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Biomedical subjects

R R Roy

Publications and source records attributed to R R Roy.

At least 19 recordsLinked to original sources

Is spinal cord isolation a good model of muscle disuse?

The patterns of normal daily activity that are required to maintain normal skeletal muscle properties remain unknown. The present study was designed to determine whether spinal cord isolation can be used as a reliable experimental model of neuromuscular inactivity, that is, as a baseline for the absence of activity. Electromyograms (EMGs) were recorded from selected hindlimb muscles of unanesthetized rats over 24-hour periods before and 7, 30, 60, and 90 days after surgical isolation of the lumbar spinal cord. Our data indicate that some rat slow muscle fibers pre-surgery were activated for less than 3 hours per day. Spinal cord isolation (SI) reduced the mean daily integrated EMG (IEMG) and daily EMG duration in the primary slow extensor muscle (soleus) to <1% of control, and in the primary fast extensor muscles [medial gastrocnemius (MG) and vastus lateralis (VL)] to <2% of control. These parameters were decreased to <8% and 3% of control, respectively, in a primary fast flexor muscle, the tibialis anterior (TA). From 30 to 90 days post-SI, the mean amplitudes of the spontaneous EMG bursts were relatively normal in the soleus, increased approximately 2-fold in the MG and VL, and increased approximately 4-fold in the TA. Some evidence of the normal antagonistic flexor-extensor relationship was apparent in the brief periods of recorded activity post-SI. These results indicate that SI eliminates nearly all of the normal EMG activity in the hindlimb muscles in the presence of relatively normal muscle innervation and functional intraspinal neural circuitry.

Action Potentials↗

Differential modulation of myosin heavy chain phenotype in an inactive extensor and flexor muscle of adult rats.

The effects of chronic neuromuscular inactivity on the phenotype and size of muscle fibres in a fast ankle extensor (medial gastrocnemius, MG) and a fast ankle flexor (tibialis anterior, TA) muscle of the rat hindlimb were determined. Inactivity was produced by spinal cord isolation (SI), i.e. complete spinal cord transections at a mid-thoracic and high sacral level and bilateral deafferentation between the transection sites. After 90 days of SI, the MG and TA muscle weights were 53 and 45% lower than in age-matched controls. Overall mean fibre sizes in the deep (close to the bone) and superficial (away from the bone) regions were approximately 60 and 65% smaller in the MG and approximately 40 and 50% smaller in the TA of SI than control rats, respectively. The myosin heavy chain (MHC) composition shifted towards the faster isoforms after SI: the MG showed an increase in both types IIx (20%) and IIb (23%), whereas the TA showed a marked increase in type IIx (94%) and a decrease in type IIb (18%) MHC. Both muscles in SI rats showed no type IIa and only one MG muscle had approximately 5% type I MHC. These results show that prolonged inactivity has a stronger effect on a fast extensor compared with a fast flexor in the rat hindlimb. The larger decrease in mass and fibre size in the MG than the TA most probably reflects the larger impact of chronic inactivity on the normally more highly recruited extensor than flexor muscle. The primary shift to type IIb MHC in the MG and type IIx MHC in the TA indicate a different default mode for an inactive extensor vs. flexor muscle, and may reflect differing activity-independent neural influences, i.e. neurotrophic factors, on muscle fibre phenotype in extensors vs. flexors.

Animals↗

Plasticity of functional connectivity in the adult spinal cord.

This paper emphasizes several characteristics of the neural control of locomotion that provide opportunities for developing strategies to maximize the recovery of postural and locomotor functions after a spinal cord injury (SCI). The major points of this paper are: (i) the circuitry that controls standing and stepping is extremely malleable and reflects a continuously varying combination of neurons that are activated when executing stereotypical movements; (ii) the connectivity between neurons is more accurately perceived as a functional rather than as an anatomical phenomenon; (iii) the functional connectivity that controls standing and stepping reflects the physiological state of a given assembly of synapses, where the probability of these synaptic events is not deterministic; (iv) rather, this probability can be modulated by other factors such as pharmacological agents, epidural stimulation and/or motor training; (v) the variability observed in the kinematics of consecutive steps reflects a fundamental feature of the neural control system and (vi) machine-learning theories elucidate the need to accommodate variability in developing strategies designed to enhance motor performance by motor training using robotic devices after an SCI.

Aging↗

Basal and evoked levels of bioassayable growth hormone are altered by hindlimb unloading.

Bioassayable growth hormone (BGH) in rats is released in large quantities from the pituitary in response to the activation of large, proprioceptive afferent fibers from fast and mixed fiber-type hindlimb musculature. We hypothesized that hindlimb unloading (HU) of adult male rats would 1) reduce the basal levels of plasma BGH, and 2) abolish stimulus-induced BGH release. Rats were exposed to HU for 1, 4, or 8 wk. Plasma and pituitaries were collected under isoflurane anesthesia for hormone analyses. Additionally, at 4 and 8 wk, a subset of rats underwent an in situ electrical stimulation (Stim) of tibial nerve proprioceptive afferents. Basal plasma BGH levels were significantly reduced (-51 and -23%) after 1 and 8 wk of HU compared with ambulatory controls (Amb). Although Amb-Stim rats exhibited increased plasma BGH levels (88 and 143%) and decreased pituitary BGH levels (-27 and -22%) at 4 and 8 wk, respectively, stimulation in HU rats had the opposite effect, reducing plasma BGH (-25 and -33%) and increasing pituitary BGH levels (47 and 10%) relative to HU alone at 4 and 8 wk. The 22-kDa form of GH measured by immunoassay and the plasma corticosterone, T3, T4, and testosterone levels were unchanged by HU or Stim at all time points. These data suggest that BGH synthesis and release from the pituitary are sensitive both to chronically reduced neuromuscular loading and to acute changes in neuromuscular activation, independent of changes in other circulating hormones. Thus BGH may play a role in muscle, bone, and metabolic adaptations that occur in response to chronically unloaded states.

Animals↗

Hindlimb stepping movements in complete spinal rats induced by epidural spinal cord stimulation.

The locomotor ability of the spinal cord of adult rats deprived of brain control was tested by epidural spinal cord stimulation. The studies were performed on six rats that had a complete spinal cord transection (T7-T9) and epidural electrode implantations 2-3 weeks before testing was initiated. The stimulating epidural electrodes were implanted at the T12-L6 spinal segments. Epidural electrical stimulation of the dorsal surface of the spinal cord at frequencies between 1 and 50 Hz and intensities between 1 and 10 V without any pharmacological facilitation was used. Stimulation at each of the lumbar spinal cord segments elicited some rhythmic activity in the hindlimbs. However, stimulation at most segmental levels usually evoked activity in only one leg and was maintained for short periods of time (< 10s). Bilateral hindlimb locomotor activity was evoked most often with epidural stimulation at 40-50 Hz applied at the L2 segment. A necessary condition for initiation of locomotor activity was providing a specific amount (at least 5%) of body weight support. Therefore, the rat spinal cord isolated from brain control is capable of producing bilateral stepping patterns induced most readily by epidural stimulation applied at the L2 spinal segment. Furthermore, the induced stepping patterns were dependent on sensory feedback associated with weight bearing.

Animals↗

L1 CAM expression is increased surrounding the lesion site in rats with complete spinal cord transection as neonates.

L1 is a cell adhesion molecule associated with axonal outgrowth, fasciculation, and guidance during development and injury. In this study, we examined the long-term effects of spinal cord injury with and without exercise on the re-expression of L1 throughout the rat spinal cord. Spinal cords from control rats were compared to those from rats receiving complete mid-thoracic spinal cord transections at postnatal day 5, daily treadmill step training for up to 8 weeks, or both transection and step training. Three months after spinal cord transection, we observed substantially higher levels of L1 expression by both Western blot analysis and immunocytochemistry in rats with and without step training. Higher expression levels of L1 were seen in the dorsal gray matter and in the dorsal lateral funiculus both above and below the lesion site. In addition, L1 was re-expressed on the descending fibers of the corticospinal tract above the lesion. L1-labeled axons also expressed GAP-43, a protein associated with axon outgrowth and regeneration. Treadmill step training had no effect on L1 expression in either control or transected rats despite the fact that spinal transected rats displayed improved stepping patterns indicative of spinal learning. Thus, spinal cord transection at an early age induced substantial L1 expression on axons near the lesion site, but was not additionally augmented by exercise.

Aging↗

Effects of innervation state on Hsp25 content and phosphorylation in inactive rat plantaris muscles.

AIM: Previous reports suggest a role for neuromuscular activity levels and/or connectivity in modulating Hsp25 expression and phosphorylation (pHsp25) in skeletal muscles. However, pHsp25 has only been studied in denervated muscles and/or muscles exposed to high levels of residual neuromuscular activity. Spinal cord isolation (SI) provides a model in which the muscle is exposed to nearly complete inactivity with maintenance of the nerve-muscle connection. To parcel out the roles of innervation state and activity-independent neural factors, we compared Hsp25 and pHsp25 in the plantaris of control (Con), SI, and denervated (Den, inactivity without neural connectivity) rats. METHODS: Hsp25 and pHsp25 protein levels (soluble and insoluble fractions) were measured with Western blot analysis after 1, 3, 8, 14, or 28 days of SI or Den. pHsp25 was normalized to non-pHsp25 at each time point. RESULTS: Hsp25 was unchanged (days 1, 3 and 14) or increased (days 8 and 28) in the soluble fraction, and decreased (day 1) or increased (days 3, 8 and 14) in the insoluble fraction in Den compared with Con rats. pHsp25 was reduced after 1 and 28 days of Den, but near control levels on days 3, 8, and 14 in the soluble fraction. In the insoluble fraction, pHsp25 levels were lower in Den than Con rats on all days. In both fractions, Hsp25 was lower in SI than Con rats. pHsp25 levels were lower in the soluble fraction and higher in the insoluble fraction in SI than Con rats. CONCLUSION: These results suggest that an intact innervation, even in the absence of muscle activation and/or loading, is critical for Hsp25 phosphorylation in the insoluble fraction. However, the time-dependent decrease in Hsp25 with SI suggests a role for minimal levels of muscle activation and/or loading in maintaining Hsp25 expression during sustained inactivity.

Animals↗

Vibration-induced activation of muscle afferents modulates bioassayable growth hormone release.

The effects of tendon vibration on bioassayable growth hormone (BGH) secretion from the pituitary gland were investigated in anesthetized adult male rats. The tendons from predominantly fast-twitch ankle extensor muscles (gastrocnemius and plantaris) or a predominantly slow-twitch ankle extensor (soleus) were vibrated by using a paradigm that selectively activates group Ia afferent fibers from muscle spindles. The lower hindlimb was secured with the muscles near physiological length, and the tendons were vibrated for 15 min at 150 Hz and a displacement of 1 mm. Control rats were prepared similarly, but the tendons were not vibrated. Compared with control, vibration of the tendons of the fast ankle extensors markedly increased (160%), whereas vibration of the slow soleus decreased (68%), BGH secretion. Complete denervation of the hindlimb had no independent effects on the normal resting levels of BGH, but it prevented the effects of tendon vibration on BGH secretion. The results are consistent with previous findings showing modulation of BGH release in response to in vivo activation or in situ electrical stimulation of muscle afferents (Bigbee AJ, Gosselink KL, Grindeland RE, Roy RR, Zhong H, and Edgerton VR. J Appl Physiol 89: 2174-2178, 2000; Gosselink KL, Grindeland RE, Roy RR, Zhong H, Bigbee AJ, and Edgerton VR. J Appl Physiol 88: 142-148, 2000; Gosselink KL, Grindeland RE, Roy RR, Zhong H, Bigbee AJ, Grossman EJ, and Edgerton VR. J Appl Physiol 84: 1425-1430, 1998). These data provide evidence that this previously described muscle afferent-pituitary axis is neurally mediated via group Ia afferents from peripheral skeletal muscle. Furthermore, these data show that activation of this group Ia afferent pathway from fast muscles enhances, whereas the same sensory afferent input from a slow muscle depresses, BGH release.

Afferent Pathways↗

Flexor bias of joint position in humans during spaceflight.

The ability to estimate ankle and elbow joint position was tested before, during, and after a 17-day spaceflight. Subjects estimated targeted joint angles during isovelocity (IsoV) joint movements with agonist muscle groups either active or relaxed. These movements included elbow extension (EE) and elbow flexion (EF), and plantarflexion (PF) and dorsiflexion (DF) of the ankle. Subjects also estimated these joint positions while moving the dynamometer at their chosen (variable) velocity (VarV) during EE and PF. For IsoV tests, no differences were observed between active and passive movements for either the ankle or elbow. Compared with those of pre-flight test days, estimates of targeted elbow joint angles were approximately 5 degrees to 15 degrees more flexed in-flight, and returned toward the pre-flight values during recovery. The spaceflight effects for the ankle were inconsistent and less prevalent than those for the elbow. The VarV PF test condition for the 120 degrees target angle at the ankle exhibited approximately 5 degrees to 7 degrees more DF target angle estimates in-flight compared with those pre- or post-flight. In contrast, during IsoV PF there was a tendency for ankle estimates to be approximately 2 degrees to 3 degrees more PF after 2-3 days exposure to spaceflight. These data indicate that during spaceflight the perception of elbow extension is greater than actuality, and are consistent with the interpretation that microgravity induced a flexor bias in the estimation of the actual elbow joint position. Moreover, these effects in joint proprioception during spaceflight were observed in individual isolated single-joint movements during tasks in which vestibular function in maintaining posture were minimal.

Adult↗

Atrophy responses to muscle inactivity. I. Cellular markers of protein deficits.

The goal of this study was to use the model of spinal cord isolation (SI), which blocks nearly all neuromuscular activity while leaving the motoneuron muscle-fiber connections intact, to characterize the cellular processes linked to marked muscle atrophy. Rats randomly assigned to normal control and SI groups were studied at 0, 2, 4, 8, and 15 days after SI surgery. The slow soleus muscle atrophied by approximately 50%, with the greatest degree of loss occurring during the first 8 days. Throughout the SI duration, muscle protein concentration was maintained at the control level, whereas myofibrillar protein concentration steadily decreased between 4 and 15 days of SI, and this was associated with a 50% decrease in myosin heavy chain (MHC) normalized to total protein. Actin relative to the total protein was maintained at the control level. Marked reductions occurred in total RNA and DNA content and in total MHC and actin mRNA expressed relative to 18S ribosomal RNA. These findings suggest that two key factors contributing to the muscle atrophy in the SI model are 1). a reduction in ribosomal RNA that is consistent with a reduction in protein translational capacity, and 2). insufficient mRNA substrate for translating key sarcomeric proteins comprising the myofibril fraction, such as MHC and actin. In addition, the marked selective depletion of MHC protein in the muscles of SI rats suggests that this protein is more vulnerable to inactivity than actin protein. This selective MHC loss could be a major contributor for the previously reported loss in the functional integrity of SI muscles. Collectively, these data are consistent with the involvement of pretranslational and translational processes in muscle atrophy due to SI.

Actins↗

Atrophy responses to muscle inactivity. II. Molecular markers of protein deficits.

We examined the expression of several molecular markers of protein balance in response to skeletal muscle atrophy induced by spinal cord isolation (SI; i.e., a complete transection of the spinal cord at both a midthoracic and a high sacral level plus complete deafferentation between the two transection sites). This treatment nearly eliminates neuromuscular activity (activation and loading) of the hindlimb muscles while maintaining neuromuscular connectivity. SI was associated with a reduced transcriptional activity (via pre-mRNA analyses) of myosin heavy chain (MHC) and actin. In addition, there was an increased gene expression of enzyme systems impacting protein degradation (calpain-1; plus enzymes associated with polyubquitination processes) that could further contribute to the protein deficits in the SI muscles via degradative pathways. IGF-I receptor and binding protein-5 mRNA expression was induced throughout the 15-day period of SI, whereas IGF-I mRNA was induced at 8 and 15 days. These responses occurred in the absence of an upregulation of translational regulatory proteins (p70 S6 kinase; eukaryotic 4E binding protein 1) to compensate for the decreased protein translational capacity. These data collectively demonstrate that 1). the molecular changes accompanying SI-induced muscle atrophy are not necessarily the reverse of those occurring during muscle hypertrophy, and 2). the rapid and marked atrophy that defines this model of muscle inactivity is likely the result of multifactorial processes affecting transcription, translation, and protein degradation.

Actins↗

Effect of altered thyroid state on the in situ mechanical properties of adult cat soleus.

To determine the responsiveness of cat hindlimb muscles to thyroid manipulation, adult female cats were made hypothyroid (thyroidectomy plus tapazole treatment), hyperthyroid (synthroid pellets), or maintained euthyroid. After 4 months, the hypothyroid soleus had slower time-to-peak (TPT, 80%) and half-relaxation (HRT) times, whereas the hyperthyroid soleus had faster TPT (20%) and HRT than euthyroid cats. The tension at low stimulation frequencies (5-15 Hz) was higher in hypothyroid and lower in hyperthyroid cats compared to euthyroid cats. Muscle weight, maximum twitch and tetanic (Po) tensions, and maximum rates of shortening (Vmax) were similar across groups. The soleus of hypothyroid cats was more fatigable than normal. The myosin heavy chain (MHC) composition, based on gel electrophoresis, was unaffected by thyroid hormone manipulation. Based on the reaction of monoclonal antibodies for specific MHCs, some fast fibers in the hypothyroid cats coexpressed developmental MHC. These data indicate that 4 months of an altered thyroid state result in changes in the isometric twitch speed properties of the cat soleus, but not the tension-related or isotonic properties. Further, a chronic decrease in thyroid hormone had a greater impact than a chronic increase in thyroid hormone on the mechanical properties of the adult cat soleus.

Animals↗

Use of Wigglesworth classification for the assessment of perinatal mortality in Bangladesh--a preliminary study.

The Wigglesworth pathophysiological classification was used to analyse perinatal deaths occurring in 5 health centres in Bangladesh. The aims were to assess the feasibility of this classification, to determine the causes of perinatal deaths and thereby to identify the areas in need of intervention. A total of 8058 births were recorded at 5 centres during the period of 11 months from mid-January to mid-December 2001. There were 1069 deaths in the perinatal period. Stillbirths were slightly more frequent (53.5%) than early neonatal deaths (46.5%). Among the stillbirths, fresh stillbirths predominated over normally formed macerated ones at all centers except BIRDEM, where the majority (52.5%) was macerated. The majority (71.6%) of perinatal deaths were in the groups comprising asphyxial conditions (46.8%), conditions associated with immaturity (13.3%), and normally formed macerated stillbirths (NFMSB, 11.5%). In the group, 'other specific conditions' which was responsible for 9.3% of perinatal deaths, all but one case was attributed to sepsis. When the cases were subdivided by birth groups, asphyxia predominated in all but the <1000g group, in whom immaturity was responsible. Conditions associated with immaturity were second highest in number. The majority of the perinatal deaths (83.4%) was in babies less than 2500g. The study has shown that the Wigglesworth classification can be used in different types of health facilities in Bangladesh by doctors, nurses and midwives. The areas which need intervention are antepartum care, obstetric and newborn care practices, and environmental factors responsible for the high prevalence of prematurity and low birth weight.

Asphyxia Neonatorum↗

Effects of aging and exercise on density and cross-sectional area of femur in senescence-accelerated mouse prone 6.

The densities and cross-sectional areas (CSAs) of the femur in 40- and 60-week-old senescence-accelerated mice prone 6 (SAMP6) were determined using peripheral quantitative computed tomography (pQCT) and compared with those in age-matched control mice (ICR). In addition, the effects of 20 weeks of voluntary running exercise with increasing loads on femur density and CSA were examined in SAMP6. There were no differences in the cortical and trabecular densities or CSAs between the 40- and 60-week-old ICR. The cortical and trabecular densities of the 60-week-old control SAMP6 were lower than those of the 40-week-old control SAMP6. There was no difference in the cortical CSA between the 40- and 60-week-old control SAMP6, while the trabecular CSA of the 60-week-old control SAMP6 was higher than that of the 40-week-old control SAMP6. It was concluded that an age-related decline in femur cortical and trabecular densities occurs at an earlier age in control SAMP6, indicating that SAMP6 show accelerated progression of age-associated osteoporosis. There were no differences in the cortical density between the 40-week-old control and 60-week-old exercised SAMP6. These data indicate that running exercise with increasing loads prevents age-associated osteoporosis in this senescence-accelerated mouse strain.

Journal Article↗

Gravitational unloading effects on muscle fiber size, phenotype and myonuclear number.

The effects of gravitational unloading with or without intact neural activity and/or tension development on myosin heavy chain (MHC) composition, cross-sectional area (CSA), number of myonuclei, and myonuclear domain (cytoplasmic volume per myonucleus ratio) in single fibers of both slow and fast muscles of rat hindlimbs are reviewed briefly. The atrophic response to unloading is generally graded as follows: slow extensors > fast extensors > fast flexors. Reduction of CSA is usually greater in the most predominant fiber type of that muscle. The percentage of fibers expressing fast MHC isoforms increases in unloaded slow but not fast muscles. Myonuclear number per mm of fiber length and myonuclear domain is decreased in the fibers of the unloaded predominantly slow soleus muscle, but not in the predominantly fast plantaris. Decreases in myonuclear number and domain, however, are observed in plantaris fibers when tenotomy, denervation, or both are combined with hindlimb unloading. All of these results are consistent with the view that a major factor for fiber atrophy is an inhibition or reduction of loading of the hindlimbs. These data also indicate that predominantly slow muscles are more responsive to unloading than predominantly fast muscles.

Animals↗

Clenbuterol induces expression of multiple myosin heavy chain isoforms in rat soleus fibres.

Clenbuterol, a beta2-agonist, administration results in hypertrophy of fast fibres and an increase in the fast myosin heavy chain (MHC) composition of both fast and slow muscles. The present study was designed to determine the phenotypic response at the single fibre level. Clenbuterol was added to the drinking water (30 mg L(-1)) of adult male Wistar rats for 4 weeks. Single fibres from the soleus muscle of control (10 rats; 555 fibres) and clenbuterol-treated (10 rats; 577 fibres) were dissected and their MHC isoform composition was determined using sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis. Body, heart, and soleus weights were 9, 24, and 27% higher in clenbuterol-treated than control rats. The mean cross-sectional areas of fast and slow/fast hybrid fibres were approximately 64 and approximately 74% larger in the clenbuterol-treated than control rats, whereas the size of the slow fibres were similar in the two groups. Fibres from control soleus showed three MHC patterns: pure type I (84%), pure type IIa (4%), and type I + IIa (12%) MHC. Some fibres from clenbuterol-treated soleus showed a de novo expression of type IIx MHC resulting in the following fibre type proportions: pure type I (62%), pure type IIa (2%), type I + IIa (26%), type I + IIa + IIx (6%), and type IIa + IIx (1%). In those fibres containing multiple MHCs, there was a shift towards the faster MHC isoforms after clenbuterol treatment. These data indicate that clenbuterol results in muscle fibre hypertrophy, stimulates a de novo expression of type IIx MHC and increases the percentage of fibres containing multiple MHC isoforms in the rat soleus muscle. These phenotypic changes at the single fibre level are consistent with a clenbuterol-related shift in the functional properties of the soleus towards those observed in a faster muscle.

Animals↗

Transcriptional regulation of the type I myosin heavy chain promoter in inactive rat soleus.

Chronic muscle inactivity with spinal cord isolation (SI) decreases expression of slow type I myosin heavy chain (MHC) while increasing expression of the faster MHC isoforms, primarily IIx. The purpose of this study was to determine whether type I MHC downregulation in the soleus muscle of SI rats is regulated transcriptionally and to identify cis-acting elements or regions of the rat type I MHC gene promoter involved in this response. One week of SI significantly decreased in vivo activity of the -3500-, -408-, -299-, -215-, and -171-bp type I MHC promoters. The activity of all tested deletions of the type I MHC promoter, relative to the human skeletal alpha-actin promoter, were significantly reduced in the SI soleus, except activity of the -171-bp promoter, which increased. Mutation of the betae3 element (-214/-190 bp) in the -215- and -408-bp promoters and deletion of this element (-171-bp promoter) attenuated type I downregulation with SI. Gel mobility shift assays demonstrated a decrease in transcription enhancer factor-1 binding to the betae3 element with SI, despite an increase in total binding to this region. These results demonstrate that type I MHC downregulation with SI is transcriptionally regulated and suggest that interactions between transcription enhancer factor-1 and the betae3 element are likely involved in this response.

Animals↗

The rat lumbosacral spinal cord adapts to robotic loading applied during stance.

Load-related afferent information modifies the magnitude and timing of hindlimb muscle activity during stepping in decerebrate animals and spinal cord-injured humans and animals, suggesting that the spinal cord mediates load-related locomotor responses. In this study, we found that stepping on a treadmill by adult rats that received complete, midthoracic spinal cord transections as neonates could be altered by loading the hindlimbs using a pair of small robotic arms. The robotic arms applied a downward force to the lower shanks of the hindlimbs during the stance phase and measured the position of the lower shank during stepping. No external force was applied during the swing phase of the step. When applied bilaterally, this stance force field perturbed the hindlimb trajectories so that the ankle position was shifted downward during stance. In response to this perturbation, both the stance and step cycle durations decreased. During swing, the hindlimb initially accelerated toward the normal, unperturbed swing trajectory and then tracked the normal trajectory. Bilateral loading increased the magnitude of the medial gastrocnemius electromyographic (EMG) burst during stance and increased the amplitude of the semitendinosus and rectus femoris EMG bursts. When the force field was applied unilaterally, stance duration decreased in the loaded hindlimb, while swing duration was decreased in the contralateral hindlimb, thereby preserving interlimb coordination. These results demonstrate the feasibility of using robotic devices to mechanically modulate afferent input to the injured spinal cord during weight-supported locomotion. In addition, these results indicate that the lumbosacral spinal cord responds to load-related input applied to the lower shank during stance by modifying step timing and muscle activation patterns, while preserving normal swing kinematics and interlimb coordination.

Adaptation, Physiological↗