naive CD4+ T cells cocultured with Ccl19-deficient dendritic cells or fibroblastic reticular cells produced lower amounts of type 2 cytokines than did T cells cocultured with their wild-type counterparts. Recombinant CCL19 increased phosphorylation of STAT5 and induced expression of genes associated with TH2 cell and IL-2 signaling pathways. CONCLUSIONS: These results reveal a novel, TH2 cell-inducing function of CCL19 in allergic airway disease and suggest that strategies to block this pathway might help to reduce the incidence or severity of allergic asthma.

Relationship between Mild Cognitive Impairment, Pre-Frailty, Physical and Psychological Functioning, and Functional Capacity among Community-Dwelling Older Adults.

Mild cognitive impairment (MCI) is associated with a high risk of dementia. Reportedly, 54.6% of older adults with MCI fall into the pre-frailty category. However, it is unclear what differences exist in older adults with regard to their physical, psychological, and functional capacities, which depend on MCI, pre-frailty, or a combination of the two. This study aimed to examine the differences between the association between physical function, psychological function, and functional capacity by examining a combination of MCI and pre-frailty among community-dwelling older Japanese individuals. The participants in the analysis were 236 older people living in the community. They were classified into four groups, as follows: normal, MCI only, pre-frailty only, and pre-frailty/MCI; furthermore, their physical, psychological, and functional capacities were compared. In addition, a multinomial logistic regression analysis was performed using MCI and pre-frailty as dependent variables. No associated factors were identified for MCI only, and a depressive mood was only associated with pre-frailty. When pre-frailty and MCI were combined, knee extension muscle strength, fastest gait speed, the s30 s chair stand test, depressed moods, and the instrumental activities of daily living (IADL) were correlated. Our results suggest that when MCI and pre-frailty are combined, declines in both physical and psychological functions and IADL are likely to occur.

Excessive excitability of inhibitory cortical circuit and disturbance of ballistic targeting movement in degenerative cerebellar ataxia.

This study aimed to investigate abnormalities in inhibitory cortical excitability and motor control during ballistic-targeting movements in individuals with degenerative cerebellar ataxia (DCA). Sixteen participants took part in the study (DCA group [n = 8] and healthy group [n = 8]). The resting motor-threshold and cortical silent period (cSP) were measured in the right-hand muscle using transcranial magnetic stimulation over the left primary motor cortex. Moreover, the performance of the ballistic-targeting task with right wrist movements was measured. The Scale for the Assessment and Rating of Ataxia was used to evaluate the severity of ataxia. The results indicated that the cSP was significantly longer in participants with DCA compared to that in healthy controls. However, there was no correlation between cSP and severity of ataxia. Furthermore, cSP was linked to the ballistic-targeting task performance in healthy participants but not in participants with DCA. These findings suggest that there is excessive activity in the gamma-aminobutyric acid-mediated cortical inhibitory circuit in individuals with DCA. However, this increase in inhibitory activity not only fails to contribute to the control of ballistic-targeting movement but also shows no correlation with the severity of ataxia. These imply that increased excitability in inhibitory cortical circuits in the DCA may not contribute the motor control as much as it does in healthy older adults under limitations associated with a small sample size. The study's results contribute to our understanding of motor control abnormalities in people with DCA and provide potential evidence for further research in this area.

DNASE1L3 enhances antitumor immunity and suppresses tumor progression in colon cancer.

DNASE1L3, an enzyme highly expressed in DCs, is functionally important for regulating autoimmune responses to self-DNA and chromatin. Deficiency of DNASE1L3 leads to development of autoimmune diseases in both humans and mice. However, despite the well-established causal relationship between DNASE1L3 and immunity, little is known about the involvement of DNASE1L3 in regulation of antitumor immunity, the foundation of modern antitumor immunotherapy. In this study, we identify DNASE1L3 as a potentially new regulator of antitumor immunity and a tumor suppressor in colon cancer. In humans, DNASE1L3 is downregulated in tumor-infiltrating DCs, and this downregulation is associated with poor patient prognosis and reduced tumor immune cell infiltration in many cancer types. In mice, Dnase1l3 deficiency in the tumor microenvironment enhances tumor formation and growth in several colon cancer models. Notably, the increased tumor formation and growth in Dnase1l3-deficient mice are associated with impaired antitumor immunity, as evidenced by a substantial reduction of cytotoxic T cells and a unique subset of DCs. Consistently, Dnase1l3-deficient DCs directly modulate cytotoxic T cells in vitro. To our knowledge, our study unveils a previously unknown link between DNASE1L3 and antitumor immunity and further suggests that restoration of DNASE1L3 activity may represent a potential therapeutic approach for anticancer therapy.

Effects of Robot-Assisted Activity Using a Communication Robot on Neurological Activity in Older Adults with and without Cognitive Decline.

Robot-assisted activity (RAA) using a communication robot (RAA-CR) has been proposed as a tool for alleviating behavioral and psychological symptoms accompanying dementia (BPSD) in patients with cognitive decline. This study aimed to clarify the effects of differences in cognitive function among older adults on changes in active brain areas induced by RAA-CR. Twenty-nine older adults were divided into a cognitive decline group (n = 11) and a control group (n = 18). The participants individually received a 5-minute RAA session, and their resting EEG activity was measured before and after the session. Brain spatial analysis was performed on recorded EEG data using standardized low-resolution brain electromagnetic tomography. In addition, statistical comparisons of neural activity in the brain were made before and after RAA-CR and between the cognitively impaired and control groups. These results suggest that RAA-CR stimulates neural activity in the region centered on the posterior cingulate gyrus and precuneus in cognitively healthy older adults but does not significantly alter brain neural activity in cognitively impaired older adults. Therefore, modifications to the implementation methods may be necessary to effectively implement RAA-CR in cognitively impaired individuals.

Effects of neurofeedback on standing postural control task with combined imagined and executed movements.

Introduction: Motor imagery (MI) is a method of imagining movement without actual movement, and its use in combination with motor execution (ME) enhances the effects of motor learning. Neurofeedback (NFB) is another method that promotes the effects of MI. This study aimed to investigate the effects of NFB on combined MI and ME (MIME) training in a standing postural control task. Methods: Sixteen participants were randomly divided into MIME and MIME + NFB groups and performed 10 trials of a postural control task on an unstable board, with nine trials of MI in between. Electroencephalogram was assessed during MI, and the MIME + NFB group received neurofeedback on the degree of MI via auditory stimulation. A postural control task using an unstable board was performed before and after the MIME task, during which postural instability was evaluated. Results: Postural instability was reduced after the MIME task in both groups. In addition, the root mean square, which indicates the sway of the unstable board, was significantly reduced in the MIME + NFB group compared to that in the MIME group. Conclusion: Our results indicate that MIME training is effective for motor learning of standing postural control. Furthermore, when MI and ME are combined, the feedback on the degree of MI enhances the learning effect.

Race/ethnicity-stratified fine-mapping of the MHC locus reveals genetic variants associated with late-onset asthma.

Introduction: Asthma is a chronic disease of the airways that impairs normal breathing. The etiology of asthma is complex and involves multiple factors, including the environment and genetics, especially the distinct genetic architecture associated with ancestry. Compared to early-onset asthma, little is known about genetic predisposition to late-onset asthma. We investigated the race/ethnicity-specific relationship among genetic variants within the major histocompatibility complex (MHC) region and late-onset asthma in a North Carolina-based multiracial cohort of adults. Methods: We stratified all analyses by self-reported race (i.e., White and Black) and adjusted all regression models for age, sex, and ancestry. We conducted association tests within the MHC region and performed fine-mapping analyses conditioned on the race/ethnicity-specific lead variant using whole-genome sequencing (WGS) data. We applied computational methods to infer human leukocyte antigen (HLA) alleles and residues at amino acid positions. We replicated findings in the UK Biobank. Results: The lead signals, rs9265901 on the 5' end of HLA-B, rs55888430 on HLA-DOB, and rs117953947 on HCG17, were significantly associated with late-onset asthma in all, White, and Black participants, respectively (OR = 1.73, 95%CI: 1.31 to 2.14, p = 3.62 × 10-5; OR = 3.05, 95%CI: 1.86 to 4.98, p = 8.85 × 10-6; OR = 19.5, 95%CI: 4.37 to 87.2, p = 9.97 × 10-5, respectively). For the HLA analysis, HLA-B*40:02 and HLA-DRB1*04:05, HLA-B*40:02, HLA-C*04:01, and HLA-DRB1*04:05, and HLA-DRB1*03:01 and HLA-DQB1 were significantly associated with late-onset asthma in all, White, and Black participants. Conclusion: Multiple genetic variants within the MHC region were significantly associated with late-onset asthma, and the associations were significantly different by race/ethnicity group.

Effects of θ High Definition-Transcranial Alternating Current Stimulation in the Anterior Cingulate Cortex on the Dominance of Attention Focus in Standing Postural Control.

Attention focus affects performance in postural control while standing, and it is divided into internal focus (IF) and external focus (EF). Each individual has a predominant attention focus, and research has revealed that the dominance of attention focus may be an acquired trait. However, the impact of non-invasive brain stimulation on attention-focus dominance remains unexplored in the current literature. Here, we examined the effect of high-definition transcranial alternating current stimulation (HD-tACS) on θ waves in the anterior cingulate cortex (ACC) on standing postural control tasks in an EF condition for IF- and EF-dominant groups. The effect of θ HD-tACS on the ACC differed between IF- and EF-dominant groups, and θ HD-tACS in the IF-dominant group decreased the performance of standing postural control under the EF condition. The forced activation of the ACC with θ HD-tACS may have conversely reduced the activity of brain regions normally activated by the IF-dominant group. Additionally, the activation of ACC prioritized visual information processing and suppressed the superficial sensory processing that is normally potentially prioritized by the IF-dominant group. These results highlight the importance of changing the type of rehabilitation and sports training tasks to account for the individual's dominance of attention focus.

Effects of neurofeedback training combined with transcranial direct current stimulation on motor imagery: A randomized controlled trial.

Introduction: Neurofeedback (NFB) training and transcranial direct current stimulation (tDCS) have been shown to individually improve motor imagery (MI) abilities. However, the effect of combining both of them with MI has not been verified. Therefore, the aim of this study was to examine the effect of applying tDCS directly before MI with NFB. Methods: Participants were divided into an NFB group (n = 10) that performed MI with NFB and an NFB + tDCS group (n = 10) that received tDCS for 10 min before MI with NFB. Both groups performed 60 MI trials with NFB. The MI task was performed 20 times without NFB before and after training, and µ-event-related desynchronization (ERD) and vividness MI were evaluated. Results: µ-ERD increased significantly in the NFB + tDCS group compared to the NFB group. MI vividness significantly increased before and after training. Discussion: Transcranial direct current stimulation and NFB modulate different processes with respect to MI ability improvement; hence, their combination might further improve MI performance. The results of this study indicate that the combination of NFB and tDCS for MI is more effective in improving MI abilities than applying them individually.

Factors Influencing the Use of Walking Aids by Frail Elderly People in Senior Day Care Centers.

BACKGROUND: Senior day care centers in Japan are the most commonly used insurance service for frail elderly people, and it is important to examine the factors that influence the use of walking aids at these centers. We aimed to investigate the factors affecting the use of walking aids by frail elderly patients in senior daycare centers. METHODS: A total of 131 frail elderly people (mean age 82.7 ± 6.4 years) formed our study population. They were divided into two groups: solo walking (n = 87) and walking aid (n = 44). Individuals with cognitive decline were excluded. All participants were assessed using Functional Independence Measure Motor (FIM-M) sub-scores. Grip strength, knee extension strength, the 10 s Chair Stand test for Frail elderly (Frail CS-10), Single Leg Standing (SLS), and Timed Up and Go (TUG) tests were measured and compared between the two groups. RESULTS: The walking aid group scored significantly lower than the solo walking group for five items: FIM-M, knee extension muscle strength, Frail CS-10, SLS, and TUG (p < 0.05). Logistic regression analysis revealed that knee extension muscle strength was the only factor that affected the use or disuse of walking aids (p < 0.05). The cut-off value of the knee extensor muscle strength-to-weight ratio for walking alone was 28.5%. CONCLUSIONS: Knee extensor muscle strength was the most important factor in determining the use of a walking aid.

Impact of Repetitive Transcranial Magnetic Stimulation to the Cerebellum on Performance of a Ballistic Targeting Movement.

This study aimed to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) of the cerebellum on changes in motor performance during a series of repetitive ballistic-targeting tasks. Twenty-two healthy young adults (n = 12 in the active-rTMS group and n = 10 in the sham rTMS group) participated in this study. The participants sat on a chair in front of a monitor and fixed their right forearms to a manipulandum. They manipulated the handle with the flexion/extension of the wrist to move the bar on the monitor. Immediately after a beep sound was played, the participant moved the bar as quickly as possible to the target line. After the first 10 repetitions of the ballistic-targeting task, active or sham rTMS (1 Hz, 900 pulses) was applied to the right cerebellum. Subsequently, five sets of 100 repetitions of this task were conducted. Participants in the sham rTMS group showed improved reaction time, movement time, maximum velocity of movement, and targeting error after repetition. However, improvements were inhibited in the active-rTMS group. Low-frequency cerebellar rTMS may disrupt motor learning during repetitive ballistic-targeting tasks. This supports the hypothesis that the cerebellum contributes to motor learning and motor-error correction in ballistic-targeting movements.

Repetitive Peripheral Magnetic Stimulation Combined with Motor Imagery Changes Resting-State EEG Activity: A Randomized Controlled Trial.

Repetitive peripheral magnetic stimulation is a novel non-invasive technique for applying repetitive magnetic stimulation to the peripheral nerves and muscles. Contrarily, a person imagines that he/she is exercising during motor imagery. Resting-state electroencephalography can evaluate the ability of motor imagery; however, the effects of motor imagery and repetitive peripheral magnetic stimulation on resting-state electroencephalography are unknown. We examined the effects of motor imagery and repetitive peripheral magnetic stimulation on the vividness of motor imagery and resting-state electroencephalography. The participants were divided into a motor imagery group and motor imagery and repetitive peripheral magnetic stimulation group. They performed 60 motor imagery tasks involving wrist dorsiflexion movement. In the motor imagery and repetitive peripheral magnetic stimulation group, we applied repetitive peripheral magnetic stimulation to the extensor carpi radialis longus muscle during motor imagery. We measured the vividness of motor imagery and resting-state electroencephalography before and after the task. Both groups displayed a significant increase in the vividness of motor imagery. The motor imagery and repetitive peripheral magnetic stimulation group exhibited increased ß activity in the anterior cingulate cortex by source localization for electroencephalography. Hence, combined motor imagery and repetitive peripheral magnetic stimulation changes the resting-state electroencephalography activity and may promote motor imagery.

Effects of Insole with Toe-Grip Bar on Barefoot Balance and Walking Function in Patients with Parkinson's Disease: A Randomized Controlled Trial.

The maintenance and improvement of balance and walking function in patients with Parkinson's disease (PD) is essential. Toe dysfunction in patients with PD is related to balance and walking. Recently, insoles have been developed to improve toe function, but their effects on the physical functions of patients with PD remain unclear. In this randomized controlled study, we investigated the effects of insoles with a toe-grip bar on balance and walking function in such patients. Twenty-nine patients with PD in Hoehn and Yahr stages II−IV were randomly assigned to an intervention or control group. Patients in the intervention and control groups wore shoes having insoles with and without a toe-grip bar for 4 weeks, respectively. The center of gravity sway of standing posture (total trajectory length, envelope area, and maximum anterior−posterior center of pressure [AP-COP] distance) and walking parameters at normal and fast speeds were measured pre- and post-intervention in the rehabilitation room. All measurements were performed with the participants being barefoot. The maximum AP-COP distance and step length of the fast-walking condition were significantly improved in the intervention compared to the control group (p < 0.05). Thus, insoles with a toe-grip bar may improve balance and walking function in patients with PD.

Gait Characteristics of Dynapenia, Sarcopenia, and Presarcopenia in Community-Dwelling Japanese Older Women: A Cross-Sectional Study.

Age-related decline in skeletal muscle mass and function are risk factors for reduced walking ability. This study aimed to understand the characteristic gait parameters of presarcopenia (low muscle mass only), dynapenia (low muscle function only), and sarcopenia (low muscle mass and function), which have differing skeletal muscle characteristics. Skeletal muscle mass, grip strength, and gait parameters (walking speed, cadence, step length, step width, gait angle, foot angle, stance time, swing time, and double stance time) were evaluated in 307 older Japanese women. Low muscle function was determined by grip strength and normal walking speed. Participants were assessed and divided into the normal (60.9%, n = 187), presarcopenia (25.7%, n = 79), dynapenia (5.2%, n = 16), and sarcopenia (8.1%, n = 25) groups. When compared to the normal group, the sarcopenia group had significantly slower walking speed and shorter step length (p < 0.05); the dynapenia group had significantly slower walking speed, smaller cadence, shorter step length, wider step width, and longer stance time (p < 0.05); and the presarcopenia group showed no differences. Skeletal muscle function may therefore be more strongly related to reduced walking function in older adults than body composition factors. The decrease in walking function was most pronounced in older women with dynapenia.

Reliability and validity of the Japanese movement imagery questionnaire-revised second version.

OBJECTIVE: Developing a Japanese version of the Movement Imagery Questionnaire-Revised Second Version (MIQ-RS) is essential for widespread evaluation and treatment based on motor imagery in physically disabled persons and patients in rehabilitation. This study aimed to investigate the reliability and validity of the Movement Imagery Questionnaire-Revised Second Version (MIQ-RS), which assesses motor imagery ability, by translating it into Japanese. RESULTS: This study enrolled twenty healthy participants (10 men and 10 women, mean age 21.17 ± 1.10 years). Reliability was examined for internal consistency using Cronbach's alpha coefficient. Spearman's rank correlation coefficient was used to examine the criterion-related validity of the MIQ-RS and the Kinesthetic and Visual Imagery Questionnaire (KVIQ-20). Results showed that Cronbach's alpha coefficients for the MIQ-RS were 0.81 and 0.82 for visual and kinesthetic imagery, respectively. Significant positive correlations were found between each visual and kinesthetic imagery score, and each total on the MIQ-RS and KVIQ-20 scores (r = 0.73, p < 0.01; r = 0.84, p < 0.01; r = 0.80, p < 0.01, respectively). This study suggests that the Japanese version of the MIQ-RS is a reliable and valid method of assessing motor imagery ability.

Comparison of Physical Function among Elderly Japanese Women with and without Low Bone Mass and Low Muscle Mass: A Cross-Sectional Study of Older Women Who Engage in Regular Physical Activity.

A decline in physical function is common among elderly people who have lost both bone and muscle mass. The aim of this study was to investigate the relationship between low bone and muscle mass and physical function in elderly women of different age groups who exercise regularly. The analysis included 299 elderly women. Low bone mass was determined by a T-score of −2.5 or less, and low muscle mass was determined by a skeletal muscle mass index of <5.7 kg/m2. Physical function was measured by grip strength, knee extension strength, standing ability, gait function, and balance function. The participants were divided into four groups based on bone and muscle mass (healthy, low bone mass, low muscle mass, and low bone and muscle mass groups), and their physical functions were compared. There were no statistically significant differences in physical function between the low bone and muscle mass and the healthy groups. There were also no statistically significant differences in physical function among the four groups in the late elderly stage (75 and older). Elderly women who exercise regularly are less likely to experience a decline in physical function, even if they have reduced bone and muscle mass.