Human Motor Function Research Articles

Coenzyme Q10 supplementation improves the motor function of middle-aged mice by restoring the neuronal activity of the motor cortex

Physiological aging causes motor function decline and anatomical and biochemical changes in the motor cortex. We confirmed that middle-aged mice at 15–18 months old show motor function decline, which can be restored to the young adult level by supplementing with mitochondrial electron transporter coenzyme Q10 (CoQ10) as a water-soluble nanoformula by drinking water for 1 week. CoQ10 supplementation concurrently improved brain mitochondrial respiration but not muscle strength. Notably, we identified an age-related decline in field excitatory postsynaptic potential (fEPSP) amplitude in the pathway from layers II/III to V of the primary motor area of middle-aged mice, which was restored to the young adult level by supplementing with CoQ10 for 1 week but not by administering CoQ10 acutely to brain slices. Interestingly, CoQ10 with high-frequency stimulation induced NMDA receptor-dependent long-term potentiation (LTP) in layer V of the primary motor cortex of middle-aged mice. Importantly, the fEPSP amplitude showed a larger input‒output relationship after CoQ10-dependent LTP expression. These data suggest that CoQ10 restores the motor function of middle-aged mice by improving brain mitochondrial function and the basal fEPSP level of the motor cortex, potentially by enhancing synaptic plasticity efficacy. Thus, CoQ10 supplementation may ameliorate the age-related decline in motor function in humans.

Anthropomorphic Reaching Movement Generating Method for Human-Like Upper Limb Robot.

How to generate anthropomorphic reaching movement remains a challenging problem in service robots and human motor function repair/reconstruction equipment. However, there is no universally accepted computational model in the literature for reproducing the motion of the human upper limb. In response to the problem, this article presents a computational framework for generating reaching movement endowed with human motion characteristics that imitated the mechanism in the control and realization of human upper limb motions. This article first establishes the experimental paradigm of human upper limb functional movements and proposes the characterization of human upper limb movement characteristics and feature movement clustering methods in the joint space. Then, according to the specific task requirements of the upper limb, combined with the human sensorimotor model, the estimation method of the human upper limb natural postures was established. Next, a continuous task parametric model matching the characteristic motion class is established by using the Gaussian mixture regression method. The anthropomorphic motion generation method with the characteristics of the smooth trajectory and the ability of natural obstacle avoidance is proposed. Finally, the anthropomorphic motion generation method proposed in this article is verified by a human-like robot. The measurement index of the human-likeness degree of the trajectory is given. The experimental results show that for all four tested tasks, the human-likeness degrees were greater than 90.8%, and the trajectories' jerk generated by this method is very similar to the trajectories' jerk of humans, which validates the proposed method.

EEG Signal Classification of Motor Imagery Right and Left Hand using Common Spatial Pattern and Multilayer Perceptron Back Propagation

The number of people with disabilities is increasing, so it requires bionic devices to replace human motor functions. Brain-Computer Interface (BCI) can be a tool for the bionic device to communicate with the brain. Signal brain or Electroencephalogram (EEG) signal need to classify to drive the corresponding bionic device. This research goal is to classify the imagination of the right and left-hand movements based on the EEG signal. The system design in this research consists of EEG channel selection using Finite Impulse Response (FIR) filter, feature extraction using Common Spatial Pattern (CSP), and classification using Multilayer Perceptron Back Propagation (MLP-BP). The data used a secondary dataset from BCI Competition IV (2b) with 9 research subjects. The research scenario is carried out by trying to use several variations in the number of hidden layer nodes on each EEG channel. Based on the test, the best accuracy for MLP-BP is 68.7% using 24 nodes in the alpha channel.

Longitudinal electrophysiological changes after mesenchymal stem cell transplantation in a spinal cord injury rat model.

Transcranial electrically stimulated motor-evoked potentials (tcMEPs) are widely used to evaluate motor function in humans and animals. However, the relationship between tcMEPs and the recovery of paralysis remains unclear. We previously reported that transplantation of mesenchymal stem cells to a spinal cord injury (SCI) rat model resulted in various degrees of recovery from paraplegia. As a continuation of this work, in the present study, we aimed to establish the longitudinal electrophysiological changes in this SCI rat model after mesenchymal stem cell transplantation. SCI rats were established using the weight-drop method. The model rats were transvenously transplanted with two types of mesenchymal stem cells (MSCs), one derived from rat cranial bones and the other from the bone marrow of the femur and tibia bone, 24 h after SCI. A phosphate-buffered saline (PBS) group that received only PBS was also created for comparison. The degree of paralysis was evaluated over 28 days using the Basso-Beattie-Bresnahan (BBB) scale and inclined plane task score. Extended tcMEPs were recorded using a previously reported bone-thinning technique, and the longitudinal electrophysiological changes in tcMEPs were investigated. In addition, the relationship between the time course of recovery from paralysis and reappearance of tcMEPs was revealed. The appearance of the tcMEP waveform was earlier in MSC-transplanted rats than in PBS-administered rats (earliest date was 7 days after SCI). The MEP waveforms also appeared at approximately the same level on the BBB scale (average score, 11 points). Ultimately, this study can help enhance our understanding of the relationship between neural regeneration and tcMEP recording. Further application of tcMEP in regenerative medicine research is expected.

Evaluation of a Portable fMRI Compatible Robotic Wrist Interface.

This paper presents evaluation of a portable fMRI compatible haptic interface to study the brain correlates of sensorimotor control during wrist motion. The interface is actuated by a shielded DC motor located more than 2 m away from the 3T MR scanner's bore. The achievable wrist torque of the interface is up to 2 Nm, and the interface provides sufficient bandwidth for human motor control experiments. Ergonomic and fMRI compatibility testing with a 3T MR scanner showed that the interface is MR safe, compatible with a strong static magnetic field and radio frequency emission, and its operation does not affect the quality of the acquired images. Clinical Relevance- We present and evaluate an fMRI compatible robotic interface to study human wrist joint motor function.

REM Sleep Rebound Following Acute Intermittent Hypoxia in Freely Behaving Rats

Core components of the circadian clock and molecules involved in neuroplasticity elicited by acute intermittent hypoxia (AIH) exhibit 24‐hour rhythms in gene expression in the phrenic/diaphragm motor system. Ongoing investigations of time‐of‐day effects on AIH‐induced motor plasticity must account for changes in time spent across vigilance states since sleep architecture profoundly influences other biological rhythms across the rest‐active cycle. Previous investigations from our group reported a marginal increase in wakefulness during the AIH exposure in unanesthetized rats (10, 5‐min hypoxic episodes; 5 min intervals). Following AIH, we also observed a prolonged increase in slow‐wave sleep lasting hours, but changes in REM were not assessed (Terada et al., J. Appl. Physiol., 2011). Given the significant effects disruptions of the sleep‐wake cycle can have on daily biological rhythms, further characterization of sleep architecture following AIH is needed. In this preliminary analysis, from an extensive study of diaphragm long‐term facilitation (LTF) in rats at opposite stages of the diurnal cycle (mid‐active vs. mid‐rest), we added second set of intracortical EEG leads (ECoG) not used by Terada et al. (2011) to enhance detection of hippocampal theta bursts and sleep spindling. In 8 unanesthetized, instrumented rats exposed to AIH, ECoG, and nuchal EMG signals acquired via radiotelemetry were analyzed in 10‐second epochs using Fast Fourier transformation spectral analysis. Power spectra were averaged in frequency bands: delta (1.5‐4.0Hz), theta (4.0‐10.0Hz), beta (10.0‐30.0 Hz), and sigma (10.0‐14.0Hz). We assessed vigilance state at baseline, during AIH, and 90 minutes post‐AIH; there were significant effects of AIH protocol period (p < 0.05) and sleep state (p<0.001). There were marginal, non‐significant trends towards increased active wakefulness during AIH, with decreased quiet wakefulness, slow‐wave sleep, and REM. Time spent in REM sleep rebounded to levels nearly two‐fold above baseline at 60 and 90 min post‐AIH; there were non‐significant trends towards reduced quiet wakefulness without apparent change in NREM sleep post‐AIH. In this preliminary analysis, we report an acute AIH protocol (3, 5 min hypoxic episodes, 13% O2; 5‐min normoxic intervals) has minimal impact on NREM sleep during or following AIH but increases REM post‐AIH. Additional analyses will be performed during and following AIH during the mid‐active and mid‐rest phases, using the 5‐min AIH protocol and a modified protocol with similar cumulative duration of hypoxia (15, 1 min hypoxic episodes; 1 min intervals) often used in human studies of repetitive AIH as a neurotherapeutic modality to improve breathing and non‐respiratory motor function in humans living with chronic spinal cord injury and ALS. REM sleep is essential for mechanisms of neuroplasticity in neural networks controlling diverse physiological systems. These results warrant future research to delineate the influence REM may play in initiating and maintaining memory in the respiratory system.

Design and Experimental Verification of a Parallel Hip Exoskeleton System for Full-Gait-Cycle Rehabilitation

Abstract Rehabilitation with exoskeletons after hip joint replacement is a tendency to achieve efficient recovery of people to rebuild their human motor functions. However, the kinematic mismatch between the kinematic and biological hip is a problem in most existing exoskeletons that can cause additional stress in the hip. To avoid secondary damage, the misalignment between the mechanical and biological hip joint of an exoskeleton must be compensated. This paper introduces a novel hip exoskeleton system based on parallel structure. The exoskeleton can inherently address the kinematic mismatch by introducing additional kinematic redundancy, while requiring no additional kinematic components and volumes. To achieve bidirectional full-gait-cycle walking assistance, a remote actuation system is designed for power delivery, and a control scheme is proposed to reject disturbances caused by gait dynamics during walking exercises. Human testing was carried out to evaluate the performance of the system. The results show that the exoskeleton has good human–machine kinematic compatibility and can achieve promising force tracking in the presence of gait dynamics.

Motor Ability Evaluation of the Upper Extremity with Point-To-Point Training Movement Based on End-Effector Robot-Assisted Training System.

Assessment is critical during the procedure of stroke rehabilitation. However, traditional assessment methods are time-consuming, laborious, and dependent on the skillfulness of the therapist. Moreover, they cannot distinguish whether the improvement comes from the abnormal compensation or the improvement of upper extremity motor function. To make up for the shortcomings of the traditional methods, this study proposes a novel assessment system, which consisted of a rehabilitation robot and motion capture (MoCAP) system. A 9-degree-of-freedom (DOF) kinematic model is established, which consists of the shoulder girdle, shoulder, elbow, and wrist joints. And seven assessment indices are selected for this assessment system, including a range of motion (ROM), shoulder girdle compensation (SGC), trunk compensation (TC), aiming angle (AA), motion error (ME), motion length ratio (MLR), and useful force (UF). For AA, ME, and MLR, all describe the motor ability of the upper extremity, and a linear model was proposed to map these three indices into one index, called motor control ability (MCA). Then, this system can quantitatively evaluate human upper extremity motor function from joint space kinematics, Cartesian space kinematics, and dynamics. Three healthy participants were invited to verify the effectiveness of this system. The preliminary results show that all participants' handedness performs a little better than the nonhandedness. And the performance of the participants and the change of all the upper limb joints can be directly watched from the trajectory of the hand and joint angles' curve. Therefore, this assessment system can evaluate the human upper limb motor function well. Future studies are planned to recruit elderly volunteers or stroke patients to further verify the effectiveness of this system.

Characterization and Categorization of Various Human Lower Limb Movements Based on Kinematic Synergies.

A proper movement categorization reduces the complexity of understanding or reproducing human movements in fields such as physiology, rehabilitation, and robotics, through partitioning a wide variety of human movements into representative sub-motion groups. However, how to establish a categorization (especially a quantitative categorization) for various human lower limb movements is rarely investigated in literature and remains challenging due to the diversity and complexity of the lower limb movements (diverse gait modes and interaction styles with the environment). Here we present a quantitative categorization for the various lower limb movements. To this end, a similarity measure between movements was first built based on limb kinematic synergies that provide a unified and physiologically meaningful framework for evaluating the similarities among different types of movements. Then, a categorization was established via hierarchical cluster analysis for thirty-four lower limb movements, including walking, running, hopping, sitting-down-standing-up, and turning in different environmental conditions. According to the movement similarities, the various movements could be divided into three distinct clusters (cluster 1: walking, running, and sitting-down-standing-up; cluster 2: hopping; cluster 3: turning). In each cluster, cluster-specific movement synergies were required. Besides the uniqueness of each cluster, similarities were also found among part of the synergies employed by these different clusters, perhaps related to common behavioral goals in these clusters. The mix of synergies shared across the clusters and synergies for specific clusters thus suggests the coexistence of the conservation and augmentation of the kinematic synergies underlying the construction of the diverse and complex motor behaviors. Overall, the categorization presented here yields a quantitative and hierarchical representation of the various lower limb movements, which can serve as a basis for the understanding of the formation mechanisms of human locomotion and motor function assessment and reproduction in related fields.

High Gamma and Beta Temporal Interference Stimulation in the Human Motor Cortex Improves Motor Functions.

Background: Temporal interference (TI) stimulation is a new technique of non-invasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidated.Objective: To assess the effectiveness of the envelope-modulated waveform of TI stimulation on the human primary motor cortex (M1).Methods: Participants attended three sessions of 30-min TI stimulation during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation.Results: In the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time (RT) performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential.Conclusion: These results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time and paving the way for further explorations.

Comparative Study of Foot Fixation Methods and Sensor Arrangements in Ankle Joint Torque Measurement Equipment

Joint torque estimation techniques are used for evaluating human motor function. Particularly, ankle joint torque is essential for evaluating the walking function. Ankle joint torque can be derived by fixing the metatarsophalangeal (MTP) joint and ankle circumference and measuring force and torque from force sensors placed at the two fixation points. Considering implementation effort, it is desirable to use a 6-axis sensor or a sensor with fewer measurable axes. Therefore, in this study, we compared multiple sensor arrangements and calculation methods in the measurement of ankle joint torque. Through theoretical and empirical evaluations, the conditions under which these methods are effective were clarified. Based on the investigation, we propose a method to arrange a 6-axis force sensor only at the toe. One concern in the theoretical investigation was the error due to the moment caused by the fixation of the heel side. However, in measurement experiments using an ankle model and subjects, the accuracy was almost the same as when two 6-axis force sensors were used. The results indicates that the effect of this error factor is limited: hence, this method is considered to be useful as a method of both accuracy and sensor reduction.

The role of pre-participation sports evaluation: A review

Background and Introduction: The purpose of the study is about create awareness for pre-participating evaluation, diversity of application, ethical standard maintenance, health promotion and evidence based practice. "Physiotherapists evaluate, plan and put into practice rehabilitative programs that improve or maximize movement ability, restore human motor functions, relieve pain syndromes, and care for or prevent physical challenges associated with injuries, diseases and other impairments. They apply a broad range of physical therapies and techniques such as movement, heating, ultrasound, laser and other techniques. They may build up and implement programmes for screening and prevention of general physical ailments and disorders“. For prevention of more injuries and diminish the rate of sudden death. Objective: The aim of this study is to cognize the role of Pre-participation sports evaluation as a health promoter, researcher, innovator, manager and physiotherapy-student. Methodology: A. Data Source: Relevant articles were identified by searching from: PuBMed, Science Direct, EBSCO, SCOPUS, Web of Science, shodhganga, Elsevier, Google Scholar. B. Data Selection: Few significant scientific studies were found relating to the role of pre-participation sports evaluation. Five studies were selected based on inclusion criteria. Two pilot studies included as The Role of Pre-participation Assessment and Screening. Results: The sports physical therapist is uniquely prepared to participate in the PPE process. Prevention of injury and performance enhancement is important, and PPEs can help make an impact on both areas. It focuses on prevention, evaluation, treatment, and rehabilitation and performance enhancement of the physically‐active individual. Conclusion: The well‐designed and implemented PPEs will be welcome by the sports community and benefit everyone. Ensuring an athlete's safety can promote a lifelong health habit of physical activity in which the athlete can learn discipline, teamwork and physical fitness.

Supraphysiological effects of pancreatic polypeptide on gastric motor function and nutrient tolerance in humans.

Pancreatic polypeptide (PP) is known to affect food intake. In this exploratory study, we set out to investigate its supraphysiological effect on food tolerance, gastric accommodation, and emptying. In 12 healthy volunteers, 0, 3, or 10 pmol*kg−1*min−1 PP was administered intravenously (PP0, PP3 or PP10). Thirty minutes thereafter, nutrient drink infusion (60 ml*min−1) through a nasogastric feeding tube was started until maximum satiation. Gastric accommodation was assessed by measuring the intragastric pressure (IGP; nasogastric manometry). In a separate test, the effect of PP0 or PP10 on gastric emptying was tested in 10 healthy volunteers and assessed using the 13C breath test. Results are presented as mean ± SEM, and p < 0.05 was considered significant. For the IGP test, PP increased ingested nutrient volume: 886 ± 93, 1059 ± 124, and 1025 ± 125 ml for PP0, PP3, and PP10, respectively (p = 0.048). In all groups, Nadir IGP values were reached upon food intake (transformed values: 1.5 ± 0.2, 1.7 ± 0.3, and 1.6 ± 0.3 mmHg for PP0, PP3, and PP10, respectively; NS) to return to baseline thereafter. For the gastric emptying study, volunteers ingested a similar nutrient volume: 802 ± 119 and 1089 ± 128 ml (p = 0.016), and gastric half‐emptying time was 281 ± 52 and 249 ± 37 min for PP0 and PP10, respectively (NS). No significant correlation between tolerated nutrient volume and IGP drop (R² < 0.01; p = 0.88 for PP0 vs. PP3 and R² =0.07; p = 0.40 for PP0 vs. PP10, respectively) or gastric half‐emptying time (R² = 0.12; p = 0.32) was found. A supraphysiological PP dose enhances food tolerance; however, this effect is not mediated through gastric motility.Clinical Trial registry numberNCT03854708 is obtained from clinicaltrials.gov.

A novel bone-thinning technique for transcranial stimulation motor-evoked potentials in rats

Transcranial electrical stimulated motor-evoked potentials (tcMEPs) are widely used to evaluate motor function in humans, and even in animal studies, tcMEPs are used to evaluate neurological dysfunction. However, there is a dearth of reports on extended tcMEP recordings in both animal models and humans. Therefore, this study examined a new technique for stably recording tcMEPs over several weeks in six healthy female Sprague–Dawley rats. We thinned the skull bone using the skull base and spinal surgery technique to reduce electrical resistance for electrical stimulation. tcMEPs were recorded on days 1, 7, 14, 21, and 28 after surgery. The onset latency and amplitude of tcMEPs from the hindlimbs were recorded and evaluated, and histological analysis was performed. Stable amplitude and onset latency could be recorded over several weeks, and histological analysis indicated no complications attributable to the procedure. Thus, our novel technique allows for less invasive, safer, easier, and more stable extended tcMEP recordings than previously reported techniques. The presently reported technique may be applied to the study of various nerve injury models in rats: specifically, to evaluate the degree of nerve dysfunction and recovery in spinal cord injury, cerebral infarction, and brain contusion models.

Low composite functional movement screen score associated with decline of gait stability in young adults.

BackgroundThe functional movement screen (FMS)TM is a screening tool used to evaluate fundamental motor function. A score of 14 for the composite total FMS score (TFMS) is generally used as the cut-off point (≤14/21). In addition, gait analysis is used to evaluate fundamental motor function in humans. Thus, evaluating the fundamental motor function using the FMSTM test and gait analysis at various speeds can provide further understanding of any decline in gait stability. In this study, we aimed to investigate the association between gait ability and fundamental movement patterns in young adults according to the cut-off point.MethodsA total of 439 participants (male: 203, female: 236) successfully completed the FMS test and a 1 min treadmill test; the participants were classified into two groups: low TFMS (≤14) and high TFMS (>14).ResultsThe low TFMS group exhibited slower and shortened walking patterns and worsen gait variability than the high TFMS group. The coefficient of variance (CV) for the double support phase at a faster speed (male) and the stride length at a slower speed (female) were classifiers between the two groups. In addition, the low TFMS group demonstrated insufficient gait adaptation at the preferred and faster speeds based on the CV of the double support phase and gait asymmetry. Lower TFMS is associated with a decline in gait ability. Therefore, participants with a lower TFMS and poor gait ability may require intervention programs to prevent risk of future injury and to enhance motor function.

Translational Value of Skilled Reaching Assessment in Clinical and Preclinical Studies on Motor Recovery After Stroke

Background Assessment of skilled reaching enables extensive analysis of upper limb function in clinical and preclinical studies on poststroke outcome. However, translational research if often limited by lack of correspondence between tests of human and rodent motor function. Objectives To determine (1) the translational value of skilled reaching performance for preclinical research by comparing the behavioral recovery profiles of skilled reaching characteristics between humans and rats recovering from stroke and (2) the relationship between skilled reaching performance and commonly used clinical outcome measures after stroke. Methods Twelve patients with ischemic or hemorrhagic stroke and 17 rats with photothrombotic stroke underwent an equivalent skilled reaching test at different time points, representing early to late subacute stages poststroke. Success scores and a movement element rating scale were used to measure the skilled reaching performance. The Fugl-Meyer Upper Extremity (FM-UE) assessment and the Action Research Arm Test (ARAT) were used as clinical outcome measures. Results Both species had muscle flaccidity at the early subacute stage after stroke and showed motor recovery following a proximal-distal principle toward the early subacute stage, albeit for rats within a shorter time course. Human skilled reaching scores and FM-UE and ARAT scores in the first 3 months poststroke were significantly correlated (P < .05). Conclusions Our study demonstrates that poststroke changes in skilled reaching performance are highly similar between rats and humans and correspond with standard clinical outcome measures. Skilled reaching testing therefore offers an effective and highly translational means for assessment of motor recovery in experimental and clinical stroke settings.

The Comparative Effects of Mesenchymal Stem Cell Transplantation Therapy for Spinal Cord Injury in Humans and Animal Models: A Systematic Review and Meta-Analysis.

Simple SummaryThe effects of mesenchymal stem cell (MSC) transplants on functional recovery after spinal cord injury have been compared in humans and animal models. Data show that MSC transplants increase functional outcomes across species. However, modes and timings of MSC delivery mean that the animal studies cannot be used to predict outcome, suggesting that alternative models are required to improve translation of research to clinical trial.Animal models have been used in preclinical research to examine potential new treatments for spinal cord injury (SCI), including mesenchymal stem cell (MSC) transplantation. MSC transplants have been studied in early human trials. Whether the animal models represent the human studies is unclear. This systematic review and meta-analysis has examined the effects of MSC transplants in human and animal studies. Following searches of PubMed, Clinical Trials and the Cochrane Library, published papers were screened, and data were extracted and analysed. MSC transplantation was associated with significantly improved motor and sensory function in humans, and significantly increased locomotor function in animals. However, there are discrepancies between the studies of human participants and animal models, including timing of MSC transplant post-injury and source of MSCs. Additionally, difficulty in the comparison of functional outcome measures across species limits the predictive nature of the animal research. These findings have been summarised, and recommendations for further research are discussed to better enable the translation of animal models to MSC-based human clinical therapy.

The effect of motor and cognitive placebos on the serial reaction time task.

Motor learning is a key component of human motor functions. Repeated practice is essential to gain proficiency over time but may induce fatigue. The aim of this study was to determine whether motor performance and motor learning (as assessed with the serial reaction time task, SRTT) and perceived fatigability (as assessed with subjective scales) are improved after two types of placebo interventions (motor and cognitive). A total of 90 healthy volunteers performed the SRTT with the right hand in three sessions (baseline, training and final). Before the training and the final session, one group underwent a motor-related placebo intervention in which inert electrical stimulation (TENS) was applied over the hand and accompanied by verbal suggestion that it improves movement execution (placebo-TENS). The other group underwent a cognitive-related placebo intervention in which sham transcranial direct current stimulation (tDCS) was delivered to the supraorbital area and accompanied by verbal suggestion that it increases attention (placebo-tDCS). A control group performed the same task without receiving treatment. Overall better performance on the SRTT (not ascribed to sequence-specific learning) was noted for the placebo-TENS group, which also reported less perceived fatigability at the physical level. The same was observed in a subgroup tested 24hr later. The placebo-tDCS group reported less perceived fatigability, both at the mental and physical level. These findings indicate that motor- and cognitive-related placebo effects differently shape motor performance and perceived fatigability on a repeated motor task.

Acute intermittent hypoxia enhances regeneration of surgically repaired peripheral nerves in a manner akin to electrical stimulation

The intrinsic repair response of injured peripheral neurons is enhanced by brief electrical stimulation (ES) at time of surgical repair, resulting in improved regeneration in rodents and humans. However, ES is invasive. Acute intermittent hypoxia (AIH) - breathing alternate cycles of regular air and air with ~50% normal oxygen levels (11% O2), considered mild hypoxia, is an emerging, promising non-invasive therapy that promotes motor function in spinal cord injured rats and humans. AIH can increase neural activity and under moderately severe hypoxic conditions improves repair of peripherally crushed nerves in mice. Thus, we posited an AIH paradigm similar to that used clinically for spinal cord injury, will improve surgically repaired peripheral nerves akin to ES, including an impact on regeneration-associated gene (RAG) expression–a predictor of growth states. Alterations in early RAG expression were examined in adult male Lewis rats that underwent tibial nerve coaptation repair with either 2 days AIH or normoxia control treatment begun on day 2 post-repair, or 1 h ES treatment (20 Hz) at time of repair. Three days post-repair, AIH or ES treatments effected significant and parallel elevated RAG expression relative to normoxia control at the level of injured sensory and motor neuron cell bodies and proximal axon front. These parallel impacts on RAG expression were coupled with significant improvements in later indices of regeneration, namely enhanced myelination and increased numbers of newly myelinated fibers detected 20 mm distal to the tibial nerve repair site or sensory and motor neurons retrogradely labeled 28 mm distal to the repair site, both at 25 days post nerve repair; and improved return of toe spread function 5–10 weeks post-repair. Collectively, AIH mirrors many beneficial effects of ES on peripheral nerve repair outcomes. This highlights its potential for clinical translation as a non-invasive means to effect improved regeneration of injured peripheral nerves.

Prolonged acute intermittent hypoxia improves forelimb reach-to-grasp function in a rat model of chronic cervical spinal cord injury

Repetitive acute intermittent hypoxia (AIH – brief, episodes of low inspired oxygen) elicits spinal motor plasticity, resulting in sustained improvements of respiratory and non-respiratory motor function in both animal models and humans with chronic spinal cord injury (SCI). We previously demonstrated that 7 days of AIH combined with task-specific training improves performance on a skilled locomotor task for at least 3 weeks post-treatment in rats with incomplete SCI. Here we investigated the effect of repetitive AIH administered for 12 wks on a forelimb reach-to-grasp task in a rat model of chronic, incomplete cervical SCI. In a replicated, sham-controlled, randomized and blinded study, male Spraque-Dawley rats were subject to partial hemisection at the 3rd cervical spinal segment, and exposed to daily AIH (10, 5 min episodes of 11% inspired O2; 5 min intervals of 21% O2) or sham normoxia (continuous 21% O2) for 7 days beginning 8 weeks post-injury. Treatments were then reduced to 4 daily treatments per week, and continued for 11 weeks. Performance on 2 pre-conditioned motor tasks, single pellet reaching and horizontal ladder walking, was recorded each week for up to 12 weeks after initiating treatment; performance on spontaneous adhesive removal was also tested. SCI significantly impaired reach-to-grasp task performance 8 weeks post-injury (pre-treatment). Daily AIH improved reaching success by the first week of treatment versus sham controls, and this difference was maintained at 12 weeks (p < 0.0001). Daily AIH did not affect step asymmetry or stride length during ladder walking or adhesive removal time. Thus, prolonged AIH combined with task-specific training improved forelimb reach-to-grasp function in rats with a chronic cervical hemisection, but not off-target motor tasks. This study further supports the idea that daily AIH improves limb function when combined with task-specific training.