Effect of cervicolumbar coupling on spinal reflexes during cycling after incomplete spinal cord injury.

Spinal networks in the cervical and lumbar cord are actively coupled during locomotion to coordinate arm and leg activity. The goals of this project were to investigate the intersegmental cervicolumbar connectivity during cycling after incomplete spinal cord injury (iSCI) and to assess the effect of rehabilitation training on improving reflex modulation mediated by cervicolumbar pathways. Two studies were conducted. In the first, 22 neurologically intact (NI) people and 10 people with chronic iSCI were recruited. The change in H-reflex amplitude in flexor carpi radialis (FCR) during leg cycling and H-reflex amplitude in soleus (SOL) during arm cycling were investigated. In the second study, two groups of participants with chronic iSCI underwent 12 wk of cycling training: one performed combined arm and leg cycling (A&L) and the other legs only cycling (Leg). The effect of training paradigm on the amplitude of the SOL H-reflex was assessed. Significant reduction in the amplitude of both FCR and SOL H-reflexes during dynamic cycling of the opposite limbs was found in NI participants but not in participants with iSCI. Nonetheless, there was a significant reduction in the SOL H-reflex during dynamic arm cycling in iSCI participants after training. Substantial improvements in SOL H-reflex properties were found in the A&L group after training. The results demonstrate that cervicolumbar modulation during rhythmic movements is disrupted in people with chronic iSCI; however, this modulation is restored after cycling training. Furthermore, involvement of the arms simultaneously with the legs during training may better regulate the leg spinal reflexes. NEW & NOTEWORTHY This work systematically demonstrates the disruptive effect of incomplete spinal cord injury on cervicolumbar coupling during rhythmic locomotor movements. It also shows that the impaired cervicolumbar coupling could be significantly restored after cycling training. Actively engaging the arms in rehabilitation paradigms for the improvement of walking substantially regulates the excitability of the lumbar spinal networks. The resulting regulation may be better than that obtained by interventions that focus on training of the legs only.

Modulation of corticospinal input to the legs by arm and leg cycling in people with incomplete spinal cord injury.

The spinal cervico-lumbar interaction during rhythmic movements in humans has recently been studied; however, the role of arm movements in modulating the corticospinal drive to the legs is not well understood. The goals of this study were to investigate the effect of active rhythmic arm movements on the corticospinal drive to the legs (study 1) and assess the effect of simultaneous arm and leg training on the corticospinal pathway after incomplete spinal cord injury (iSCI) (study 2). In study 1, neurologically intact (NI) participants or participants with iSCI performed combinations of stationary and rhythmic cycling of the arms and legs while motor evoked potentials (MEPs) were recorded from the vastus lateralis (VL) muscle. In the NI group, arm cycling alone could facilitate the VL MEP amplitude, suggesting that dynamic arm movements strongly modulate the corticospinal pathway to the legs. No significant difference in VL MEP between conditions was found in participants with iSCI. In study 2, participants with iSCI underwent 12 wk of electrical stimulation-assisted cycling training: one group performed simultaneous arm and leg (A&L) cycling and the other legs-only cycling. MEPs in the tibialis anterior (TA) muscle were compared before and after training. After training, only the A&L group had a significantly larger TA MEP, suggesting increased excitability in the corticospinal pathway. The findings demonstrate the importance of arm movements in modulating the corticospinal drive to the legs and suggest that active engagement of the arms in lower limb rehabilitation may produce better neural regulation and restoration of function.NEW & NOTEWORTHY This study aimed to demonstrate the importance of arm movements in modulating the corticospinal drive to the legs. It provides direct evidence in humans that active movement of the arms could facilitate corticospinal transmission to the legs and, for the first time, shows that facilitation is absent after spinal cord injury. Active engagement of the arms in lower limb rehabilitation increased the excitability of the corticospinal pathway and may produce more effective improvement in leg function.

Intraspinal microstimulation produces over-ground walking in anesthetized cats.

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 <100 µA. These exciting results suggest that ISMS may be an effective intervention for restoring functional walking after spinal cord injury.

Real-time control of walking using recordings from dorsal root ganglia.

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.

How does muscle stiffness affect the internal deformations within the soft tissue layers of the buttocks under constant loading?

Mechanical loading of soft tissues covering bony prominences can cause skeletal muscle damage, ultimately resulting in a severe pressure ulcer termed deep tissue injury (DTI). Deformation plays an important role in the aetiology of DTI. Therefore, it is essential to minimise internal muscle deformations in subjects at risk of DTI. As an example, spinal cord-injured (SCI) individuals exhibit structural changes leading to a decrease in muscle thickness and stiffness, which subsequently increase the tissue deformations. In the present study, an animal-specific finite element model, where the geometry and boundary conditions were derived from magnetic resonance images, was developed. It was used to investigate the internal deformations in the muscle, fat and skin layers of the porcine buttocks during loading. The model indicated the presence of large deformations in both the muscle and the fat layers, with maximum shear strains up to 0.65 in muscle tissue and 0.63 in fat. Furthermore, a sensitivity analysis showed that the tissue deformations depend considerably on the relative stiffness values of the different tissues. For example, a change in muscle stiffness had a large effect on the muscle deformations. A 50% decrease in stiffness caused an increase in maximum shear strain from 0.65 to 0.99, whereas a 50% increase in stiffness resulted in a decrease in maximum shear strain from 0.65 to 0.49. These results indicate the importance of restoring tissue properties after SCI, with the use of, for example, electrical stimulation, to prevent the development of DTI.

Feed forward and feedback control for over-ground locomotion in anaesthetized cats.

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.

A silicon central pattern generator controls locomotion in vivo.

We present a neuromorphic silicon chip that emulates the activity of the biological spinal central pattern generator (CPG) and creates locomotor patterns to support walking. The chip implements ten integrate-and-fire silicon neurons and 190 programmable digital-to-analog converters that act as synapses. This architecture allows for each neuron to make synaptic connections to any of the other neurons as well as to any of eight external input signals and one tonic bias input. The chip's functionality is confirmed by a series of experiments in which it controls the motor output of a paralyzed animal in real-time and enables it to walk along a three-meter platform. The walking is controlled under closed-loop conditions with the aide of sensory feedback that is recorded from the animal's legs and fed into the silicon CPG. Although we and others have previously described biomimetic silicon locomotor control systems for robots, this is the first demonstration of a neuromorphic device that can replace some functions of the central nervous system in vivo.

Intraspinal microstimulation excites multisegmental sensory afferents at lower stimulus levels than local alpha-motoneuron responses.

Microstimulation within the motor regions of the spinal cord is often assumed to activate motoneurons and propriospinal neurons close to the electrode tip. However, previous work has shown that intraspinal microstimulation (ISMS) in the gray matter activates sensory afferent axons as well as alpha-motoneurons (MNs). Here we report on the recruitment of sensory afferent axons and MNs as ISMS amplitudes increased. Intraspinal microstimulation was applied through microwires implanted in the dorsal horn, intermediate region and ventral horn of the L(5)-L(7) segments of the spinal cord in four acutely decerebrated cats, two of which had been chronically spinalized. Activation of sensory axons was detected with electroneurographic recordings from dorsal roots. Activation of MNs was detected with electromyographic (EMG) recordings from hindlimb muscles. Sensory axons were nearly always activated at lower stimulus levels than MNs irrespective of the stimulating electrode location. EMG response latencies decreased as ISMS stimulus intensities increased, suggesting that MNs were first activated transsynaptically and then directly as intensity increased. ISMS elicited antidromic activity in dorsal root filaments with entry zones up to 17 mm rostral and caudal to the stimulation sites. We posit that action potentials elicited in localized terminal branches of afferents spread antidromically to all terminal branches of the afferents and transsynaptically excite MNs and interneurons far removed from the stimulation site. This may help explain how focal ISMS can activate many MNs of a muscle even though they are distributed in long thin columns.

BCI Meeting 2005--workshop on clinical issues and applications.

This paper describes the outcome of discussions held during the Third International BCI Meeting at a workshop charged with reviewing and evaluating the current state of and issues relevant to brain-computer interface (BCI) clinical applications. These include potential BCI users, applications, validation, getting BCIs to users, role of government and industry, plasticity, and ethics.

Intraspinal microstimulation preferentially recruits fatigue-resistant muscle fibres and generates gradual force in rat.

Intraspinal microstimulation (ISMS), a novel rehabilitative therapy consisting of stimulation through fine, hair-like microwires targeted at the ventral spinal cord, has been proposed for restoring standing and walking following spinal cord injury. This study compared muscle recruitment characteristics of ISMS with those produced by peripheral nerve cuff stimulation (NCS). Thirty-three minutes of either ISMS or NCS at 1, 20 or 50 s(-1) and 1.2 x threshold (T) amplitude depleted glycogen from muscle fibres of vastus lateralis and rectus femoris. ISMS and NCS were also carried out at 20 s(-1) and 3.0T. Muscle serial sections were stained for glycogen and for myosin heavy chain (MHC)-based fibre types using a panel of monoclonal antibodies. The results of this study show that ISMS recruited fatigue-resistant (FR) fibres at 2.9, 1.9, 1.7 and 2.5 times their relative MHC content at 1, 20 and 50 s(-1) 1.2T and 20 s(-1) 3.0T, respectively. In contrast, NCS recruited FR fibres at 1.2, 1.0, 2.1 and 0.0 times their MHC content at 1, 20 and 50 s(-1) 1.2T and 20 s(-1) 3.0T, respectively. The proportion of FR fibres recruited by ISMS and NCS was significantly different in the 20 s(-1) 3.0T condition (P < 0.0001). We also report that force recruitment curves were 4.9-fold less steep (P < 0.019) for ISMS than NCS. The findings of this study provide evidence for the efficacy of ISMS and further our understanding of muscle recruitment properties of this novel rehabilitative therapy.

Movements generated by intraspinal microstimulation in the intermediate gray matter of the anesthetized, decerebrate, and spinal cat.

The intermediate laminae of the lumbosacral spinal cord are suggested to contain a small number of specialized neuronal circuits that form the basic elements of movement construction ("movement primitives"). Our aim was to study the properties and state dependence of these hypothesized circuits in comparison with movements elicited by direct nerve or muscle stimulation. Microwires for intraspinal microstimulation (ISMS) were implanted in intermediate laminae throughout the lumbosacral enlargement. Movement vectors evoked by ISMS were compared with those evoked by stimulation through muscle and nerve electrodes in cats that were anesthetized, then decerebrated, and finally spinalized. Similar movements could be evoked under anesthesia by ISMS and nerve and muscle stimulation, and these covered the full work space of the limb. ISMS-evoked movements were associated with the actions of nearby motoneuron pools. However, after decerebration and spinalization, ISMS-evoked movements were dominated by flexion, with few extensor movements. This indicates that the outputs of neuronal networks in the intermediate laminae depend significantly on descending input and on the state of the spinal cord. Frequently, the outputs also depended on stimulus intensity. These experiments suggest that interneuronal circuits in the intermediate and ventral regions of the spinal cord overlap and their function may be to process reflex and descending activity in a flexible manner for the activation of nearby motoneuron pools.

The role of neuromuscular properties in determining the end-point of a movement.

How does the activation of several muscles combine to produce reliable multijoint movements? To study this question, we stimulated up to six sites in muscles, nerves, and the spinal cord. Flexion and extension of the hip, knee, and ankle were elicited in anesthetized and decerebrate cats. The movements occurred largely in the sagittal plane against a constant spring load and covered most of the passive range of motion of the cat's limb. The movements of the end-point (foot) were compared with predictions based on vectorial summation of end-point movements elicited by stimulating single electrodes. The lengths of the movements produced by stimulating more than one site exceeded what was expected from linear summation for small movements (<3 cm) and showed a less than linear summation for large movements (>11 cm). The data were compared with muscle and limb models. Since the deviations from linearity were predictable as a function of distance, adjustments might easily be learned by trial and error. The summation was less complete for spinal stimulation, compared to nerve and muscle stimulation, so spinal circuits do not appear to compensate for the nonlinearities. Movements were elicited from positions of the limb not only in a neutral position, but also in front and behind the neutral position. A degree of convergence was seen, even with stimulation of some individual muscles, but the convergence increased as more muscles were stimulated and more joints were actively involved. This suggests that convergence to an equilibrium-point arises at least partly from muscle properties. In conclusion, there are deviations from linear vectorial summation, and these deviations increase when more muscles are stimulated. The convergence to an equilibrium-point may simplify the computations needed to produce movements involving many muscles.

Limb movements generated by stimulating muscle, nerve and spinal cord.

We have compared the movements generated by stimulation of muscle, nerve, spinal roots and spinal cord in anesthetized, decerebrate and spinalized cats. Each method produced a full range of movements of the cat's hind limb in the sagittal plane against a spring load, except for stimulation of the roots. Stimulation of the dorsal roots produced movements that were mainly up and forward, whereas stimulation of the ventral roots produced complementary movements (down and backward). Results from stimulation in the intermediate areas of the spinal cord were compared to predictions of the "movement primitives" hypothesis. We could not confirm that the directions were independent of stimulus amplitude or the state of descending inputs. Pros and cons of stimulating at some sites were provisionally considered for the reliable control of limb movements with functional electrical stimulation (FES) in clinical conditions.

Neural prostheses.

Assuming that neural regeneration after spinal cord injury (SCI) will eventually become a clinical reality, functional recovery will probably remain incomplete. Assistive devices will therefore continue to play an important role in rehabilitation. Neural prostheses (NPs) are assistive devices that restore functions lost as a result of neural damage. NPs electrically stimulate nerves and are either external or implanted devices. Surface stimulators for muscle exercise are now commonplace in rehabilitation clinics and many homes. Regarding implantable NPs, since 1963 over 40 000 have been implanted to restore hearing, bladder control and respiration. Epidural spinal cord stimulators and deep brain stimulators are routinely implanted to control pain, spasticity, tremor and rigidity. Implantable NPs have also been developed to restore limb movements using electrodes tunnelled under the skin to muscles and nerves. Spinal cord microstimulation (SC[mu]stim) is under study as an alternative way of restoring movement and bladder control. Improvement in bladder and bowel function is a high priority for many SCI people. Sacral root stimulation to elicit bladder contraction is the current NP approach, but this usually requires dorsal rhizotomies to reduce reflex contractions of the external urethral sphincter. It is possible that the spinal centres coordinating the bladder-sphincter synergy could be activated with SC[mu]stim. Given the large and growing number of NPs in use or development, it is surprising how little is known about their long-term interactions with the nervous system. Physiological research will play an important role in elucidating the mechanisms underlying these interactions.

Spinal cord microstimulation generates functional limb movements in chronically implanted cats.

Spinal cord injuries disrupt the communication between the brain and peripheral nerves, but leave motoneurons and networks of interneurons below the level of the lesion intact. It is therefore possible to restore some function following injury by providing an artificial stimulus to the surviving neurons below the level of the lesion. We report here on a novel approach for generating functional movements by electrically stimulating the spinal cord through chronically implanted ultrafine, hair-like electrodes. Six to 12 microwires were implanted in the lumbar enlargement of intact cats for 6 months. Twice a week, trains of stimuli were delivered through each microwire and the evoked electromyographic and torque responses were recorded. Strong coordinated hindlimb movements were obtained by stimulating through individual electrodes. The joint torques elicited were capable of supporting the animals' hindquarters. The responses were stable over time and the contractions caused no apparent discomfort to the animals. No obvious motor deficits were seen throughout the 6-month duration of implantation. The results demonstrate that microwires implanted in the spinal cord remain stably in place and stimulation through these electrodes produces strong, controllable movements. This provides a promising basis for the use of spinal cord neuroprostheses in restoring mobility following spinal cord injury.

Selective activation of muscle groups in the feline hindlimb through electrical microstimulation of the ventral lumbo-sacral spinal cord.

Selective activation of muscle groups in the feline hindlimb by electrical stimulation of the ventral lumbo-sacral spinal cord was investigated. Spinal cord segments L5 to S1 were mapped using a penetrating tungsten needle electrode. Locations that produced isolated contraction of quadriceps, tibialis anterior or triceps surae/plantaris muscles when stimulated with a current of 40 microA or less, and in which spread of activity to other muscles was not detected after increasing the stimulus to at least twice the threshold level, were defined as belonging to the target muscle's "activation pool." The quadriceps activation pool was found to extend from the beginning of L5 to the middle of L6. The tibialis anterior activation pool extended from the beginning of L6 to the middle of L7, and the triceps surae/plantaris activation pool extended from the caudal end of L6 to the beginning of S1. The three activation pools were located in Rexed motor lamina IX and their spatial organization was found to correspond well with that of the anatomically defined motor pools innervating the same muscles. The spatial and functional segregation of motor pools manifested at the spinal cord level can have direct applications in the areas of functional electrical stimulation and motor control.

Muscle recruitment through electrical stimulation of the lumbo-sacral spinal cord.

The goal of this study was to determine the feasibility of producing graded muscle contraction in individual muscles or muscle groups by electrically stimulating motor neurons in the lumbo-sacral spinal cord. Recruitment curves were obtained for quadriceps, tibialis anterior and triceps surae/plantaris by stimulating their activation pools in the ventral horn of the feline spinal cord. Mean twitch times-to-peak for quadriceps, tibialis anterior and triceps surae/plantaris were 33.0, 41.0, and 36.0 ms, respectively. Twitch duration as a function of stimulus strength demonstrated a mixed motor unit recruitment order, distinctively different from the inverse recruitment order exhibited by conventional methods of electrical stimulation of peripheral nerve. The recruitment curve slopes (expressed as a percentage of maximum force per nanocurrent of delivered charge) were shallow: 7.9 for quadriceps, 2.6 for tibialis anterior and 8.5 for triceps surae/plantaris. These results show that graded control of force in individual muscles or muscle groups can be obtained through spinal cord stimulation, and suggest that spinal cord stimulation could be used for functional neuromuscular stimulation applications.

Proposed specifications for a lumbar spinal cord electrode array for control of lower extremities in paraplegia.

The goal of the study was to provide specifications for a stimulating electrode array to be implanted in the lumbosacral spinal cord as part of a functional neuromuscular stimulation (FNS) system for control of lower extremity muscles in paralyzed individuals. Dual channel stimulation of the quadriceps activation pool in the feline ventral lumbo-sacral spinal cord was performed to measure electrode interactions and to explore the effect of various stimulation paradigms on muscle fatigue. There was no measurable overlap in the populations of motor neurons activated from two different electrodes for spacings > or = 1 mm with currents below 100 microA. However, a statistically significant increase in the population of activated fibers due to current summation was observed when stimuli > or = 70 microA were simultaneously presented through pairs of electrodes within 3 mm of each other. Fatigue effects were studied with three paradigms: 1) stimuli were delivered through a single electrode, 2) stimuli were delivered through two electrodes with the stimulus to the second electrode presented during the refractory period of fibers stimulated by the first electrode, and 3) stimuli were interleaved between the two electrodes such that the stimulus to one electrode was presented midway between stimuli to the other electrode, and the rate of stimulation through a single electrode was half that used in the first two paradigms. Dual channel refractory and single channel stimulation did not differ from each other in the rate at which the muscle fatigued, in both cases the force decayed to 30% of its initial level within 2 min of the initiation of the stimulation regime, whereas the force with interleaved stimulation was still above the initial force at this time due to strong potentiation. Based on these results and on and activation pool dimensions obtained in an earlier study, preliminary specifications are presented for an electrode array to be implanted in the human spinal cord for functional neuromuscular stimulation.