Antagonism of 5-HT2 receptors attenuates self-sustained firing of human motor units.

5-HT2 receptors on motoneurones play a critical role in facilitating persistent inward currents (PICs). Although facilitation of PICs can enhance self-sustained firing after periods of excitation, the relationship between 5-HT2 receptor activity and self-sustained firing in human motor units (MUs) has not been resolved. MU activity was assessed from the tibialis anterior of 10 healthy adults (24.9 ± 2.8 years) during two contraction protocols. Both protocols featured steady-state isometric contractions with constant descending drive to the motoneurone pool. However, one protocol also included an additional phase of superimposed descending drive. Adding and then removing descending drive in the middle of steady-state contractions altered MU firing behaviour across the motor pool, where newly recruited units in the superimposed phase were unable to switch off (P = 0.0002), and units recruited prior to additional descending drive reduced their discharge rates (P < 0.0001, difference in estimated marginal means (∆) = 2.24 pulses/s). The 5-HT2 receptor antagonist, cyproheptadine, was then administered to determine whether changes in MU firing were mediated by serotonergic mechanisms. 5-HT2 receptor antagonism caused reductions in MU discharge rate (P < 0.001, ∆ = 1.65 pulses/s), recruitment threshold (P = 0.00112, ∆ = 1.09% maximal voluntary contraction) and self-sustained firing duration (P < 0.0001, ∆ = 1.77s) after the additional descending drive was removed in the middle of the steady-state contraction. These findings indicate that serotonergic neuromodulation plays a key role in facilitating discharge and self-sustained firing of human motoneurones, where adaptive changes in MU recruitment must occur to meet the demands of the contraction. KEY POINTS: Animal and cellular preparations indicate that somato-dendritic 5-HT2 receptors regulate the intrinsic excitability of motoneurones. 5-HT2 receptor antagonism reduces estimates of persistent inward currents in motoneurones, which contribute to self-sustained firing when synaptic inputs are reduced or removed. This human study employed a contraction task that slowly increased (and then removed) the additional descending drive in the middle of a steady-state contraction where marked self-sustained firing occurred when the descending drive was removed. 5-HT2 receptor antagonism caused widespread reductions in motor unit (MU) discharge rates during contractions, which was accompanied by reduced recruitment threshold and attenuation of self-sustained firing duration after the removal of the additional descending drive to motoneurones. These findings support the role that serotonergic neuromodulation is a key facilitator of MU discharge and self-sustained firing of human motoneurones, where adaptative changes in MU recruitment must occur to meet the demands of the contraction.

Intrinsic motoneuron properties in typical human development.

Motoneuron properties and their firing patterns undergo significant changes throughout development and in response to neuromodulators such as serotonin. Here, we examined the age-related development of self-sustained firing and general excitability of tibialis anterior motoneurons in a young development (7-17 years), young adult (18-28 years) and adult (32-53 years) group, as well as in a separate group of participants taking selective serotonin reuptake inhibitors (SSRIs, aged 11-28 years). Self-sustained firing, as measured by ΔF, was larger in the young development (∼5.8 Hz, n = 20) compared to the young adult (∼4.9 Hz, n = 13) and adult (∼4.8 Hz, n = 8) groups, consistent with a developmental decrease in self-sustained firing mediated by persistent inward currents (PIC). ΔF was also larger in participants taking SSRIs (∼6.5 Hz, n = 9) compared to their age-matched controls (∼5.3 Hz, n = 26), consistent with increased levels of spinal serotonin facilitating the motoneuron PIC. Participants in the young development and SSRI groups also had higher firing rates and a steeper acceleration in initial firing rates (secondary ranges), consistent with the PIC producing a steeper acceleration in membrane depolarization at the onset of motoneuron firing. In summary, both the young development and SSRI groups exhibited increased intrinsic motoneuron excitability compared to the adults, which, in the young development group, was also associated with a larger unsteadiness in the dorsiflexion torque profiles. We propose several intrinsic and extrinsic factors that affect both motoneuron PICs and cell discharge which vary during development, with a time course similar to the changes in motoneuron firing behaviour observed in the present study. KEY POINTS: Neurons in the spinal cord that activate muscles in the limbs (motoneurons) undergo increases in excitability shortly after birth to help animals stand and walk. We examined whether the excitability of human ankle flexor motoneurons also continues to change from child to adulthood by recording the activity of the muscle fibres they innervate. Motoneurons in children and adolescents aged 7-17 years (young development group) had higher signatures of excitability that included faster firing rates and more self-sustained activity compared to adults aged ≥18 years. Participants aged 11-28 years of age taking serotonin reuptake inhibitors had the highest measures of motoneuron excitability compared to their age-matched controls. The young development group also had more unstable contractions, which might partly be related to the high excitability of the motoneurons.

Estimates of persistent inward currents in lower limb motoneurons are larger in females than in males.

Noninvasive recordings of motor unit (MU) spike trains help us understand how the nervous system controls movement and how it adapts to various physiological conditions. The majority of participants in human and nonhuman animal physiology studies are male, and it is assumed that mechanisms uncovered in these studies are shared between males and females. However, sex differences in neurological impairment and physical performance warrant the study of sex as a biological variable in human physiology and performance. To begin addressing this gap in the study of biophysical properties of human motoneurons, we quantified MU discharge rates and estimates of persistent inward current (PIC) magnitude in both sexes. We decomposed MU spike trains from the tibialis anterior (TA), medial gastrocnemius (MG), and soleus (SOL) using high-density surface electromyography and blind source separation algorithms. Ten participants of each sex performed slow triangular (10 s up and down) isometric contractions to a peak of 30% of their maximum voluntary contraction. We then used linear mixed-effects models to determine if peak discharge rate and estimates of PICs were predicted by the fixed effects of sex, muscle, and their interaction. Despite a lack of sex-differences in peak discharge rates across all muscles, estimates of PICs were larger [χ2(1) = 6.26, P = 0.012] in females [4.73 ± 0.242 pulses per second (pps)] than in males (3.81 ± 0.240 pps). These findings suggest that neuromodulatory drive, inhibitory input, and/or biophysical properties of motoneurons differ between the sexes and may contribute to differences in MU discharge patterns.NEW & NOTEWORTHY Sex-related differences in motoneuron analyses have emerged with greater inclusion of female participants, however, mechanisms for these differences remain unclear. Estimates of persistent inward currents (i.e., ΔF) in motoneurons of the lower limb muscles were larger in females than in males. This suggests neuromodulatory drive, monoaminergic signaling, intrinsic motoneuron properties, and/or descending motor commands may differ between the sexes, which provides a potential mechanism underlying previously reported sex-related differences in motoneuron discharge patterns.

Sensory enhancement of warm-up amplifies subsequent grip strength and cycling performance.

PURPOSE: In sport and exercise, warm-ups induce various physiological changes that facilitate subsequent performance. We have shown that delivering patterned stimulation to cutaneous afferents during sprint cycling mitigates fatigue-related decrements in performance, and that repeated sensory stimulation amplifies spinal reflex excitability. Therefore, the purpose of this study was to assess whether sensory enhancement of warm-up would affect subsequent high-intensity arm cycling performance. METHODS: Participants completed three experimental sessions, in which they randomly performed either a control, stim, or sleeve warm-up condition prior to maximal duration arm cycling. During the control condition, warmup consisted of low-intensity arm cycling for 15 min. The stim condition was the same, except they received alternating pulses (400 ms, 50 Hz) of stimulation just above their perceptual threshold to the wrists during warm-up. The third condition required participants to wear custom fabricated compression sleeves around the elbow during warm-up. Grip strength and spinal reflex excitability were measured before and after each warm-up and fatigue protocol, which required participants to arm cycle at 85% of peak power output until they reached volitional fatigue. Peak power output was determined during an incremental test at minimum 72 h prior to the first session. RESULTS: Both sensory enhanced warm-up conditions amplified subsequent high-intensity arm cycling performance by ~ 30%. Additionally, the stim and sleeve warm-up conditions yielded improvements in grip strength (increased by ~ 5%) immediately after the sensory enhanced warm-ups. Ergogenic benefits from the sensory enhanced warm-up conditions did not differ between one another. CONCLUSION: These findings demonstrate that enhanced sensory input during warm-up can elicit improvements in both maximal and submaximal performance measures.

Estimates of persistent inward currents are reduced in upper limb motor units of older adults.

Ageing is a natural process causing alterations in the neuromuscular system, which contributes to reduced quality of life. Motor unit (MU) contributes to weakness, but the mechanisms underlying reduced firing rates are unclear. Persistent inward currents (PICs) are crucial for initiation, gain control and maintenance of motoneuron firing, and are directly proportional to the level of monoaminergic input. Since concentrations of monoamines (i.e. serotonin and noradrenaline) are reduced with age, we sought to determine if estimates of PICs are reduced in older (>60 years old) compared to younger adults (<35 years old). We decomposed MU spike trains from high-density surface electromyography over the biceps and triceps brachii during isometric ramp contractions to 20% of maximum. Estimates of PICs (ΔFrequency; or simply ΔF) were computed using the paired MU analysis technique. Regardless of the muscle, peak firing rates of older adults were reduced by ∼1.6 pulses per second (pps) (P = 0.0292), and ΔF was reduced by ∼1.9 pps (P < 0.0001), compared to younger adults. We further found that age predicted ΔF in older adults (P = 0.0261), resulting in a reduction of ∼1 pps per decade, but there was no relationship in younger adults (P = 0.9637). These findings suggest that PICs are reduced in the upper limbs of older adults during submaximal isometric contractions. Reduced PIC magnitude represents one plausible mechanism for reduced firing rates and function in older individuals, but further work is required to understand the implications in other muscles and during a variety of motor tasks. KEY POINTS: Persistent inward currents play an important role in the neural control of human movement and are influenced by neuromodulation via monoamines originating in the brainstem. During ageing, motor unit firing rates are reduced, and there is deterioration of brainstem nuclei, which may reduce persistent inward currents in alpha motoneurons. Here we show that estimates of persistent inward currents (ΔF) of both elbow flexor and extensor motor units are reduced in older adults. Estimates of persistent inward currents have a negative relationship with age in the older adults, but not in the young. This novel mechanism may play a role in the alteration of motor firing rates that occurs with ageing, which may have consequences for motor control.

Moving forward: methodological considerations for assessing corticospinal excitability during rhythmic motor output in humans.

The use of transcranial magnetic stimulation to assess the excitability of the central nervous system to further understand the neural control of human movement is expansive. The majority of the work performed to-date has assessed corticospinal excitability either at rest or during relatively simple isometric contractions. The results from this work are not easily extrapolated to rhythmic, dynamic motor outputs, given that corticospinal excitability is task-, phase-, intensity-, direction-, and muscle-dependent (Power KE, Lockyer EJ, Forman DA, Button DC. Appl Physiol Nutr Metab 43: 1176-1185, 2018). Assessing corticospinal excitability during rhythmic motor output, however, involves technical challenges that are to be overcome, or at the minimum considered, when attempting to design experiments and interpret the physiological relevance of the results. The purpose of this narrative review is to highlight the research examining corticospinal excitability during a rhythmic motor output and, importantly, to provide recommendations regarding the many factors that must be considered when designing and interpreting findings from studies that involve limb movement. To do so, the majority of work described herein refers to work performed using arm cycling (arm pedaling or arm cranking) as a model of a rhythmic motor output used to examine the neural control of human locomotion.

We Are Upright-Walking Cats: Human Limbs as Sensory Antennae During Locomotion.

Humans and cats share many characteristics pertaining to the neural control of locomotion, which has enabled the comprehensive study of cutaneous feedback during locomotion. Feedback from discrete skin regions on both surfaces of the human foot has revealed that neuromechanical responses are highly topographically organized and contribute to "sensory guidance" of our limbs during locomotion.

Repeated and patterned stimulation of cutaneous reflex pathways amplifies spinal cord excitability.

Priming with patterned stimulation of antagonist muscle afferents induces modulation of spinal cord excitability as evidenced by changes in group Ia reciprocal inhibition. When assessed transiently with a condition-test pulse paradigm, stimulating cutaneous afferents innervating the foot reduces Ia presynaptic inhibition and facilitates soleus Hoffmann (H)-reflex amplitudes. Modulatory effects (i.e., priming) of longer lasting sensory stimulation of cutaneous afferents innervating the foot have yet to be examined. As a first step, we examined how priming with 20 min of patterned and alternating stimulation between the left and right foot affects spinal cord excitability. During priming, stimulus trains (550 ms; consisting of twenty-eight 1-ms pulses at 51 Hz, 1.2 times the radiating threshold) were applied simultaneously to the sural and plantar nerves of the ankle. Stimulation to the left and right ankle was out of phase by 500 ms. We evoked soleus H-reflexes and muscle compound action potentials (M waves) before and following priming stimulation to provide a proxy measure of spinal cord excitability. H-reflex and M-wave recruitment curves were recorded at rest, during brief (<2 min) arm cycling, and with sural conditioning [train of five 1-ms pulses at 2 times the radiating threshold (RT) with a condition-test interval (C-T) = 80 ms]. Data indicate an increase in H-reflex excitability following priming via patterned sensory stimulation. Transient sural conditioning was less effective following priming, indicating that the increased excitability of the H-reflex is partially attributable to reductions in group Ia presynaptic inhibition. Sensory stimulation to cutaneous afferents, which enhances spinal cord excitability, may prove useful in both rehabilitation and performance settings.NEW & NOTEWORTHY Priming via patterned stimulation of the nervous system induces neuroplasticity. Yet, accessing previously known cutaneous reflex pathways to alter muscle reflex excitability has not yet been examined. Here, we show that sensory stimulation of the cutaneous afferents that innervate the foot sole can amplify spinal cord excitability, which, in this case, is attributed to reductions in presynaptic inhibition.

Plantarflexion force is amplified with sensory stimulation during ramping submaximal isometric contractions.

Stimulating cutaneous nerves, causing tactile sensations, reduces the perceived heaviness of an object, suggesting that either descending commands are facilitated or the perception of effort is reduced when tactile sensation is enhanced. Sensory stimulation can also mitigate decrements in motor output and spinal cord excitability that occur with fatigue. The effects of sensory stimulation applied with coincident timing of voluntary force output, however, are yet to be examined. Therefore, the purpose of this study was to examine effects of sensory enhancement to nerves innervating opposed skin areas of the foot (top or bottom) on force production during voluntary plantarflexion or dorsiflexion contractions. Stimulation trains were applied for 2 s at either a uniform 150 Hz or a modulated frequency that increased linearly from 50 to 150 Hz and were delivered at the initiation of the contraction. Participants were instructed to perform a ramp contraction [~10% maximal voluntary contraction (MVC)/s] to ~20% MVC and then to hold ~20% MVC for 2 s while receiving real-time visual feedback. Cutaneous reflexes were evoked 75 ms after initiating the hold (75 ms after sensory enhancement ended). Force output was greater for all sensory-enhanced conditions compared with control during plantarflexion; however, force output was not amplified during dorsiflexion. Cutaneous reflexes evoked after sensory enhancement were unaltered. These results indicate that sensory enhancement can amplify plantarflexion but not dorsiflexion, likely as a result of differences in neuroanatomical projections to the flexor and extensor motor pools. Further work is required to elucidate the mechanisms of enhanced force during cutaneous stimulation.NEW & NOTEWORTHY The efficacy of behaviorally timed sensory stimulation to enhance sensations and amplify force output has not been examined. Here we show cutaneous nerve sensory stimulation can amplify plantarflexion force output. This amplification in force occurs irrespective of whether the cutaneous field that is stimulated resides on the surface that is producing the force or the opposing surface. This information may provide insights for the development of technologies to improve performance and/or rehabilitation training.

Enhanced somatosensory feedback modulates cutaneous reflexes in arm muscles during self-triggered or prolonged stimulation.

Somatosensory feedback plays important roles in regulating all animal movement. The effects of sensory feedback on spinally mediated neural excitability are widely studied using cutaneous electrical stimulation paradigms. Cutaneous reflex amplitudes are reduced when stimulation is self-triggered instead of externally triggered. Altered spinal excitability and motor output are also observed following sustained stimulation with various parameters. Our purpose was to probe for interactions between mode and duration by investigating muscle responses following enhanced cutaneous stimulation. Fifteen neurologically intact participants were recruited. Cutaneous reflexes in the extensor carpi radialis (ECR) were evoked with brief (15 ms, 300 Hz) or sustained (300 ms, 50 Hz) stimulation trains. Stimulation was applied to the superficial radial or median nerve at the wrist and triggered by: (1) a computer program (random-triggered); (2) muscle contraction (EMG-triggered); (3) the participant pressing a button themselves (button-triggered). During each condition, isometric contractions were performed with ECR muscle activity maintained at 10, 25, 35, and 50% of maximal voluntary contraction. Stronger inhibitory reflexes were found following brief superficial radial nerve stimulation was EMG-triggered suggesting that modulation of cutaneous reflex excitability is specific to the timing when sensory 'cues' are applied during muscle contraction. No difference was observed following sustained stimulation applied to the superficial radial nerve meaning that brief and sustained stimulation affect the cutaneous pathways differentially. Nerve-specific responses were found between superficial radial and median nerve stimulation, such that greater inhibition was induced by EMG-triggered sustained stimulation to the median nerve. These observations are critical in moving beyond pathway phenomenology toward targeted sensory enhancement and amplified motor output in rehabilitation and training.

Changing coupling between the arms and legs with slow walking speeds alters regulation of somatosensory feedback.

Arm swing movement is coordinated with movement of the legs during walking, where the frequency of coordination depends on walking speed. At typical speeds, arm and leg movements, respectively, are frequency locked in a 1:1 ratio but at slow speeds this changes to a 2:1 ratio. It is unknown if the changes in interlimb ratio that accompany slow walking speeds alters regulation of somatosensory feedback. To probe the neural interactions between the arms and legs, somatosensory linkages in the form of interlimb cutaneous reflexes were examined. It was hypothesized that different interlimb frequencies and walking speeds would result in changes in the modulation of cutaneous reflexes between the arms and legs. To test this hypothesis, participants walked in four combinations of walking speed (typical, slow) and interlimb coordination (1:1, and 2:1), while cutaneous reflexes and background muscle activity were evaluated with stimulation applied to the superficial peroneal nerve at the ankle and superficial radial nerve at the wrist. Results show main effects of interlimb coordination and walking speed on cutaneous reflex modulation, effects are largest in the swing phase, and a directional coupling was observed, where changes in the frequency of arm movements had a greater effect on muscle activity in the legs compared to the reverse. Task-dependent modulation was also revealed from stimulation at local and remote sources. Understanding the underlying neural mechanisms for the organization of rhythmic arm movement, and its coordination with the legs in healthy participants, can give insight into pathological walking, and will facilitate the development of effective strategies for the rehabilitation of walking.

Exploiting cervicolumbar connections enhances short-term spinal cord plasticity induced by rhythmic movement.

Arm cycling causes suppression of soleus (SOL) Hoffmann (H-) reflex that outlasts the activity period. Arm cycling presumably activates propriospinal networks that modulate Ia presynaptic inhibition. Interlimb pathways are thought to relate to the control of quadrupedal locomotion, allowing for smooth, coordinated movement of the arms and legs. We examined whether the number of active limb pairs affects the amount and duration of activity-dependent plasticity of the SOL H-reflex. On separate days, 14 participants completed 4 randomly ordered 30 min experimental sessions: (1) quiet sitting (CTRL); (2) arm cycling (ARM); (3) leg cycling (LEG); and (4) arm and leg cycling (A&L) on an ergometer. SOL H-reflex and M-wave were evoked via electrical stimulation of the tibial nerve. M-wave and H-reflex recruitment curves were recorded, while the participants sat quietly prior to, 10 and 20 min into, immediately after, and at 2.5, 5, 7.5, 10, 15, 20, 25, and 30 min after each experimental session. Normalized maximal H-reflexes were unchanged in CTRL, but were suppressed by > 30% during the ARM, LEG, and A&L. H-reflex suppression outlasted activity duration for ARM (≤ 2.5 mins), LEG (≤ 5 mins), and A&L (≤ 30 mins). The duration of reflex suppression after A&L was greater than the algebraic summation of ARM and LEG. This non-linear summation suggests that using the arms and legs simultaneously-as in typical locomotor synergies-amplifies networks responsible for the short-term plasticity of lumbar spinal cord excitability. Enhanced activity of spinal networks may have important implications for the implementation of locomotor training for targeted rehabilitation.

Robot controlled, continuous passive movement of the ankle reduces spinal cord excitability in participants with spasticity: a pilot study.

Spasticity of the ankle reduces quality of life by impeding walking and other activities of daily living. Robot-driven continuous passive movement (CPM) is a strategy for lower limb spasticity management but effects on spasticity, walking ability and spinal cord excitability (SCE) are unknown. The objectives of this experiment were to evaluate (1) acute changes in SCE induced by 30 min of CPM at the ankle joint, in individuals without neurological impairment and those with lower limb spasticity; and, (2) the effects of 6 weeks of CPM training on SCE, spasticity and walking ability in those with lower limb spasticity. SCE was assessed using soleus Hoffmann (H-) reflexes, collected prior to and immediately after CPM for acute assessments, whereas a multiple baseline repeated measures design assessed changes following 18 CPM sessions. Spasticity and walking ability were assessed using the Modified Ashworth Scale, the 10 m Walk test, and the Timed Up and Go test. Twenty-one neurologically intact and nine participants with spasticity (various neurological conditions) were recruited. In the neurologically intact group, CPM caused bi-directional modulation of H-reflexes creating 'facilitation' and 'suppression' groups. In contrast, amongst participants with spasticity, acute CPM facilitated H-reflexes. After CPM training, H-reflex excitability on both the more-affected and less-affected sides was reduced; on the more affected side H@Thres, H@50 and H@100 all significantly decreased following CPM training by 96.5 ± 7.7%, 90.9 ± 9.2%, and 62.9 ± 21.1%, respectively. After training there were modest improvements in walking and clinical measures of spasticity for some participants. We conclude that CPM of the ankle can significantly alter SCE. The use of CPM in those with spasticity can provide a temporary period of improved walking, but efficacy of treatment remains unknown.

Effects of a compression garment on sensory feedback transmission in the human upper limb.

Compression apparel is popular in both medical and sport performance settings. Perceived benefits are suggested to include changes in sensory feedback transmission caused by activation of mechanoreceptors. However, little is known about effects of compression apparel on sensorimotor control. Our purpose was to mechanistically examine whether compression apparel modulates sensory feedback transmission and reaching accuracy in the upper limb. Two experiments were completed under CONTROL and COMPRESSION (sleeve applied across the elbow joint) conditions. M-waves and H-reflexes were elicited by stimulating the median nerve and were recorded via surface electromyography (EMG). In experiment 1, H-reflexes and M-H recruitment curves were assessed at REST, during wrist flexion (10% EMGmax), and during a cutaneous conditioning of the superficial radial (SR) or distal median (MED) nerve. Cutaneous reflexes were elicited during 10% wrist flexion via stimulation of SR or MED. In experiment 2, unconditioned H-reflex measures were assessed at rest, during arm cycling, and during a discrete reaching task. Results indicate that compression apparel modulates spinal cord excitability across multiple sensory pathways and movement tasks. Interestingly, there was a significant improvement in reaching accuracy while wearing the compression sleeve. Taken together, the compression sleeve appears to increase precision and sensitivity around the joint where the sleeve is applied. Compression apparel may function as a "filter" of irrelevant mechanoreceptor information allowing for optimal task-related sensory information to enhance proprioception. NEW & NOTEWORTHY Wearing a customized compression sleeve was shown to alter the excitability of multiple pathways within the central nervous system regardless of conditioning input or movement task and was accompanied by improved accuracy of reaching movements and determination of movement end point. Compression apparel may assist as a type of "filter function" of tonic and nonspecific mechanoreceptor information leading to increased precision and movement sensitivity around the joint where compression is applied.

Rhythmic arm cycling training improves walking and neurophysiological integrity in chronic stroke: the arms can give legs a helping hand in rehabilitation.

Training locomotor central pattern-generating networks (CPGs) through arm and leg cycling improves walking in chronic stroke. These outcomes are presumed to result from enhanced interlimb connectivity and CPG function. The extent to which rhythmic arm training activates interlimb CPG networks for locomotion remains unclear and was assessed by studying chronic stroke participants before and after 5 wk of arm cycling training. Strength was assessed bilaterally via maximal voluntary isometric contractions in the legs and hands. Muscle activation during arm cycling and transfer to treadmill walking were assessed in the more affected (MA) and less affected (LA) sides via surface electromyography. Changes to interlimb coupling during rhythmic movement were evaluated using modulation of cutaneous reflexes elicited by electrical stimulation of the superficial radial nerve at the wrist. Bilateral soleus stretch reflexes were elicited at rest and during 1-Hz arm cycling. Clinical function tests assessed walking, balance, and motor function. Results show significant changes in function and neurophysiological integrity. Training increased bilateral grip strength, force during MA plantarflexion, and muscle activation. "Normalization" of cutaneous reflex modulation was found during arm cycling. There was enhanced activity in the dorsiflexor muscles on the MA side during the swing phase of walking. Enhanced interlimb coupling was shown by increased modulation of MA soleus stretch reflex amplitudes during arm cycling after training. Clinical evaluations showed enhanced walking ability and balance. These results are consistent with training-induced changes in CPG function and interlimb connectivity and underscore the need for arm training in the functional rehabilitation of walking after neurotrauma. NEW & NOTEWORTHY It has been suggested but not tested that training the arms may influence rehabilitation of walking due to activation of interneuronal patterning networks after stroke. We show that arm cycling training improves strength, clinical function, coordination of muscle activity during walking, and neurological connectivity between the arms and the legs. The arms can, in fact, give the legs a helping hand in rehabilitation of walking after stroke.

Neuromechanical interactions between the limbs during human locomotion: an evolutionary perspective with translation to rehabilitation.

During bipedal locomotor activities, humans use elements of quadrupedal neuronal limb control. Evolutionary constraints can help inform the historical ancestry for preservation of these core control elements support transfer of the huge body of quadrupedal non-human animal literature to human rehabilitation. In particular, this has translational applications for neurological rehabilitation after neurotrauma where interlimb coordination is lost or compromised. The present state of the field supports including arm activity in addition to leg activity as a component of gait retraining after neurotrauma.

Cross-education of strength and skill: an old idea with applications in the aging nervous system.

Edward Wheeler Scripture's 1894 work out of the Yale Psychological Laboratory has been influential in identifying the nervous system's contribution to the bilateral improvements that are seen with unilateral strength and skill training. Scripture coined the term "cross-education" to describe this improvement in the untrained contralateral limb. While physiological changes accompany aging that may negatively affect the performance of physical tasks, far too much credit has been given to the natural aging process rather than the effects of inactivity. Emerging evidence indicates strength or skill training interventions induce significant neuroplasticity in an aging population. The model of unilateral training provides a unique approach in which to elicit such plasticity. This brief review highlights the innate ability of the nervous system to adapt to unilateral strength and skill training interventions, regardless of age, and provides a novel perspective on the robust plastic ability of the aging nervous system.

Neuromuscular fatigue of the knee extensors during repeated maximal intensity intermittent-sprints on a cycle ergometer.

INTRODUCTION: We studied the time course of neuromuscular fatigue during maximal intensity intermittent-sprint cycling. METHODS: Eight participants completed 10, 10-s sprints interspersed with 180 s of recovery. The power outputs were recorded for each sprint. Knee extensor maximum voluntary contraction (MVC) force, voluntary activation, and evoked contractile properties were recorded presprint, postsprint 5, and postsprint 10. RESULTS: Total work over the 10 sprints decreased significantly (P < 0.05) and could be described by 2 linear relationships from sprints 1-5 compared with sprints 6-10. Participants had significantly (P < 0.05) lower MVC and twitch forces postsprint 5 compared with presprint. MVC, voluntary activation, and twitch force were decreased (P < 0.05) postsprint 10 compared with postsprint 5. CONCLUSIONS: The maximal intermittent sprints induced neuromuscular fatigue. Neuromuscular fatigue in the first 5 sprints was mainly peripheral, whereas in the last 5 sprints it was both peripheral and central.