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

Posterior cricoid region fluoroscopic findings: the posterior cricoid plication.

The region posterior to the cricoid cartilage is challenging to assess fluoroscopically. The purpose of this investigation is to critically evaluate the posterior cricoid (PC) region on fluoroscopy and describe patterns of common findings. This was a case control study. All fluoroscopic swallowing studies performed between June 16, 2009, and February 9, 2010, were reviewed for features seen in the PC region. These findings were categorized into distinct patterns and compared to fluoroscopic studies performed in a cohort of normal volunteers. Two hundred patient studies and 149 healthy volunteer studies were reviewed. The mean age of the referred patient cohort and the volunteer cohort was 57 years (±19) and 61 years (±16), respectively (p > 0.05). The patient cohort was 53% male and the control cohort was 56% female (p > 0.05). Four groups were identified. Pharyngoesophageal webs were seen in 7% (10/149) of controls and 14% (28/200) of patients (p = 0.03). A PC arch impression was seen in 16% of patients (32/200) and controls (24/149) (p = 1). A PC plication was demonstrated in 23% (34/149) of controls and 30% (60/200) of patients (p = 0.13). No distinctive PC region findings were seen in 54% (81/149) of controls and 42% (84/200) of referred patients (p = 0.02). Four patients (2%) had both a web and a PC plication. Four categories of PC region findings were identified (unremarkable PC region, web, PC arch impression, and PC plication). Both patients referred for swallowing studies and healthy volunteers demonstrated esophageal webs, PC arch impressions, and PC plications. Only webs were more common in patients than in control subjects (p = 0.03). The PC impression and PC plication are likely to represent normal variants that may be identified on fluoroscopic swallow studies

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

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

Radial Velocities as an Exoplanet Discovery Method

The precise radial velocity technique is a cornerstone of exoplanetary astronomy. Astronomers measure Doppler shifts in the star's spectral features, which track the line-of/sight gravitational accelerations of a star caused by the planets orbiting it. The method has its roots in binary star astronomy, and exoplanet detection represents the low-companion-mass limit of that application. This limit requires control of several effects of much greater magnitude than the signal sought: the motion of the telescope must be subtracted, the instrument must be calibrated, and spurious Doppler shifts "jitter" must be mitigated or corrected. Two primary forms of instrumental calibration are the stable spectrograph and absorption cell methods, the former being the path taken for the next generation of spectrographs. Spurious, apparent Doppler shifts due to non-center-of-mass motion (jitter) can be the result of stellar magnetic activity or photospheric motions and granulation. Several avoidance, mitigation, and correction strategies exist, including careful analysis of line shapes and radial velocity wavelength dependence.Comment: Invited review chapter. 13pp. v2 includes corrections to Eqs 3-6, updated references, and minor edit

Mymou: A low-cost, wireless touchscreen system for automated training of non-human primates

Training nonhuman primates (NHPs) to perform cognitive tasks is essential for many neuroscientific investigations, yet laboratory training is a time-consuming process with inherent limitations. Habituating NHPs to the laboratory staff and experimental equipment can take months before NHPs are ready to proceed to the primary tasks. Laboratory training also necessarily separates NHPs from their home-room social group and typically involves some form of restraint or limited mobility, and data collection is often limited to a few hours per day so that multiple NHPs can be trained on the same equipment. Consequently, it can often take a year to train NHPs on complex cognitive tasks. To overcome these issues, we developed a low-cost, open-source, wireless touchscreen training system that can be installed in the home-room environment. The automated device can run continuously all day, including over weekends, without experimenter intervention. The system utilizes real-time facial recognition to initiate subject-specific tasks and provide accurate data logging, without the need for implanted microchips or separation of the NHPs. The system allows NHPs to select their preferred reward on each trial and to work when and for as long as they desire, and it can analyze task performance in real time and adapt the task parameters in order to expedite training. We demonstrate that NHPs consistently use this system on a daily basis to quickly learn complex behavioral tasks. The system therefore addresses many of the welfare and experimental limitations of laboratory-based training of NHPs and provides a platform for wireless electrophysiological investigations in more naturalistic, freely moving environments

Rapid assessment of surface-water flood-management options in urban catchments

This is the final version of the article. Available from the publisher via the DOI in this record.Surface-water flooding in urban areas has become a pressing issue due to changing precipitation patterns, expanding urban areas and ageing drainage infrastructure. Selection of flood-management options for widespread implementation using quantitative performance measures is both technically and computationally demanding, which limits the evidence available for decision support. This study presents a new framework for surface-water flood-intervention assessment at high resolution. The framework improves computational efficiency through utilisation of accessible data, simplified representations of interventions and a resource efficient cellular automata flood model. The advantages of this framework are demonstrated through an example case study where the performance of 12 high-level intervention strategies has been evaluated. Results from the case study demonstrate that the framework is able to provide quantitative performance values for a range of interventions. The speed of analysis supports the application of the framework as a decision-making tool for urban water planning.This research was supported by three UK research council funded programmes: the EPSRC Centre for Doctoral Training in Water Informatics Science and Engineering [grant number EP/L016214/1], the EPSRC research fellowship Safe & SuRe water management [grant number EP/K006924/1], and the NERC project SINATRA - Susceptibility of catchments to INTense RAinfall and flooding [grant number NE/K008765/1]. LiDAR was provided by the Environment Agency and mapping was provided through OS Mastermap data on the Digimap service

Muscle fiber and motor unit behavior in the longest human skeletal muscle

The sartorius muscle is the longest muscle in the human body. It is strap-like, up to 600 mm in length, and contains five to seven neurovascular compartments, each with a neuromuscular endplate zone. Some of its fibers terminate intrafascicularly, whereas others may run the full length of the muscle. To assess the location and timing of activation within motor units of this long muscle, we recorded electromyographic potentials from multiple intramuscular electrodes along sartorius muscle during steady voluntary contraction and analyzed their activity with spike-triggered averaging from a needle electrode inserted near the proximal end of the muscle. Approximately 30% of sartorius motor units included muscle fibers that ran the full length of the muscle, conducting action potentials at 3.9 +/- 0.1 m/s. Most motor units were innervated within a single muscle endplate zone that was not necessarily near the midpoint of the fiber. As a consequence, action potentials reached the distal end of a unit as late as 100 ms after initiation at an endplate zone. Thus, contractile activity is not synchronized along the length of single sartorius fibers. We postulate that lateral transmission of force from fiber to endomysium and a wide distribution of motor unit endplates along the muscle are critical for the efficient transmission of force from sarcomere to tendon and for the prevention of muscle injury caused by overextension of inactive regions of muscle fibers

Supraspinal fatigue in human inspiratory muscles with repeated sustained maximal efforts

To investigate the involvement of supraspinal fatigue in the loss of maximal inspiratory pressure (PImax), we fatigued the inspiratory muscles. Six participants performed 5 sustained maximal isometric inspiratory efforts (15-s contractions, duty cycle ~75%) which reduced PImax, as measured from esophageal and mouth pressure, to around half of their initial maximums. Transcranial magnetic stimulation (TMS) delivered over the motor cortex near the beginning and end of each maximal effort evoked superimposed twitch-like increments in the ongoing PImax, increasing from ~1.0% of PImax in the unfatigued contractions to ≥40% of ongoing PImax for esophageal and mouth pressures. The rate of increase in the superimposed twitch as PImax decreased with fatigue was not significantly different between the esophageal and mouth pressure measures. The inverse relationship between superimposed twitch pressure and PImax indicates a progressive decline in the ability of motor cortical output to drive the inspiratory muscles maximally, leading to the development of supraspinal fatigue. TMS also evoked silent periods in the electromyographic recordings of diaphragm, scalenes, and parasternal intercostal. The duration of the silent period increased with fatigue in all three muscles, which suggests greater intracortical inhibition, with the largest change observed in the diaphragm. The peak rate of relaxation in pressure during the silent period slowed as fatigue developed, indicating peripheral contractile changes in the active inspiratory muscles. These changes in the markers of fatigue show that both central and peripheral fatigue contribute to the loss in PImax when inspiratory muscles are fatigued with repeated sustained maximal efforts. NEW & NOTEWORTHY When the inspiratory muscles are fatigued with repeated sustained maximal efforts, supraspinal fatigue, a component of central fatigue, contributes to the loss in maximal inspiratory pressure. The presence of supraspinal fatigue was confirmed by the increase in amplitude of twitch-like increments in pressure evoked by motor cortical stimulation during maximal efforts, indicating that motor cortical output was not maximal as extra muscle force could be generated to increase inspiratory pressure

Probable detection of starlight reflected from the giant exoplanet orbiting tau Bootis

Giant planets orbiting stars other than the Sun are clearly detectable through precise radial-velocity measurements of the orbital reflex motion of the parent star. In the four years since the discovery of the companion to the star 51 Peg, similar low-amplitude ``Doppler star wobbles'' have revealed the presence of some 20 planets orbiting nearby solar-type stars. Several of these newly-discovered planets are very close to their parent stars, in orbits with periods of only a few days. Being an indirect technique, however, the reflex-velocity method has little to say about the sizes or compositions of the planets, and can only place lower limits on their masses. Here we report the use of high-resolution optical spectroscopy to achieve a probable detection of the Doppler-shifted signature of starlight reflected from one of these objects, the giant exoplanet orbiting the star tau Bootis. Our data give the planet's orbital inclination i=29 degrees, indicating that its mass is some 8 times that of Jupiter, and suggest strongly that the planet has the size and reflectivity expected for a gas-giant planet.Comment: 15 pages, 4 figures. (Fig 1 and equation for epsilon on p1 para 2 revised; changed from double to single spacing