A Principle of Neuromechanical Matching for Motor Unit Recruitment in Human Movement

What determines which motor units are active in a motor task? In the respiratory muscles, motor units are recruited according to their mechanical advantages. We describe a principle of motor unit recruitment by neuromechanical matching due to mechanisms in the spinal cord that sculpt descending drive to motoneurons. This principle may be applicable to movements in nonrespiratory muscles

Geochronological challenges posed by continuously developing tectonometamorphic systems: insights from Rb–Sr mica ages from the Cycladic Blueschist Belt, Syros (Greece).

Is metamorphism and its causative tectonics best viewed as a series of punctuated events or as a continuum? This question is addressed through examination of the timing of exhumation of the Cycladic Blueschist Belt (CBB). The cause of scatter beyond analytical error in Rb–Sr geochronology was investigated using a suite of 39 phengite samples. Rb–Sr ages have been measured on phengite microsamples drilled from specific microstructures in thin sections of calcschists and metabasites from the CBB on Syros. The majority are from samples that have well-preserved blueschist facies mineral assemblages with limited greenschist facies overprint. The peak metamorphic temperatures involved are below the closure temperature for white mica so that crystallization ages are expected to be preserved. This is supported by the coexistence of different ages in microstructures of different relative age; in one sample phengite from the dominant extensional blueschist facies fabric preserves an age of 35 Ma while post-tectonic mica, millimetres away, has an age of 26 Ma. The results suggest that micro-sampling techniques linked to detailed microstructural analysis are critical to understanding the timing and duration of deformation in tectonometamorphic systems. North of the Serpentinite Belt in northern Syros, phengite Rb–Sr ages are generally between 53 and 46 Ma, comparable to previous dates from this area. South of the Serpentinite Belt phengite in blueschist facies assemblages associated with extensional fabrics linked to exhumation have ages that range from 42 Ma down to c. 30 Ma indicating that extensional deformation while still under blueschist facies conditions continued until 30 Ma. No age measurements on samples with unambiguous evidence of deformation under greenschist facies conditions were made; two rocks with greenschist facies assemblages gave phengite ages that overlap with the younger blueschist samples, suggesting blueschist facies phengite is preserved in these rocks. Two samples yielded ages below 27 Ma; one is from a post-tectonic microstructure, the other from a greenschist in which the fabric developed during earlier blueschist facies conditions. These ages are consistent with previous evidence of greenschist facies conditions from c. 25 Ma onwards. The data are consistent with a model of deformation that is continuous on a regional scale

Respiratory muscle activity in voluntary breathing tracking tasks: Implications for the assessment of respiratory motor control

How the involuntary (bulbospinal) and voluntary (corticospinal) pathways interact in respiratory muscle control is not established. To determine the role of excitatory corticobulbar pathways in humans, studies typically compare electromyographic activity (EMG) or evoked responses in respiratory muscles during hypercapnic and voluntary tasks. Although ventilation is matched between tasks by having participants track signals of ventilation, these tasks may not result in matched respiratory muscle activity. The aim of this study was to describe respiratory muscle activity and ribcage and abdominal excursions during two different voluntary conditions, compared to hypercapnic hyperventilation. Ventilation was matched in the voluntary conditions via (i) a simple target of lung volume (‘volume tracking’) or (ii) targets of both ribcage and abdominal excursions, adjusted to end-expiratory lung volume in hypercapnic hyperventilation (‘bands tracking’). Compared to hypercapnic hyperventilation, respiratory parameters such as tidal volume were similar, but the ratio of ribcage to abdominal excursion was higher for both voluntary tasks. Inspiratory scalene and parasternal intercostal muscle activity was higher in volume tracking, but diaphragm and abdominal muscle activity showed little to no change. There were no differences in muscle activity in bands tracking for any muscle, compared to hypercapnic hyperventilation. An elevated ratio of ribcage to abdominal excursion in the bands tracking task indicates that participants could not accurately match the targets in this condition. Inspiratory muscle activity is altered in some muscles in some voluntary tasks, compared to hypercapnia. Therefore, differences in muscle activity should be considered in interpretation of studies that use these protocols to investigate respiratory muscle control

The effect of paired corticospinal–motoneuronal stimulation on maximal voluntary elbow flexion in cervical spinal cord injury: an experimental study

Study design: Randomised, controlled, crossover study. Objectives: Paired corticospinal–motoneuronal stimulation (PCMS) involves repeatedly pairing stimuli to corticospinal neurones and motoneurones to induce changes in corticospinal transmission. Here, we examined whether PCMS could enhance maximal voluntary elbow flexion in people with cervical spinal cord injury. Setting: Neuroscience Research Australia, Sydney, Australia. Methods: PCMS comprised 100 pairs of transcranial magnetic and electrical peripheral nerve stimulation (0.1 Hz), timed so corticospinal potentials arrived at corticospinal–motoneuronal synapses 1.5 ms before antidromic motoneuronal potentials. On two separate days, sets of five maximal elbow flexions were performed by 11 individuals with weak elbow flexors post C4 or C5 spinal cord injury before and after PCMS or control (100 peripheral nerve stimuli) conditioning. During contractions, supramaximal biceps brachii stimulation elicited superimposed twitches, which were expressed as a proportion of resting twitches to give maximal voluntary activation. Maximal torque and electromyographic activity were also assessed. Results: Baseline median (range) maximal torque was 11 Nm (6–41 Nm) and voluntary activation was 92% (62–99%). Linear mixed modelling revealed no significant differences between PCMS and control protocols after conditioning (maximal torque: p = 0.87, superimposed twitch: p = 0.87, resting twitch: p = 0.44, voluntary activation: p = 0.36, biceps EMG: p = 0.25, brachioradialis EMG: 0.67). Conclusions: Possible explanations for the lack of effect include a potential ceiling effect for voluntary activation, or that PCMS may be less effective for elbow flexors than distal muscles. Despite results, previous studies suggest that PCMS is worthy of further investigation

Involvement of N-methyl-D-aspartate receptors in plasticity induced by paired corticospinal-motoneuronal stimulation in humans

Plasticity can be induced at human corticospinalmotoneuronal synapses by delivery of repeated, paired stimuli to corticospinal axons and motoneurons in a technique called paired corticospinal-motoneuronal stimulation (PCMS). To date, the mechanisms of the induced plasticity are unknown. To determine whether PCMS-induced plasticity is dependent on N-methyl-D-aspartate receptors (NMDARs), the effect of the noncompetitive NMDAR antagonist dextromethorphan on PCMS-induced facilitation was assessed in a 2-day, double-blind, placebo-controlled experiment. PCMS consisted of 100 pairs of stimuli, delivered at an interstimulus interval that produces facilitation at corticospinal-motoneuronal synapses that excite biceps brachii motoneurons. Transcranial magnetic stimulation elicited corticospinal volleys, which were timed to arrive at corticospinal-motoneuronal synapses just before antidromic potentials elicited in motoneurons with electrical brachial plexus stimulation. To measure changes in the corticospinal pathway at a spinal level, biceps responses to cervicomedullary stimulation (cervicomedullary motor evoked potentials, CMEPs) were measured before and for 30 min after PCMS. Individuals who displayed a ≥10% increase in CMEP size after PCMS on screening were eligible to take part in the 2-day experiment. After PCMS, there was a significant difference in CMEP area between placebo and dextromethorphan days (P ~ 0.014). On the placebo day PCMS increased average CMEP areas to 127 = 46% of baseline, whereas on the dextromethorphan day CMEP area was decreased to 86 = 33% of baseline (mean = SD; placebo: n ~ 11, dextromethorphan: n ~ 10). Therefore, dextromethorphan suppressed the facilitation of CMEPs after PCMS. This indicates that plasticity induced at synapses in the human spinal cord by PCMS may be dependent on NMDARs. NEW & NOTEWORTHY Paired corticospinal-motoneuronal stimulation can strengthen the synaptic connections between corticospinal axons and motoneurons at a spinal level in humans. The mechanism of the induced plasticity is unknown. In our 2-day, double-blind, placebo-controlled study we show that the N-methyl-D-aspartate receptor (NMDAR) antagonist dextromethorphan suppressed plasticity induced by paired corticospinal-motoneuronal stimulation, suggesting that an NMDAR-dependent mechanism is involved

Muscle electromyographic activity normalized to maximal muscle activity, not to M<inf>max</inf>, better represents voluntary activation

In human applied physiology studies, the amplitude of recorded muscle electromyographic activity (EMG) is often normalized to maximal EMG recorded during a maximal voluntary contraction. When maximal contractions cannot be reliably obtained (e.g. in people with muscle paralysis, anterior cruciate ligament injury, or arthritis), EMG is sometimes normalized to the maximal compound muscle action potiential evoked by stimulation, the Mmax. However, it is not known how these two methods of normalization affect the conclusions and comparability of studies. To address this limitation, we investigated the relationship between voluntary muscle activation and EMG normalized either to maximal EMG or to Mmax. Twenty-five able-bodied adults performed voluntary isometric ankle plantarflexion contractions to a range of percentages of maximal voluntary torque. Ankle torque, plantarflexor muscle EMG, and voluntary muscle activation measured by twitch interpolation were recorded. EMG recorded at each contraction intensity was normalized to maximal EMG or to Mmax for each plantarflexor muscle, and the relationship between the two normalization approaches quantified. A slope >1 indicated EMG amplitude normalized to maximal EMG (vertical axis) was greater than EMG normalized to Mmax (horizontal axis). Mean estimates of the slopes were large and had moderate precision: soleus 8.7 (95% CI 6.9 to 11.0), medial gastrocnemius 13.4 (10.5 to 17.0), lateral gastrocnemius 11.4 (9.4 to 14.0). This indicates EMG normalized to Mmax is approximately eleven times smaller than EMG normalized to maximal EMG. Normalization to maximal EMG gave closer approximations to the level of voluntary muscle activation assessed by twitch interpolation

Recent advances using FcRn overexpression in transgenic animals to overcome impediments of standard antibody technologies to improve the generation of specific antibodies.

This review illustrates the salutary effects of neonatal Fc receptor (FcRn) overexpression in significantly improving humoral immune responses in the generation of antibodies for immunotherapy and diagnostics. These include: (1) improved IgG protection; (2) augmented antigen-specific humoral immune response with larger numbers of antigen specific B cells, thus offering a wider spectrum of clones; (3) generation of antibodies against weakly immunogenic antigens; (4) significant improvements in the number and substantial developments in the diversity of hybridomas. FcRn transgenesis thus confers a number of practical benefits, including faster antibody production, higher antibody yields and improved generation of hybridomas for monoclonal antibody production. Notably, these efficiencies in polyclonal antibody production were also demonstrated in FcRn transgenic rabbits. Overall, FcRn transgenic animals yield more antibodies and provide a route to the generation of antibodies against antigens of low immunogenicity that are difficult to obtain using currently available methods

Discharge properties of human diaphragm motor units with ageing

Key points: Ageing is associated with changes in the respiratory system including in the lungs, rib cage and muscles. Neural drive to the diaphragm, the principal inspiratory muscle, has been reported to increase during quiet breathing with ageing. We demonstrated that low-threshold motor units of the human diaphragm recruited during quiet breathing have similar discharge frequencies across age groups and shorter discharge times in older age. With ageing, motor unit action potential area increased. We propose that there are minimal functionally significant changes in the discharge properties of diaphragm motor units with ageing despite remodelling of the motor unit in the periphery. Abstract: There are changes in the skeletal, pulmonary and respiratory neuromuscular systems with healthy ageing. During eupnoea, one study has shown relatively higher crural diaphragm electromyographic activity (EMG) in healthy older adults (>51 years) than in younger adults, but these measures may be affected by the normalisation process used. A more direct method to assess neural drive involves the measurement of discharge properties of motor units. Here, to assess age-related changes in neural drive to the diaphragm during eupnoea, EMG was recorded from the costal diaphragm using a monopolar needle electrode in participants from three age groups (n ≥ 7 each): older (65–80 years); middle-aged (43–55 years) and young (23–26 years). In each group, 154, 174 and 110 single motor units were discriminated, respectively. A mixed-effects linear model showed no significant differences between age groups for onset (group mean range 9.5–10.2 Hz), peak (14.1–15.0 Hz) or offset (7.8–8.5 Hz) discharge frequencies during eupnoea. The motor unit recruitment was delayed in the older group (by ∼15% of inspiratory time; p = 0.02 cf. middle-aged group) and had an earlier offset time (by ∼15% of inspiratory time; p = 0.04 cf. young group). However, the onset of multiunit activity was similar across groups, consistent with no global increase in neural drive to the diaphragm with ageing. The area of diaphragm motor unit potentials was ∼40% larger in the middle-aged and older groups (P < 0.02), which indicates axonal sprouting and re-innervation of muscle fibres associated with ageing, even in middle-aged participants

Reflex response to airway occlusion in human inspiratory muscles when recruited for breathing and posture

Briefly occluding the airway during inspiration produces a short-latency reflex inhibition in human inspiratory muscles. This occlusion reflex seems specific to respiratory muscles; however, it is not known whether the reflex inhibition has a uniform effect across a motoneuron pool when a muscle is recruited concurrently for breathing and posture. In this study, participants were seated and breathed through a mouthpiece that occluded inspiratory airflow for 250 ms at a volume threshold of 0.2 liters. The reflex response was measured in the scalene and sternocleidomastoid muscles during 1) a control condition with the head supported in space and the muscles recruited for breathing only, 2) a postural condition with the head unsupported and the neck flexors recruited for both breathing and to maintain head posture, and 3) a large-breath condition with the head supported and the volume threshold raised to between 0.8 and 1.0 liters to increase inspiratory muscle activity. When normalized to its preocclusion mean, the reflex response in the scalene muscles was not significantly different between the large-breath and control conditions, whereas concomitant recruitment of these muscles for posture control reduced the reflex response by half compared with the control condition. A reflex response occurred in sternocleidomastoid when it contracted phasically as an accessory muscle for inspiration during the large-breath condition. These results indicate that the occlusion reflex does not produce a uniform effect across the motoneuron pool and that afferent inputs for this reflex most likely act via intersegmental networks of premotoneurons rather than at a motoneuronal level