Ambulatory function in motor incomplete spinal cord injury: a magnetic resonance imaging study of spinal cord edema and lower extremity muscle morphometry.

STUDY DESIGN: This research utilized a cross-sectional design. OBJECTIVES: Spinal cord edema length has been measured with T2-weighted sagittal MRI to predict motor recovery following spinal cord injury. The purpose of our study was to establish the correlational value of axial spinal cord edema using T2-weighted MRI. We hypothesized a direct relationship between the size of damage on axial MRI and walking ability, motor function and distal muscle changes seen in motor incomplete spinal cord injury (iSCI). SETTING: University-based laboratory in Chicago, IL, USA. METHODS: Fourteen participants with iSCI took part in the study. Spinal cord axial damage ratios were assessed using axial T2-weighted MRI. Walking ability was investigated using the 6-min walk test and daily stride counts. Maximum plantarflexion torque was quantified using isometric dynomometry. Muscle fat infiltration (MFI) and relative muscle cross-sectional area (rmCSA) were quantified using fat/water separation magnetic resonance imaging. RESULTS: Damage ratios were negatively correlated with distance walked in 6 min, average daily strides and maximum plantarflexion torque, and a negative linear trend was found between damage ratios and lower leg rmCSA. While damage ratios were not significantly correlated with MFI, we found significantly higher MFI in the wheelchair user participant group compared to community walkers. CONCLUSIONS: Damage ratios may be useful in prognosis of motor recovery in spinal cord injury. The results warrant a large multi-site research study to investigate the value of high-resolution axial T2-weighted imaging to predict walking recovery following motor incomplete spinal cord injury.

Historical reflections on the afterhyperpolarization--firing rate relation of vertebrate spinal neurons.

In mammalian spinal motoneurons (MNs), the slow component of the afterhyperpolarization (AHP) that follows the spike of each action potential is a major but not the sole determinant of the cells' firing rate. In this brief historical review, we emphasize four points about the AHP-firing rate relation. (1) There is a relatively sparse literature across vertebrates that directly addresses this topic. (2) After the advent of intracellular recording in the early 1950s, there was evidence from mammals to the contrary of an idea that subsequently became prevalent: that the high-firing rates attainable by spinal interneurons (INs) and low-threshold MNs was attributable to their small AHP at rheobase. (3) Further work is needed to determine whether our present findings on the AHP-firing rate relation of turtle cells generalize to the spinal neurons of other vertebrate species. (4) Relevant to point 3, substantial in vivo and in vitro work is potentially available in raw data used in reports on several mammalian and non-mammalian vertebrates. In summary, the factors in addition to the slow AHP that help determine spinal INs and MN firing rate deserve further evaluation across vertebrates, with relevant data already potentially available in several laboratories.

Measurement and nature of firing rate adaptation in turtle spinal neurons.

There is sparse literature on the profile of action potential firing rate (spike-frequency) adaptation of vertebrate spinal motoneurons, with most of the work undertaken on cells of the adult cat and young rat. Here, we provide such information on adult turtle motoneurons and spinal ventral-horn interneurons. We compared adaptation in response to intracellular injection of 30-s, constant-current stimuli into high-threshold versus low-threshold motoneurons and spontaneously firing versus non-spontaneously-firing interneurons. The latter were shown to possess some adaptive properties that differed from those of motoneurons, including a delayed initial adaptation and more predominant reversal of adaptation attributable to plateau potentials. Issues were raised concerning the interpretation of changes in the action potentials' afterhyperpolarization shape parameters throughout spike-frequency adaptation. No important differences were demonstrated in the adaptation of the two motoneuron and two interneuron groups. Each of these groups, however, was modeled by its own unique combination of action potential shape parameters for the simulation of its 30-s duration of spike-frequency adaptation. Also, for a small sample of the very highest-threshold versus lowest-threshold motoneurons, the former group had significantly more adaptation than the latter. This finding was like that shown previously for cat motoneurons supplying fast- versus slow twitch motor units.

Afterhyperpolarization-firing rate relation of turtle spinal neurons.

This study addressed the afterhyperploarization-firing rate relationship of unanesthetized turtle spinal motoneurons and interneurons. The afterhyperploarization of their solitary action potential at rheobase was compared to that during the cells' minimum and maximum firing rates. Like previous mammalian findings, afterhyperpolarization duration and area at rheobase were 32 and 19% less for high- versus low-threshold motoneurons. Contrariwise, maximum firing rate was two times less for the high-threshold group. Other new findings were that for high- versus low-threshold interneurons, afterhyperpolarization duration and area were 25 and 95% less, and maximum firing rate 21% higher for the high-threshold group. For combined motoneurons versus interneurons, there were no differences in afterhyperpolarization duration and area at rheobase, whereas maximum firing rate was 265% higher for the interneurons. For high-threshold motoneurons alone, there were significant associations between minimum firing rate and afterhyperpolarization duration and area measured at rheobase. In summary, this study showed that (1) the afterhyperploarization values of both turtle spinal motoneurons and interneurons at rheobase provided little indication of their corresponding values at the cells' minimum and maximum firing states, and (2) the evolution of afterhyperploarization from rheobase to maximum firing state differed both qualitatively and quantitatively for motoneurons versus interneurons.

Contribution of muscle afferents to prolonged flexion withdrawal reflexes in human spinal cord injury.

The contribution of force-sensitive muscular afferents to prolonged flexion withdrawal reflexes, or flexor spasms, after human spinal cord injury (SCI) was investigated. In three separate experimental conditions, flexion reflexes were triggered in subjects with SCI using trains of electrocutaneous stimuli delivered at the foot and lower leg and compared with reflexes elicited via intramuscular (i.m.) electrical stimuli. In the first experiment, flexion reflexes were elicited using i.m. stimuli to the tibialis anterior (TA) in the majority of subjects tested. The ratio of peak isometric ankle to hip torques during i.m.-triggered reflexes were proportionally similar to those evoked by electrocutaneous foot or shank stimulation, although the latency to onset and peak flexion torques were significantly longer with i.m. stimulation. In the second experiments, the amplitude and frequency of i.m. TA stimulation were varied to alter the stimulus-induced muscle torque. Peak ankle and hip torques generated during the flexion reflex responses were correlated to a greater extent with stimulus-induced muscle torques as compared with the modulated stimulus parameters. In the third experimental series, i.m. stimuli delivered to the gastrocnemius (GS) elicited flexion reflexes in approximately half of the subjects tested. The combined data indicate a potentially prominent role of the stimulus-induced muscle contraction to the magnitude and latency of flexor reflex behaviors after i.m. TA stimulation. Results after i.m. GS stimulation indicate multi-joint flexion reflexes can also be elicited, although to a lesser extent than i.m. TA stimulation.

Windup of flexion reflexes in chronic human spinal cord injury: a marker for neuronal plateau potentials?

The physiological basis of flexion spasms in individuals after spinal cord injury (SCI) may involve alterations in the properties of spinal neurons in the flexion reflex pathways. We hypothesize that these changes would be manifested as progressive increases in reflex response with repetitive stimulus application (i.e., "windup") of the flexion reflexes. We investigated the windup of flexion reflex responses in 12 individuals with complete chronic SCI. Flexion reflexes were triggered using trains of electrical stimulation of plantar skin at variable intensities and inter-stimulus intervals. For threshold and suprathreshold stimulation, windup of both peak ankle and hip flexion torques and of integrated tibialis anterior electromyographic activity was observed consistently in all patients at inter-stimulus intervals < or =3 s. For subthreshold stimuli, facilitation of reflexes occurred only at intervals < or =1 s. Similarly, the latency of flexion reflexes decreased significantly at intervals < or =1 s. Patients that were receiving anti-spasticity medications (e.g., baclofen) had surprisingly larger windup of reflex responses than those who did not take such medications, although this difference may be related to differences of spasm frequency between the groups of subjects. The results indicate that the increase in spinal neuronal excitability following a train of electrical stimuli lasts for < or =3 s, similar to previous studies of nociceptive processing. Such long-lasting increases in flexion reflex responses suggest that cellular mechanisms such as plateau potentials in spinal motoneurons, interneurons, or both, may partially mediate spinal cord hyperexcitability in the absence of descending modulatory input.

Electrophysiological properties of spinal motoneurons in the adult turtle.

The purpose of this study was to develop a scheme for classifying turtle motoneurons, such that their properties could be compared to those of other vertebrate species, including, in particular, the cat. A 130-cell sample of turtle motoneurons was provisionally classified into four groups (1-4) on the basis of a cluster analysis of the cells' intracellularly recorded input resistance, rheobase, and slope of their stimulus current-spike frequency relation. These measurements, using sharp microelectrodes and an in vitro spinal cord slice preparation, were particularly robust. It is argued that the cat counterpart of our turtle type 1, 2, and 3 motoneurons innervate slow-twitch muscle fibers, fast-twitch-oxidative fibers, and fast-twitch-glycolytic fibers, respectively. Our turtle type 4 motoneuron is thought analogous to a particularly high-threshold cat and human cell that innervates highly fatigable fast-twitch muscle fibers in both species. Our turtle type 1 category may include cells that innervate non-twitch muscle fibers, which are found in other non-mammalian vertebrates. To advance comparative spinal cord neurobiology, the present results invite comparison to the motoneurons of other vertebrate species, which have yet to be subjected to similar or other classification procedures.

Associations between the passive, transitional, and active properties of turtle motoneurons.

The literature on the associations between the properties of vertebrate spinal motoneurons (MNs) is dominated by studies on the deeply anesthetized cats, with the measurements made with low-resistance microelectrodes, and limited largely to passive (cell at rest) vs. transitional (rest-to-rheobase action potential) properties. There has been far less consideration of active (repetitive-firing) firing properties, like the parameters of the stimulus current-spike frequency (I-f) relation. The present study shows that several conventionally accepted associations among MN properties, including those between the determining and defining parameters of the I-f relation, are either absent or weak when the measurements are made with high-resistance microelectrodes, and using unanesthetized slices of the adult turtle's spinal cord. The strength of such associations is even further diminished when the MNs are exhibiting modulator-induced plateau potentials. These novel and potentially controversial findings invite consideration of their relation to literature on MN repetitive firing properties, as recorded with sharp microelectrodes in spinal and brainstem slices of several other vertebrate species, including neonatal and adult mammals.

Electrophysiological and morphological properties of neurons in the ventral horn of the turtle spinal cord.

In this report, we present recent findings on the electrophysiological and morphological properties of spinal motoneurons (MNs) and interneurons (INs) of the adult turtle which were studied in slices of the spinal cord. The range of values for the measured electrophysiological parameters in 96 tested cells included: resting potential, -57 to -83 mV; input resistance, 2.5-344 M omega; time constant, 2.5-63 ms; rheobase current, 0.04-5.3 nA; after-hyperpolarization (AHP) duration, 72-426 ms; AHP half-decay time; 11-212 ms; and, slope of the stimulus current-spike frequency relationship, 3.4-235 Hz/nA. For another 20 cells, we made both morphological and electrophysiological measurements (the latter values within the above ranges). Their ranges in morphological properties included: soma diameter, 20-54 microm; soma surface area, 299-2045 microm2; soma volume, 2.3-45 microm3 x 10(4); rostro-caudal dendritic projection distance, 150-1200 microm; and, sum of dendritic lengths, 1.5-16 microm x 10(3). The emphasized findings include: 1) the quality and robustness of the intracellular recordings, which enabled accurate measurement of the action potential's shape parameters (spike, afterhyperpolarization [AHP]); 2) the substantial AHP of the INs' AP; 3) no single action-potential shape parameter (nor combination of parameters) being cardinal for its (or their combined) changes matching the profile of the initial and later phases of spike-frequency adaptation; 4) the utility and flexibility of a cluster analysis (using varying combinations of passive, transitional and active cell properties) for providing a provisional classification of low (like cat S) and high (like cat F) threshold MNs, and groups of INs with non-spontaneous versus spontaneous discharge; 5) the clear-cut morphological confirmation of the provisional classification strategy; 6) the basis for testing the possibility that one of the provisionally classified MN types innervates non-twitch muscle fibers; and 7) the heuristic value of comparing the properties of MNs versus INs across vertebrate species, with an emphasis on the lamprey, turtle, and cat.

Properties of spinal motoneurons and interneurons in the adult turtle: provisional classification by cluster analysis.

The purpose of the present study was to compare, in motoneurons (MNs) vs. interneurons (INs), selected passive, transitional, and active (firing) properties, as recorded in slices of lumbosacral spinal cord (SC) taken from the adult turtle. The cells were provisionally classified on the basis of (1) the presence (in selected INs) or absence (MNs and other INs) of spontaneous discharge, (2) a cluster analysis of selected properties of the nonspontaneously firing cells, (3) a comparison to previous data on turtle MNs and INs, and (4) a qualitative comparison of the results with those reported for other vertebrate species (lamprey, cat). The provisional nomenclature accommodated properties appropriate for solely MNs (Main MN group) vs. nonspontaneously firing INs (Main IN-N) vs. spontaneously firing INs (IN-S) and for neurons with two degrees of intermediacy between the Main MN and the Main IN-N groups (Overlap MN, Overlap MN/IN). Morphological reconstructions of additional cells, which had been injected with biocytin during the electrophysiological tests, were shown to provide clear-cut support for the provisional classification procedure. The values for the measured parameters in the 96 tested cells covered the spectrum reported previously across adult vertebrate species and were robust in measurements made on different SC slices up to 5 days after their removal from the host animal. The interspecies comparisons permitted the predictions that (1) our Main MN and Overlap MN cells would be analogous to two MN types that innervate fast-twitch and slow-twitch skeletomotor muscle fibers, respectively, in the cat, and (2) the MNs in our Overlap MN/IN group probably innervate slow (nontwitch, tonic) muscle fibers whose presence has recently been established in the turtle hindlimb. In summary, the results bring out the utility of the SC slice preparation of the turtle for study of spinal motor mechanisms in adult tetrapod vertebrates, particularly as an adjunct to the in vivo cat, because of the ease with which robust measurements can be made of the active properties of both MNs and INs.