Kelvin E. Jones

The scaling of motor noise with muscle strength and motor unit number in humans

Understanding the origin of noise, or variability, in the motor system is an important step towards understanding how accurate movements are performed. Variability of joint torque during voluntary activation is affected by many factors such as the precision of the descending motor commands, the number of muscles that cross the joint, their size and the number of motor units in each. To investigate the relationship between the peripheral factors and motor noise, the maximum voluntary torque produced at a joint and the coefficient of variation of joint torque were recorded from six adult human subjects for four muscle/joint groups in the arm. It was found that the coefficient of variation of torque decreases systematically as the maximum voluntary torque increases. This decreasing coefficient of variation means that a given torque or force can be more accurately generated by a stronger muscle than a weaker muscle. Simulations demonstrated that muscles with different strengths and different numbers of motor units could account for the experimental data. In the simulations, the magnitude of the coefficient of variation of muscle force depended primarily on the number of motor units innervating the muscle, which relates positively to muscle strength. This result can be generalised to the situation where more than one muscle is available to perform a task, and a muscle activation pattern must be selected. The optimal muscle activation pattern required to generate a target torque using a group of muscles, while minimizing the consequences of signal dependent noise, is derived.

Dendritic L-type calcium currents in mouse spinal motoneurons: implications for bistability.

The intrinsic properties of mammalian spinal motoneurons provide them with the capability to produce high rates of sustained firing in response to transient inputs (bistability). Even though it has been suggested that a persistent dendritic calcium current is responsible for the depolarizing drive underlying this firing property, such a current has not been demonstrated in these cells. In this study, calcium currents are recorded from functionally mature mouse spinal motoneurons using somatic whole‐cell patch‐clamp techniques. Under these conditions a component of the current demonstrated kinetics consistent with a current originating at a site spatially segregated from the soma. In response to step commands this component was seen as a late‐onset, low amplitude persistent current whilst in response to depolarizing–repolarizing ramp commands a low voltage clockwise current hysteresis was recorded. Simulations using a neuromorphic motoneuron model could reproduce these currents only if a noninactivating calcium conductance was placed in the dendritic compartments. Pharmacological studies demonstrated that both the late‐onset and hysteretic currents demonstrated sensitivity to both dihydropyridines and the L‐channel activator FPL‐64176. Furthermore, the α1D subunits of L‐type calcium channels were immunohistochemically demonstrated on motoneuronal dendrites. It is concluded that there are dendritically located L‐type channels in mammalian motoneurons capable of mediating a persistent depolarizing drive to the soma and which probably mediate the bistable behaviour of these cells.

Improvements in skeletal muscle strength and cardiac function induced by resveratrol during exercise training contribute to enhanced exercise performance in rats

•  Resveratrol, an antioxidant found in red wine, has beneficial effects on cardiac and skeletal muscle function, similar to the effects of endurance exercise training. •  Combining resveratrol supplementation with exercise training augments the beneficial effects of exercise alone. •  We show that endurance capacity is enhanced in rats whose diet includes resveratrol during a 12 week endurance‐training programme. •  Increased endurance was associated with increases in skeletal muscle force, cardiac function, and oxidative metabolism. •  Our results establish that resveratrol is an effective ergogenic aid that enhances exercise performance over exercise alone.

Directional tuning of human forearm muscle afferents during voluntary wrist movements

1 Single unit activity was recorded with the microneurography technique from sixteen spindle afferents and one Golgi tendon organ afferent originating from the forearm extensor muscles. Impulse rates were studied while subjects performed unobstructed aiming movements at the wrist in eight different directions 45 deg apart. In addition, similar imposed movements were performed while the subject was instructed to remain relaxed. Movement amplitudes were about 5 deg and the speed 10–30 deg s−1. Joint movements were translated to movements of a cursor on a monitor to provide visual feedback. 2 Individual spindle afferents modulated their activity over a number of targets, i.e. were broadly tuned, during these aiming movements. The preferred direction for a spindle afferent was the same during both passive and active movements, indicating that the fusimotor effects associated with active contractions had little or no effect on the direction of tuning. 3 The direction of tuning of individual spindle afferents could be predicted from the biomechanically inferred length changes of the parent muscle. Thus spindle afferents responded as stretch receptors, i.e. impulse rates increased with lengthening and decreased with shortening, in active as well as passive movements. 4 Spindles from muscles, which continuously counteracted gravity exhibited a stretch response and directional tuning during the phase of movement alone whereas their position sensitivity was poor. In contrast, spindle afferents from the muscles that had no or minimal antigravity role were directionally tuned during both the dynamic and the static phase of the aiming task and their position sensitivity was substantially higher. 5 In spite of the limited data base from three extensor muscles it could be demonstrated that wrist joint position was remarkably well encoded in the ensemble muscle spindle data. In some cases the ensemble muscle spindle data encoded the instantaneous trajectory of movement as well.

Ankle position and voluntary contraction alter maximal M waves in soleus and tibialis anterior

Compound muscle action potentials (CMAPs) recorded using surface electrodes are often used to assess the excitability of neural pathways to skeletal muscle. However, the amplitude of CMAPs can be influenced by changes at the recording site, independent of mechanisms within the central nervous system. We quantified how joint angle and background contraction influenced CMAP amplitude. In seven subjects CMAPs evoked by supramaximal transcutaneous electrical stimulation of motor axons (Mmax) were recorded using surface electrodes from soleus and tibialis anterior (TA) at static positions over the full range of ankle movement at 5° intervals. Across subjects the peak‐to‐peak amplitude of Mmax was 155% and 159% larger at the shortest than longest muscle lengths for soleus and TA, respectively. In five subjects the effect of ankle position and voluntary contraction on M‐wave/H‐reflex recruitment curves was assessed in the soleus. Both ankle position and level of contraction significantly influenced Mmax, Hmax, and the Hmax to Mmax ratio, but there were no interactions between the two parameters. These peripheral changes that influence Mmax will also impact other CMAPs such as submaximal M‐waves, H‐reflexes, and responses to transcranial magnetic stimulation. As such, during experimental studies CMAPs evoked at a given joint angle and contraction level should be normalized to Mmax recorded at similar joint angle and contraction strength. Muscle Nerve, 2007

Erbstatin blocks platelet activating factor-induced protein-tyrosine phosphorylation, polyphosphoinositide hydrolysis, protein kinase C activation, serotonin secretion and aggregation of rabbit platelets

The role of protein‐tyrosine phosphorylation in the signal transduction of platelet activating factor (PAF) was investigated in rabbit platelets with a range of synthetic compounds that inhibit protein‐tyrosine kinases. In particular, erbstatin (IC50~20 ) abrogated a wide range of platelet responses to PAF, including tyrosine phosphorylation of cellular proteins, polyphosphoinositide turnover, activation of membranous protein kinase C, platelet aggregation, and serotonin secretion. With about a third of the potency of erbstatin, compound RG50864 also inhibited many of these responses, whereas at 100 , genistein, 670C88 and ST271 were without effect. Finally, the ability of thrombin to cause platelet aggregation and serotonin secretion was also compromised by erbstatin.

Proprioceptive feedback is reduced during adaptation to a visuomotor transformation: preliminary findings.

Adapting movements in relation to visual feedback is a ubiquitous characteristic of sensorimotor control and involves the integration of multiple sources of sensory information. We recorded sensory feedback from muscle spindle afferents during visuomotor adaptation while subjects performed an aiming task to investigate whether the activity of the muscle spindles was modulated by the fusimotor system under these learning conditions. None of the muscle spindles showed an increase in activity, rather in 83% of the trials the firing rates were decreased. These preliminary results suggest that the CNS reduces the sensory signals arising from muscle spindles perhaps as a means of resolving the conflict between visual and proprioceptive feedback during the task.

Comparison of the depression of H-reflexes following previous activation in upper and lower limb muscles in human subjects

Abstract When conditioning-testing (C-T) stimuli are applied to Ia afferents to elicit H-reflexes, the test reflex is abolished immediately following the conditioning reflex. As the C-T interval is increased, the test response slowly begins to recover, taking several hundred milliseconds to attain control values. The time course of this recovery is known as the H-reflex recovery curve. H- reflex recovery curves were compared using surface EMG and single motor unit activities in lower limb soleus and upper limb flexor carpi radialis (FCR) muscles in seven healthy human subjects. Under rest conditions, the recovery of H-reflexes and single motor unit activity was slow for soleus; the recovery was not complete even in 1 s. In comparison, the recovery was very fast for FCR motor units, occurring in 200–300 ms. The effects of rate of stimulation (0.1–10.0 imp/s) were also examined on the magnitude of H-reflex responses. The reflex response declined with increasing rate of stimulation, the decline being slightly greater in soleus than in FCR. When these phenomena were examined with voluntary facilitation of the spinal cord, the time of recovery shortened and the effect of stimulus rate also diminished. Changes with background facilitation were greater in FCR than in soleus. The differences between the two muscles are attributed mainly to differences in presynaptic inhibition in the two spinal segments, and/or to the differences in dynamics of the transmitter release in terminals of Ia afferents synapsing with slow soleus motoneurons and those synapsing with the fast FCR motoneurons.

A modelling study of locomotion‐induced hyperpolarization of voltage threshold in cat lumbar motoneurones

During fictive locomotion the excitability of adult cat lumbar motoneurones is increased by a reduction (a mean hyperpolarization of ≈6.0 mV) of voltage threshold (Vth) for action potential (AP) initiation that is accompanied by only small changes in AP height and width. Further examination of the experimental data in the present study confirms that Vth lowering is present to a similar degree in both the hyperpolarized and depolarized portions of the locomotor step cycle. This indicates that Vth reduction is a modulation of motoneurone membrane currents throughout the locomotor state rather than being related to the phasic synaptic input within the locomotor cycle. Potential ionic mechanisms of this locomotor‐state‐dependent increase in excitability were examined using three five‐compartment models of the motoneurone innervating slow, fast fatigue resistant and fast fatigable muscle fibres. Passive and active membrane conductances were set to produce input resistance, rheobase, afterhyperpolarization (AHP) and membrane time constant values similar to those measured in adult cat motoneurones in non‐locomoting conditions. The parameters of 10 membrane conductances were then individually altered in an attempt to replicate the hyperpolarization of Vth that occurs in decerebrate cats during fictive locomotion. The goal was to find conductance changes that could produce a greater than 3 mV hyperpolarization of Vth with only small changes in AP height (< 3 mV) and width (< 1.2 ms). Vth reduction without large changes in AP shape could be produced either by increasing fast sodium current or by reducing delayed rectifier potassium current. The most effective Vth reductions were achieved by either increasing the conductance of fast sodium channels or by hyperpolarizing the voltage dependency of their activation. These changes were particularly effective when localized to the initial segment. Reducing the conductance of delayed rectifier channels or depolarizing their activation produced similar but smaller changes in Vth. Changes in current underlying the AHP, the persistent Na+ current, three Ca2+ currents, the ‘h’ mixed cation current, the ‘A’ potassium current and the leak current were either ineffective in reducing Vth or also produced gross changes in the AP. It is suggested that the increased excitability of motoneurones during locomotion could be readily accomplished by hyperpolarizing the voltage dependency of fast sodium channels in the axon hillock by a hitherto unknown neuromodulatory action.

Control of the wrist joint in humans.

Abstract As one considers changes in motor activity from lower mammals to higher primates, one of the major changes one observes lies in the cortical control of forelimb muscles. There has been a shift from disynaptic control of spinal motoneurons in, for example, the cat, to a greater and greater percentage of monosynaptic control of hand and forelimb motoneurons in the primate. In spite of the species and evolutionary changes in the synaptic connections of the corticospinal tract, it appears that the interneurons identified in the cat are retained in the monkey and human. These interneurons, under the influence of descending pathways, modulate the output of motoneuron pools. Perhaps the control of these interneurons has also changed towards finer control of movement, as has been suggested by recent studies in the monkey. Whether in cat or human, the recruitment pattern for motor units is the same; the change from disynaptic to monosynaptic connections has not changed the recruitment pattern of muscles. Differences in the recruitment patterns of muscles may lie in the finer control of inputs to motoneurons in the primate. This review seeks to integrate the current knowledge of the mechanisms involved in the motor control of the wrist joint and especially in the recruitment patterns of the muscles. These motor control mechanisms include the biomechanics of the wrist joint, recruitment patterns of wrist muscles, interneurons and spinal cord circuits in the cervical regions mediating the output of spinal motoneurons, and the supraspinal control of these muscles.