Safety of mapping the motor networks in the spinal cord using penetrating microelectrodes in Yucatan minipigs.

OBJECTIVE: The goal of this study was to assess the safety of mapping spinal cord locomotor networks using penetrating stimulation microelectrodes in Yucatan minipigs (YMPs) as a clinically translational animal model. METHODS: Eleven YMPs were trained to walk up and down a straight line. Motion capture was performed, and electromyographic (EMG) activity of hindlimb muscles was recorded during overground walking. The YMPs underwent a laminectomy and durotomy to expose the lumbar spinal cord. Using an ultrasound-guided stereotaxic frame, microelectrodes were inserted into the spinal cord in 8 animals. Pial cuts were made to prevent tissue dimpling before microelectrode insertion. Different locations within the lumbar enlargement were electrically stimulated to map the locomotor networks. The remaining 3 YMPs served as sham controls, receiving the laminectomy, durotomy, and pial cuts but not microelectrode insertion. The Porcine Thoracic Injury Behavioral Scale (PTIBS) and hindlimb reflex assessment results were recorded for 4 weeks postoperatively. Overground gait kinematics and hindlimb EMG activity were recorded again at weeks 3 and 4 postoperatively and compared with preoperative measures. The animals were euthanized at the end of week 4, and the lumbar spinal cords were extracted and preserved for immunohistochemical analysis. RESULTS: All YMPs showed transient deficits in hindlimb function postoperatively. Except for 1 YMP in the experimental group, all animals regained normal ambulation and balance (PTIBS score 10) at the end of weeks 3 and 4. One animal in the experimental group showed gait and balance deficits by week 4 (PTIBS score 4). This animal was excluded from the kinematics and EMG analyses. Overground gait kinematic measures and EMG activity showed no significant (p > 0.05) differences between preoperative and postoperative values, and between the experimental and sham groups. Less than 5% of electrode tracks were visible in the tissue analysis of the animals in the experimental group. There was no statistically significant difference in damage caused by pial cuts between the experimental and sham groups. Tissue damage due to the pial cuts was more frequently observed in immunohistochemical analyses than microelectrode tracks. CONCLUSIONS: These findings suggest that mapping spinal locomotor networks in porcine models can be performed safely, without lasting damage to the spinal cord.

Skin and not dorsal root stimulation reduces hypertonus in thoracic motor complete spinal cord injury: a single case report.

On demand and localized treatment for excessive muscle tone after spinal cord injury (SCI) is currently not available. Here, we examine the reduction in leg hypertonus in a person with mid-thoracic, motor complete SCI using a commercial transcutaneous electrical stimulator (TES) applied at 50 or 150 Hz to the lower back and the possible mechanisms producing this bilateral reduction in leg tone. Hypertonus of knee extensors without and during TES, with both cathode (T11-L2) and anode (L3-L5) placed over the spinal column (midline, MID) or 10 cm to the left of midline (lateral, LAT) to only active underlying skin and muscle afferents, was simultaneously measured in both legs with the pendulum test. Spinal reflexes mediated by proprioceptive (H-reflex) and cutaneomuscular reflex (CMR) afferents were examined in the right leg opposite to the applied LAT TES. Hypertonus disappeared in both legs but only during thoracolumbar TES, and even during LAT TES. The marked reduction in tone was reflected in the greater distance both lower legs first dropped to after being released from a fully extended position, increasing by 172.8% and 94.2% during MID and LAT TES, respectively, compared with without TES. Both MID and LAT (left) TES increased H-reflexes but decreased the first burst, and lengthened the onset of subsequent bursts, in the cutaneomuscular reflex of the right leg. Thoracolumbar TES is a promising method to decrease leg hypertonus in chronic, motor complete SCI without activating spinal cord structures and may work by facilitating proprioceptive inputs that activate excitatory interneurons with bilateral projections that in turn recruit recurrent inhibitory neurons.NEW & NOTEWORTHY We present proof of concept that surface stimulation of the lower back can reduce severe leg hypertonus in a participant with motor complete, thoracic spinal cord injury (SCI) but only during the applied stimulation. We propose that activation of skin and muscle afferents from thoracolumbar transcutaneous electrical stimulation (TES) may recruit excitatory spinal interneurons with bilateral projections that in turn recruit recurrent inhibitory networks to provide on demand suppression of ongoing involuntary motoneuron activity.

Overground gait kinematics and muscle activation patterns in the Yucatan mini pig.

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-1walking 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.

Timing and dosage of FES cycling early after acute spinal cord injury: A case series report.

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.

Comparative neuroanatomy of the lumbosacral spinal cord of the rat, cat, pig, monkey, and human.

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.

Functional organization of motor networks in the lumbosacral spinal cord of non-human primates.

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.

Brachial Artery Catheterization in Swine.

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.

Effect of anesthesia on motor responses evoked by spinal neural prostheses during intraoperative procedures.

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.

A speed-adaptive intraspinal microstimulation controller to restore weight-bearing stepping in a spinal cord hemisection model.

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 (<110 µA). The control strategy used signals from ground reaction forces and angular velocity from the manually-moved limb to anticipate states of the gait cycle, and controlled ISMS to move the other hind-limb into the opposite state. Adaptive control strategies were developed to ensure weight-bearing at different stepping speeds. The step period was predicted using generalizations obtained through four supervised machine learning algorithms and used to adapt the control strategy for faster steps. MAIN RESULTS: At a single speed, 100% of the steps had sufficient weight-bearing; at faster speeds without adaptation, 97.6% of steps were weight-bearing (significantly less than that for single speed; p = 0.002). By adapting the control strategy for faster steps using the predicted step period, weight-bearing was achieved in more than 99% of the steps in three of four methods (significantly more than without adaptation p < 0.04). Overall, a multivariate model tree increased the number of weight-bearing steps, restored step symmetry, and maintained alternation at faster stepping speeds. SIGNIFICANCE: Through the adaptive control strategies guided by supervised machine learning, we were able to restore weight-bearing and maintain alternation and step symmetry at varying stepping speeds.

Ultrasound-guided spinal stereotactic system for intraspinal implants.

OBJECTIVE The 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. METHODS A 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. RESULTS The 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). CONCLUSIONS The 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.

Mechanically Stable Intraspinal Microstimulation Implants for Human Translation.

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.

A Mixed-Signal VLSI System for Producing Temporally Adapting Intraspinal Microstimulation Patterns for Locomotion.

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.

Effect of a foot-drop stimulator and ankle-foot orthosis on walking performance after stroke: a multicenter randomized controlled trial.

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.

Facilitation of corticospinal connections in able-bodied people and people with central nervous system disorders using eight interventions.

BACKGROUND: Voluntary contractions (VOL), functional electrical stimulation (FES), and transcranial magnetic stimulation (TMS) can facilitate corticospinal connections. OBJECTIVE: 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. METHODS: 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. RESULTS: Three interventions (PAS, PAS + VOL, and double-pulse TMS + VOL) caused 15% to 20% increases (P < 0.05) 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). CONCLUSIONS: (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.

Restoring stepping after spinal cord injury using intraspinal microstimulation and novel control strategies.

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.

Long-term therapeutic and orthotic effects of a foot drop stimulator on walking performance in progressive and nonprogressive neurological disorders.

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.

Does functional electrical stimulation for foot drop strengthen corticospinal connections?

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 (M(max)) 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 (R(2) = .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 M(max) 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.

Bilateral vestibular loss in cats leads to active destabilization of balance during pitch and roll rotations of the support surface.

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.

A multicenter trial of a footdrop stimulator controlled by a tilt sensor.

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.

Decoding sensory feedback from firing rates of afferent ensembles recorded in cat dorsal root ganglia in normal locomotion.

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 microm 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 +/- 22% (mean +/- S.D. for hip, knee, and ankle) of the variance in joint angle and 72 +/- 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.