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Biomedical subjects

Vivian K Mushahwar

Publications and source records attributed to Vivian K Mushahwar.

9 recordsLinked to original sources

Physiologically based controller for generating overground locomotion using functional electrical stimulation.

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.

Animals↗

Intraspinal microstimulation using cylindrical multielectrodes.

A cylindrical multielectrode system specifically designed for intraspinal microstimulation was mechanically and electrically evaluated in the ventral horn of the feline lumbo-sacral spinal cord. Electrode insertions proved to be straight as evaluated from radiographs. Impedances were measured in situ and force recruitment curves from quadriceps muscles were collected over a wide range of stimulus parameters. For a given charge, higher current amplitudes produced greater forces than proportionally longer pulse durations, indicating that charge is not the sole indicator of evoked force in applications utilizing electrical stimulation. Overlap measurements for calculating current-distance constants were collected at a variety of current amplitudes, electrode pair separations, and pair orientations in the spinal grey matter. Forces obtained in the majority of these trials demonstrated an order effect, presumably due to asymmetric neuronal connectivity within the spinal cord. In the cases showing no order effect, the dorso-ventral electrode pair orientation yielded a higher average current-distance constant (278 microA/mm2) than either the medio-lateral or rostro-caudal electrode pair orientations (197 microA/mm2). Specifications of an array of cylindrical multielectrodes for use in future intraspinal microstimulation prostheses were updated.

Animals↗

Could cortical signals control intraspinal stimulators? A theoretical evaluation.

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.

Animals↗

Locomotor-related networks in the lumbosacral enlargement of the adult spinal cat: activation through intraspinal microstimulation.

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.

Action Potentials↗

Simulation of Ca2+ persistent inward currents in spinal motoneurones: mode of activation and integration of synaptic inputs.

The goal of this study was to investigate the nature of activation of the dendritic calcium persistent inward current (Ca(2+) PIC) and its contribution to the enhancement and summation of synaptic inputs in spinal motoneurones. A compartmental cable model of a cat alpha-motoneurone was developed comprising the realistic dendritic distribution of Ia-afferent synapses and low-voltage-activated L-type calcium (Ca(v)1.3) channels distributed over the dendrites in a manner that was previously shown to match a wide set of experimental measurements. The level of synaptic activation was systematically increased and the resulting firing rate, somatic and dendritic membrane potentials, dendritic Ca(v)1.3 channel conductance, and dendritic Ca(2+) PIC were measured. Our simulation results suggest that during cell firing the dendritic Ca(2+) PIC is not activated in an all-or-none manner. Instead, it is initially activated in a graded manner with increasing synaptic input until it reaches its full activation level, after which additional increases in synaptic input result in minimal changes in the Ca(2+) PIC (PIC saturated). The range of graded activation of Ca(2+) PIC occurs when the cell is recruited and causes a steep increase in the firing frequency as the synaptic current is increased, coinciding with the secondary range of the synaptic frequency-current (F-I) relationship. Once the Ca(2+) PIC is saturated the slope of the F-I relationship is reduced, corresponding to the tertiary range of firing. When the post-spike afterhyperpolarization (AHP) is blocked, either directly by blocking the calcium-activated potassium channels, or indirectly by blocking the sodium spikes, the PIC is activated in an all-or-none manner with increasing synaptic input. Thus, the AHP serves to limit the depolarization of the cell during firing and enables graded, rather than all-or-none, activation of the Ca(2+) PIC. The graded activation of the Ca(2+) PIC with increasing synaptic input results in a graded (linear) enhancement and linear summation of synaptic inputs. In contrast, the saturated Ca(2+) PIC enhances synaptic inputs by a constant amount (constant current), and leads to less-than linear summation of multiple synaptic inputs. These model predictions improve our understanding of the mode of activation of the dendritic Ca(2+) PIC and its role in the enhancement and integration of synaptic inputs.

Animals↗

Simulation of dendritic CaV1.3 channels in cat lumbar motoneurons: spatial distribution.

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.

Animals↗

Movements elicited by electrical stimulation of muscles, nerves, intermediate spinal cord, and spinal roots in anesthetized and decerebrate cats.

Electrical stimulation offers the possibility of restoring motor function of paralyzed limbs after spinal-cord injury or stroke, but few data are available to compare possible sites of stimulation, such as muscle, nerve, spinal roots, or spinal cord. The aim of this study was to establish some characteristics of stimulation at these sites in the anesthetized and midcollicular decerebrate cat. The hind limb was constrained to move in the sagittal plane against a spring load. Ventral-root stimulation only produced movements down and back; the direction moved systematically backward the more caudal the stimulated roots. In contrast, dorsal-root stimulation only produced movements up and forward. Thus, neither method alone could produce the full range of normal movements. Muscle, nerve, and intraspinal stimulation within the intermediate regions of the gray matter generated discrete, selective movements in a wide range of directions. Muscle stimulation required an order of magnitude more current. Single microwire electrodes located in the spinal gray matter could activate a synergistic group of muscles, and generally had graded recruitment curves, but the direction of movement occasionally changed abruptly as stimulus strength increased. Nerve stimulation produced the largest movements against the spring load (>80% of the passive range of motion) and was the most reproducible from animal to animal. However, recruitment curves with nerve stimulation were quite steep, so fine control of movement might be difficult. The muscle, nerve, and spinal cord all seem to be feasible sites to restore motor function. The pros and cons from this study may be helpful in deciding the best site for a particular application, but further tests are needed in the chronically transected spinal cord to assess the applicability of these results to human patients.

Anesthesia↗

Intraspinal microstimulation generates functional movements after spinal-cord injury.

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.

Animals↗

Intraspinal micro stimulation generates locomotor-like and feedback-controlled movements.

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.

Animals↗