Contribution of sensory feedback to soleus muscle activity during voluntary contraction in humans.

Sensory feedback through spinal interneurons contributes to plantar flexor muscle activity during walking, but it is unknown whether this is also the case during nonlocomotor movements. Here, we explored the effect of temporary reduction of sensory feedback to ankle plantar flexors during voluntary contraction in sitting subjects. Thirteen healthy adults (mean age 32 yr) were seated with the right leg attached to a foot plate which could be moved in dorsi- or plantarflexion direction by a computer-controlled motor. EMG was recorded from the tibialis anterior (TA) and soleus (Sol) muscles. During static plantar flexion, while the plantar flexors were slowly stretched, a sudden plantar flexion caused a decline in Sol EMG at the same latency as the stretch reflex. This decline in EMG activity was still observed when transmission from dorsiflexors was blocked. It disappeared when transmission from ankle plantar flexors was also blocked. The same quick plantarflexion failed to produce a decline in EMG activity at the latency of the stretch reflex in the absence of slow stretch of the plantar flexors. Instead, a decline in EMG activity was observed 15-20 ms later. This decline disappeared following block of transmission from antagonists, suggesting that reciprocal inhibition was involved. These findings show that unload of ankle plantar flexors does not cause a similar drop in Sol EMG during voluntary contraction as during walking. This implies that sensory feedback through spinal interneurons only contributes little to the neural drive to plantar flexor muscles during human voluntary contraction in sitting subjects.NEW & NOTEWORTHY Sensory feedback through spinal reflex pathways makes only a minor contribution to neural drive to muscles during voluntary ankle plantar flexion. This differs distinctly from observations during walking and suggests that the neural drive to ankle plantar flexors during voluntary contraction do not rely on sensory feedback through similar spinal interneuronal networks as during walking. In line with animal studies this suggests that the integration of sensory feedback in CNS is task specific.

Can Operant Conditioning of EMG-Evoked Responses Help to Target Corticospinal Plasticity for Improving Motor Function in People With Multiple Sclerosis?

Corticospinal pathway and its function are essential in motor control and motor rehabilitation. Multiple sclerosis (MS) causes damage to the brain and descending connections, and often diminishes corticospinal function. In people with MS, neural plasticity is available, although it does not necessarily remain stable over the course of disease progress. Thus, inducing plasticity to the corticospinal pathway so as to improve its function may lead to motor control improvements, which impact one's mobility, health, and wellness. In order to harness plasticity in people with MS, over the past two decades, non-invasive brain stimulation techniques have been examined for addressing common symptoms, such as cognitive deficits, fatigue, and spasticity. While these methods appear promising, when it comes to motor rehabilitation, just inducing plasticity or having a capacity for it does not guarantee generation of better motor functions. Targeting plasticity to a key pathway, such as the corticospinal pathway, could change what limits one's motor control and improve function. One of such neural training methods is operant conditioning of the motor-evoked potential that aims to train the behavior of the corticospinal-motoneuron pathway. Through up-conditioning training, the person learns to produce the rewarded neuronal behavior/state of increased corticospinal excitability, and through iterative training, the rewarded behavior/state becomes one's habitual, daily motor behavior. This minireview introduces operant conditioning approach for people with MS. Guiding beneficial CNS plasticity on top of continuous disease progress may help to prolong the duration of maintained motor function and quality of life in people living with MS.

Sensory Feedback in Interlimb Coordination: Contralateral Afferent Contribution to the Short-Latency Crossed Response during Human Walking.

A constant coordination between the left and right leg is required to maintain stability during human locomotion, especially in a variable environment. The neural mechanisms underlying this interlimb coordination are not yet known. In animals, interneurons located within the spinal cord allow direct communication between the two sides without the need for the involvement of higher centers. These may also exist in humans since sensory feedback elicited by tibial nerve stimulation on one side (ipsilateral) can affect the muscles activation in the opposite side (contralateral), provoking short-latency crossed responses (SLCRs). The current study investigated whether contralateral afferent feedback contributes to the mechanism controlling the SLCR in human gastrocnemius muscle. Surface electromyogram, kinematic and kinetic data were recorded from subjects during normal walking and hybrid walking (with the legs moving in opposite directions). An inverse dynamics model was applied to estimate the gastrocnemius muscle proprioceptors' firing rate. During normal walking, a significant correlation was observed between the magnitude of SLCRs and the estimated muscle spindle secondary afferent activity (P = 0.04). Moreover, estimated spindle secondary afferent and Golgi tendon organ activity were significantly different (P ≤ 0.01) when opposite responses have been observed, that is during normal (facilitation) and hybrid walking (inhibition) conditions. Contralateral sensory feedback, specifically spindle secondary afferents, likely plays a significant role in generating the SLCR. This observation has important implications for our understanding of what future research should be focusing on to optimize locomotor recovery in patient populations.

Size, Accumulation and Performance for Research Grants: Examining the Role of Size for Centres of Excellence.

The present paper examines the relation between size, accumulation and performance for research grants, where we examine the relation between grant size for Centres of Excellence (CoE) funded by the Danish National Research Foundation (DNRF) and various ex post research performance measures, including impact and shares of highly cited articles. We examine both the relation between size and performance and also how performance for CoEs evolves over the course of grant periods. In terms of dynamics, it appears that performance over the grant period (i.e. 10 years) is falling for the largest CoEs, while it is increasing for those among the smallest half. Overall, multivariate econometric analysis finds evidence that performance is increasing in grant size and over time. In both cases, the relation appears to be non-linear, suggesting that there is a point at which performance peaks. The CoEs have also been very successful in securing additional funding, which can be viewed as a 'cumulative effect' of center grants. In terms of new personnel, the far majority of additional funding is spent on early career researchers, hence, this accumulation would appear to have a 'generational' dimension, allowing for scientific expertise to be passed on to an increasing number of younger researchers.

Interlimb communication following unexpected changes in treadmill velocity during human walking.

Interlimb reflexes play an important role in human walking, particularly when dynamic stability is threatened by external perturbations or changes in the walking surface. Interlimb reflexes have recently been demonstrated in the contralateral biceps femoris (cBF) following knee joint rotations applied to the ipsilateral leg (iKnee) during the late stance phase of human gait (Stevenson AJ, Geertsen SS, Andersen JB, Sinkjær T, Nielsen JB, Mrachacz-Kersting N. J Physiol 591: 4921-4935, 2013). This interlimb reflex likely acts to slow the forward progression of the body to maintain dynamic stability following the perturbations. We examined this hypothesis by unexpectedly increasing or decreasing the velocity of the treadmill before (-100 and -50 ms), at the same time, or following (+50 ms) the onset of iKnee perturbations in 12 healthy volunteers. We quantified the cBF reflex amplitude when the iKnee perturbation was delivered alone, the treadmill velocity change was delivered alone, or when the two perturbations were combined. When the treadmill velocity was suddenly increased (or decreased) 100 or 50 ms before the iKnee perturbations, the combined cBF reflex was significantly larger (or smaller) than the algebraic sum of the two perturbations delivered separately. Furthermore, unexpected changes in treadmill velocity increased the incidence of reflexes in other contralateral leg muscles when the iKnee perturbations were elicited alone. These results suggest a context dependency for interlimb reflexes. They also show that the cBF reflex changed in a predictable manner to slow the forward progression of the body and maintaining dynamic stability during walking, thus signifying a functional role for interlimb reflexes.

Sensory feedback to ankle plantar flexors is not exaggerated during gait in spastic hemiplegic children with cerebral palsy.

It is still widely believed that exaggerated stretch reflexes and increased muscle tone in ankle plantar flexors contribute to reduced ankle joint movement during gait in children with cerebral palsy (CP). However, no study has directly measured stretch reflex activity during gait in these children. We investigated sensory feedback mechanisms during walking in 20 CP children and 41 control children. Stretch responses in plantar flexor muscles evoked in stance showed an age-related decline in control but not CP children. In swing the responses were abolished in control children, but significant responses were observed in 14 CP children. This was related to reduced activation of dorsiflexors in swing. Removal of sensory feedback in stance produced a drop in soleus activity of a similar size in control and CP children. Soleus activity was observed in swing to the same extent in control and CP children. Removal of sensory feedback in swing caused a larger drop in soleus activity in control children than in CP children. The lack of age-related decline in stretch reflexes and the inability to suppress reflexes in swing is likely related to lack of maturation of corticospinal control in CP children. Since soleus activity was not seen more frequently than in control children in swing and since sensory feedback did not contribute more to their soleus activity, spasticity is unlikely to contribute to foot drop and toe walking. We propose that altered central drive to the ankle muscles and increased passive muscle stiffness are the main causes of foot drop and toe walking.

Interlimb communication to the knee flexors during walking in humans.

A strong coordination between the two legs is important for maintaining a symmetric gait pattern and adapting to changes in the external environment. In humans as well as animals, receptors arising from the quadriceps muscle group influence the activation of ipsilateral muscles. Moreover, strong contralateral spinal connections arising from quadriceps and hamstring afferents have been shown in animal models. Therefore, the aims of the present study were to assess if such connections also exist in humans and to elucidate on the possible pathways. Contralateral reflex responses were investigated in the right leg following unexpected unilateral knee joint rotations during locomotion in either the flexion or extension direction. Strong reflex responses in the contralateral biceps femoris (cBF) muscle with a mean onset latency of 76 ± 6 ms were evoked only from ipsilateral knee extension joint rotations in the late stance phase. To investigate the contribution of a transcortical pathway to this response, transcranial magnetic and electrical stimulation were applied. Motor evoked potentials elicited by transcranial magnetic stimulation, but not transcranial electrical stimulation, were facilitated when elicited at the time of the cBF response to a greater extent than the algebraic sum of the cBF reflex and motor evoked potentials elicited separately, indicating that a transcortical pathway probably contributes to this interlimb reflex. The cBF reflex response may therefore be integrated with other sensory input, allowing for responses that are more flexible. We hypothesize that the cBF reflex response may be a preparation of the contralateral leg for early load bearing, slowing the forward progression of the body to maintain dynamic equilibrium during walking.

Passive muscle properties are altered in children with cerebral palsy before the age of 3 years and are difficult to distinguish clinically from spasticity.

AIM: Clinical determination of spasticity is confounded by the difficulty in distinguishing reflex from passive contributions to muscle stiffness. There is, therefore, a risk that children with cerebral palsy (CP) receive antispasticity treatment unnecessarily. To investigate this, we aimed to determine the contribution of reflex mechanisms to changes in the passive elastic properties of muscles and tendons in children with CP. METHOD: Biomechanical and electrophysiological measures were used to determine the relative contribution of reflex and passive mechanisms to ankle muscle stiffness in 35 children with spastic CP (21 males, 14 females; mean age 9 y, SD 3 y 4 mo; range 3-15 y) and 28 control children without CP (19 males, nine females; mean age 8 y 11 mo, SD 2 y 10 mo; range 3-15 y). Twenty-seven children were diagnosed as having spastic hemiplegia, six with spastic diplegia, and two with spastic tetraplegia. According to the Gross Motor Function Classification System, 31 children were classified in level I, two in level II, and two in level III. RESULTS: Only seven children with spastic CP showed reflex stiffness outside the range of the control children. In contrast, 20 children with spastic CP showed abnormal passive muscle stiffness (p<0.001). No correlation between increased reflex or increased passive muscle stiffness and age was observed within the age range studied. INTERPRETATION: These data suggest that increased reflex-mediated muscle stiffness is difficult to distinguish clinically from changes in passive muscle stiffness and that signs of changes in muscle properties are already present from the age of 3 years in children with CP. This emphasizes the importance of accurately distinguishing different contributions to muscle stiffness to avoid unnecessary antispasticity treatment.

Crossed reflex reversal during human locomotion.

During human walking, precise coordination between the two legs is required in order to react promptly to any sudden hazard that could threaten stability. The networks involved in this coordination are not yet completely known, but a direct spinal connection between soleus (SOL) muscles has recently been revealed. For this response to be functional, as previously suggested, we hypothesize that it will be accompanied by a reaction in synergistic muscles, such as gastrocnemius lateralis (GL), and that a reversal of the response would occur when an opposite reaction is required. In the present study, surface EMGs of contralateral SOL and GL were analyzed after tibial nerve (TN), sural nerve (SuN), and medial plantar nerve (MpN) stimulation during two tasks in which opposite reactions are functionally expected: normal walking (NW), just before ipsilateral heel strike, and hybrid walking (HW) (legs walking in opposite directions), at ipsilateral push off and contralateral touchdown. Early crossed facilitations were observed in the contralateral GL after TN stimulation during NW, and a reversal of such responses occurred during HW. These results underline the functional significance of short-latency crossed responses and represent the first evidence for short-latency reflex reversal in the contralateral limb for humans. Muscle afferents seem to mediate the response during NW, while during HW cutaneous afferents are likely involved. It is thus possible that different afferents mediate the crossed response during different tasks.

Spasticity.

Antispastic medications that are directed to reduce clinical signs of spasticity, such as exaggerated reflexes and muscle tone, do not improve the movement disorder. Medication can even increase weakness which might interfere with functional movements, such as walking. In this chapter we address how spasticity affects mobility and how this should be taken into account in the treatment of spasticity. In clinical practice, signs of exaggerated tendon tap reflexes associated with muscle hypertonia are the consequence of spinal cord injury (SCI). They are generally thought to be responsible for spastic movement disorders. Most antispastic treatments are, therefore, directed at the reduction of reflex activity. In recent years, a discrepancy between spasticity as measured in the clinic and functional spastic movement disorder was noticed, which is primarily due to the different roles of reflexes in passive and active states, respectively. We now know that central motor lesions are associated with loss of supraspinal drive and defective use of afferent input with impaired behavior of short-latency and long-latency reflexes. These changes lead to paresis and maladaptation of the movement pattern. Secondary changes in mechanical muscle fiber, collagen tissue, and tendon properties (e.g., loss of sarcomeres, subclinical contractures) result in spastic muscle tone, which in part compensates for paresis and allows functional movements on a simpler level of organization. Antispastic drugs should primarily be applied in complete SCI. In mobile patients they can accentuate paresis and therefore should be applied with caution.

[New knowledge of spasticity and its treatment]. / Ny viden om spasticitet og dens behandling.

Spasticity is a frequently used diagnosis, and anti-spastic medication is used widespread. In this systematic review article we highlight difficulties in diagnosing spasticity correctly and thus limit the value of the diagnosis in ensuring the best possible treatment. We review recent neuroscience research and conclude that it is necessary to develop better tools for clinical diagnosis of spasticity in order to avoid potential malpractice and to limit treatment with anti-spastic drugs for patients with documented increased reflex-mediated muscle tone as their main annoyance.

Interaction of electrical stimulation and voluntary hand movement in SII and the cerebellum during simulated therapeutic functional electrical stimulation in healthy adults.

The therapeutic application of functional electrical stimulation (FES) has shown promising clinical results in the rehabilitation of post-stroke hemiplegia. It appears that the effect is optimal when the patterned electrical stimulation is used in close synchrony with voluntary movement, although the neural mechanisms that underlie the clinical successes reported with therapeutic FES are unknown. One possibility is that therapeutic FES takes advantage of the sensory consequences of an internal model. Here, we investigate fMRI cortical activity when FES is combined with voluntary effort (FESVOL) and we compare this activity to that produced when FES and voluntary activity (VOL) are performed alone. FESVOL revealed greater cerebellar activity compared with FES alone and reduced activity bilaterally in secondary somatosensory areas (SII) compared with VOL alone. Reduced activity was also observed for FESVOL compared with FES alone in the angular gyrus, middle frontal gyrus and inferior frontal gyrus. These findings indicate that during the VOL condition the cerebellum predicts the sensory consequences of the movement and this reduces the subsequent activation in SII. The decreased SII activity may reflect a better match between the internal model and the actual sensory feedback. The greater cerebellar activity coupled with reduced angular gyrus activity in FESVOL compared with FES suggests that the cortex may interpret sensory information during the FES condition as an error-like signal due to the lack of a voluntary component in the movement.

Crossed spinal soleus muscle communication demonstrated by H-reflex conditioning.

INTRODUCTION: A conditioning volley to the ipsilateral tibial nerve (iTN) inhibits contralateral soleus (cSOL) electromyographic activity at latencies of 37-41 ms. This is evidence for spinal muscular communication in opposing limbs. The aim of our study was to determine whether the cSOL H-reflex would be inhibited in a similar manner. METHODS: Thirteen subjects participated in two experiments: (1) stimuli delivered to the iTN at 85% of the maximal peak-to-peak M-wave (85% M-max) with a pre-contracted cSOL; (2) 510 stimuli delivered at 85% M-max to the iTN with a test volley delivered to the contralateral tibial nerve at interstimulus intervals of -6 to 100 ms. RESULTS: Significant inhibition was observed in the cSOL H-reflex when conditioning stimuli were delivered 3-33 ms before the test H-reflex. CONCLUSIONS: The activity of this spinal pathway can be quantified using H-reflex conditioning to provide a controlled model for further studies of this response.

Positive afferent feedback to the human soleus muscle during quiet standing.

INTRODUCTION: In this study we investigated the mechanisms responsible for soleus muscle contraction during quiet standing. METHODS: Subjects stood on a platform that was randomly moved forward or downward or rotated around the ankle. RESULTS: Downward perturbation caused a short-latency drop in averaged rectified soleus electromyography (SOL EMG). SOL drop increased monotonically with downward acceleration amplitude. Ischemia above the knee abolished or diminished this drop. Ischemia above the ankle had no diminishing effect. Vibration of the Achilles tendon had a diminishing effect on the amplitude of SOL responses. CONCLUSIONS: The short-latency drop in SOL observed for downward perturbation might be due to a decrease in positive afferent feedback due to the sudden decrease in body weight. This implies the existence of an ongoing afferent feedback loop toward the SOL motoneuron pool from force-sensitive receptors. Both Ia and Ib afferents probably play a role in the responses observed.

Ultrasonography as a tool to study afferent feedback from the muscle-tendon complex during human walking.

In humans, one of the most common tasks in everyday life is walking, and sensory afferent feedback from peripheral receptors, particularly the muscle spindles and Golgi tendon organs (GTO), makes an important contribution to the motor control of this task. One factor that can complicate the ability of these receptors to act as length, velocity and force transducers is the complex pattern of interaction between muscle and tendinous tissues, as tendon length is often considerably greater than muscle fibre length in the human lower limb. In essence, changes in muscle-tendon mechanics can influence the firing behaviour of afferent receptors, which may in turn affect the motor control. In this review we first summarise research that has incorporated the use of ultrasound-based techniques to study muscle-tendon interaction, predominantly during walking. We then review recent research that has combined this method with an examination of muscle activation to give a broader insight to neuromuscular interaction during walking. Despite the advances in understanding that these techniques have brought, there is clearly still a need for more direct methods to study both neural and mechanical parameters during human walking in order to unravel the vast complexity of this seemingly simple task.

Neural compensation within the human triceps surae during prolonged walking.

During human walking, muscle activation strategies are approximately constant across consecutive steps over a short time, but it is unknown whether they are maintained over a longer duration. Prolonged walking may increase tendinous tissue (TT) compliance, which can influence neural activation, but the neural responses of individual muscles have not been investigated. This study investigated the hypothesis that muscle activity is up- or down-regulated in individual triceps surae muscles during prolonged walking. Thirteen healthy subjects walked on a treadmill for 60 min at 4.5 km/h, while triceps surae muscle activity, maximal muscle compound action potentials, and kinematics were recorded every 5 min, and fascicle lengths were estimated at the beginning and end of the protocol using ultrasound. After 1 h of walking, soleus activity increased by 9.3 ± 0.2% (P < 0.05) and medial gastrocnemius activity decreased by 9.3 ± 0.3% (P < 0.01). Gastrocnemius fascicle length at ground contact shortened by 4.45 ± 0.99% (P < 0.001), whereas soleus fascicle length was unchanged (P = 0.988). Throughout the stance phase, medial gastrocnemius fascicle lengthening decreased by 44 ± 13% (P < 0.001), whereas soleus fascicle lengthening amplitude was unchanged (P = 0.650). The data suggest that a compensatory neural strategy exists between triceps surae muscles and that changes in muscle activation are generally mirrored by changes in muscle fascicle length. These findings also support the notion of muscle-specific changes in TT compliance after prolonged walking and highlight the ability of the CNS to maintain relatively constant movement patterns in spite of neuromechanical changes in individual muscles.