Progress in neurorehabilitation research and the support by the National Natural Science Foundation of China from 2010 to 2022

The National Natural Science Foundation of China is one of the major funding agencies for neuro rehabilitation research in China.This study reviews the frontier directions and achievements in the field of neurorehabilitation in China and wo rldwide.We used data from the Web of Science Core Collection(WoSCC) database to analyze the publications and data provided by the National Natural Science Foundation of China to analyze funding information.In addition,the prospects for neurorehabilitation research in China are discussed.From 2010 to 2022,a total of 74,220 publications in neurorehabilitation were identified,with there being an overall upward tendency.During this period,the National Natural Science Foundation of China has funded 476 research projects with a total funding of 192.38 million RMB to support neuro rehabilitation research in China.With the support of the National Natural Science Foundation of China,China has made some achievements in neurorehabilitation research.Research related to neurorehabilitation is believed to be making steady and significant progress in China.

Go to the back before going forward:Addressing psychological responses in anterior cruciate ligament reconstruction rehabilitation

Helping athletes return to sports participation is a primary goal of anterior cruciate ligament(ACL)reconstruction rehabilitation.To facilitate the achievement of this goal,decades of research studies have sought to identify knee impairments that reduce knee function as well as interventions to resolve them.1Yet,over the past 10 years,research pertaining to psychological responses(i.e.,cognitions and emotions)after ACL reconstruction has grown exponentially—a phenomenon that can be visualized by entering the search terms"psychological"and"anterior cruciate ligament reconstruction"into the PubMed search engine.

Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

Passive activity enhances residual control ability in patients with complete spinal cord injury

Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.

Commentary on:“Human neural stem cell-derived artificial organelles to improve oxidative phosphorylation”

Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024).

Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

Aphasia rehabilitation based on mirror neuron theory: a randomized-block-design study of neuropsychology and functional magnetic resonance imaging

When watching someone performs an action, mirror neurons are activated in a way that is very similar to the activation that occurs when actually performing that action. Previous single-sample case studies indicate that hand-action observation training may lead to activation and remodeling of mirror neuron systems, which include important language centers, and may improve language function in aphasia patients. In this randomized-block-design experiment, we recruited 24 aphasia patients from, Zhongda Hospital, Southeast University, China. The patients were divided into three groups where they underwent hand-action observation and repetition, dynamic-object observation and repetition, or conventional speech therapy. Training took place 5 days per week, 35 minutes per day, for 2 weeks. We assessed language function via picture naming tests for objects and actions and the Western Aphasia Battery. Among the participants, one patient, his wife and four healthy student volunteers underwent functional magnetic resonance imaging to analyze changes in brain activation during hand-action observation and dynamic-object observation. Results demonstrated that, compared with dynamic-object observation, hand-action observation led to greater performance with respect to the aphasia quotient and affiliated naming sub-tests and a greater Western Aphasia Battery test score. The overall effect was similar to that of conventional aphasia training, yet hand-action observation had advantages compared with conventional training in terms of vocabulary extraction and spontaneous speech. Thus, hand-action observation appears to more strongly activate the mirror neuron system compared with dynamic-object observation. The activated areas included Broca's area, Wernicke's area, and the supramarginal gyrus. These results suggest that hand-action observation combined with repetition might better improve language function in aphasia patients compared with dynamic-object observation combined with repetition. The therapeutic mechanism of this intervention may be associated with activation of additional mirror neuron systems, and may have implications for the possible repair and remodeling of damaged nerve networks. The study protocol was approved by the Ethical Committee of Nanjing Medical University, China(approval number: 2011-SRFA-086) on March 11, 2011. This trial has been registered in the ISRCTN Registry(ISRCTN84827527).

Prospects for intelligent rehabilitation techniques to treat motor dysfunction

More than half of stroke patients live with different levels of motor dysfunction after receiving routine rehabilitation treatments.Therefore,new rehabilitation technologies are urgently needed as auxiliary treatments for motor rehabilitation.Based on routine rehabilitation treatments,a new intelligent rehabilitation platform has been developed for accurate evaluation of function and rehabilitation training.The emerging intelligent rehabilitation techniques can promote the development of motor function rehabilitation in terms of informatization,standardization,and intelligence.Traditional assessment methods are mostly subjective,depending on the experience and expertise of clinicians,and lack standardization and precision.It is therefore difficult to track functional changes during the rehabilitation process.Emerging intelligent rehabilitation techniques provide objective and accurate functional assessment for stroke patients that can promote improvement of clinical guidance for treatment.Artificial intelligence and neural networks play a critical role in intelligent rehabilitation.Multiple novel techniques,such as braincomputer interfaces,virtual reality,neural circuit-magnetic stimulation,and robot-assisted therapy,have been widely used in the clinic.This review summarizes the emerging intelligent rehabilitation techniques for the evaluation and treatment of motor dysfunction caused by nervous system diseases.

Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach

Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and posttransplant patient care and rehabilitation researchers.

Chronic Kidney Disease is a New Target of Cardiac Rehabilitation

Chronic heart failure is increasingly prevalent worldwide and is associated with signifi cant morbidity and mortality.The Cochrane review demonstrated that cardiac rehabilitation(CR)resulted in improvements in QOL and a reduction in long-term mortality.Chronic kidney disease(CKD)is another worldwide public health problem.This review focuses on the importance and effi cacy of rehabilitation for CKD patients as a new target of CR.Patients with CKD on hemodialysis(HD)have a high mortality rate,with cardiovascular diseases,such as chronic heart failure.A new systematic review and meta-analysis of randomized controlled trials reported that exercise-based renal rehabilitation improved aerobic capacity,muscular functioning,cardiovascular function,walking capacity,and QOL in CKD patients with HD.Moreover,exercise training may have renal protective effects,not only in some animal models of pre-HD CKD,but also in pre-HD CKD patients.Exercise therapy could be an effective clinical strategy in improving renal function,lowering the need for renal replacement therapy,such as HD,and reducing renal transplant risk in pre-HD CKD patients.This led the Ministry of Health,Labor and Welfare of Japan to extend renal rehabilitation partial coverage to stage4pre-HD CKD patients for the first time in the world in 2016.

Asserted and neglected issues linking evidence-based and Chinese medicines for cardiac rehabilitation

High blood pressure is among the most prevalent chronic disease in adults that impacts on the quality of life of patients, which are often subjected to physical rehabilitation. Chinese medicine intervention in patients with hypertension presents promising albeit inconclu-sive results, mostly due to methodological issues. This paper discusses asserted and neglected issues linking evidence-based and Chinese medicines as related to systemic arterial hypertension, as well as their impact on the physical rehabilitation of those patients. On the one hand, natural history of hypertension, pulse palpa-tion, and herbal therapy are among the asserted issues because of the scientific evidence collected about them, either in favor or against its integration to the current medical practice. On the other hand, anatomical varia-tions of vessels and comparative physiology are among the most commonly neglected issues because previous researches on integrative medicine ignored the pos-sible effects of these issues as related to the study's outcome. The asserted issues highlighted in this paperstimulate the increasing use of Chinese medicine for health care and the continuity of research on integra-tive medicine in the cardiovascular field for rehabilita-tion. The neglected issues poses additional challenges that must not be overlooked in future research on this topic so that the integration of both traditional and cur-rent knowledge may be of benefit to the population with cardiovascular disease.

Stress and Resources in Women Attending an Inpatient Prevention/Rehabilitation Measure for Parents: Secondary Analysis of Quality Assurance Data

Questionnaire data from two projects on the development of quality assurance instruments for an inpatient rehabilitation/prevention program for parents were used for a secondary analysis. In this analysis, the associations of gains in a psychosocial resource (parenting self-efficacy) and two types of stressors experienced by mothers at the start of treatment (parenting hassles, depressive symptoms) with general life satisfaction and satisfaction with health at the end of treatment were explored. Structural equation modeling was applied to data from N = 1724 female patients. Potential resource-stressor interactions were tested using the Latent Moderated Structural Equations approach. Results showed that parenting hassles were negatively associated with general life satisfaction and satisfaction with health while self-efficacy gains were weakly positively correlated with both variables. No interaction of parenting hassles and self-efficacy gains was found. Depressive symptoms were negatively associated with both satisfaction measures. In these models, self-efficacy gains were not substantially correlated with life satisfaction, but showed a small association with satisfaction with health. There was no significant interaction of depressive symptoms and self-efficacy gains. The findings imply that interventions for distressed mothers—as exemplarily illustrated by this inpatient setting—should focus on identifying and reducing initial stressors as these may continue to impair mothers’ subjective health despite gains in parenting-related resources.

Vestibular rehabilitation in cerebellar ataxia with neuropathy and vestibular areflexia syndrome(CANVAS)-A case report

Background and purpose:Cerebellar ataxia,neuropathy,and vestibular areflexia syndrome(CANVAS)is a neurodegenerative disease of the cerebellum.The disease progression is slow,with up to 25%of people diagnosed needing to use a wheelchair after 15 years from diagnosis.Vestibular symptoms arise from centrally-mediated ocular movement degradation and the reduced vestibular-ocular reflex functioning bilaterally.To date,no report has shown an improvement in VOR gain or gait outcome measures in someone with CANVAS after a course of vestibular physical therapy.Case description:A 65-year-old male,Patient X,first noticed symptoms in his fourth decade of life and was diagnosed with(CANVAS)in his seventh decade.Patient X reported numbness and tingling in his hands and feet,decreased ability to perform daily activities,and several falls.Intervention:Patient X completed a four-month course of vestibular physical therapy,including vestibular ocular reflex exercises,balance training,gait training,and the VestAid application for eye gaze compliance monitoring.The Vestaid application uses eyes and facial recognition software to record the percentage of time that the patient kept their eyes on the target.Outcomes:After vestibular therapy,Patient X had a clinically meaningful improvement in gait speed:from 1.02 m/s to 1.13 m/s and in the Functional Gait Assessment from 20/30 to 27/30.Patient X's eye gaze compliance improved from a median of 43%(range 25e68%)to a median of 67%(58e83%).Discussion:This case study demonstrates that vestibular rehabilitation improved eye gaze compliance and functional outcomes in a person living with CANVAS.

Seasonal variation and living alone are related to pulmonary rehabilitation non-completion

AIM: To identify baseline characteristics that independently predict pulmonary rehabilitation non-completion and compare these findings against the participant's reasons for non-completion. METHODS: Participants with chronic obstructive pulmonary disease(COPD) who attended a standardised twice weekly, eight week pulmonary rehabilitation program(located in the sub-tropics, latitude 27°29' South) between 2010 and 2012 were recruited. Thebaseline characteristics of program completers and non-completers were compared in a case-controlled design. Participants who attended < 12/16 sessions were classified as a non-completer. Non-completers(those who missed > 4 session of the program) were asked by one independent investigator to participate in a survey about their pulmonary rehabilitation experience. Baseline characteristics were assessed for differences between program completers and non-completers. The baseline characteristics included disease severity, exercise capacity, smoking history, participant's social support and the season when each participant commenced rehabilitation. Non-completers that agreed to participate in the survey were asked to indicate what personal factors or external factors contributed to their program non-completion. Comparisons of completers and non-completers baseline characteristics were performed using cross-tabulations and t-tests, with significant measures analysed in a multivariate binary logistic regression model. Non-completers survey responses were compared to the identified independent predictors using cross-tabulations.RESULTS: Twenty-six participants(23.4%) of the 111 participants with COPD [(mean ± SD) age was 67.4 ± 9.2 years and FEV1 54.6% ± 22.3%)], were classified as non-completers. Forty-five participants(40.5%) commenced pulmonary rehabilitation during winter. Thirty-six participants(32.4%) were living alone at program commencement. In the multivariate analysis(n = 111), only programs that commenced in winter(Exp B: 0.255, 95%CI: 0.090-0.727, P = 0.011) and participants that lived alone(Exp B: 2.925, 95%CI: 1.039-8.229, P = 0.042) were identified as independent predictors of program non-completion. Twenty participants of the twenty-six non-completers agreed to participate in the survey about their pulmonary rehabilitation experience. The reasons given for non-completion were grouped into: medical reasons(75%), other personal reasons(30%) and external barriers(45%), with ten non-completers reporting more than one reason.No participant reported living alone or that the program commenced during winter as a reason for noncompletion. There was no relationship between illness being the participant's reason for non-completion and the programs that commenced in winter(P = 0.135). CONCLUSION: Despite winter commencing programs and participants who lived alone being independent predictors of program non-completion, neither measure was reported by participants as a reason for noncompletion.

The minimal clinically important difference for gait speed in significant unilateral vestibular hypofunction after vestibular rehabilitation

Gait speed is a valid measure of both physical function and vestibular health.Vestibular rehabilitation is useful to improve gait speed for patients with vestibular hypofunction,yet there is little data to indicate how changes in gait speed reflect changes in patient-reported health outcomes.We determined the minimal clinically important difference in the gait speed of patients with unilateral vestibular hypofunction,mostly due to deafferentation surgery,as anchored to the Dizziness Handicap Index and the Activities Balance Confidence scale,validated using regression analysis,change difference,receiveroperator characteristic curve,and average change methods.After six weeks of vestibular rehabilitation,a change in gait speed from 0.20 to 0.34 m/s with 95%confidence was required for the patients to perceive a significant reduction in perception of dizziness and improved balance confidence.

Supported Rehabilitation for Individuals Who Have Experienced a Stroke: A Pilot Control Trial

The purpose of this study was to pilot an innovative and supported intervention for individuals with a stroke. A pilot control trial with qualitative interviews was undertaken within a university- community setting. Thirteen individuals who had experienced a stroke for periods of least 6 months (6 male, average 71 years) were assigned to the intervention group and 7 individuals (2 male, average age 67.9 years) assigned to the control group. Eight individuals from the intervention group completed a single interview. The procedures that related to recruitment and retention and data collection methods were considered. Outcome measures including;self-efficacy, falls self-efficacy and group membership, for both groups were taken at baseline, 11 weeks, 22 weeks. There was an additional assessment at 52 weeks for the intervention group. The structured interview was designed to focus on experiences of the intervention. Self-efficacy remained stable across time for both groups. An improvement in falls self-efficacy was noted in the intervention group at 11 weeks. Consistent improvement (from baseline) was observed in the identity scale across the 52 weeks. Qualitative data provided additional findings related to identity and confidence. Details considering recruitment and retention are also provided. This pilot study provided data that can be used for a further full-scale trial to be considered.

Exercise-with-melatonin therapy improves sleep disorder and motor dysfunction in a rat model of ischemic stroke

Exercise-with-melatonin therapy has complementary and synergistic effects on spinal cord injury and Alzheimer's disease,but its effect on stroke is still poorly understood.In this study,we established a rat model of ischemic stroke by occluding the middle cerebral artery for 60 minutes.We treated the rats with exercise and melatonin therapy for 7 consecutive days.Results showed that exercise-with-melatonin therapy significantly prolonged sleep duration in the model rats,increased delta power values,and regularized delta power rhythm.Additionally,exercise-with-melatonin therapy improved coordination,endurance,and grip strength,as well as learning and memory abilities.At the same time,it led to higher hippocampal CA1 neuron activity and postsynaptic density thickness and lower expression of glutamate receptor 2 than did exercise or melatonin therapy alone.These findings suggest that exercise-withmelatonin therapy can alleviate sleep disorder and motor dysfunction by increasing glutamate receptor 2 protein expression and regulating hippocampal CA1 synaptic plasticity.

Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy

Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.

2024 Wheelchair Compendium of Physical Activities:An update of activity codes and energy expenditure values

Purpose:This paper presents an update of the 2011 Wheelchair Compendium of Physical Activities designed for wheelchair users and is referred to as the 2024 Wheelchair Compendium.The Wheelchair Compendium aims to curate existing knowledge of the energy expenditure for wheelchair physical activities(PAs).Methods:A systematic review of the published energy expenditure of PA for wheelchair users was completed between 2011 and May 2023.We added these data to the 2011 Wheelchair Compendium data that was compiled previously in a systematic review through 2011.Results:A total of 47 studies were included,and 124 different wheelchair PA reported energy expenditure values ranging from 0.8 metabolic equivalents for wheelchair users(filing papers,light effort)to 11.8 metabolic equivalents for wheelchair users(Nordic sit skiing).Conclusion:In introducing the updated 2024 Wheelchair Compendium,we hope to bridge the resource gap and challenge the prevailing narratives that inadvertently exclude wheelchair users from physical fitness and health PAs.