. The aim of this study was to produce a dynamic model of the spatiotemporal activation of ensembles of alpha motoneurons (MNs) in the cat lumbosacral spinal cord during the locomotor step cycle. The coordinates of MNs of 27 hindlimb muscles of the cat were digitized from transverse sections of spinal cord spanning the entire lumbosacral enlargement from the caudal part of L 4 to the rostral part of S 1 segments. Outlines of the spinal cord gray matter were also digitized. Models of the spinal cord were generated from these digitized data and displayed on a computer screen as threedimensional (3-D) images. We compiled a chart of electromyographic (EMG) profiles of the same 27 muscles during the cat step cycle from previous studies and used these to modulate the number of active MNs in the 3-D images. The step cycle was divided into 100 equal intervals corresponding to about 7 ms each for gait of moderate speed. For each of these 100 intervals, the level of EMG of each muscle was used to scale the number of dots displayed randomly within the volume of the corresponding MN pool in the digital model. One hundred images of the spinal cord were thereby generated, and these could be played in sequence as a continuous-loop movie representing rhythmical stepping. A rostrocaudal oscillation of activity in hindlimb MN pools emerged. This was confirmed by computing the locus of the center of activation of the MNs in the 100 consecutive frames of the movie. The caudal third of the lumbosacral enlargement showed intense MN activity during the stance phase of locomotion. During the swing phase, the focus of activation shifted abruptly to the rostral part of the enlargement. At the stance-swing transition, a transient focus of activity formed in the most caudal part of the lumbosacral enlargement. This was associated with activation of gracilis, posterior biceps, posterior semimembranosus, and semitendinosus muscles. These muscles move the foot back and up to clear the ground during locomotion, a role that could be described as retraction. The spatiotemporal distribution of neuronal activity in the spinal cord during normal locomotion with descending control and sensory inputs intact has not been visualized before. The model can be used in the future to characterize spatiotemporal activity of spinal MNs in the absence of descending and sensory inputs and to compare these to spatiotemporal patterns in spinal MNs in normal locomotion.

Spasticity, resulting in involuntary and sustained contractions of muscles, may evolve in patients with stroke, cerebral palsy, multiple sclerosis, brain injury, and spinal cord injury (SCI). The authors critically review the neural mechanisms that may contribute to spasticity after SCI and assess their likely degree of involvement and relative significance to its pathophysiology. Experimental data from patients and animal models of spasticity as well as computer simulations are evaluated. The current clinical methods used for the management of spasticity and the pharmacological actions of drugs are discussed in relation to their effects on spinal mechanisms. Critical assessment of experimental findings indicates that increased excitability of both motoneurons and interneurons plays a crucial role in pathophysiology of spasticity. New interventions, including forms of spinal electrical stimulation to suppress increased neuronal excitability, may reduce the severity of spasticity and its complications.

We used computer simulations to study the dendritic spatial distribution of low voltage-activated L-type calcium (Ca(V)1.3 type) channels, which mediate hysteretic persistent inward current (PIC) in spinal motoneurons. This study was prompted by the growing experimental evidence of the functional interactions between synaptic inputs and active conductances over the motoneuron dendritic tree. A compartmental cable model of an adult cat alpha-motoneuron was developed in NEURON simulation environment constituting the detailed morphology of type-identified triceps surae alpha-motoneuron and realistic distribution of group Ia afferent-to-motoneuron contacts. Simulations of different distributions of Ca(V)1.3 channels were conducted and the resultant behavior was compared to experimental data. Our results suggest that Ca(V)1.3 channels do not uniformly cover the whole motoneuron dendritic tree. Instead, their distribution is similar to that of synaptic contacts. We found that Ca(V)1.3 channels are primarily localized to a wide intermediate band overlapping with the dendritic Ia-synaptic territory at dendritic distances of 300 to 850 microm (0.62 +/- 0.21lambda) from the soma in triceps surae alpha-motoneurons. These findings explain the functional interaction between synaptic inputs and the Ca(V)1.3 channels over the motoneuron dendritic tree.

Restoring locomotion after spinal-cord injury has been a difficult problem to solve with traditional functional electrical stimulation (FES) systems. Intraspinal microstimulation (ISMS) is a novel approach to FES that takes advantage of spinal-cord locomotor circuits by stimulating in the spinal cord directly. Previous studies in spinal-cord intact cats showed near normal recruitment order, reduced fatigue, and functional, synergistic movements induced by stimulation through a few microwires implanted over a 3-cm region in the lumbosacral cord. The present study sought to test the feasibility of ISMS for restoring locomotion after complete spinal-cord transection. In four adult male cats, the spinal cord was severed at T10, T11, or T12. Two to four weeks later, 30 wires (30 microm, stainless steel) were implanted, under anesthesia, in both sides of the lumbosacral cord. The cats were then decerebrated. Stimulus pulses (40-50 Hz, 200 micros, biphasic) with amplitudes ranging from 1-4x threshold (threshold = 32 +/- 19 microA) were delivered through each unipolar electrode. Kinetics, kinematics, and electromyographic (EMG) measurements were obtained with the cats suspended over a stationary treadmill with embedded force platforms for the hindlimbs. Phasic, interleaved stimulation through electrodes generating flexor or extensor movements produced bilateral weight-bearing stepping of the hindlimbs with ample foot clearance during swing. Minimal changes in kinematics and little fatigue were seen during episodes of 40 consecutive steps. The results indicate that ISMS is a promising technique for restoring locomotion after injury.

Synopsis Spinal cord injuries (SCI) can disrupt communications between the brain and the body, leading to a loss of control over otherwise intact neuromuscular systems. The use of electrical stimulation (ES) of the central and peripheral nervous system can take advantage of these intact neuromuscular systems to provide therapeutic exercise options, to allow functional restoration, and even to manage or prevent many medical complications following SCI. The use of ES for the restoration of upper extremity, lower extremity and truncal functions can make many activities of daily living a potential reality for individuals with SCI. Restoring bladder and respiratory functions and preventing pressure ulcers may significantly decrease the morbidity and mortality following SCI. Many of the ES devices are already commercially available and should be considered by all SCI clinicians routinely as part of the lifelong rehabilitation care plan for all eligible individuals with SCI.

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Intraspinal microstimulation (ISMS) may provide a means for improving motor function in people suffering from spinal cord injuries, head trauma, or stroke. The goal of this study was to determine whether microstimulation of the mammalian spinal cord could generate locomotor-like stepping and feedback-controlled movements of the hindlimbs. Under pentobarbital anesthesia, 24 insulated microwires were implanted in the lumbosacral cord of three adult cats. The cats were placed in a sling leaving all limbs pendent. Bilateral alternating stepping of the hindlimbs was achieved by stimulating through as few as two electrodes in each side of the spinal cord. Typical stride lengths were 23.5 cm, and ample foot clearance was achieved during swing. Mean ground reaction force during stance was 36.4 N, sufficient for load-bearing. Feedback-controlled movements of the cat's foot were achieved by reciprocally modulating the amplitude of stimuli delivered through two intraspinal electrodes generating ankle flexion and extension such that the distance between a sensor on the cat's foot and a free sensor moved back and forth by the investigators was minimized. The foot tracked the displacements of the target sensor through its normal range of motion. Stimulation through electrodes with tips in or near lamina IX elicited movements most suitable for locomotion. In chronically implanted awake cats, stimulation through dorsally located electrodes generated paw shakes and flexion-withdrawals consistent with sensory perception but no weight-bearing extensor movements. These locations would not be suitable for ISMS in incomplete spinal cord injuries. Despite the complexity of the spinal neuronal networks, our results demonstrate that by stimulating through a few intraspinal microwires, near-normal bipedal locomotor-like stepping and feedback-controlled movements could be achieved.

Intraspinal microstimulation (ISMS),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.