Sex differences in the neural control of muscle

Sex-differences in muscle strength have been linked to differences in muscle size, involved limb, and daily activities. Early work has shown that sex-differences are greater in the upper compared to lower limb, making the upper limb an ideal model to investigate the best statistical approaches for sex comparison. Large differences in the upper limb reveals how biomechanical factors may impact neural control. Since males and females are more comparable with respect to strength in the lower limb, it allows for a determination of whether potential sex-differences in neural control exist without large differences in biomechanics. Understanding sex-differences allows for prescription of rehabilitation and training modalities, taking into account potential specificities in sex-related neuromuscular and musculoskeletal factors. The overall purpose was to examine neural and biomechanical differences that would account for sex-differences in neural control of muscle. Manuscript 1 examined normalization versus an ANCOVA to assess sex-differences. Sex-differences were seen in elbow flexor strength and rate of force development (RFD). Normalization by either maximum strength or neural factors couldn’t account for all sex-differences in RFD, resulting in an ambiguous interpretation. In contrast, both variables were able to be incorporated in an ANCOVA to determine their relative contribution. Manuscript 2 examined the effect of task familiarization and the contribution of maximum strength, twitch contraction time, muscle fiber condition velocity, and rate of muscle activation to sex-differences in the RFD during dorsiflexion. There were no significant differences between the sexes in muscle properties, but there were differences in neural control. Additionally, across days females exhibited a neural adaptation leading to an improvement in the RFD. Manuscript 3 directly assessed potential sex-differences in neural control during force gradation by recording motor unit activity during maximal and submaximal contractions. Females had less force steadiness (FS), which may have resulted from neural compensation for a less optimal pennation angle or a tendency towards greater joint laxity. Higher motor unit discharge rates and incidence of doublets may increase twitch force summation leading to a reduction in FS. Thus, biomechanical, not inherent sex-differences in neural drive led to neural compensation strategies manifesting as a difference in FS

Neuromuscular fatigue in healthy muscle: Underlying factors and adaptation mechanisms

AbstractObjectivesThis review aims to define the concept of neuromuscular fatigue and to present the current knowledge of the central and peripheral factors at the origin of this phenomenon. This review also addresses the literature that focuses on the mechanisms responsible for the adaption to neuromuscular fatigue.MethodOne hundred and eighty-two articles indexed in PubMed (1954–2010) have been considered.ResultsNeuromuscular fatigue has central and peripheral origins. Central fatigue, preponderant during long-duration, low-intensity exercises, may involve a drop in the central command (motor, cortex, motoneurons) elicited by the activity of cerebral neurotransmitters and muscular afferent fibers. Peripheral fatigue, associated with an impairment of the mechanisms from excitation to muscle contraction, may be induced by a perturbation of the calcium ion movements, an accumulation of phosphate, and/or a decrease of the adenosine triphosphate stores. To compensate for the consequent drop in force production, the organism develops several adaptation mechanisms notably implicating motor units.ConclusionFatigue onset is associated with an alteration of the mechanisms involved in force production. Then, the interaction between central and peripheral mechanisms leads to a series of events that ultimately contribute to the observed decrease in force production

Increased Ipsilateral M1 Activation after Incomplete Spinal Cord Injury Facilitates Motor Performance

Incomplete spinal cord injury (SCI) may result in muscle weakness and difficulties with force gradation. Although these impairments arise from the injury and subsequent changes at spinal levels, changes have also been demonstrated in the brain. Blood-oxygen-level dependent (BOLD) imaging was used to investigate these changes in brain activation in the context of unimanual contractions with the first dorsal interosseous muscle. BOLD- and force data were obtained in 19 individuals with SCI (AISA Impairment Scale [AIS] C/D, level C4-C8) and 24 able-bodied controls during maximal voluntary contractions (MVCs). To assess force modulation, participants performed 12 submaximal contractions with each hand (at 10, 30, 50, and 70% MVC) by matching their force level to a visual target. MVCs were weaker in the SCI group (both hands p < 0.001), but BOLD activation did not differ between SCI and control groups. For the submaximal contractions, force (as %MVC) was similar across groups. However, SCI participants showed increased activity of the ipsilateral motor cortex and contralateral cerebellum across all contractions, with no differential effect of force level. Activity of ipsilateral M1 was best explained by force of the target hand (vs. the non-target hand). In conclusion, the data suggest that after incomplete cervical SCI, individuals remain capable of producing maximal supraspinal drive and are able to modulate this drive adequately. Activity of the ipsilateral motor network appears to be task related, although it remains uncertain how this activity contributes to task performance and whether this effect could potentially be harnessed to improve motor functioning

Parameter interdependence and success of skeletal muscle modelling

In muscle and movement modelling it is almost invariably assumed that force actually exerted is determined by several independent factors. This review considers the fact that length force characteristics are not a relatively fixed property of muscle but should be considered the product of a substantial number of interacting factors. Level of activation and recruitment are influential factors in relation to aspects of muscle architecture. For the level of activation effects of its short term history (potentiation, fatigue in sustained contractions) have to be taken into account and are reviewed on the basis of recent experimental results as well as available literature. History is also an important determinant for the effect of length changes. This concept is introduced on the basis of recent experimental evidence as well as available literature. Regarding effects of muscle architecture, the concepts of primary and secondary distribution of fibre mean sarcomere length are introduced as well as effects of muscle geometry for mono- and bi-articular muscles on those distributions. Implications for motor control are discussed and the need for intramuscular coordination indicated

Task-Dependent Properties of the Human Anconeus Muscle

Recording motor unit (MU) action potentials during fast muscle contractions, specifically during movement, presents unique challenges that constrain the investigation of the upper limits of human MU performance. The anconeus muscle exhibits many advantageous characteristics that suggest it is an appealing model for the study of MU behaviour in challenging experiment paradigms. Thus, the purpose was to determine the MU recruitment and discharge properties associated with the generation of movement up to maximal angular velocities of elbow extension and to determine the effect of submaximal fatiguing movements on these MU properties. Due to the synergistic nature of the anconeus in the elbow extensor muscle group, a secondary purpose was to determine whether MUs of the muscles comprising the elbow extensor group behave differently during the production of high forces. Discharge rates and recruitment thresholds were tracked in 24 and 17 MUs, respectively. It was revealed that anconeus MUs increase discharge rates over two distinct linear ranges possessing different input-output gain relationships relative to elbow extension velocity. Anconeus MUs exhibited variable responses to increased resultant velocity when recruitment thresholds were considered. These variable responses, that were more common in higher threshold MUs, indicated that a compression of the MU recruitment range of the anconeus occurred as elbow extension velocity increased. Using the same recording techniques, fatigue-related changes in discharge rates and recruitment thresholds of 12 MUs were determined throughout a protocol comprised of fast, maximal, static muscle contractions, and submaximal and periodic maximal movements. Results of this study demonstrated that MU properties are graded differently in response to submaximal fatiguing movements depending on the intensity of the movement, but that contraction type did not affect the relative changes in these MU properties. Lastly, MUs in three elbow extensors including the anconeus were tracked during constant joint angle force production to near maximal intensities. Differences between the elbow extensors were observed for MU discharge rates and recruitment thresholds with increasing force. These findings support an integrated model of earlier established MU control strategies for the elbow extensors and show anconeus MU recruitment occurs over a greater range than previously believed

The relation between neuromechanical parameters and Ashworth score in stroke patients

Quantifying increased joint resistance into its contributing factors i.e. stiffness and viscosity ("hypertonia") and stretch reflexes ("hyperreflexia") is important in stroke rehabilitation. Existing clinical tests, such as the Ashworth Score, do not permit discrimination between underlying tissue and reflexive (neural) properties. We propose an instrumented identification paradigm for early and tailor made interventions.BioMechanical EngineeringMechanical, Maritime and Materials Engineerin

Peptidergic modulation of motor neuron output via CART signaling at C bouton synapses

Funding: This work was supported by the General Secretariat for Research and Technology (ARISTEIA II 4257, L.Z.), Fondation SANTE (L.Z.), a Marie Curie Re-Integration Grant (268323, L.Z.), the Hellenic Foundation for Research and Innovation (spinMNALS, 4013, L.Z.) and by a St. Andrews Restarting Research Fund (S.A.S. and G.B.M.). S.A.S. was funded by a Royal Society Newton International Fellowship (NIF/R1/180091) and a Natural Sciences and Engineering Research Council of Canada (NSERC) Postdoctoral Fellowship (NSERC-PDF-517295-2018) and M.M. by the National Scholarship Foundation (IKY).The intensity of muscle contraction, and therefore movement vigour, needs to be adaptable to enable complex motor behaviors. This can be achieved by adjusting the properties of motor neurons, which form the final common pathway for all motor output from the central nervous system. Here we identify novel roles for a neuropeptide, Cocaine and Amphetamine Regulated Transcript (CART), in the control of movement vigour. We reveal distinct, but parallel mechanisms by which CART and acetylcholine, both released at C bouton synapses on motor neurons, selectively amplify the output of subtypes of motor neurons that are recruited during intense movement. We find that mice with broad genetic deletion of CART or selective elimination of acetylcholine from C boutons exhibit deficits in behavioral tasks that require higher levels of motor output. Overall, these data uncover novel spinal modulatory mechanisms that control movement vigour to support movements that require a high degree of muscle force.Publisher PDFPeer reviewe

Differential behaviour of distinct motoneuron pools that innervate the triceps surae

It has been shown that when humans lean in various directions, the central nervous system (CNS) recruits different motoneuron pools for task completion; common units that are active during different leaning directions, and unique units that are active in only one leaning direction. We used high-density surface electromyography (HD-sEMG) to examine if motor unit (MU) firing behaviour was dependent on leaning direction, muscle (medial and lateral gastrocnemius; soleus), limits of stability, or whether a MU is considered common or unique. Fourteen healthy participants stood on a force platform and maintained their center of pressure in five different leaning directions. HD-sEMG recordings were decomposed into MU action potentials and the average firing rate (AFR), coefficient of variation (CoVISI) and firing intermittency were calculated on the MU spike trains. During the 30-90º leaning directions both unique units and common units had higher firing rates (F = 31.31, p \u3c 0.0001). However, the unique units achieved higher firing rates compared to the common units (mean estimate difference = 3.48 Hz, p \u3c 0.0001). The CoVISI increased across directions for the unique units but not for the common units (F = 23.65. p \u3c 0.0001). Finally, intermittent activation of MUs was dependent on the leaning direction (F = 11.15, p \u3c 0.0001), with less intermittent activity occurring during diagonal and forward-leaning directions. These results provide evidence that the CNS can preferentially control separate motoneuron pools within the ankle plantarflexors during voluntary leaning tasks for the maintenance of standing balance

Kinematic Basis for Body Specific Locomotor Mechanics and Perturbation Responses

Animals have evolved mechanical and neural strategies for locomotion in almost every environment, overcoming the complexities of their habitats using specializations in body structure and animal behavior. These specializations are created by neural networks responsible for generating and altering muscle activation. Species specific musculoskeletal anatomy and physiology determine how locomotion is controlled through the transformation of motor patterns into body movements. Furthermore, when these species specific locomotor systems encounter perturbations during running and walking their behavioral and mechanical attributes determine how stability is established during and after the perturbation. It is still not understood how species specific structural and behavioral variables contribute to locomotion in non-uniform environments. To understand how these locomotor properties produce unique gaits and stability strategies we compared three species of brachyuran crabs during normal and perturbed running. Although all crabs ran sideways, morphological and kinematic differences explained how each species produced its unique gait and stability response. Despite the differences in running behavior and perturbation response, animals tended to use locomotor resources that were in abundance during stabilizing responses. Each crab regained stability during the perturbation response by altering leg joint movements or harnessing the body\u27s momentum. These species body designs and running behavior show how slight changes in body structure and joint kinematics can produce locomotor systems with unique mechanical profiles and abilities. Understanding how evolutionary pressures have optimized animals\u27 locomotor ability to successfully move in different environments will provide a deeper understanding of how to mimic these movements through mathematical models and robotics

Acetylcholine Receptors and Concanavalin A-Binding Sites on Cultured Xenopus Muscle Cells: Electrophoresis, Diffusion, and Aggregation

Using digitally analyzed fluorescence videomicroscopy, we have examined the behavior of acetylcholine receptors and concanavalin A binding sites in response to externally applied electric fields. The distributions of these molecules on cultured Xenopus myoballs were used to test a simple model which assumes that electrophoresis and diffusion are the only important processes involved. The model describes the distribution of concanavalin A sites quite well over a fourfold range of electric field strengths; the results suggest an average diffusion constant of ~2.3 X 10^(-9) cm^2/s. At higher electric field strengths, the asymmetry seen is substantially less than that predicted by the model. Acetylcholine receptors subjected to electric fields show distributions substantially different from those predicted on the basis of simple electrophoresis and diffusion, and evidence a marked tendency to aggregate. Our results suggest that this aggregation is due to lateral migration of surface acetylcholine receptors, and is dependent on surface interactions, rather than the rearrangement of microfilaments or microtubules. The data are consistent with a diffusion-trap mechanism of receptor aggregation, and suggest that the event triggering receptor localization is a local increase in the concentration of acetylcholine receptors, or the electrophoretic concentration of some other molecular species. These observations suggest that, whatever mechanism(s) trigger initial clustering events in vivo, the accumulation of acetylcholine receptors can be substantially enhanced by passive, diffusion-mediated aggregation