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

Neurophysiological responses and adaptation to muscle shortening and lengthening in young and older adults

Healthy aging is characterised by alterations in the nervous system, leading to decrements in neuromuscular performance, particularly during dynamic contractions. Muscle shortening and lengthening differently modulate the corticospinal output, with the possibility of this modulation being altered in aging adults, which might affect the adaptability of an aging neuromuscular system to maximal lengthening contractions. The aim of this thesis was to elucidate the differences in neurophysiological responses and adaptation to muscle shortening and lengthening between young and older adults. It was hypothesised that the age-related alterations in the nervous system will lead to impaired sensorimotor integration with muscle length changes and reduced corticospinal responses during dynamic contractions, impairing the adaptability of older adults to maximal lengthening contractions. In Study 1, a novel method for assessment of subcortical excitability of descending tracts was developed, followed by investigation of corticospinal responses during passive muscle shortening and lengthening. Corticospinal excitability was modulated by muscle length changes in young adults, likely through inhibitory input of muscle spindle afferents on cortical areas. In contrast, older adults showed no modulation, which may be linked to altered sensorimotor integration. In Study 2, a method for normalising torque outputs during submaximal dynamic contractions was developed, followed by assessment of muscle fascicle behaviour. Subsequently, evoked responses were assessed during submaximal contractions of different types in young and older individuals. Despite preserved maximal torque producing capacity, corticospinal responses were reduced in older compared with younger adults across contraction types, along with increased torque variability during dynamic contractions. Study 3 assessed the contribution of spinal and supraspinal properties in adaptation to repeated bouts of maximal lengthening contractions in young and older adults. Less damage was incurred in older individuals, but the rate of adaptation was similar between young and older adults. However, the corticospinal processes played a limited role in the adaptive response. This work extends the understanding of the modulation of corticospinal networks with muscle shortening and lengthening and age-related alterations in corticospinal pathway during dynamic contractions. It also suggests that the adaptability of an aging neuromuscular system to maximal dynamic contractions remains preserved

Linear Parameter Varying Identification of Dynamic Joint Stiffness during Time-Varying Voluntary Contractions

Dynamic joint stiffness is a dynamic, nonlinear relationship between the position of a joint and the torque acting about it, which can be used to describe the biomechanics of the joint and associated limb(s). This paper models and quantifies changes in ankle dynamic stiffness and its individual elements, intrinsic and reflex stiffness, in healthy human subjects during isometric, time-varying (TV) contractions of the ankle plantarflexor muscles. A subspace, linear parameter varying, parallel-cascade (LPV-PC) algorithm was used to identify the model from measured input position perturbations and output torque data using voluntary torque as the LPV scheduling variable (SV). Monte-Carlo simulations demonstrated that the algorithm is accurate, precise, and robust to colored measurement noise. The algorithm was then used to examine stiffness changes associated with TV isometric contractions. The SV was estimated from the Soleus EMG using a Hammerstein model of EMG-torque dynamics identified from unperturbed trials. The LPV-PC algorithm identified (i) a non-parametric LPV impulse response function (LPV IRF) for intrinsic stiffness and (ii) a LPV-Hammerstein model for reflex stiffness consisting of a LPV static nonlinearity followed by a time-invariant state-space model of reflex dynamics. The results demonstrated that: (a) intrinsic stiffness, in particular ankle elasticity, increased significantly and monotonically with activation level; (b) the gain of the reflex pathway increased from rest to around 10–20% of subject's MVC and then declined; and (c) the reflex dynamics were second order. These findings suggest that in healthy human ankle, reflex stiffness contributes most at low muscle contraction levels, whereas, intrinsic contributions monotonically increase with activation level

Cortical Involvement During Sustained Lower Limb Contractions

Despite the critical role of the lower limb during functional tasks such as walking, most studies examining the role of the cortex during muscle contractions have been conducted in upper limb muscles. Modulation of force by the cortex in the lower extremity and the influence of cortical inputs are poorly understood. The purpose of this dissertation was to investigate the role the cortex plays in modulating force control during static contractions with the lower limb and to determine the influence of manipulating cortical inputs. Aim 1 determined the cortical regions involved in force-related changes between low and high forces and those areas that modulate steadiness (force fluctuations) during sustained isometric ankle dorsiflexion contractions in young men and women. This was achieved using functional magnetic imaging (fMRI). Both motor and some typically associated non-motor brain areas were active during lower limb force production and scaled linearly as force increased. Steadiness was associated with both motor and non-motor brain areas with minimal differences in areas activated between men and women. Aim 2 examined the influence of cognitive demand (null, low-cognitive demand, high-cognitive demand) on fatigability and steadiness of low- to moderate-force isometric contractions in young and older men and women. Women demonstrated greater force fluctuations than men during both the low- and moderate-force contractions and their motor output was influenced by changes in cognitive demand. Older adults were less steady than young during low- and moderate-force contractions, had greater age-related reductions in steadiness, and greater variability in fatigability when cognitive demand was increased. This dissertation shows that cortical inputs are very important to lower limb motor control of static voluntary contractions. Cortical motor and non-motor regions that are important for control of force intensity and steadiness of lower limb contractions were identified and are key areas for potential cortical plasticity with impaired or enhanced leg function. Steadiness was altered by increasing cortical inputs (cognitive demand) especially in older adults whose motor performance was impaired and more variable than young. These results have important performance implications for cognitively demanding and low- to moderate-force tasks that are common to daily function in older adults

Muscular Properties and Balance Control in Older Adults

The goal of this dissertation was to understand the role of age-related changes in muscle mechanical properties in the control of upright posture in humans. First, a methodology for estimating subject-specific muscle properties in healthy young and older individuals was developed. Magnetic resonance and ultrasound imaging were used in conjunction with dynamometer experiments, musculoskeletal modeling, and numerical optimization to estimate the properties of the dorsiflexor and individual plantarflexor (gastrocnemius and soleus) muscles for 12 young and 12 older adults (balanced for gender). With aging there were declines in maximal isometric strength and increases in series-elastic stiffness in the male subjects, but no differences in the female subjects. Regardless of gender, there were age-related changes in the shape of the force-velocity relation, such that the older subjects produced less relative force during both concentric and eccentric muscle contractions. The second study tested the balance abilities of the same subjects under a variety of static (quiet stance, leaning forward/backward) and dynamic (swaying at preferred/imposed frequencies, maximal reaching, external perturbation) conditions. The older adults performed more poorly on most of the balance tasks. While maximal isometric force made a smaller than expected contribution to predicting balancing ability, the force-length, force-velocity and force-extension properties of the muscles were all predictive of the age-related declines in balance control, explaining ~40% of the variance as independent predictors and ~50% when these factors were combined. Finally, a feedback-driven inverted pendulum model of postural control was developed, which incorporated realistic representations of young and old dorsiflexor and individual plantarflexor muscles using the previously estimated mechanical properties. A sensitivity analysis was performed by manipulating the properties of the plantarflexor muscles. The balancing ability of the model was most influenced by the optimal length of the contractile component and the slack length of the series elastic component of the plantarflexor muscle models. The quiet stance model highlighted the importance of the force-length relation of muscle to the stabilization of upright posture. This dissertation demonstrated that there are age-related changes in the dorsi- and plantarflexor mechanical properties, and these changes are associated with the declines in postural control that accompany aging

The influence of training and athletic performance on the neural and mechanical determinants of muscular rate of force development

Neuromuscular explosive strength (defined as rate of force development; RFD) is considered important during explosive functional human movements; however this association has been poorly documented. It is also unclear how different variants of strength training may influence RFD and its neuromuscular determinants. Furthermore, RFD has typically been measured in isometric situations, but how it is influenced by the types of contraction (isometric, concentric, eccentric) is unknown. This thesis compared neuromuscular function in explosive power athletes (athletes) and untrained controls, and assessed the relationship between RFD in isometric squats with sprint and jump performance. The athletes achieved a greater RFD normalised to maximum strength (+74%) during the initial phase of explosive contractions, due to greater agonist activation (+71%) in this time. Furthermore, there were strong correlations (r2 = 0.39) between normalised RFD in the initial phase of explosive squats and sprint performance, and between later phase absolute explosive force and jump height (r2 = 0.37), confirming an association between explosive athletic performance and RFD. This thesis also assessed the differential effects of short-term (4 weeks) training for maximum vs. explosive strength, and whilst the former increased maximum strength (+20%) it had no effect on RFD. In contrast explosive strength training improved explosive force production over short (first 50 ms; +70%) and long (>50 ms; +15%) time periods, due to improved agonist activation (+65%) and maximum strength (+11%), respectively. Explosive strength training therefore appears to have greater functional benefits than maximum strength training. Finally, the influence of contraction type on RFD was assessed, and the results provided unique evidence that explosive concentric contractions are 60% more effective at utilising the available force capacity of the muscle, that was explained by superior agonist activation. This work provides a comprehensive analysis of the association between athletic performance and RFD, the differential effects of maximum vs. explosive strength training, and the influence of contraction type on the capacity for RFD

Mathematical description of in-vivo muscle function

Mathematical relationships have long been used to describe many aspects of muscle function such as the relationship between muscle force and muscle length, muscle force and velocity of contraction or the degree of muscle activation during a contraction. During this work various mathematical expressions have been employed in order to gain an insight into different aspects of muscle activity. The first part of the work examined whether performing a strength protocol on a dynamometer can lead to an increase in eccentric strength output as well as in the neuromuscular activation of the quadriceps group of muscles that appears inhibited during slow concentric and fast eccentric contractions. Neuromuscular activation was modelled via a three-parameter sigmoid function that was also tested for robustness to perturbations in the maximum activation values. During the second part of the study the "functional" hamstrings to quadriceps ratio H:Qfun was expressed as a function of two variables i.e., angular velocity and joint angle. Initially nine-parameter torque-angular velocity-angle profiles were obtained for the knee extensors and flexors from a group of participants. A theoretical 17- parameter H:Qfun function was then derived for each dataset. Subsequently, a simpler, 6-parameter function was derived, RE = aexp(bωn + cθm)-dω1/2θ2 that best reproduced the original 17-parameter fit. Finally, a six-segment subject specific torque-driven model of the Snatch lift was developed in order to investigate the optimal mechanics of the lift. The model simulated the lift from its initiation until the end of the second pull when the feet of the athlete momentarily leave the platform. The six-segment model comprised of foot, shank, thigh, torso (head + trunk), arm and forearm segments with torque generators at the ankle, knee, hip and shoulder joints respectively. The torque profiles were obtained using an isokinetic dynamometer

You are as fast as your motor neurons: speed of recruitment and maximal discharge of motor neurons determine the maximal rate of force development in humans

During rapid contractions, motor neurons are recruited in a short burst and begin to discharge at high frequencies (up to >200 Hz). In the present study, we investigated the behaviour of relatively large populations of motor neurons during rapid (explosive) contractions in humans, applying a new approach to accurately identify motor neuron activity simultaneous to measuring the rate of force development. The activity of spinal motor neurons was assessed by high-density electromyographic decomposition from the tibialis anterior muscle of 20 men during isometric explosive contractions. The speed of motor neuron recruitment and the instantaneous motor unit discharge rate were analysed as a function of the impulse (the time–force integral) and the maximal rate of force development. The peak of motor unit discharge rate occurred before force generation and discharge rates decreased thereafter. The maximal motor unit discharge rate was associated with the explosive force variables, at the whole population level (r 2  = 0.71 ± 0.12; P < 0.001). Moreover, the peak motor unit discharge and maximal rate of force variables were correlated with an estimate of the supraspinal drive, which was measured as the speed of motor unit recruitment before the generation of afferent feedback (P < 0.05). We show for the first time the full association between the effective neural drive to the muscle and human maximal rate of force development. The results obtained in the present study indicate that the variability in the maximal contractile explosive force of the human tibialis anterior muscle is determined by the neural activation preceding force generation

Mechanisms of Impaired Motor Unit Firing Behavior in the Vastus Lateralis Muscle after Stroke

The purpose of this dissertation research project was to examine the role of impaired motor unit firing behavior on force generation after a stroke. We studied the relationship between intrinsic motoneuron properties and inhibitory sensory pathways to deficient motoneuron activity in the vastus lateralis muscle after a stroke. Individuals with stroke often have deficits with force generation and volitional relaxation. Current models of impaired force output after a stroke focus primarily on the pathology within the corticospinal pathway because of decreased descending drive. Though this is an important aspect of deficient motoneuron output, it is incomplete because motoneurons receive other inputs that can shape motor output. Because the motoneuron is the last site of signal integration for muscle contractions, using methods that study motor unit activity can provide a window to the activity in the spinal circuitry. This research study utilized a novel algorithm that decomposed electromyography (EMG) signals into the contributions of the individual motor units. This provided the individual firing instances for a large number of concurrently active motor units during isometric contractions of the knee extensors. In the first aim, the association between the hyperemic response and motor unit firing rate modulation to intermittent, fatiguing contractions was investigated. It was found that the magnitude of blood flow was lower for individuals with stroke compared to healthy controls, but both groups increased blood flow similarly in response to fatiguing contractions. This did not relate to changes in muscle fiber contractibility for the participants with stroke; rather, participants better able to increase blood flow showed greater modulation in motor unit firing rates. To further investigate how ischemic conditions impact motor unit output, the second aim used a blood pressure cuff to completely occlude blood flow through the femoral artery with the intent of activating inhibitory afferent pathways. We found that ischemic conditions had a greater inhibitory impact on motor unit output for individuals with stroke compared to healthy controls, possibly because of hyper-excitable group III/IV afferent pathways. The final aim investigated how stroke related changes in the intrinsic excitability of the motoneurons impacted prolonged motor unit firing during voluntary relaxation. A serotonin reuptake inhibitor was administered to quantify motoneuron sensitivity to neuromodulatory inputs. This study found that the serotonin reuptake inhibitor increased muscle relaxation and may have reduced persistent inward current contributions to prolonged motor unit firing. In conclusion, while damage to the corticospinal tract is a major component to poor functionality, the intrinsic properties of the motoneuron and sensory pathways to the motoneuron pool are essential for understanding deficient motor control after a stroke