Electromyography-Driven Exergaming in Wheelchairs on a Mobile Platform: Bench and Pilot Testing of the WOW-Mobile Fitness System.

BACKGROUND: Implementing exercises in the form of video games, otherwise known as exergaming, has gained recent attention as a way to combat health issues resulting from sedentary lifestyles. However, these exergaming apps have not been developed for exercises that can be performed in wheelchairs, and they tend to rely on whole-body movements. OBJECTIVE: This study aims to develop a mobile phone app that implements electromyography (EMG)-driven exergaming, to test the feasibility of using this app to enable people in wheelchairs to perform exergames independently and flexibly in their own home, and to assess the perceived usefulness and usability of this mobile health system. METHODS: We developed an Android mobile phone app (Workout on Wheels, WOW-Mobile) that senses upper limb muscle activity (EMG) from wireless body-worn sensors to drive 3 different video games that implement upper limb exercises designed for people in wheelchairs. Cloud server recordings of EMG enabled long-term monitoring and feedback as well as multiplayer gaming. Bench testing of data transmission and power consumption were tested. Pilot testing was conducted on 4 individuals with spinal cord injury. Each had a WOW-Mobile system at home for 8 weeks. We measured the minutes for which the app was used and the exergames were played, and we integrated EMG as a measure of energy expended. We also conducted a perceived usefulness and usability questionnaire. RESULTS: Bench test results revealed that the app meets performance specifications to enable real-time gaming, cloud storage of data, and live cloud server transmission for multiplayer gaming. The EMG sampling rate of 64 samples per second, in combination with zero-loss data communication with the cloud server within a 10-m range, provided seamless control over the app exergames and allowed for offline data analysis. Each participant successfully used the WOW-Mobile system at home for 8 weeks, using the app for an average of 146 (range 89-267) minutes per week with the system, actively exergaming for an average of 53% of that time (39%-59%). Energy expenditure, as measured by integrated EMG, was found to be directly proportional to the time spent on the app (Pearson correlation coefficient, r=0.57-0.86, depending on the game). Of the 4 participants, 2 did not exercise regularly before the study; these 2 participants increased from reportedly exercising close to 0 minutes per week to exergaming 58 and 158 minutes on average using the WOW-Mobile fitness system. The perceived usefulness of WOW-Mobile in motivating participants to exercise averaged 4.5 on a 5-point Likert scale and averaged 5 for the 3 participants with thoracic level injuries. The mean overall ease of use score was 4.25 out of 5. CONCLUSIONS: Mobile app exergames driven by EMG have promising potential for encouraging and facilitating fitness for individuals in wheelchairs who have maintained arm and hand mobility.

Cloud-based Multiplayer Exergaming: Developing a platform for social interaction as a motivational tool for exercising in the wheelchair community.

In the recent decade, mobile exergaming has emerged as a way to motivate physical activity and thereby increase fitness. It has been found that those which encourage social interaction and multiplayer gaming leads to better fitness outcomes than single player games [1]. However, none have yet to tailor exergames for people who use wheelchairs due to lower mobility impairment. We present a mobile exergaming and fitness tracking app in which the exergames are tailored toward people in wheelchairs and features a virtual community which allows social interaction through multiplayer gaming and leaderboard features. We hypothesized that users would find the multiplayer games more useful for improving fitness than the single player games. However, perceived usefulness survey results indicate overall satisfaction with the main design features but not a particular preference for the multiplayer gaming over single player gaming. Users overall found the app useful and easy to use, and the results provide indication that the virtual community created through the multiplayer feature of the mobile exergaming app does promote and enhance exercising.Clinical relevance- Multiplayer gaming was designed into a mobile fitness app to encourage exercise amongst individuals in wheelchairs. The virtual community created is expected to increase activity levels and its many associated health benefits in this community, promote a greater sense of belonging, and increase social participation.

Association between muscle aerobic capacity and whole-body peak oxygen uptake.

PURPOSE: Decline in skeletal muscle mitochondrial oxidative capacity (MOC) is associated with reduced aerobic capacity and increased risk of cardiovascular and metabolic disease. Measuring skeletal muscle MOC may be an alternative method to assess aerobic capacity, especially for individuals unable to perform a whole-body maximum oxygen uptake protocol. In this study, linear regression analysis in two leg muscles was performed to determine whether MOC values could be used to predict whole-body peak oxygen uptake. METHODS: MOC was measured with near infrared spectroscopy (NIRS) in the medial gastrocnemius (MG) and vastus lateralis (VL) muscles of 26 participants (age, 27.1 ± 5.8 years old). Whole-body peak oxygen uptake (VO2 peak) was determined by indirect calorimetry during a continuous ramp protocol on a cycle ergometer. RESULTS: VO2 peak values were significantly correlated with the muscle recovery rate constant (k) of the MG (kMG, r = 0.59; p < 0.01) and VL (kVL, r = 0.63; p < 0.01) muscles. Summing recovery rate constants of both muscles together (kMG + kVL) improved the strength of the correlation with VO2 peak (r = 0.78; p < 0.0001) and could explain a majority of the variance (R2 = 0.61) between the two measurements. CONCLUSION: Data suggest that NIRS can provide reliable MOC measurements on two leg muscles that correlate well with whole-body peak oxygen uptake.

A Molecular Method to Detect Wound Cells in Bloodstains Resultant of Sharp Force Injuries for Crime Scene Reconstruction.

Previous research by the authors on an animal model showed that bloodstains can contain additional information about their somatic origin in the form of wound cells. Bloodstains produced by a gunshot wound to the head were distinguished from bloodstains produced by a gunshot wound to the chest by testing the stains for a brain microRNA marker. In this study, the effectiveness of the technique was examined on blood drops shed externally from a stab wound to the liver of rat carcasses. Specifically, investigations were conducted on the liver microRNA marker, rno-mir-122-3p, with the QIAGEN miScript System, and PCR analysis. Between the two stabbing methods used, 67% of the scalpel blades and 57% of the blood drops tested positive for rno-mir-122-3p; however, other samples tested negative giving inconclusive results as to the wound-of-origin. The amount of the liver cells in the bloodstains appeared to be related to the extent of trauma.

Robot-Applied Resistance Augments the Effects of Body Weight-Supported Treadmill Training on Stepping and Synaptic Plasticity in a Rodent Model of Spinal Cord Injury.

BACKGROUND: The application of resistive forces has been used during body weight-supported treadmill training (BWSTT) to improve walking function after spinal cord injury (SCI). Whether this form of training actually augments the effects of BWSTT is not yet known. OBJECTIVE: To determine if robotic-applied resistance augments the effects of BWSTT using a controlled experimental design in a rodent model of SCI. METHODS: Spinally contused rats were treadmill trained using robotic resistance against horizontal (n = 9) or vertical (n = 8) hind limb movements. Hind limb stepping was tested before and after 6 weeks of training. Two control groups, one receiving standard training (ie, without resistance; n = 9) and one untrained (n = 8), were also tested. At the terminal experiment, the spinal cords were prepared for immunohistochemical analysis of synaptophysin. RESULTS: Six weeks of training with horizontal resistance increased step length, whereas training with vertical resistance enhanced step height and movement velocity. None of these changes occurred in the group that received standard (ie, no resistance) training or in the untrained group. Only standard training increased the number of step cycles and shortened cycle period toward normal values. Synaptophysin expression in the ventral horn was highest in rats trained with horizontal resistance and in untrained rats and was positively correlated with step length. CONCLUSIONS: Adding robotic-applied resistance to BWSTT produced gains in locomotor function over BWSTT alone. The impact of resistive forces on spinal connections may depend on the nature of the resistive forces and the synaptic milieu that is present after SCI.

The Utility of Interappendicular Connections in Bipedal Locomotion.

Homo sapiens constitute the only currently obligate bipedal mammals and, as it stands, upright bipedal locomotion is a defining characteristic of humans. Indeed, while the evolution to bipedalism has allowed for the upper limbs to be liberated from ground contact during ambulation, their role in locomotion is far from obsolete. Rather, there is reason to believe that arm swing offers important mechanical and neurological advantages to bipedal locomotion. In this short review, we present some compelling findings on the neural connections between the arms and legs during human locomotion. We begin with a description of the importance of arm swing during walking from a mechanical perspective. Then, we examine evidence for the existence of interappendicular connections that converge along with peripheral afferents, descending inputs, and propriospinal projections, onto the neural circuits innervating the muscles of the arms and legs. The varied effects of interappendicular coupling on the neural control of locomotion are also examined in cases of neurological injury. We use the insight gained from these collected works as well as those from our own studies on locomotor training to discuss strategies to use interappendicular connections to rehabilitate walking in individuals experiencing loss of function after debilitating spinal cord injury.

What Did We Learn from the Animal Studies of Body Weight-Supported Treadmill Training and Where Do We Go from Here?

Body weight-supported treadmill training (BWSTT) developed from animal studies of spinal cord injury (SCI). Evidence that spinal cats (i.e., cats that have a complete surgical transection of the cord) could regain the ability to step on a moving treadmill indicated a vast potential for spinal circuits to generate walking without the brain. BWSTT represented a means to unlock that potential. As the technique was adapted as a rehabilitation intervention for humans with SCI, shortcomings in the translation to walking in the real world were exposed. Evidence that BWSTT has not been as successful for humans with SCI leads us to revisit key animal studies. In this short review, we describe the task-specific nature of BWSTT and discuss how this specificity may pose limits on the recovery of overground walking. Also discussed are more recent studies that have introduced new strategies and tools that adapt BWSTT ideas to more functionally-relevant tasks. We introduce a new device for weight-supported overground walking in rats called Circular BART (Body weight supported Ambulatory Rat Trainer) and demonstrate that it is relatively easy and inexpensive to produce. Future animal studies will benefit from the development of simple tools that facilitate training and testing of overground walking.

Energy expenditure and heart rate responses to increased loading in individuals with motor complete spinal cord injury performing body weight-supported exercises.

OBJECTIVE: To examine acute metabolic and heart rate responses in individuals with motor complete spinal cord injury (SCI) during stepping and standing with body weight support (BWS). DESIGN: Cohort study. SETTING: Therapeutic exercise research laboratory. PARTICIPANTS: Nonambulatory individuals with chronic, motor complete SCI between T5 and T12 (n=8) and healthy, able-bodied controls (n=8). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Oxygen consumption (V˙o2) and heart rate. RESULTS: Individuals with motor complete SCI performed standing and stepping exercises in a BWS system with manual assistance of lower body kinematics. V˙o2 and heart rate responses were assessed in relation to level of BWS. Weight support was provided by an overhead lift at high (≥50% BWS) or low (20%-35% BWS) levels during stepping and standing. Although participants with motor complete SCI were unable to stand or step without assistance, levels of V˙o2 and heart rate were elevated by 38% and 37%, respectively, when load was maximized during stepping (ie, low BWS). Participants without an SCI (able-bodied group) had a similar acute response to exercise. None of the participants met the target range for V˙o2 response in any of the tasks. However, stepping was sufficient to enable half of the participants in the SCI group to attain the target range for heart rate response to exercise. CONCLUSIONS: Individuals with motor complete SCI exhibit cardiovascular responses during body weight-supported exercise. Findings indicate that body weight-supported stepping provides a minimal cardiovascular challenge for individuals with paraplegia. Emphasis on low weight support during locomotor training can trigger additional heart rate adaptations.

A novel device for studying weight supported, quadrupedal overground locomotion in spinal cord injured rats.

BACKGROUND: Providing weight support facilitates locomotion in spinal cord injured animals. To control weight support, robotic systems have been developed for treadmill stepping and more recently for overground walking. NEW METHOD: We developed a novel device, the body weight supported ambulatory rodent trainer (i.e. BART). It has a small pneumatic cylinder that moves along a linear track above the rat. When air is supplied to the cylinder, the rats are lifted as they perform overground walking. We tested the BART device in rats that received a moderate spinal cord contusion injury and in normal rats. Locomotor training with the BART device was not performed. RESULTS: All of the rats learned to walk in the BART device. In the contused rats, significantly greater paw dragging and dorsal stepping occurred in the hindlimbs compared to normal. Providing weight support significantly raised hip position and significantly reduced locomotor deficits. Hindlimb stepping was tightly coupled to forelimb stepping but only when the contused rats stepped without weight support. Three weeks after the contused rats received a complete spinal cord transection, significantly fewer hindlimb steps were performed. COMPARISON WITH EXISTING METHODS: Relative to rodent robotic systems, the BART device is a simpler system for studying overground locomotion. The BART device lacks sophisticated control and sensing capability, but it can be assembled relatively easily and cheaply. CONCLUSIONS: These findings suggest that the BART device is a useful tool for assessing quadrupedal, overground locomotion which is a more natural form of locomotion relative to treadmill locomotion.

A molecular method to correlate bloodstains with wound site for crime scene reconstruction.

Bloodstain pattern analysis to determine the wound-of-origin of bloodstains is problematic with nonspecific patterns. In this proof-of-concept study, the authors examined a molecular approach to correlate bloodstains with injuries using the rat as a model. Specifically, investigations were conducted on the rat brain marker, rno-miR-124-3p, with the QIAGEN miScript System and real-time PCR analysis. Rno-miR-124-3p was detected in brain homogenates diluted 100,000 times; in 3-week-old, room temperature stored, simulated brain-blood stains; and in bloodstains from head gunshot wounds collected with swabs and subsequently frozen for 9-18 months; however, rno-miR-124-3p was not detected in whole blood. Proof-of-principle was demonstrated by the ability to distinguish bloodstains from a gunshot wound to the head versus bloodstains from a gunshot wound to the chest, by the testing of otherwise identical bloodstains from the two patterns for the presence of the marker. The results suggest a viable approach to a longstanding problem in casework.

The effect of timing electrical stimulation to robotic-assisted stepping on neuromuscular activity and associated kinematics.

Results of previous studies raise the question of how timing neuromuscular functional electrical stimulation (FES) to limb movements during stepping might alter neuromuscular control differently than patterned stimulation alone. We have developed a prototype FES system for a rodent model of spinal cord injury (SCI) that times FES to robotic treadmill training (RTT). In this study, one group of rats (n = 6) was trained with our FES+RTT system and received stimulation of the ankle flexor (tibialis anterior [TA]) muscle timed according to robot-controlled hind-limb position (FES+RTT group); a second group (n = 5) received a similarly patterned stimulation, randomly timed with respect to the rats' hind-limb movements, while they were in their cages (randomly timed stimulation [RS] group). After 4 wk of training, we tested treadmill stepping ability and compared kinematic measures of hind-limb movement and electromyography (EMG) activity in the TA. The FES+RTT group stepped faster and exhibited TA EMG profiles that better matched the applied stimulation profile during training than the RS group. The shape of the EMG profile was assessed by "gamma," a measure that quantified the concentration of EMG activity during the early swing phase of the gait cycle. This gamma measure was 112% higher for the FES+RTT group than for the RS group. The FES+RTT group exhibited burst-to-step latencies that were 41% shorter and correspondingly exhibited a greater tendency to perform ankle flexion movements during stepping than the RS group, as measured by the percentage of time the hind limb was either dragging or in withdrawal. The results from this study support the hypothesis that locomotor training consisting of FES timed to hind-limb movement improves the activation of hind-limb muscle more so than RS alone. Our rodent FES+RTT system can serve as a tool to help further develop this combined therapy to target appropriate neurophysiological changes for locomotor control.

Multivariate assessment of differences between a neuromuscular electrical stimulation therapy and robotic treadmill training in the rehabilitation of spinal cord injured rats.

A study was conducted to evaluate and compare the effects of two different rehabilitation therapies on spinal cord injured (SCI) rats: neuromuscular electrical stimulation which is timed to robotic treadmill training (NMES+RTT) and RTT alone. Several electromyography (EMG) based variables were measured, but most did not change significantly after treatment, contrary to observations of overall qualitative stepping ability. However, when the variables are viewed in multi-dimensional space, there are visible differences between changes after NMES+RTT vs. those after RTT only. Principal component analysis (PCA) and k-means clustering were applied to the multivariate data. The data in principal component space was significantly separated, according to the Euclidean distance. PCA also provided a straightforward tool for selecting which combination of measures to compare. The measures which best separated out the differences between NMES+RTT and RTT were percentage of steps associated with bursts, burst-to-step latency, and the standard deviation of this latency, even though these measures did not always show the greatest statistical significance individually. Thus, the rehabilitative effects of NMES+RTT are not necessarily reflected in individual EMG measures, but rather in a combination of the measures representing a multi-dimensional space.

Robotic loading during treadmill training enhances locomotor recovery in rats spinally transected as neonates.

Loading on the limbs has a powerful influence on locomotion. In the present study, we examined whether robotic-enhanced loading during treadmill training improved locomotor recovery in rats that were spinally transected as neonates. A robotic device applied a force on the ankle of the hindlimb while the rats performed bipedal stepping on a treadmill. The robotic force enhanced loading during the stance phase of the step cycle. One group of spinally transected rats received 4 wk of bipedal treadmill training with robotic loading while another group received 4 wk of bipedal treadmill training but without robotic loading. The two groups exhibited similar stepping performance during baseline tests of bipedal treadmill stepping. However, after 4 wk, the spinally transected rats that received bipedal treadmill training with robotic loading performed significantly more weight-bearing steps than the bipedal treadmill training only group. Bipedal treadmill training with robotic loading enhanced the ankle trajectory and ankle velocity during the step cycle. Based on immunohistochemical analyses, the expression of the presynaptic marker, synaptophysin, was significantly greater in the ventral horn of the lumbar spinal cord of the rats that received bipedal treadmill training with robotic loading. These findings suggested that robotic loading during bipedal treadmill training improved the ability of the lumbar spinal cord to generate stepping. The results have implications for the use of robotic-enhanced gait training therapies that encourage motor learning after spinal cord injury.

A system to integrate electrical stimulation with robotically controlled treadmill training to rehabilitate stepping after spinal cord injury.

A functional electrical stimulation (FES) system was engineered to integrate information from a robotically controlled position during stepping in order to time stimulation to continuous gait information in a rodent model of spinal cord injury (SCI). In contrast to conventional FES systems which have a fixed timing pattern relative to gait cycle onset (i.e., toe off/heel off or paw contact/heel strike), this system allows adaptation of stimulation to a robotically controlled position. Rationale for the system design is presented along with bench-test results verifying the timing of the stimulation with respect to hindlimb position. This robotically timed FES system will enable studies investigating the capability of this FES therapy to encourage rehabilitation by way of spinal plasticity.

Accommodation of the spinal cat to a tripping perturbation.

Adult cats with a complete spinal cord transection at T12-T13 can relearn over a period of days-to-weeks how to generate full weight-bearing stepping on a treadmill or standing ability if trained specifically for that task. In the present study, we assessed short-term (milliseconds to minutes) adaptations by repetitively imposing a mechanical perturbation on the hindlimb of chronic spinal cats by placing a rod in the path of the leg during the swing phase to trigger a tripping response. The kinematics and EMG were recorded during control (10 steps), trip (1-60 steps with various patterns), and then release (without any tripping stimulus, 10-20 steps) sequences. Our data show that the muscle activation patterns and kinematics of the hindlimb in the step cycle immediately following the initial trip (mechanosensory stimulation of the dorsal surface of the paw) was modified in a way that increased the probability of avoiding the obstacle in the subsequent step. This indicates that the spinal sensorimotor circuitry reprogrammed the trajectory of the swing following a perturbation prior to the initiation of the swing phase of the subsequent step, in effect "attempting" to avoid the re-occurrence of the perturbation. The average height of the release steps was elevated compared to control regardless of the pattern and the length of the trip sequences. In addition, the average impact force on the tripping rod tended to be lower with repeated exposure to the tripping stimulus. EMG recordings suggest that the semitendinosus, a primary knee flexor, was a major contributor to the adaptive tripping response. These results demonstrate that the lumbosacral locomotor circuitry can modulate the activation patterns of the hindlimb motor pools within the time frame of single step in a manner that tends to minimize repeated perturbations. Furthermore, these adaptations remained evident for a number of steps after removal of the mechanosensory stimulation.

Modulation of ankle EMG in spinally contused rats through application of neuromuscular electrical stimulation timed to robotic treadmill training.

While neuromuscular electrical stimulation (NMES) has enabled patients of neuromotor dysfunction to effectively regain some functions, analysis of neuromuscular changes underlying these functional improvements is lacking. We have developed an NMES system for a rodent model of SCI with the long term goal of creating a therapy which restores control over stepping back to the spinal circuitry. NMES was applied to the tibialis anterior (TA) and timed to the afferent feedback generated during robotic treadmill training (RTT). The effect of NMES+RTT on modifications in EMG was compared with that of RTT alone. A longitudinal study with a crossover design was conducted in which group 1 (n=7) received 2 weeks of RTT only followed by 2 weeks of NMES+RTT; group 2 (n=7) received 2 weeks of NMES+RTT followed by RTT only. On average, both types of training helped to modulate TA EMG activity over a gait cycle, resulting in EMG profiles across steps with peaks occurring just before or at the beginning of the swing phase, when ankle flexion is most needed. However, NMES+RTT resulted in concentration of EMG activation during the initial swing phase more than RTT only. In conjunction with these improvements in EMG activation presented here, a more complete analyses comparing changes after NMES+RTT vs. RTT is expected to further support the notion that NMES timed appropriately to hindlimb stepping could help to reinforce the motor learning that is induced by afferent activity generated by treadmill training.

Adaptations in glutamate and glycine content within the lumbar spinal cord are associated with the generation of novel gait patterns in rats following neonatal spinal cord transection.

After spinal cord transection, the generation of stepping depends on neurotransmitter systems entirely contained within the local lumbar spinal cord. Glutamate and glycine likely play important roles, but surprisingly little is known about how the content of these two key neurotransmitters changes to achieve weight-bearing stepping after spinal cord injury. We studied the levels of glutamate and glycine in the lumbar spinal cord of spinally transected rats. Rats (n = 48) received spinal cord transection at 5 days of age, and 4 weeks later half were trained to step using a robotic treadmill system and the remaining half were untrained controls. Analyses of glutamate and glycine content via high-performance liquid chromatography showed training significantly raised the levels of both neurotransmitters in the lumbar spinal cord beyond normal. The levels of both neurotransmitters were significantly correlated with the ability to perform independent stepping during training. Glutamate and glycine levels were not significantly different between Untrained and Normal rats or between Trained and Untrained rats. There was a trend for higher expression of VGLUT1 and GLYT2 around motor neurons in Trained versus Untrained rats based on immunohistochemical analyses. Training improved the ability to generate stepping at a range of weight support levels, but normal stepping characteristics were not restored. These findings suggested that the remodeling of the lumbar spinal circuitry in Trained spinally transected rats involved adaptations in the glutamatergic and glycinergic neurotransmitter systems. These adaptations may contribute to the generation of novel gait patterns following complete spinal cord transection.

Differential effects of low versus high amounts of weight supported treadmill training in spinally transected rats.

Intensive weight-supported treadmill training (WSTT) improves locomotor function following spinal cord injury. Because of a number of factors, undergoing intensive sessions of training may not be feasible. Whether reduced amounts of training are sufficient to enhance spinal plasticity to a level that is necessary for improving function is not known. The focus of the present study was to assess differences in recovery of locomotor function and spinal plasticity as a function of the amount of steps taken during WSTT in a rodent model of spinal cord injury. Rats were spinally transected at 5 days of age. When they reached 28 days of age, a robotic system was used to implement a weight-supported treadmill training program of either 100 or 1000 steps/training session daily for 4 weeks. Antibodies for brain-derived neurotrophic factor (BDNF), TrkB, and the pre-synaptic marker, synaptophysin, were used to examine the expression of these proteins in the ventral horn of the lumbar spinal cord. Rats that received weight-supported treadmill training performed better stepping relative to untrained rats, but only the rats that received 1000 steps/training session recovered locomotor function that resembled normal patterns. Only the rats that received 1000 steps/training session recovered normal levels of synaptophysin immunoreactivity around motor neurons. Weight-supported treadmill training consisting of either 100 or 1000 steps/training session increased BDNF immunoreactivity in the ventral horn of the lumbar spinal cord. TrkB expression in the ventral horn was not affected by spinal cord transection or weight-supported treadmill training. Synaptophysin expression, but not BDNF or TrkB expression was correlated with the recovery of stepping function. These findings suggested that a large amount of weight-supported treadmill training was necessary for restoring synaptic connections to motor neurons within the locomotor generating circuitry. Although a large amount of training was best for recovery, small amounts of training were associated with incremental gains in function and increased BDNF levels.

Robotic assistance that encourages the generation of stepping rather than fully assisting movements is best for learning to step in spinally contused rats.

Robotic devices have been developed to assist body weight-supported treadmill training (BWSTT) in individuals with spinal cord injuries (SCIs) and stroke. Recent findings have raised questions about the effectiveness of robotic training that fully assisted (FA) stepping movements. The purpose of this study was to examine whether assist-as-needed robotic (AAN) training was better than FA movements in rats with incomplete SCI. Electromyography (EMG) electrodes were implanted in the tibialis anterior and medial gastrocnemius hindlimb muscles of 14 adult rats. Afterward, the rats received a severe midthoracic spinal cord contusion and began daily weight-supported treadmill training 1 wk later using a rodent robotic system. During training, assistive forces were applied to the ankle when it strayed from a desired stepping trajectory. The amount of force was proportional to the magnitude of the movement error, and this was multiplied by either a high or low scale factor to implement the FA (n = 7) or AAN algorithms (n = 7), respectively. Thus FA training drove the ankle along the desired trajectory, whereas greater variety in ankle movements occurred during AAN training. After 4 wk of training, locomotor recovery was greater in the AAN group, as demonstrated by the ability to generate steps without assistance, more normal-like kinematic characteristics, and greater EMG activity. The findings suggested that flexible robotic assistance facilitated learning to step after a SCI. These findings support the rationale for the use of AAN robotic training algorithms in human robotic-assisted BWSTT.

Assessment of the role of MAP kinase in mediating activity-dependent transcriptional activation of the immediate early gene Arc/Arg3.1 in the dentate gyrus in vivo.

Different physiological and behavioral events activate transcription of Arc/Arg3.1 in neurons in vivo, but the signal transduction pathways that mediate induction in particular situations remain to be defined. Here, we explore the relationships between induction of Arc/Arg3.1 transcription in dentate granule cells in vivo and activation of mitogen-activated protein (MAP) kinase as measured by extracellular-regulated kinase 1/2 (ERK1/2) phosphorylation. We show that ERK1/2 phosphorylation is strongly induced in dentate granule cells within minutes after induction of perforant path long-term potentiation (LTP). Phospho-ERK staining appears in nuclei within minutes after stimulation commences, and ERK phosphorylation returns to control levels within 60 min. Electroconvulsive seizures, which strongly induce prolonged Arc/Arg3.1 transcription in dentate granule cells, induced ERK1/2 phosphorylation in granule cells that returned to control levels within 30 min. Following 30, 60, and 120 min of exploration in a novel complex environment, Arc/Arg3.1 transcription was activated in many more granule cells than stained positively for p-ERK at all time points. Although Arc/Arg3.1 transcription was induced in most pyramidal neurons in CA1 following exploration, very few pyramidal neurons exhibited nuclear p-ERK1/2 staining. Local delivery of U0126 during the induction of perforant path LTP blocked transcriptional activation of Arc/Arg3.1 in a small region near the injection site and blocked Arc/Arg3.1 protein expression over a wider region. Our results indicate that activation of Arc/Arg3.1 transcription in dentate granule cells in vivo is mediated in part by MAP kinase activation, but other signaling pathways also contribute, especially in the case of Arc/Arg3.1 induction in response to experience.