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.

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.

Spinal cord injury (SCI) often results in the loss of the ability to stand. The goal of this study was to implement a functional electrical stimulation (FES) system for restoring prolonged periods of standing after SCI. For this purpose, we tested two control strategies: open-loop and closed-loop control, and two stimulation paradigms: non-interleaved intramuscular stimulation (IM-S) and interleaved intraspinal microstimulation (ISMS). The experiments were conducted in anesthetized cats. Stimulation was applied to the muscles through IM-S electrodes implanted in the main knee and ankle extensor muscles, or to the spinal cord through ultra-fine ISMS wires implanted within the ventral horn of the lumbosacral enlargement. The cats were partially supported over parallel force plates and accelerometers were secured to the hindlimbs above and below the ankle joint. Ground reaction forces and knee and ankle joint angles were measured by the force plates and accelerometers, respectively. The closed-loop controller used these feedback signals to modulate the amplitude of stimulation applied to the extensor muscles. The open-loop controller applied constant levels of stimulation which were determined before the onset of each trial. The duration of standing achieved using closed-loop control of IM-S was significantly longer than that achieved with open-loop control (approximately 2 times longer). The increase in the duration of standing corresponded with a decrease in the rate of force decay and a lower average injected current during closed-loop control. Standing was further improved with the use of ISMS. Closed-loop control of interleaved ISMS resulted in a period of standing > 3 times longer than the best trial generated using non-interleaved IM-S. There was also a significant improvement in the balance of force between the two hindlimbs. The results suggest that a system which uses closed-loop control in conjunction with interleaved ISMS could achieve prolonged FES standing in people with SCI.

It is commonly accepted that locomotor-related neuronal circuitry resides in the lumbosacral spinal cord. Pharmacological agents, epidural electrical stimulation, and sensory stimulation can be used to activate these instrinsic networks in in vitro neonatal rat and in vivo cat preparations. In this study, we investigated the use of low-level tonic intraspinal microstimulation (ISMS) as a means of activating spinal locomotor networks in adult cats with complete spinal transections. Trains of low-amplitude electrical pulses were delivered to the spinal cord via groups of fine microwires implanted in the ventral horns of the lumbosacral enlargement. In contrast to published reports, tonic ISMS applied through microwires in the caudal regions of the lumbosacral enlargement (L7-S1) was more effective in eliciting alternating movements in the hindlimbs than stimulation in the rostral regions. Possible mechanisms of action of tonic ISMS include depolarization of locally oscillating networks in the lumbosacral cord, backfiring of primary afferents, or activation of propriospinal neurons.

The physiological control of stepping is governed both by signals descending from supraspinal systems and by circuitry residing within the lumbosacral spinal cord. The goal of this study was to evaluate the capacity of physiologically based controllers to restore functional overground locomotion after neurological damage, such as spinal cord injury when used in conjunction with functional electrical stimulation. For this purpose we implemented and tested two controllers: 1) an intrinsically timed system that generated a predetermined rhythmic output and 2) a sensory-based system that used feedback signals to make appropriate transitions between the unloaded (flexion) and loaded (extension) phases of the gait cycle. A third controller, a combination of the intrinsically timed and sensory-driven controllers, was implemented and two sessions were conducted to demonstrate the functional advantages of this approach. The controllers were tested in anesthetized cats, implanted with intramuscular electrodes in six major extensor and flexor muscles of the hindlimbs. The cats were partially supported on a sliding trolley that was propelled by the hindlimbs along a 2.5-m instrumented walkway. Ground reaction forces and limb positions were measured by force plates in the walkway and by accelerometers secured to the legs of the cat, respectively. The controllers were used to generate patterns of stimulation that would elicit alternating flexor (swing) and extensor (stance) movements in the hindlimbs. Using either the intrinsically timed or sensory-driven controllers, the cats were able to travel a distance of 2.5 m, taking five to 12 steps. Functional stepping sequences were more easily achieved using the intrinsically timed controller as the result of a lower sensitivity to the selection of initial stimulation parameters. However, unlike the sensory-driven controller, the intrinsically timed controller was unable to adjust to overcome walkway resistance and muscle fatigue. Neither system was consistently able to ensure load-bearing stepping. Therefore we propose the use of a "combined controller" that relies heavily on intrinsic timing but that can be reset based on sensory signals. A combined controller such as this one may provide the best solution for restoring robust overground locomotion after spinal cord injury.

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In this paper, we examine the control signals that are required to generate stepping using two different intraspinal microstimulation (ISMS) paradigms and discuss the theoretical feasibility of controlling ISMS-evoked stepping using a brain computer interface. Tonic (constant amplitude) and phasic (modulated amplitude) ISMS protocols were used to produce stepping in the hind limbs of paralyzed cats. Low-amplitude tonic ISMS activated a spinal locomotor-like network that resulted in bilateral stepping of the hind limbs. Phasic ISMS generated coordinated stepping by simultaneously activating flexor synergies in one limb coupled with extensor synergies in the other. Using these ISMS paradigms, we propose that one or two independent cortical signals will be adequate for controlling ISMS-induced stepping after SCI.