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The role of afferent feedback and central motor drive in muscle activation has a profound impact on our understanding of movement control in health and disease. Dr. Richard B. Stein was a pioneer who made major contributions to the field. In addition to fundamental discoveries using animal models, he translated this to the clinic to benefit patients with spinal cord and other neurological injuries. Along the way, he inspired a generation of scientists around the world.

The overall goal of this work was to create a high-resolution MRI atlas of the lumbosacral enlargement of the spinal cord of the rat (Sprague–Dawley), cat, domestic pig, rhesus monkey, and human. These species were chosen because they are commonly used in basic and translational research in spinal cord injuries and diseases. Six spinal cord specimens from each of the studied species (total of 30 specimens) were fixed, extracted, and imaged. Sizes of the spinal cord segments, cross-sectional dimensions, and locations of the spinal cord gray and white matter were quantified and compared across species. The lumbar enlargement spans spinal cord levels L3-S1 in rats, L4-S1 in cats, L3-S1 in pigs, L2/L3-L7/S1 in monkeys, and T12/L1-S1/S2 in humans. The enlargements in pigs and humans are largest and most similar in size (length and cross-sectional area); followed by monkeys and cats; and followed by rats. The obtained atlas establishes a neuroanatomical reference for the intact lumbosacral spinal cord in these species. It can also be used to guide the planning of surgical procedures of the spinal cord and technology design and development of spinal cord neuroprostheses, as well as precise delivery of cells/drugs into target regions within the spinal cord parenchyma.

A growing number of spinal cord injury, neuromodulation, and cell therapy studies on porcine models, especially the Yucatan minipigs (YMPs), have been recently reported. This is due to the large similarities between human and porcine neuroanatomy and biomechanics. To assess treatment modalities and locomotor recovery in this model, there is an obvious need for detailed characterization of normative overground gait in neurologically intact YMPs. The objective of this study was to assess gait biomechanics and the effect of overground walking speed on gait parameters, kinematics, and electromyographic (EMG) activity in the hindlimb muscles of YMPs. Nine neurologically-intact adult YMPs were trained to walk overground in a straight line. Whole-body kinematics and EMG activity of hindlimb muscles were recorded and analyzed at 6 different speed ranges (0.4-0.59, 0.6-0.79, 0.8-0.99, 1.0-1.19, 1.2-1.39, and 1.4-1.6 m/s). A MATLAB program was developed to detect strides and gait events automatically from motion-captured data. Significant decreases in stride duration, stance and swing times and an increase in stride length were observed with increasing speed. A transition in gait pattern occurred at the 1.0m/s walking speed. Significant increases in the range of motion of the knee and ankle joints were observed at higher speeds. Also, the points of minimum and maximum knee and ankle joint angles occurred earlier in the gait cycle at higher speeds. The onset of EMG activity in the biceps femoris muscle occurred significantly earlier in the gait cycle with increasing speed. A comprehensive characterization of overground walking in neurologically-intact YMPs is provided. These normative measures set the basis against which the effects of future interventions on locomotor capacity in YMPs can be compared.

Implantable spinal-cord-neuroprostheses aiming to restore standing and walking after paralysis have been extensively studied in animal models (mainly cats) and have shown promising outcomes. This study aimed to take a critical step along the clinical translation path of these neuroprostheses, and investigated the organization of the neural networks targeted by these implants in a non-human primate. This was accomplished by advancing a microelectrode into various locations of the lumbar enlargement of the spinal cord, targeting the ventral horn of the gray matter. Microstimulation in these locations produced a variety of functional movements in the hindlimb. The resulting functional map of the spinal cord in monkeys was found to have a similar overall organization along the length of the spinal cord to that in cats. This suggests that the human spinal cord may also be organized similarly. The obtained spinal cord maps in monkeys provide important knowledge that will guide the very first testing of these implants in humans.

OBJECTIVE To understand the progression in parameters of functional electrical stimulation (FES) cycling dosage (including duration, velocity, stimulation amplitudes, power output), and the resulting changes in muscle mass early after acute spinal cord injury (SCI). METHODS Three participants, 24-38 years old, with neurological injury level C4-T4, severity AIS (American Spinal Injury Association Impairment Scale) A-C, started FES cycling 16-20 days post injury while admitted at a level-1 trauma center in Canada, and continued for 8-13 weeks in a rehabilitation hospital. They performed three sessions/week of 15-45 min FES cycling, supine or sitting. FES parameters, cycling performance, and muscle cross-sectional area (CSA) in thighs and calves were measured every 2 weeks. RESULTS Progression in power output, but not in session duration, was limited in two participants who experienced stimulation-associated referred pain or apprehension, requiring limitation of stimulation amplitudes for up to 65 days after the start of FES cycling. Participants started with 15 min cycling at 20 RPM with no resistance (0 W), and progressed to 30-45 min at 30 RPM producing 8.8-19.0 W average power/session after 2-3 months. Initially, muscle CSA decreased in all 3 participants (up to 16% after 6 weeks), and recovered later after a variable period of FES cycling (up to 16% at 13.3 weeks). CONCLUSION Progression of FES cycling in the first 3 months after injury required a highly individualized approach, guided by participant response, rather than standardized increments in stimulation intensity or duration. Changes in muscle CSA did not always correspond with the dose of FES cycling.

Objective. The objectives of this study were to assess gait biomechanics and the effect of overground walking speed on gait parameters, kinematics, and electromyographic (EMG) activity in the hindlimb muscles of Yucatan minipigs (YMPs). Approach. Nine neurologically-intact, adult YMPs were trained to walk overground in a straight line. Whole-body kinematics and EMG activity of hindlimb muscles were recorded and analyzed at six different speed ranges (0.4–0.59, 0.6–0.79, 0.8–0.99, 1.0–1.19, 1.2–1.39, and 1.4–1.6 m s−1). A MATLAB program was developed to detect strides and gait events automatically from motion-captured data. The kinematics and EMG activity were analyzed for each stride based on the detected events. Main results. Significant decreases in stride duration, stance and swing times and an increase in stride length were observed with increasing speed. A transition in gait pattern occurred at the 1.0 m s−1 walking speed. Significant increases in the range of motion of the knee and ankle joints were observed at higher speeds. Also, the points of minimum and maximum joint angles occurred earlier in the gait cycle as the walking speed increased. The onset of EMG activity in the biceps femoris muscle occurred significantly earlier in the gait cycle with increasing speed. Significance. YMPs are becoming frequently used as large animal models for preclinical testing and translation of novel interventions to humans. A comprehensive characterization of overground walking in neurologically-intact YMPs is provided in this study. These normative measures set the basis against which the effects of future interventions on locomotor capacity in YMPs can be compared.

The video describes in detail the catheterization of the distal brachial artery in swine. This technique enables researchers to measure arterial blood pressure continuously and collect arterial blood samples to assess arterial blood gas measurements. Arterial blood pressures and arterial blood gases are important physiological parameters to monitor during experimental procedures. In swine, four common methods of arterial catheterization have been described, including catheterization of the carotid, femoral, auricular, and medial saphenous arteries. Each of these techniques have advantages, such as ease of access for the auricular artery, and disadvantages that include deep tissue dissection for carotid artery catheterization. The described alternative method of arterial catheterization in swine, the catheterization of the distal aspect of the brachial artery, is a rapid procedure that requires relatively minimal tissue dissection and provides information that is in line with data collected from other arterial catheterization sites. The procedure uses a medial approach along an oblique plane of the lower brachium, positioned between the olecranon and the flexor aspect of the elbow joint, and this approach allows researchers the major advantage of unimpeded freedom for procedures that involve the caudoventral, caudodorsal back, or hind limbs of the pig. Due to the location of the upper forelimb of the catheterized vessel and potential challenges of effective homeostasis following catheter removal from the artery, this technique may be limited to non-recovery procedures.

OBJECTIVE The goal of this study was to develop control strategies to produce alternating, weight-bearing stepping in a cat model of hemisection spinal cord injury (SCI) using intraspinal microstimulation (ISMS). APPROACH Six cats were anesthetized and the functional consequences of a hemisection SCI were simulated by manually moving one hind-limb through the gait cycle over a moving treadmill belt. ISMS activated the muscles in the other leg by stimulating motor networks in the lumbosacral enlargement using low levels of current (

OBJECTIVEThe overall goal of this study was to develop an image-guided spinal stereotactic setup for intraoperative intraspinal microstimulation (ISMS). System requirements were as follows: 1) ability to place implants in various segments of the spinal cord, targeting the gray matter with a < 0.5-mm error; 2) modularity; and 3) compatibility with standard surgical tools.METHODSA spine-mounted stereotactic system was developed, optimized, and tested in pigs. The system consists of a platform supporting a micromanipulator with 6 degrees of freedom. It is modular and flexible in design and can be applied to various regions of the spine. An intraoperative ultrasound imaging technique was also developed and assessed for guidance of electrode alignment prior to and after electrode insertion into the spinal cord. Performance of the ultrasound-guided stereotactic system was assessed both in pigs (1 live and 6 fresh cadaveric pigs) and on the bench using four gelatin-based surrogate spinal cords. Pig experiments were conducted to evaluate the performance of ultrasound imaging in aligning the electrode trajectory using three techniques and under two conditions. Benchtop experiments were performed to assess the performance of ultrasound-guided targeting more directly. These experiments were used to quantify the accuracy of electrode alignment as well as assess the accuracy of the implantation depth and the error in spatial targeting within the gray matter of the spinal cord. As proof of concept, an intraoperative ISMS experiment was also conducted in an additional live pig using the stereotactic system, and the resulting movements and electromyographic responses were recorded.RESULTSThe stereotactic system was quick to set up (< 10 minutes) and provided sufficient stability and range of motion to reach the ISMS targets reliably in the pigs. Transverse ultrasound images with the probe angled at 25°–45° provided acceptable contrast between the gray and white matter of the spinal cord. In pigs, the largest electrode alignment error using ultrasound guidance, relative to the minor axis of the spinal cord, was ≤ 3.57° (upper bound of the 95% confidence interval). The targeting error with ultrasound guidance in bench testing for targets 4 mm deep into the surrogate spinal cords was 0.2 ± 0.02 mm (mean ± standard deviation).CONCLUSIONSThe authors developed and evaluated an ultrasound-guided spinal stereotactic system for precise insertion of intraspinal implants. The system is compatible with existing spinal instrumentation. Intraoperative ultrasound imaging of the spinal cord aids in alignment of the implants before insertion and provides feedback during and after implantation. The ability of ultrasound imaging to distinguish between spinal cord gray and white matter also improves confidence in the localization of targets within the gray matter. This system would be suitable for accurate guidance of intraspinal electrodes and drug or cell injections.

Objective The overall goal of this study was to investigate the effects of various anesthetic protocols on the intraoperative responses to intraspinal microstimulation (ISMS). ISMS is a neuroprosthetic approach that targets the motor networks in the ventral horns of the spinal cord to restore function after spinal cord injury. In preclinical studies, ISMS in the lumbosacral enlargement produced standing and walking by activating networks controlling the hindlimb muscles. ISMS implants are placed surgically under anesthesia, and refinements in placement are made based on the evoked responses. Anesthesia can have a significant effect on the responses evoked by spinal neuroprostheses; therefore, in preparation for clinical testing of ISMS, we compared the evoked responses under a common clinical neurosurgical anesthetic protocol with those evoked under protocols commonly used in preclinical studies. Approach Experiments were conducted in seven pigs. An ISMS microelectrode array was implanted in the lumbar enlargement and responses to ISMS were measured under three anesthetic protocols: (1) isoflurane, an agent used pre-clinically and clinically, (2) total intravenous anesthesia (TIVA) with propofol as the main agent commonly used in clinical neurosurgical procedures, (3) TIVA with sodium pentobarbital, an anesthetic agent used mostly preclinically. Responses to ISMS were evaluated based on stimulation thresholds, movement kinematics, and joint torques. Motor evoked potentials (MEP) and plasma concentrations of propofol were also measured. Main results ISMS under propofol anesthesia produced large and functional responses that were not statistically different from those produced under pentobarbital anesthesia. Isoflurane, however, significantly suppressed the ISMS-evoked responses. Significance This study demonstrated that the choice of anesthesia is critical for intraoperative assessments of motor responses evoked by spinal neuroprostheses. Propofol and pentobarbital anesthesia did not overly suppress the effects of ISMS; therefore, propofol is expected to be a suitable anesthetic agent for clinical intraoperative testing of an intraspinal neuroprosthetic system.

Background. Studies have demonstrated the efficacy of functional electrical stimulation in the management of foot drop after stroke. Objective. To compare changes in walking performance with the WalkAide (WA) foot-drop stimulator and a conventional ankle–foot orthosis (AFO). Methods. Individuals with stroke within the previous 12 months and residual foot drop were enrolled in a multicenter, randomized controlled, crossover trial. Subjects were assigned to 1 of 3 parallel arms for 12 weeks (6 weeks/device): arm 1 (WA–AFO), n = 38; arm 2 (AFO–WA), n = 31; arm 3 (AFO–AFO), n = 24. Primary outcomes were walking speed and Physiological Cost Index for the Figure-of-8 walking test. Secondary measures included 10-m walking speed and perceived safety during this test, general mobility, and device preference for arms 1 and 2 for continued use. Walking tests were performed with (On) and without a device (Off) at 0, 3, 6, 9, and 12 weeks. Results. Both WA and AFO had significant orthotic (On–Off difference), therapeutic (change over time when Off), and combined (change over time On vs baseline Off) effects on walking speed. An AFO also had a significant orthotic effect on Physiological Cost Index. The WA had a higher, but not significantly different therapeutic effect on speed than an AFO, whereas an AFO had a greater orthotic effect than the WA (significant at 12 weeks). Combined effects on speed after 6 weeks did not differ between devices. Users felt as safe with the WA as with an AFO, but significantly more users preferred the WA. Conclusions. Both devices produce equivalent functional gains.

OBJECTIVE Spinal cord injury causes a drastic loss of motor, sensory and autonomic function. The goal of this project was to investigate the use of intraspinal microstimulation (ISMS) for producing long distances of walking over ground. ISMS is an electrical stimulation method developed for restoring motor function by activating spinal networks below the level of an injury. It produces movements of the legs by stimulating the ventral horn of the lumbar enlargement using fine penetrating electrodes (≤50 μm diameter). APPROACH In each of five adult cats (4.2-5.5 kg), ISMS was applied through 16 electrodes implanted with tips targeting lamina IX in the ventral horn bilaterally. A desktop system implemented a physiologically-based control strategy that delivered different stimulation patterns through groups of electrodes to evoke walking movements with appropriate limb kinematics and forces corresponding to swing and stance. Each cat walked over an instrumented 2.9 m walkway and limb kinematics and forces were recorded. MAIN RESULTS Both propulsive and supportive forces were required for over-ground walking. Cumulative walking distances ranging from 609 to 835 m (longest tested) were achieved in three animals. In these three cats, the mean peak supportive force was 3.5 ± 0.6 N corresponding to full-weight-support of the hind legs, while the angular range of the hip, knee, and ankle joints were 23.1 ± 2.0°, 29.1 ± 0.2°, and 60.3 ± 5.2°, respectively. To further demonstrate the viability of ISMS for future clinical use, a prototype implantable module was successfully implemented in a subset of trials and produced comparable walking performance. SIGNIFICANCE By activating inherent locomotor networks within the lumbosacral spinal cord, ISMS was capable of producing bilaterally coordinated and functional over-ground walking with current amplitudes

The goal of this study was to develop stable intraspinal microstimulation (ISMS) implants for use in humans to restore standing and walking after spinal cord injury. ISMS electrically activates locomotor networks within the lumbar region of the spinal cord. In animals, ISMS produced better functional outcomes than those obtained by other interventions, and recent efforts have focused on translating this approach to humans. This study used domestic pigs to: (1) quantify the movements and length changes of the implant region of the spinal cord during spine flexion and extension movements; and (2) measure the forces leading to the dislodgement of the ISMS electrodes. The displacement of the spinal cord implant region was 5.66 ± 0.57 mm relative to the implant fixation point on the spine. The overall length change of the spinal cord implant region was 5.64 ± 0.59 mm. The electrode dislodgment forces were 60.9 ± 35.5 mN. Based on these results, six different coil types were fabricated and their strain relief capacity assessed. When interposed between the electrodes and the stimulator, five coil types successfully prevented the dislodgement of the electrodes. The results of this study will guide the design of mechanically stable ISMS implants for ultimate human use.

Neural pathways can be artificially activated through the use of electrical stimulation. For individuals with a spinal cord injury, intraspinal microstimulation, using electrical currents on the order of 125 μ A, can produce muscle contractions and joint torques in the lower extremities suitable for restoring walking. The work presented here demonstrates an integrated circuit implementing a state-based control strategy where sensory feedback and intrinsic feed forward control shape the stimulation waveforms produced on-chip. Fabricated in a 0.5 μ m process, the device was successfully used in vivo to produce walking movements in a model of spinal cord injury. This work represents progress towards an implantable solution to be used for restoring walking in individuals with spinal cord injuries.

Background. Long-term use of a foot-drop stimulator applying functional electrical stimulation (FES) to the common peroneal nerve improves walking performance even when the stimulator is off. This “therapeutic” effect might result from neuroplastic changes. Objective. To determine the effect of long-term use of a foot-drop stimulator on residual corticospinal connections in people with central nervous system disorders. Methods. Ten people with nonprogressive disorders (eg, stroke) and 26 with progressive disorders (eg, multiple sclerosis) used a foot-drop stimulator for 3 to 12 months while walking in the community. Walking performance and electrophysiological variables were measured before and after FES use. From the surface electromyogram of the tibialis anterior muscle, we measured the following: (1) motor-evoked potential (MEP) from transcranial magnetic stimulation over the motor cortex, (2) maximum voluntary contraction (MVC), and (3) maximum motor wave (Mmax) from stimulating the common peroneal nerve. Results. After using FES, MEP and MVC increased significantly by comparable amounts, 50% and 48%, respectively, in the nonprogressive group and 27% and 17% in the progressive group; the changes were positively correlated ( R2 = .35; P < .001). Walking speed increased with the stimulator off (therapeutic effect) by 24% ( P = .008) and 7% ( P = .014) in the nonprogressive and progressive groups, respectively. The changes in Mmax were small and not correlated with changes in MEP. Conclusions. The large increases in MVC and MEP suggest that regular use of a foot-drop stimulator strengthens activation of motor cortical areas and their residual descending connections, which may explain the therapeutic effect on walking speed.

Use of electrical stimulation to correct foot drop in hemiplegia was proposed over 40 years ago. Recently, improved control strategies have been developed and implemented in commercially available devices. In this article we review the control methods that have been used and present some results from a multi-center clinical trial. A foot-drop stimulator improves the gait pattern and results in an immediate increase in walking speed. In this sense it acts like an ankle-foot orthosis and this immediate increase will be referred to as an orthotic effect. Prolonged use of a foot drop stimulator over a period of months results in further, large increases in walking speed both with the stimulator on and off. Evidence indicates that a part of this increase results from daily use that strengthens residual cortico-spinal connections. Therefore the improvement over time will be referred to as a therapeutic effect. We found that people with non-progressive and progressive conditions of the central nervous system have an orthotic benefit, as well as a therapeutic up to 3 months of use. In generally non-progressive conditions such as stroke, further therapeutic increases are seen up to at least 11 months of use. In disorders such as multiple sclerosis, the progression of the disease eventually overcomes the early therapeutic effects. In conclusion, many individuals can benefit from commercially available foot-drop stimulators with improved control strategies and cosmetic design.

Functional electrical stimulation (FES) holds great potential for restoring motor functions after brain and spinal cord injury. Currently, most FES systems are under simple finite state control, using external sensors which tend to be bulky, uncomfortable and prone to failure. Sensory nerve signals offer an interesting alternative, with the possibility of continuous feedback control. To test feasibility, we recorded from ensembles of sensory neurons with microelectrode arrays implanted in the dorsal root ganglion (DRG) of walking cats. Limb position and velocity variables were estimated accurately (average R2 values0.5) over a range of walking speeds (0.1-0.5 m s(-1)) using a linear combination of firing rates from 10 or more neurons. We tested the feasibility of sensory control of intraspinal FES by recording from DRG neurons during hindlimb movements evoked by intraspinal microstimulation of the lumbar spinal cord in an anesthetized cat. Although electrical stimulation generated artifacts, this problem was overcome by detecting and eliminating events that occurred synchronously across the array of microelectrodes. The sensory responses to limb movement could then be measured and decoded to generate an accurate estimate of the limb state. Multichannel afferent recordings may thus provide FES systems with the feedback needed for adaptive control and perturbation compensation, though long-term stability remains a challenge.

Objectives. To test the efficacy and acceptance of a footdrop stimulator controlled by a tilt sensor. Methods. A nonrandomized, test-retest study of 26 subjects with footdrop of more than 1 year’s duration, resulting from various central nervous system disorders, was performed in 4 centers for at least 3 months. Speed of walking in a straight line, speed around a figure of 8, and physiological cost index (PCI) were measured with and without the device. Hours/day and steps/day using the device were recorded. Results.All but 2 subjects used the tilt sensor at home, rather than a foot switch. Walking speed increased by 15% after 3 months ( n = 26; P < 0.01), 32% after 6 months ( n = 16; P < 0.01), and 47% after 12 months ( n = 8; P < 0.05), while PCI decreased. The number of steps taken per day of use increased significantly over time, and increased speed was directly correlated with usage. Walking speed also increased with the stimulator off, but to a lesser extent, indicating a training effect. Subject feedback from a questionnaire indicated satisfaction with the stimulator. Conclusions. Both efficacy and acceptance of the stimulator were good in a population of subjects with chronic footdrop.

Single session, repeated-measures design.To analyze the impact of different components of the neural tissue provocation test for the median nerve (NTPT1) on the range of motion (ROM) of the elbow and wrist and the sensory responses elicited by the test.The assessment of minor peripheral nerve injuries by neurodynamic tests is becoming more integrated in physical therapy practice. The influence of different test components on the nervous system has been analyzed in numerous in vitro studies, but in vivo studies are still lacking.Five test variations were performed on 35 asymptomatic men (23.5 +/- 2.3 years). Elbow extension was performed (1) without additional components (NTPT1NEUTRAL), (2) with wrist extension (NTPT1WE), (3) with cervical contralateral lateral flexion (NTPT1CLLF), and (4) with both wrist extension and cervical contralateral lateral flexion (NTPT1WE+CLLF). In the fifth variant, the wrist was extended from a preloaded position (WENTPT1). The range of elbow and wrist extension when a submaximal discomfort was elicited was measured with 2 electrogoniometers.The addition of each test component resulted in a significantly reduced ROM (NTPT1NEUTRAL: 179.5 +/- 8.8 degrees, NTPT1WE: 169.0 +/- 13.9 degrees, NTPT1CLLF: 154.7 +/- 13.2 degrees, NTPT1WE+CLLF: 143.9 +/- 16.1 degrees; WENTPT1: 67.1 +/- 11.0 degrees). Sensory responses were predominantly evoked at the region of the added component.The different test components, whose mechanical influence on the nervous system has been demonstrated in anatomical studies, also have an effect on joint ROM and sensory responses during neurodynamic testing, when individually or simultaneously added. If the nerve bedding is elongated throughout its whole length, the available ROM is markedly reduced and sensory responses can be elicited throughout the entire arm.

To determine accuracy, precision, and smallest detectable difference for a three-dimensional (3D) video motion analysis system specifically configured for measuring small and slow displacements within a small measurement volume (0.7 x 0.5 x 0.3 m).Repeated measurements with random sequence of conditions.Rehabilitation research laboratory.A reference sliding device was used to control cyclic displacements of two reflective markers over 5 calibrated ranges (1, 3, 10, 30, and 60 mm). Nine cycles were performed for each of 9 conditions (3 directions x 3 zones). Four cameras recorded all trials on tapes, which were digitized with a Kinemetrix system.Change in distance of the moving markers relative to a third static marker was averaged over 50 frames per trial. Mean error, mean absolute error, and intertrial and intratrial standard deviations (SDs) were calculated for each zone and direction.For 810 trials, mean error and absolute error were, respectively, .034 mm and .094 mm. The mean intertrial and intratrial SDs and 99% confidence interval were .047 mm (CI = +/- .121 mm) and .030 mm (CI = +/- .077 mm). The corresponding smallest detectable differences were .171 mm and .109 mm.Motion analysis configured for registration within small volumes allows measurement of minuscule displacements with great accuracy and may therefore be suitable for many applications in rehabilitation research other than gait analysis.

The purpose of this study was to determine if the mobility of soft tissues in theparaspinal region is measurable in vivo, and to test the feasibility of obtaining useful data with a newly developed method. A small handheld device was developed to apply and measure oblique forces to the paraspinal tissues, resulting in gliding, which was measured using videoanalysis. Forces were transmitted to the tissues through disks adhered to the skin. The tissue mobility at the levels T8-9 and L1-2 was measured in four directions (cranial-caudal, and medial-lateral). Soft tissue mobility was measured in 16 subjects and the obtained force-displacement curves were representative for visco-elastic tissues. The range of motion (ROM) at 4 kg load in the 4 directions showed a consistent pattern, with soft tissues gliding most medially (5.64 ± 0.58 cm), followed by cranially (4.30 ± 0.48 cm), laterally (3.50 ± 0.46 cm) and caudally (2.68 ± 0.49 cm), at the thoracic level. The pattern at the lumbar level was similar a...

Voluntary contractions (VOL), functional electrical stimulation (FES), and transcranial magnetic stimulation (TMS) can facilitate corticospinal connections.To find the best methods for increasing corticospinal excitability by testing eight combinations: (1) VOL, (2) FES, (3) FES + VOL, (4) TMS, (5) TMS + VOL, (6) paired associative stimulation (PAS) consisting of FES + TMS, (7) PAS + VOL, and (8) double-pulse TMS + VOL.Interventions were applied for 3 × 10 minutes in 15 able-bodied subjects, 14 subjects with stable central nervous system lesions (e.g., chronic stroke, and incomplete spinal cord injury) and 16 subjects with progressive central nervous system conditions (e.g., secondary progressive multiple sclerosis). Motor-evoked potentials (MEP), M-waves, and H-reflexes were monitored over a 1-hour period.Three interventions (PAS, PAS + VOL, and double-pulse TMS + VOL) caused 15% to 20% increases (P0.05) in the MEP at a stimulus level that initially produced a half-maximal response (MEP(half)) during a contraction. Interventions were less effective in both clinical groups than in the able-bodied group. Interventions with VOL were more effective in increasing the MEP(half) than those without (P = 0.022). When more modalities were combined, the MEP increases were larger (P = 0.022).(1) Short-term application of FES, TMS, and VOL can facilitate corticospinal pathways, particularly when methods are combined. (2) The effects may depend on the total activation of neural pathways, which is reduced in central nervous system disorders.

This paper reports on a wireless stimulator device for use in animal experiments as part of an ongoing investigation into intraspinal stimulation (ISMS) for restoration of walking in humans with spinal cord injury. The principle behind using ISMS is the activation of residual motor-control neural networks within the spinal cord ventral horn below the level of lesion following a spinal cord injury. The attractiveness to this technique is that a small number of electrodes can be used to induce bilateral walking patterns in the lower limbs. In combination with advanced feedback algorithms, ISMS has the potential to restore walking for distances that exceed that produced by other types of functional electrical stimulation. Recent acute animal experiments have demonstrated the feasibility of using ISMS to produce the coordinated walking patterns. Here we described a wireless implantable stimulation system to be used in chronic animal experiments and for providing the basis for a system suitable for use in humans. Electrical operation of the wireless system is described, including a demonstration of reverse telemetry for monitoring the stimulating electrode voltages.

The overall objective of this project is to develop a feedback-driven intraspinal microstimulation (ISMS) system. We hypothesize that ISMS will enhance the functionality of stepping by reducing muscle fatigue and producing synergistic movements by activating neural networks in the spinal cord. In the present pilot study, the controller was tested with ISMS and external sensors (force plates, gyroscopes, and accelerometers). Cats were partially supported in a sling and bi-laterally stepped overground on a 4-m instrumented walkway. The walkway had variable friction. Limb angle was controlled to within 10° even in the presence of variable friction. Peak ground reaction forces in each limb were approximately 12% of body weight (12.5% was full load bearing in this experimental setup); rarely, the total supportive force briefly decreased to as low as 4.1%. Magnetic resonance images were acquired of the excised spinal cord and the implanted array. The majority of electrodes (75%) were implanted successfully into their target regions. This represents the first successful application of ISMS for overground walking.

A proposed Locomotion Processing Unit (LPU) is described for generating stimulation patterns for restoring walking in individuals with spinal cord injury (SCI). The LPU operates using sensory and timing based control providing feed forward and feedback information. By breaking down different components of locomotion into states, the LPU activates different muscle groups, or synergies, to recreate the desired functional movements. The LPU circuitry was simulated and compared against another controller designed to restore locomotion in an anesthetized cat to validate its performance.

Background. Stimulators applying functional electrical stimulation (FES) to the common peroneal nerve improve walking with a foot drop, which occurs in several disorders. Objective. To compare the orthotic and therapeutic effects of a foot drop stimulator on walking performance of subjects with chronic nonprogressive (eg, stroke) and progressive (eg, multiple sclerosis) disorders. Methods . Subjects with nonprogressive (41) and progressive (32) conditions used a foot drop stimulator for 3 to 12 months while walking in the community. Walking speed was measured with a 10-m test and a 4-minute figure-8 test; physiological cost index (PCI) and device usage were also measured. The subjects were tested with FES on and off (orthotic effect) before and after (therapeutic effect) stimulator use. Results. After 3 months of FES use, the nonprogressive and progressive groups had a similar, significant orthotic effect (5.0% and 5.7%, respectively, P < .003; percentage change in mean values) and therapeutic effect with FES off (17.8% and 9.1%, respectively, P < .005) on figure-8 walking speed. Overall, PCI showed a decreasing trend ( P = .031). The therapeutic effect on figure-8 speed diverged later between both groups to 28.0% ( P < .001) and 7.9% at 11 months. The combined therapeutic plus orthotic effect on figure-8 speed at 11 months was, respectively, 37.8% ( P < .001) and 13.1% ( P = .012); PCI decreased 18.2% ( P = .038) and 6.5%, respectively. Conclusions. Subjects with progressive and nonprogressive disorders had an orthotic benefit from FES up to 11 months. The therapeutic effect increased for 11 months in nonprogressive disorders but only for 3 months in progressive disorders. The combined effect remained significant and clinically relevant.

Although the balance difficulties accompanying vestibular loss are well known, the underlying cause remains unclear. We examined the role of vestibular inputs in the automatic postural response (APR) to pitch and roll rotations of the support surface in freely standing cats before and in the first week after bilateral labyrinthectomy. Support surface rotations accelerate the body center of mass toward the downhill side. The normal APR consists of inhibition in the extensors of the uphill limbs and excitation in the downhill limbs to decelerate the body and maintain the alignment of the limbs with respect to earth-vertical. After vestibular lesion, cats were unstable during rotation perturbations and actively pushed themselves downhill rather than uphill, using a postural response that was opposite to that seen in the control trials. The extensors of the uphill rather than downhill limbs were activated, whereas those of the downhill limbs were inhibited rather than being excited. We propose that vestibular inputs provide an important reference to earth-vertical, which is critical to computing the appropriate postural response during active orientation to the vertical. In the absence of this vestibular information, subjects orient to the support surface using proprioceptive inputs, which drives the body downhill resulting in instability and falling. This is consistent with current models of sensory integration for computation of body posture and orientation.

Sensory feedback is required by biological motor control systems to maintain stability, respond to perturbations, and adapt. Similarly, motor neuroprostheses require feedback to provide natural and complete restoration of motor functions. In this paper, we show that ensemble firing rates from the body's mechanoreceptors can provide a natural source of kinematic state feedback and could be useful for prosthetic control. Single unit recordings from multiple primary afferent neurons were obtained during walking using multichannel electrode arrays implanted chronically in the L7 dorsal root ganglia of three cats. We typically recorded simultaneously from over 20-30 neurons during the first 7-14 days after surgery, but recordings gradually worsened thereafter. Histology indicates that a ring of inflammatory and connective tissues (100 /spl mu/m thick) develops around each microelectrode and likely contributes to the degradation in recording quality. Accurate estimates of the hindlimb trajectory were made using a linear filter with inputs from only a few neurons highly correlated with limb kinematics. The coefficients for the linear filter were identified in a least-squares fit with 5-10 s of walking data (model training stage). The estimated and actual trajectories of separate walking data generally match well for walking at a range of speeds accounting for 63/spl plusmn/22% (mean/spl plusmn/S.D. for hip, knee, and ankle) of the variance in joint angle and 72/spl plusmn/4% of the variance in joint angular velocities. These results indicate that a neural interface with primary sensory neurons in the dorsal root ganglion can provide accurate kinematic state information that may be useful for closed loop control of a neuroprosthesis.

One of the signs advocated for monitoring during neurodynamic testing in the assessment of patients with upper quadrant disorders, is the response of the shoulder girdle. It is stated that a protective rising of the shoulder girdle is present when patients with neurogenic disorders are assessed and that the elevation is absent in asymptomatic subjects. As sensory responses are elicited in the majority of asymptomatic subjects and as the range of motion (ROM) is often limited during neurodynamic testing, it is questionable whether the elevation of the shoulder girdle would be absent in asymptomatic subjects. The aim of this study was to measure the shoulder girdle elevation force during five variants of the neural tissue provocation test for the median nerve. Thirty-five asymptomatic male subjects were assessed. A load cell was used to measure the amount of shoulder girdle elevation force and two electrogoniometers were used to measure the ROM at the elbow and wrist. When the ROM at the end of the test was restricted, a gradual increase in shoulder girdle elevation force could be observed throughout the test. Compared to the initial force at the start of the test, all variants resulted in a significant increase in force. It is concluded that a gradual increase in shoulder girdle elevation force should not be regarded as an abnormal sign in the interpretation of neurodynamic tests.

Objective. The goal of this study was to decode sensory information from the dorsal root ganglia (DRG) in real time, and to use this information to adapt the control of unilateral stepping with a state-based control algorithm consisting of both feed-forward and feedback components. Approach. In five anesthetized cats, hind limb stepping on a walkway or treadmill was produced by patterned electrical stimulation of the spinal cord through implanted microwire arrays, while neuronal activity was recorded from the DRG. Different parameters, including distance and tilt of the vector between hip and limb endpoint, integrated gyroscope and ground reaction force were modelled from recorded neural firing rates. These models were then used for closed-loop feedback. Main results. Overall, firing-rate-based predictions of kinematic sensors (limb endpoint, integrated gyroscope) were the most accurate with variance accounted for >60% on average. Force prediction had the lowest prediction accuracy (48 ± 13%) but produced the greatest percentage of successful rule activations (96.3%) for stepping under closed-loop feedback control. The prediction of all sensor modalities degraded over time, with the exception of tilt. Significance. Sensory feedback from moving limbs would be a desirable component of any neuroprosthetic device designed to restore walking in people after a spinal cord injury. This study provides a proof-of-principle that real-time feedback from the DRG is possible and could form part of a fully implantable neuroprosthetic device with further development.

The biological central pattern generator (CPG) integrates open and closed loop control to produce over-ground walking. The goal of this study was to develop a physiologically based algorithm capable of mimicking the biological system to control multiple joints in the lower extremities for producing over-ground walking. The algorithm used state-based models of the step cycle each of which produced different stimulation patterns. Two configurations were implemented to restore over-ground walking in five adult anaesthetized cats using intramuscular stimulation (IMS) of the main hip, knee and ankle flexor and extensor muscles in the hind limbs. An open loop controller relied only on intrinsic timing while a hybrid-CPG controller added sensory feedback from force plates (representing limb loading), and accelerometers and gyroscopes (representing limb position). Stimulation applied to hind limb muscles caused extension or flexion in the hips, knees and ankles. A total of 113 walking trials were obtained across all experiments. Of these, 74 were successful in which the cats traversed 75% of the 3.5 m over-ground walkway. In these trials, the average peak step length decreased from 24.9 ± 8.4 to 21.8 ± 7.5 (normalized units) and the median number of steps per trial increased from 7 (Q1 = 6, Q3 = 9) to 9 (8, 11) with the hybrid-CPG controller. Moreover, within these trials, the hybrid-CPG controller produced more successful steps (step length ≤ 20 cm; ground reaction force ≥ 12.5% body weight) than the open loop controller: 372 of 544 steps (68%) versus 65 of 134 steps (49%), respectively. This supports our previous preliminary findings, and affirms that physiologically based hybrid-CPG approaches produce more successful stepping than open loop controllers. The algorithm provides the foundation for a neural prosthetic controller and a framework to implement more detailed control of locomotion in the future.