Christine J. Dy

Epidural stimulation induced modulation of spinal locomotor networks in adult spinal rats

The importance of the in vivo dynamic nature of the circuitries within the spinal cord that generate locomotion is becoming increasingly evident. We examined the characteristics of hindlimb EMG activity evoked in response to epidural stimulation at the S1 spinal cord segment in complete midthoracic spinal cord-transected rats at different stages of postlesion recovery. A progressive and phase-dependent modulation of monosynaptic (middle) and long-latency (late) stimulation-evoked EMG responses was observed throughout the step cycle. During the first 3 weeks after injury, the amplitude of the middle response was potentiated during the EMG bursts, whereas after 4 weeks, both the middle and late responses were phase-dependently modulated. The middle- and late-response magnitudes were closely linked to the amplitude and duration of the EMG bursts during locomotion facilitated by epidural stimulation. The optimum stimulation frequency that maintained consistent activity of the long-latency responses ranged from 40 to 60 Hz, whereas the short-latency responses were consistent from 5 to 130 Hz. These data demonstrate that both middle and late evoked potentials within a motor pool are strictly gated during in vivo bipedal stepping as a function of the general excitability of the motor pool and, thus, as a function of the phase of the step cycle. These data demonstrate that spinal cord epidural stimulation can facilitate locomotion in a time-dependent manner after lesion. The long-latency responses to epidural stimulation are correlated with the recovery of weight-bearing bipedal locomotion and may reflect activation of interneuronal central pattern-generating circuits.

Spinal cord reflexes induced by epidural spinal cord stimulation in normal awake rats

Motor responses in hindlimb muscles to epidural spinal cord stimulation in normal awake rats during bipedal standing were studied. Stimulation at L2 or S1 induced simultaneous and bilateral responses in the vastus lateralis, semitendinosus, tibialis anterior, and medial gastrocnemius muscles. Stimulation at S1 evoked an early (ER), middle (MR) and late (LR) response: stimulation at L2 elicited only a MR and LR. Vibration and double epidural stimulation testing suggests that the ER is a direct motor response, whereas the MR and LR are mediated synaptically. MR has properties of a monosynaptic reflex, i.e., inhibited during vibration and depressed during the second pulse of a double stimulation. Some components of the LR seem to be mediated by afferents associated with the flexor reflex and probably involve group II afferents. During bipedal treadmill stepping, the MR was modulated in extensors, whereas the LR was modulated in flexors. These results show differential modulation of monosynaptic and polysynaptic reflexes in flexor and extensor motor pools during locomotion. Monosynaptic responses to stimulation at either L2 or S1 generally were amplified in extensors during the stance phase and in flexors during the swing phase of the step cycle. No correlation was found between the ER and the EMG background during stepping, whereas both the MR and LR were closely correlated with the changes in the EMG activity level of the corresponding muscle. These data demonstrate the feasibility of using epidural stimulation for examining monosynaptic and polysynaptic pathways to motor pools associated with multiple muscles during movement and over a prolonged period.

Facilitation of Stepping with Epidural Stimulation in Spinal Rats: Role of Sensory Input

We investigated the role of afferent information during recovery of coordinated rhythmic activity of the hindlimbs in rats with a complete spinal cord section (approximately T8) and unilateral deafferentation (T12–S2) to answer the following questions: (1) Can bilateral stepping be generated with only afferent projections intact on one side? (2) Can the sensory input from the non-deafferented side compensate for the loss of the afferent input from the deafferented side through the crossed connections within the lumbosacral spinal cord? (3) Which afferent projections to the spinal cord from the non-deafferented side predominantly mediate the effect of epidural stimulation to facilitate stepping? Recovery of stepping ability was tested under the facilitating influence of epidural stimulation at the S1 spinal segment, or epidural stimulation plus quipazine, a 5-HT agonist. All chronic spinal rats were able to generate stepping-like patterns on a moving treadmill on the non-deafferented, but not deafferented, side from 3 to 7 weeks after surgery when facilitated by epidural stimulation. Adaptation to the loss of unilateral afferent input was evident at 7 weeks after surgery, when some movements occurred on the deafferented side. Spinal-cord-evoked potentials were observed on both sides, although middle (monosynaptic) and late (long latency) responses were more prominent on the non-deafferented side. The afferent information arising from the non-deafferented side, however, eventually could mediate limited restoration of hindlimb movements on the deafferented side. These data suggest that facilitation of stepping with epidural stimulation is mediated primarily through ipsilateral afferents that project to the locomotor networks.

Modulation of multisegmental monosynaptic responses in a variety of leg muscles during walking and running in humans

Motor responses evoked by stimulating the spinal cord percutaneously between the T11 and T12 spinous processes were studied in eight human subjects during walking and running. Stimulation elicited responses bilaterally in the biceps femoris, vastus lateralis, rectus femoris, medial gastrocnemius, soleus, tibialis anterior, extensor digitorum brevis and flexor digitorum brevis. The evoked responses were consistent with activation of Ia afferent fibres through monosynaptic neural circuits since they were inhibited when a prior stimulus was given and during tendon vibration. Furthermore, the soleus motor responses were inhibited during the swing phase of walking as observed for the soleus H‐reflex elicited by tibial nerve stimulation. Due to the anatomical site and the fibre composition of the peripheral nerves it is difficult to elicit H‐reflex in leg muscles other than the soleus, especially during movement. In turn, the multisegmental monosynaptic responses (MMR) technique provides the opportunity to study modulation of monosynaptic reflexes for multiple muscles simultaneously. Phase‐dependent modulation of the MMR amplitude throughout the duration of the gait cycle period was observed in all muscles studied. The MMR amplitude was large when the muscle was activated whereas it was generally reduced, or even suppressed, when the muscle was quiescent. However, during running, there was a systematic anticipatory increase in the amplitude of the MMR at the end of swing in all proximal and distal extensor muscles. The present findings therefore suggest that there is a general control scheme by which the transmission in the monosynaptic neural circuits is modulated in all leg muscles during stepping so as to meet the requirement of the motor task.

Phase-dependent modulation of percutaneously elicited multisegmental muscle responses after spinal cord injury

Phase-dependent modulation of monosynaptic reflexes has been reported for several muscles of the lower limb of uninjured rats and humans. To assess whether this step-phase-dependent modulation can be mediated at the level of the human spinal cord, we compared the modulation of responses evoked simultaneously in multiple motor pools in clinically complete spinal cord injury (SCI) compared with noninjured (NI) individuals. We induced multisegmental responses of the soleus, medial gastrocnemius, tibialis anterior, medial hamstring, and vastus lateralis muscles in response to percutaneous spinal cord stimulation over the Th11-Th12 vertebrae during standing and stepping on a treadmill. Individuals with SCI stepped on a treadmill with partial body-weight support and manual assistance of leg movements. The NI group demonstrated phase-dependent modulation of evoked potentials in all recorded muscles with the modulation of the response amplitude corresponding with changes in EMG amplitude in the same muscle. The SCI group demonstrated more variation in the pattern of modulation across the step cycle and same individuals in the SCI group could display responses with a magnitude as great as that of modulation observed in the NI group. The relationship between modulation and EMG activity during the step cycle varied from noncorrelated to highly correlated patterns. These findings demonstrate that the human lumbosacral spinal cord can phase-dependently modulate motor neuron excitability in the absence of functional supraspinal influence, although with much less consistency than that in NI individuals.

Spinal segment-specific transcutaneous stimulation differentially shapes activation pattern among motor pools in humans

Transcutaneous and epidural electrical spinal cord stimulation techniques are becoming more valuable as electrophysiological and clinical tools. Recently, we observed selective activation of proximal and distal motor pools during epidural spinal stimulation. In the present study, we hypothesized that the characteristics of recruitment curves obtained from leg muscles will reflect a relative preferential activation of proximal and distal motor pools based on their arrangement along the lumbosacral enlargement. The purpose was to describe the electrophysiological responses to transcutaneous stimulation in leg muscles innervated by motoneurons from different segmental levels. Stimulation delivered along the rostrocaudal axis of the lumbosacral enlargement in the supine position resulted in a selective topographical recruitment of proximal and distal leg muscles, as described by threshold intensity, slope of the recruitment curves, and plateau point intensity and magnitude. Relatively selective recruitment of proximal and distal motor pools can be titrated by optimizing the site and intensity level of stimulation to excite a given combination of motor pools. The slope of the recruitment of particular muscles allows characterization of the properties of afferents projecting to specific motoneuron pools, as well as to the type and size of the motoneurons. The location and intensity of transcutaneous spinal electrical stimulation are critical to target particular neural structures across different motor pools in investigation of specific neuromodulatory effects. Finally, the asymmetry in bilateral evoked potentials is inevitable and can be attributed to both anatomical and functional peculiarities of individual muscles or muscle groups.

The Utility of Interappendicular Connections in Bipedal Locomotion

Homo sapiens constitute the only currently obligate bipedal mammals and, as it stands, upright bipedal locomotion is a defining characteristic of humans. Indeed, while the evolution to bipedalism has allowed for the upper limbs to be liberated from ground contact during ambulation, their role in locomotion is far from obsolete. Rather, there is reason to believe that arm swing offers important mechanical and neurological advantages to bipedal locomotion. In this short review, we present some compelling findings on the neural connections between the arms and legs during human locomotion. We begin with a description of the importance of arm swing during walking from a mechanical perspective. Then, we examine evidence for the existence of interappendicular connections that converge along with peripheral afferents, descending inputs, and propriospinal projections, onto the neural circuits innervating the muscles of the arms and legs. The varied effects of interappendicular coupling on the neural control of locomotion are also examined in cases of neurological injury. We use the insight gained from these collected works as well as those from our own studies on locomotor training to discuss strategies to use interappendicular connections to rehabilitate walking in individuals experiencing loss of function after debilitating spinal cord injury.

Energy Expenditure and Heart Rate Responses to Increased Loading in Individuals With Motor Complete Spinal Cord Injury Performing Body Weight–Supported Exercises

OBJECTIVE To examine acute metabolic and heart rate responses in individuals with motor complete spinal cord injury (SCI) during stepping and standing with body weight support (BWS). DESIGN Cohort study. SETTING Therapeutic exercise research laboratory. PARTICIPANTS Nonambulatory individuals with chronic, motor complete SCI between T5 and T12 (n=8) and healthy, able-bodied controls (n=8). INTERVENTION Not applicable. MAIN OUTCOME MEASURES Oxygen consumption (V˙o2) and heart rate. RESULTS Individuals with motor complete SCI performed standing and stepping exercises in a BWS system with manual assistance of lower body kinematics. V˙o2 and heart rate responses were assessed in relation to level of BWS. Weight support was provided by an overhead lift at high (≥50% BWS) or low (20%-35% BWS) levels during stepping and standing. Although participants with motor complete SCI were unable to stand or step without assistance, levels of V˙o2 and heart rate were elevated by 38% and 37%, respectively, when load was maximized during stepping (ie, low BWS). Participants without an SCI (able-bodied group) had a similar acute response to exercise. None of the participants met the target range for V˙o2 response in any of the tasks. However, stepping was sufficient to enable half of the participants in the SCI group to attain the target range for heart rate response to exercise. CONCLUSIONS Individuals with motor complete SCI exhibit cardiovascular responses during body weight-supported exercise. Findings indicate that body weight-supported stepping provides a minimal cardiovascular challenge for individuals with paraplegia. Emphasis on low weight support during locomotor training can trigger additional heart rate adaptations.