Quadriceps motor evoked torque is a reliable measure of corticospinal excitability in individuals with anterior cruciate ligament reconstruction

This study comprehensively evaluated the test–retest reliability of raw and normalized quadriceps motor evoked responses elicited by transcranial magnetic stimulation (TMS) in individuals with anterior cruciate ligament (ACL) reconstruction. Fifteen participants were tested on three different days that were separated at least by 24 h. Motor evoked responses were collected during a small background contraction on the reconstructed leg across a range of TMS intensities using torque (MEP_TORQUE) and electromyographic (MEP_EMG) responses. MEP_TORQUE and MEP_EMG were evaluated using different normalization procedures (raw, normalized to maximum voluntary isometric contraction [MVIC], peak MEP, and background contraction). MEP_TORQUE was also normalized to the magnetically-evoked peripheral resting twitch torque. The area under the recruitment curve was computed for both raw and normalized MEPs. Intraclass correlation coefficients (ICCs) were determined to assess test–retest reliability. Results indicated that MEP_TORQUE generally showed greater reliability than MEP_EMG for all normalization procedures. Vastus medialis MEP_EMG generally showed greater reliability than rectus femoris MEP_EMG. Finally, both MEP_TORQUE and MEP_EMG exhibited good reliability, even when not normalized. These findings indicate that MEP_TORQUE and MEP_EMG offer reliable measures of corticospinal function and suggest that MEP_TORQUE is a suitable alternative to MEP_EMG for measuring quadriceps corticospinal excitability in individuals with ACL reconstruction.     

The magic grasp: motor expertise in deception

Background

Most of us are poor at faking actions. Kinematic studies have shown that when pretending to pick up imagined objects (pantomimed actions), we move and shape our hands quite differently from when grasping real ones. These differences between real and pantomimed actions have been linked to separate brain pathways specialized for different kinds of visuomotor guidance. Yet professional magicians regularly use pantomimed actions to deceive audiences.

Methodology and Principal Findings

In this study, we tested whether, despite their skill, magicians might still show kinematic differences between grasping actions made toward real versus imagined objects. We found that their pantomimed actions in fact closely resembled real grasps when the object was visible (but displaced) (Experiment 1), but failed to do so when the object was absent (Experiment 2).

Conclusions and Significance

We suggest that although the occipito-parietal visuomotor system in the dorsal stream is designed to guide goal-directed actions, prolonged practice may enable it to calibrate actions based on visual inputs displaced from the action.     

The relationship of corticospinal excitability with pain,motor performance and disability in subjects with chronic wrist/hand pain

There is a growing body of evidence of changes in corticospinal excitability associated with musculoskeletal disorders, however there is a lack of knowledge of how these changes relate to measures of pain, motor performance and disability. An exploratory study was performed utilizing Transcranial Magnetic Stimulation to investigate differences in corticospinal excitability in the Abductor Pollicis Brevis (APB) between 15 pain-free subjects and 15 subjects with chronic wrist/hand pain and to determine how corticospinal excitability was associated with measures of pain (visual analog scale, AUSCAN™), hand motor performance (isometric and key pinch strength, Purdue Pegboard Test), disability (AUSCAN™), and spinal motoneuronal excitability. Input–output curves demonstrated increased corticospinal excitability of the APB in the affected hand of subjects with chronic pain (p < 0.01). Changes in corticospinal excitability were significantly correlated with pain intensity (r = 0.77), disability (r = 0.58), and negatively correlated with motoneuronal excitability (r = −0.57). Corticospinal excitability in subjects with heterogeneous injuries of the wrist/hand was associated with disability and pain.     

Untangling the cortex: Advances in understanding specification and differentiation of corticospinal motor neurons

The mature cerebral cortex contains a staggering variety of projection neuron subtypes, and a number of complementary studies have recently begun to define their identity and embryonic origin. Among the different types of cortical projection neurons, subcerebral projection neurons, including corticospinal motor neurons (CSMN), have been extensively studied and some of the molecular controls over their differentiation have been elucidated. Here, we first provide an overview of the approaches used to purify and molecularly profile neuronal populations of the neocortex and, more broadly, of the central nervous system (CNS). Next, we specifically review recent progress in understanding the genes that define and control development of the CSMN population. Finally, we briefly discuss the relevance of this work to current questions regarding the mechanisms of the establishment of projection neuron subtype identity in the neocortex and its implications to direct the differentiation of CSMN for therapeutic benefit.     

Motor control: Mechanisms of motor equivalence in handwriting

Handwriting is a classic example of how the details of movement can be scale and plane invariant: letter forms reflecting personal style are unchanged, whether one is writing on a piece of paper, on a blackboard or in the sand using the foot. Recent research points to a role for the parietal cortex in such motor equivalence.     

Computational study of enhanced excitability in Hermissenda: membrane conductances modulated by 5-HT

Serotonin (5-HT) applied to the exposed but otherwise intact nervous system results in enhanced excitability of Hermissenda type-B photoreceptors. Several ion currents in the type-B photoreceptors are modulated by 5-HT, including the A-type K⁺ current (I_K,A), sustained Ca²⁺ current (I_Ca,S), Ca-dependent K⁺ current (I_K,Ca), and a hyperpolarization-activated inward rectifier current (I_h). In this study, we developed a computational model that reproduces physiological characteristics of type B photoreceptors, e.g. resting membrane potential, dark-adapted spike activity, spike width, and the amplitude difference between somatic and axonal spikes. We then used the model to investigate the contribution of different ion currents modulated by 5-HT to the magnitudes of enhanced excitability produced by 5-HT. Ion currents were systematically varied within limits observed experimentally, both individually and in combinations. A reduction of I_K,A or I_K,Ca, or an increase in I_h enhanced excitability by 20–50%. Decreasing I_Ca,S produced a dramatic decrease in excitability. Reductions of I_K,V produced only minimal increases in excitability, suggesting that I_K,V probably plays a minor role in 5-HT induced enhanced excitability. Combinations of changes in I_K,A, I_K,Ca, I_h and I_Ca,S produced increases in excitability comparable to experimental observations. After 5-HT application, the cell's depolarization force is shifted from the I_h–I_Ca,S combination to predominantly I_h.     

Prediction of motor outcome using remaining corticospinal tract in patients with pontine infarct: Diffusion tensor imaging study

The aim of this study was to investigate the relationship between the remaining corticospinal tract (CST) as determined by diffusion tensor imaging (DTI) and 6-month motor outcome in patients with pontine infarct. Ratios of fractional anisotropy (FA), fiber number (FN), and CST area were calculated, and the FN ratio and CST area ratio showed significant correlation with all 6-month motor outcome. Thus, the remaining CST in the pons measured using DTI at early stage of stroke could predict motor outcome in patients with pontine infarct.     

Favouritism in the motor system: social interaction modulates action simulation

The ability to anticipate others'' actions is crucial for social interaction. It has been shown that this ability relies on motor areas of the human brain that are not only active during action execution and action observation, but also during anticipation of another person''s action. Recording electroencephalograms during a triadic social interaction, we assessed whether activation of motor areas pertaining to the human mirror-neuron system prior to action observation depends on the social relationship between the actor and the observer. Anticipatory motor activation was stronger when participants expected an interaction partner to perform a particular action than when they anticipated that the same action would be performed by a third person they did not interact with. These results demonstrate that social interaction modulates action simulation.     

Motor activity of protozoa: Position of motor activity in the hierarchy of environmental bioassay criteria

Stable dose-independent behavioral modification in the infusorium Spirostomum ambiguum immediately after the exposure to γ-radiation in a broad dosage range has been shown in model experiments. Negative effect is observed already at a dose of 0.01 Gy and is inherited through several generations of spirostoma. Decreased motor activity is accompanied by morphological pathology, the manifestation of which is also dose-independent in a broad range of low doses. The possibility of express evaluation of changes in the motor activity of protozoa for the biotesting of radioactive contamination of the environment, as well as the prognostic character of this study, is under discussion.     

The image of motor units architecture in the mechanomyographic signal during the single motor unit contraction: in vivo and simulation study

The mechanomyographic (MMG) signal analysis has been performed during single motor unit (MU) contractions of the rat medial gastrocnemius muscle. The MMG has been recorded as a muscle surface displacement by using a laser distance sensor. The profiles of the MMG signal let to categorize these signals for particular MUs into three classes. Class MMG-P (positive) comprises MUs with the MMG signal similar to the force signal profile, where the distance between the muscle surface and the laser sensor increases with the force increase. The class MMG-N (negative) has also the MMG profile similar to the force profile, however the MMG is inverted in comparison to the force signal and the distance measured by using laser sensor decreases with the force increase. The third class MMG-M (mixed) characterize the MMG which initially increases with the force increases and when the force exceeds some level it starts to decrease towards the negative values. The semi-pennate muscle model has been proposed, enabling estimation of the MMG generated by a single MU depending on its localization. The analysis have shown that in the semi-pennate muscle the localization of the MU and the relative position of the laser distance sensor determine the MMG profile and amplitude. Thus, proposed classification of the MMG recordings is not related to the physiological types of MUs, but only to the MU localization and mentioned sensor position. When the distance sensor is located over the middle of the muscle belly, a part of the muscle fibers have endings near the location of the sensor beam. For the MU MMG of class MMG-N the deflection of the muscle surface proximal to the sensor mainly influences the MMG recording, whereas for the MU MMG class MMG-P, it is mainly the distal muscle surface deformation. For the MU MMG of MMG-M type the effects of deformation within the proximal and distal muscle surfaces overlap. The model has been verified with experimental recordings, and its responses are consistent and adequate in comparison to the experimental data.     

Intrahemispheric dysfunction in primary motor cortex without corpus callosum: a transcranial magnetic stimulation study

Background  

The two human cerebral hemispheres are continuously interacting, through excitatory and inhibitory influences and one critical structure subserving this interhemispheric balance is the corpus callosum. Interhemispheric neurophysiological abnormalities and intrahemispheric behavioral impairments have been reported in individuals lacking the corpus callosum. The aim of this study was to examine intrahemispheric neurophysiological function in primary motor cortex devoid of callosal projections.     

Neural excitability of lower extremity musculature in individuals with and without chronic ankle instability: A systematic review and meta-analysis

This systematic review and meta-analysis examined differences in lower extremity neural excitability between ankles with and without chronic ankle instability (CAI). We searched the literature for studies that compared corticomotor or spinal reflexive excitability between a CAI group and controls or copers, or between limbs of a CAI group. Random effects meta-analyses calculated pooled effect sizes for each outcome. Nineteen studies were included. Meta-analyses of motor thresholds of the fibularis longus (Z = 1.17, P = 0.24) and soleus (Z = 0.47, P = 0.64) exhibited no differences between ankles with and without CAI. Pooled data indicate that ankles with CAI had reduced soleus spinal reflexive excitability (Z = 2.18, P = 0.03) and significantly less modulation of the soleus (Z = 6.96, P < 0.01) and fibularis longus (Z = 4.75, P < 0.01) spinal reflexive excitability when transitioning to more challenging stances. Pre-synaptic inhibition was facilitated in ankles with CAI (Z = 4.05, P < 0.01), but no difference in recurrent inhibition existed (Z = 1.50, P = 0.13). Soleus spinal reflexive activity is reduced in those with CAI. Reduced ability of ankles with CAI to modulate soleus and fibularis longus reflexive activity may contribute to impaired balance.     

Nitrogenase synthesis in Klebsiella pneumoniae: enhanced nif expression without accumulation of guanosine 5'-diphosphate 3'-diphosphate

Derepression of nitrogen fixation (nif) genes in Klebsiella pneumoniae following transfer from NH+4-sufficiency to N-free medium was preceded by rapid expansion of the guanosine 5'-diphosphate 3'-diphosphate (ppGpp) pool. When derepressed in N-free medium supplemented with glutamine (600 micrograms ml-1), expression from the nifH and nifL promoters, determined as beta-galactosidase activity in nif::lac merodiploid strains, was stimulated 7-fold and nitrogenase activity 26-fold; ppGpp did not accumulate, remaining at the levels found in NH+4-repressed populations. The relaxed mutant K. pneumoniae relA40, which accumulates only very low levels of ppGpp, showed partial derepression of nitrogenase activity in the presence of glutamine, thus ppGpp is unlikely to be an effector of nif expression. ATP and GTP levels were elevated under conditions where nif expression was enhanced, consistent with previous data suggesting that maintenance of ATP levels is a prerequisite for the expression of nif genes in K. pneumoniae.     

Coupling of proton flow and rotation in the bacterial flagellar motor: stochastic simulation of a microscopic model

Summary The rotatory motor of bacterial flagella is driven by a transmembrane electrochemical gradient of protons. A model of the flagellar motor is analysed, which is based on the notion that protons passing through the motor use a channel-like pathway formed by ligand groups located partly on the rotor, partly on the stator. Proton translocation is linked to the displacement of stator elements which are elastically bound to the cell wall. The model is described by a cyclic sequence of translocation steps and proton binding and release reactions. Stochastic simulations of the model are carried out in which transitions between the states of the reaction cycle are treated as random events. In this way the rotation frequency can be predicted as a function of experimental variables such as driving force and viscous load. Furthermore, the effects of microscopic parameters such as the transition frequencies of stator elements and the force constant of elastic coupling on the dynamic properties of the motor can be studied. The model allows for intrinsic uncoupling (“slippage”) resulting from translocation steps without associated rotational movement. It is shown that mechanistic information can be obtained by studying random fluctuations of rotational speed. Offprint requests to: P. Lauger     

Escape in space from enemies: a comparison between stands with and without enhanced densities of the spruce bark beetle

1 Populations of the spruce bark beetle, Ips typographus (L.), are known to grow rapidly in storm‐disturbed stands as a result of relaxation from intraspecific competition. In the present study, it was tested whether a second mechanism, escape in space from natural enemies, also contributes to the rapid population increase. 2 The experiment was conducted during the initiation phase of five local outbreaks of I. typographus triggered by a storm‐disturbance in November 1995 in southern Sweden. 3 The impact of natural enemies on the ratio of increase (number of daughters per mother) of I. typographus was compared pairwise between disturbed stands with high numbers of storm‐felled trees and undisturbed stands without wind‐felled trees. 4 Enemy impact was assessed by comparing the ratio of increase in uncaged (exposed to enemies) and caged (protected from enemies) bolts colonized by I. typographus prior to being placed in the stands. The experiment was conducted in the second and third summers after the storm‐felling. 5 Enemy impact was about twice as high in stands without wind‐felled trees compared with in stands with wind‐felled trees in the second summer whereas there was no significant difference between the stand types in the third summer. 6 The result demonstrates that spatial escape from enemies contributes to the rapid population growth of I. typographus after storm‐disturbances.     

Motor Learning: An Analysis of 100 Trials of a Ski Slalom Game in Children with and without Developmental Coordination Disorder

ObjectiveAlthough Developmental Coordination Disorder (DCD) is often characterized as a skill acquisition deficit disorder, few studies have addressed the process of motor learning. This study examined learning of a novel motor task; the Wii Fit ski slalom game. The main objectives were to determine: 1) whether learning occurs over 100 trial runs of the game, 2) if the learning curve is different between children with and without DCD, 3) if learning is different in an easier or harder version of the task, 4) if learning transfers to other balance tasks.Method17 children with DCD (6–10 years) and a matched control group of 17 typically developing (TD) children engaged in 20 minutes of gaming, twice a week for five weeks. Each training session comprised of alternating trial runs, with five runs at an easy level and five runs at a difficult level. Wii scores, which combine speed and accuracy per run, were recorded. Standardized balance tasks were used to measure transfer.ResultsSignificant differences in initial performance were found between groups on the Wii score and balance tasks. Both groups improved their Wii score over the five weeks. Improvement in the easy and in the hard task did not differ between groups. Retention in the time between training sessions was not different between TD and DCD groups either. The DCD group improved significantly on all balance tasks.ConclusionsThe findings in this study give a fairly coherent picture of the learning process over a medium time scale (5 weeks) in children novice to active computer games; they learn, retain and there is evidence of transfer to other balance tasks. The rate of motor learning is similar for those with and without DCD. Our results raise a number of questions about motor learning that need to be addressed in future research.     

Modelling motor units in 3D: influence on muscle contraction and joint force via a proof of concept simulation

Functional heterogeneity is a skeletal muscle’s ability to generate diverse force vectors through localised motor unit (MU) recruitment. Existing 3D macroscopic continuum-mechanical finite element (FE) muscle models neglect MU anatomy and recruit muscle volume simultaneously, making them unsuitable for studying functional heterogeneity. Here, we develop a method to incorporate MU anatomy and information in 3D models. Virtual fibres in the muscle are grouped into MUs via a novel “virtual innervation” technique, which can control the units’ size, shape, position, and overlap. The discrete MU anatomy is then mapped to the FE mesh via statistical averaging, resulting in a volumetric MU distribution. Mesh dependency is investigated using a 2D idealised model and revealed that the amount of MU overlap is inversely proportional to mesh dependency. Simultaneous recruitment of a MU’s volume implies that action potentials (AP) propagate instantaneously. A 3D idealised model is used to verify this assumption, revealing that neglecting AP propagation results in a slightly less-steady force, advanced in time by approximately 20 ms, at the tendons. Lastly, the method is applied to a 3D, anatomically realistic model of the masticatory system to demonstrate the functional heterogeneity of masseter muscles in producing bite force. We found that the MU anatomy significantly affected bite force direction compared to bite force magnitude. MU position was much more efficacious in bringing about bite force changes than MU overlap. These results highlight the relevance of MU anatomy to muscle function and joint force, particularly for muscles with complex neuromuscular architecture.

     

A plausible explanation for enhanced bioavailability of P-gp substrates in presence of piperine: simulation for next generation of P-gp inhibitors

P-glycoprotein (P-gp) has a major role to play in drug pharmacokinetics and pharmacodynamics, since it effluxes many cytotoxic hydrophobic anticancer drugs from gastrointestinal tract, brain, liver and kidney. Piperine is known to enhance the bioavailability of curcumin, as a substrate of P-gp by at least 2000 %. Besides these at least 50 other substrates and inhibitors of P-gp have been reported so far. All P-gp inhibitors have diverse structures. Although little is known about binding of some flavonoids and steroids at the NBD (nucleotide binding domain) of P-gp in the vicinity of ATP binding site inhibiting its hydrolysis, a valid explanation of how P-gp accommodates such a diverse set of inhibitors is still awaited. In the present study, piperine up to 100 μM has not shown observable cytotoxic effect on MDCK cell line, and it has been shown to accumulate rhodamine by fluorescence microscopy and fluorescent activated cell sorter in MDCK cells. Computational simulation for piperine and some first and second generation P-gp inhibitors has shown that these dock at the NBD site of P-gp. A comparative simulation study has been carried out regarding their docking and binding energies. Binding conformation of P-gp co-crystallized complexes with ADP, AMP-PNP (Adenylyl-imidodiphosphate), and ATP were compared with piperine. The receptor based E-pharmacophore of docked piperine has been simulated to find common features amongst P-gp inhibitors. Finally it has been concluded that piperine could be utilized as base molecule for design and development of safe non-toxic inhibitor of P-gp in order to enhance the bioavailability of most of its substrates.

Application of the primary hydration shell approach to locally enhanced sampling simulated annealing: computer simulation of thyrotropin-releasing hormone in water

A unified model of simulated annealing with locally enhanced sampling (LES) in a primary hydration shell (PHS) aqueous environment is developed and tested by predicting the structure of the tripeptide thyrotropin-releasing hormone (TRH) in solution. The model extends the formulation of the restraining force in the PHS method as a function of temperature, number of copies in the LES method, and shell thickness. The dependence of the restraining force on temperature can be shown to follow the relationship c(1)T - c(2), which can be derived from the expression for kinetic energy in molecular dynamics simulations. The calibration of the restraining force for different simulation conditions reveals the dependence of c(1) and c(2) on the number of copies in the LES method and the thickness of the PHS. The predicted structure of TRH is in very good agreement with results from NMR experiments and from a 10-ns PHS simulation at 300 K. The method promises to be useful in predicting structure of peptides and proteins in an aqueous environment.     

Behaviour of a surface EMG based measure for motor control: Motor unit action potential rate in relation to force and muscle fatigue

Surface electromyography parameters such as root-mean-square value (RMS) and median power frequency (FMED) are commonly used to assess the input of the central nervous system (CNS) to a muscle. However, RMS and FMED are influenced not only by CNS input, but also by peripheral muscle properties. The number of motor unit action potentials (MUAPs) per second, or MUAP Rate (MR), being the sum of the firing rates of the active motor units, would reflect CNS input solely. This study explored MR behaviour in relation to force and during a fatiguing contraction in comparison to RMS and FMED.In the first experiment (n = 10) a step contraction of shoulder elevation force (20–100 N) was performed while multi-channel array EMG was recorded from the upper trapezius muscle. The sensitivity of MR for changes in force (1.8%/N) was almost twice as high as that of RMS (0.97%/N), indicating that MR may be more suitable for monitoring muscle force. The second experiment (n = 6) consisted of a 15-min isometric contraction of the biceps brachii. MR increased considerably less than RMS (0.9% vs. 4.1%), suggesting that MR selectively reflects central motor control whereas RMS also reflects peripheral changes. These results support that, at relatively low force levels, MR is a suitable parameter for non-invasive assessment of the input of the CNS to the muscle.