Can germ cell neoplasia in situ be diagnosed by measuring serum levels of microRNA371a-3p?

PURPOSE: Diagnosing germ cell neoplasia in situ (GCNis) can detect germ cell tumours (GCTs) at the pre-invasive stage. To date, testicular biopsy with the potential of surgical complications is the only way of safely diagnosing GCNis. Recently, microRNAs (miRs) 371-3, and miR 367 were shown to be valuable serum biomarkers of GCTs. We explored the usefulness of these candidate miRs as a marker for GCNis. METHODS: 27 patients with GCNis and no concomitant GCT were enrolled. All patients underwent measuring serum levels of miR-371a-3p and miR-367-3p before treatment, 11 had repeat measurement after treatment, 2 also had testicular vein blood examinations. Serum levels were measured by quantitative PCR. In addition, four orchiectomy specimens of patients with GCT were examined immunohistochemically and by in situ hybridization (ISH) with a probe specific for miR-371a-3p to look for the presence of this miR in GCNis cells. RESULTS: The median serum level of miR-371a-3p was significantly higher in patients with GCNis than in controls, miR-367 levels were not elevated. Overall, 14 patients (51.9%) had elevated serum levels of miR-371a-3p. The highest levels were found in patients with bilateral GCNis. Levels in testicular vein serum were elevated in both of the cases. After treatment, all elevated levels dropped to normal. In two orchiectomy specimens, miR-371a-3p was detected by ISH in GCNis cells. CONCLUSIONS: Measuring miR-371a-3p serum levels can replace control biopsies after treatment of GCNis. In addition, the test can guide clinical decision making regarding the need of testicular biopsy in cases suspicious of GCNis.

Corticospinal excitability during imagined and observed dynamic force production tasks: effortfulness matters.

Research on motor imagery and action observation has become increasingly important in recent years particularly because of its potential benefits for movement rehabilitation and the optimization of athletic performance (Munzert et al., 2009). Motor execution, motor imagery, and action observation have been shown to rely largely on a similar neural network in motor and motor-related cortical areas (Jeannerod, 2001). Given that motor imagery is a covert stage of an action and its characteristics, it has been assumed that modifying the motor task in terms of, for example, effort will impact neural activity. With this background, the present study examined how different force requirements influence corticospinal excitability (CSE) and intracortical facilitation during motor imagery and action observation of a repetitive movement (dynamic force production). Participants were instructed to kinesthetically imagine or observe an abduction/adduction movement of the right index finger that differed in terms of force requirements. Trials were carried out with single- or paired-pulse transcranial magnetic stimulation. Surface electromyography was recorded from the first dorsal interosseous (FDI) and the abductor digiti minimi (ADM). As expected, results showed a significant main effect on mean peak-to-peak motor-evoked potential (MEP) amplitudes in FDI but no differences in MEP amplitudes in ADM muscle. Participants' mean peak-to-peak MEPs increased when the force requirements (movement effort) of the imagined or observed action were increased. This reveals an impact of the imagined and observed force requirements of repetitive movements on CSE. It is concluded that this effect might be due to stronger motor neuron recruitment for motor imagery and action observation with an additional load. That would imply that the modification of motor parameters in movements such as force requirements modulates CSE.

Ipsilateral corticospinal responses to ballistic training are similar for various intensities and timings of TMS.

AIM: In previous studies, unilateral ballistic training either increased or decreased corticospinal excitability for the untrained opposite limb. The objective here was to investigate whether these discrepancies can be explained by methodological differences such as the intensity of stimulation assessing excitability or the timing of excitability testing after training. METHODS: Motor evoked potentials (MEP) were elicited by stimulating the ipsilateral cortex at high intensity (70% MEPmax) and low intensity (20% MEPmax) at specific time-points after performance of 300 ballistic movements of the index finger. RESULTS: Ballistic practice significantly facilitated MEP size for high-intensity stimuli, whereas responses to low-intensity stimulation were variable. MEP sizes at individual time-points were not significantly facilitated until 4 min after training, although there was no difference between early and late responses when grouped over multiple time-points. CONCLUSIONS: The data indicate that previous discrepancies in ipsilateral responses to ballistic training cannot be attributed to specific procedures used to assess corticospinal excitability as there was no tendency towards depression of MEP amplitude at any point post-exercise for both testing intensities. This suggests that other experimental factors such as locus of attention or availability of visual feedback are more likely to account for the discrepancies.

Abdominal Palpation Haptic Device for Colonoscopy Simulation Using Pneumatic Control.

In this paper, we describe the development of a haptic device to be used in a simulator aiming to train the skills of gastroenterology assistants in abdominal palpation during colonoscopy, as well as to train team interaction skills for the colonoscopy team. To understand the haptic feedback forces to be simulated by the haptic device, we conducted an experiment with five participants of varying BMI. The applied forces and displacements were measured and hysteresis modeling was used to characterize the experimental data. These models were used to determine the haptic feedback forces required to simulate a BMI case in response to the real-time user interactions. The pneumatic haptic device consisted of a sphygmomanometer bladder as the haptic interface and a fuzzy controller to regulate the bladder pressure. The haptic device showed good steady state and dynamic response was adequate for simulating haptic interactions. Tracking accuracy averaged 94.2 percent within 300 ms of the reference input while the user was actively applying abdominal palpation and minor repositioning.

Neural adaptations to strength training: moving beyond transcranial magnetic stimulation and reflex studies.

It has long been believed that training for increased strength not only affects muscle tissue, but also results in adaptive changes in the central nervous system. However, only in the last 10 years has the use of methods to study the neurophysiological details of putative neural adaptations to training become widespread. There are now many published reports that have used single motor unit recordings, electrical stimulation of peripheral nerves, and non-invasive stimulation of the human brain [i.e. transcranial magnetic stimulation (TMS)] to study neural responses to strength training. In this review, we aim to summarize what has been learned from single motor unit, reflex and TMS studies, and identify the most promising avenues to advance our conceptual understanding with these methods. We also consider the few strength training studies that have employed alternative neurophysiological techniques such as functional magnetic resonance imaging and electroencephalography. The nature of the information that these techniques can provide, as well as their major technical and conceptual pitfalls, are briefly described. The overall conclusion of the review is that the current evidence regarding neural adaptations to strength training is inconsistent and incomplete. In order to move forward in our understanding, it will be necessary to design studies that are based on a rigorous consideration of the limitations of the available techniques, and that are specifically targeted to address important conceptual questions.

Improved language performance subsequent to low-frequency rTMS in patients with chronic non-fluent aphasia post-stroke.

BACKGROUND: Low-frequency repetitive transcranial magnetic stimulation (rTMS) has emerged as a potential tool for neurorehabilitation and remediation of language in chronic non-fluent aphasia post-stroke. Inhibitory (1 Hz) rTMS has been applied to homologous language sites to facilitate behavioural language changes. Improvements in picture-naming performance and speech output over time have been reported. METHODS: Low-frequency (1 Hz) rTMS was applied to six real stimulation and six sham placebo patients for 20 min per day, for 10 days, and behavioural language outcome measures were taken at baseline (pre-stimulation) and 2 months post-stimulation. RESULTS: The findings demonstrate treatment-related changes observed in the stimulation group when compared to the placebo control group at 2 months post-stimulation on naming performance as well as other aspects of expressive language and auditory comprehension. CONCLUSIONS: These findings provide considerable evidence to support the theory of rTMS modulating mechanisms of transcallosal disinhibition in the aphasic brain and highlight the potential clinical applications for language rehabilitation post-stroke.

Superimposed vibration confers no additional benefit compared with resistance training alone.

Eighteen participants (22-43 years) were randomly allocated to one of two groups: resistance training combined with vibration (VIB; five males, four females) or resistance training alone (CON; five males, four females). Each participant trained three sessions per week (three sets of 10 seated calf raises against a load, which was increased progressively from 75% of one repetition maximum (1RM) to 90% 1RM for 4 weeks. For the VIB group, a vibratory stimulus (30 Hz, 2.5 mm amplitude) was applied to the soles of the feet by a vibration platform. The two groups did not differ significantly with respect to the total amount of work performed during training. Both groups showed a significant increase in maximum voluntary contraction and 1RM (P<0.01) with training. There were no significant changes in measures that assessed the rate at which force was developed. Countermovement jump height increased for the CON (P<0.01) but not for the VIB group. Comparisons between the groups revealed that they did not differ significantly from one another with respect to any measure of performance, before or following training. It appears that vibration superimposed upon resistance training does not alter or augment the increase in strength induced by resistance training alone.

The role of the primary motor cortex during skill acquisition on a two-degrees-of-freedom movement task.

One can partially eliminate motor skills acquired through practice in the hours immediately following practice by applying repetitive transcranial stimulation (rTMS) over the primary motor cortex. The disruption of acquired levels of performance has been demonstrated on tasks that are ballistic in nature. The authors investigated whether motor recall on a discrete aiming task is degraded following a disruption of the primary motor cortex induced via rTMS. Participants (N = 16) maintained acquired performance levels and patterns of muscle activity following the application of rTMS, despite a reduction in corticospinal excitability. Disruption of the primary motor cortex during a consolidation period did not influence the retention of acquired skill in this type of discrete visuomotor task.

The effects of viscous loading of the human forearm flexors on the stability of coordination.

This experiment investigated whether the stability of rhythmic unimanual movements is primarily a function of perceptual/spatial orientation or neuro-mechanical in nature. Eight participants performed rhythmic flexion and extension movements of the left wrist for 30s at a frequency of 2.25 Hz paced by an auditory metronome. Each participant performed 8 flex-on-the-beat trials and 8 extend-on-the-beat trials in one of two load conditions, loaded and unload. In the loaded condition, a servo-controlled torque motor was used to apply a small viscous load that resisted the flexion phase of the movement only. Both the amplitude and frequency of the movement generated in the loaded and unloaded conditions were statistically equivalent. However, in the loaded condition movements in which participants were required to flex-on-the-beat became less stable (more variable) while extend-on-the-beat movements remained unchanged compared with the unload condition. The small alteration in required muscle force was sufficient to result in reliable changes in movement stability even a situation where the movement kinematics were identical. These findings support the notion that muscular constraints, independent of spatial dependencies, can be sufficiently strong to reliably influence coordination in a simple unimanual task.

Early alterations in serum creatine kinase and total cholesterol following high intensity eccentric muscle actions.

AIM: The purpose of this experiment was to assess the levels of muscle soreness, serum total cholesterol (TC) and creatine kinase (CK) in the first 48 hours following fatiguing eccentric exercise performed with the triceps brachii. METHODS: Eleven untrained male college students performed a total of 50 eccentric elbow extensions in 8 sets (6 x 7 and 2 x 4) with a load equal to 85% of their maximal concentric elbow extension strength. Isometric elbow extension strength, muscle soreness and circumference, and serum CK and TC concentrations were measured before, immediately after, and 2, 24 and 48 hours after the exercise. RESULTS: Statistically reliable changes in isometric strength, serum CK and TC, muscle soreness and upper arm circumference occurred within the first 48 hours following eccentric exercise. Serum TC concentrations exhibited a very rapid (within 2 hours) reduction from pre-exercise values after eccentric exercise to a relatively stable concentration of approximately 85% of baseline. CONCLUSION: These results suggest that serum TC concentration may follow the time-course of reductions in force generating capacity more closely than other biochemical markers of muscle damage.

Excitability changes in human forearm corticospinal projections and spinal reflex pathways during rhythmic voluntary movement of the opposite limb.

Rhythmic movements brought about by the contraction of muscles on one side of the body give rise to phase-locked changes in the excitability of the homologous motor pathways of the opposite limb. Such crossed facilitation should favour patterns of bimanual coordination in which homologous muscles are engaged simultaneously, and disrupt those in which the muscles are activated in an alternating fashion. In order to examine these issues, we obtained responses to transcranial magnetic stimulation (TMS), to stimulation of the cervicomedullary junction (cervicomedullary-evoked potentials, CMEPs), to peripheral nerve stimulation (H-reflexes and f-waves), and elicited stretch reflexes in the relaxed right flexor carpi radialis (FCR) muscle during rhythmic (2 Hz) flexion and extension movements of the opposite (left) wrist. The potentials evoked by TMS in right FCR were potentiated during the phases of movement in which the left FCR was most strongly engaged. In contrast, CMEPs were unaffected by the movements of the opposite limb. These results suggest that there was systematic variation of the excitability of the motor cortex ipsilateral to the moving limb. H-reflexes and stretch reflexes recorded in right FCR were modulated in phase with the activation of left FCR. As the f-waves did not vary in corresponding fashion, it appears that the phasic modulation of the H-reflex was mediated by presynaptic inhibition of Ia afferents. The observation that both H-reflexes and f-waves were depressed markedly during movements of the opposite indicates that there may also have been postsynaptic inhibition or disfacilitation of the largest motor units. Our findings indicate that the patterned modulation of excitability in motor pathways that occurs during rhythmic movements of the opposite limb is mediated primarily by interhemispheric interactions between cortical motor areas.

Bimanual aiming and overt attention: one law for two hands.

Reaching to interact with an object requires a compromise between the speed of the limb movement and the required end-point accuracy. The time it takes one hand to move to a target in a simple aiming task can be predicted reliably from Fitts' law, which states that movement time is a function of a combined measure of amplitude and accuracy constraints (the index of difficulty, ID). It has been assumed previously that Fitts' law is violated in bimanual aiming movements to targets of unequal ID. We present data from two experiments to show that this assumption is incorrect: if the attention demands of a bimanual aiming task are constant then the movements are well described by a Fitts' law relationship. Movement time therefore depends not only on ID but on other task conditions, which is a basic feature of Fitts' law. In a third experiment we show that eye movements are an important determinant of the attention demands in a bimanual aiming task. The results from the third experiment extend the findings of the first two experiments and show that bimanual aiming often relies on the strategic co-ordination of separate actions into a seamless behaviour. A number of the task specific strategies employed by the adult human nervous system were elucidated in the third experiment. The general strategic pattern observed in the hand trajectories was reflected by the pattern of eye movements recorded during the experiment. The results from all three experiments demonstrate that eye movements must be considered as an important constraint in bimanual aiming tasks.

Factores neuro-músculo-esqueléticos en la coordinación de movimientos de pronosupinacion / Neuromuscular-skeletal constraints in the coordination of prono-supination

Objetivo: valorar la influencia de los cambios de posición del eje de rotación del antebrazo sobre la estabilidad de la coordinación de movimientos de pronosupinación y sobre los patrones de activación de algunos de los músculos implicados. Participantes: 15 sujetos voluntarios realizaron ciclos completos de pronosupinación del antebrazo a distintas frecuencias de movimiento controladas por un metrónomo (desde 1.75Hz hasta 3.5Hz).Métodos: se registró el desplazamiento angular (grados de movimiento) durante la realización de cielos completos de pronación-supinación del antebrazo con el eje de rotación: por encima, en línea o por debajo del eje longitudinal del antebrazo; y bajo 2 modos de coordinación: p) haciendo coincidir la señal auditiva con la posición de pronación máxima y s) haciendo coincidir la señal auditiva con la posición de supinación máxima. Los tiempos en los que se produjeron las transiciones a un modo de coordinación distinto al solicitado fueron determinados para valorar la estabilidad de cada modo de coordinación. La actividad electromiográfica de los músculos pronador redondo, bíceps braquial, palmar mayor y primer radial fue registrada en 4 sujetos. Resultados: la estabilidad del modo de coordinación pronación en la señal fue mayor cuando el eje de rotación se situó por debajo del eje longitudinal del antebrazo. Por el contrario, la estabilidad del modo de coordinación supinación en la señal fue mayor cuando el eje de rotación se situó por encima. La dominancia relativa de las fases de pronación y supinación durante la rotación del antebrazo dependió mayormente del grado de participación de los músculos palmar mayor y primer radial. Conclusión: la estabilidad de los modos de coordinación estuvo supeditada al contexto mecánico. Los cambios en el contexto mecánico alteraron los patrones de activación de los músculos que contribuyen a la pronación y supinación del antebrazo, particularmente el palmar mayor (AU)

Neural compensation for compliant loads during rhythmic movement.

An experiment was performed to characterise the movement kinematics and the electromyogram (EMG) during rhythmic voluntary flexion and extension of the wrist against different compliant (elastic-viscous-inertial) loads. Three levels of each type of load, and an unloaded condition, were employed. The movements were paced at a frequency of 1 Hz by an auditory metronome, and visual feedback of wrist displacement in relation to a target amplitude of 100 degree was provided. Electromyographic recordings were obtained from flexor carpi radialis (FCR) and extensor carpi radialis brevis (ECR). The movement profiles generated in the ten experimental conditions were indistinguishable, indicating that the CNS was able to compensate completely for the imposed changes in the task dynamics. When the level of viscous load was elevated, this compensation took the form of an increase in the rate of initial rise of the flexor and the extensor EMG burst. In response to increases in inertial load, the flexor and extensor EMG bursts commenced and terminated earlier in the movement cycle, and tended to be of greater duration. When the movements were performed in opposition to an elastic load, both the onset and offset of EMG activity occurred later than in the unloaded condition. There was also a net reduction in extensor burst duration with increases in elastic load, and an increase in the rate of initial rise of the extensor burst. Less pronounced alterations in the rate of initial rise of the flexor EMG burst were also observed. In all instances, increases in the magnitude of the external load led to elevations in the overall level of muscle activation. These data reveal that the elements of the central command that are modified in response to the imposition of a compliant load are contingent, not only upon the magnitude, but also upon the character of the load.

Reliability of the input-output properties of the cortico-spinal pathway obtained from transcranial magnetic and electrical stimulation.

The purpose of this experiment was to assess the test-retest reliability of input-output parameters of the cortico-spinal pathway derived from transcranial magnetic (TMS) and electrical (TES) stimulation at rest and during muscle contraction. Motor evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle of eight individuals on three separate days. The intensity of TMS at rest was varied from 5% below threshold to the maximal output of the stimulator. During trials in which the muscle was active, TMS and TES intensities were selected that elicited MEPs of between 150 and 300 microV at rest. MEPs were evoked while the participants exerted torques up to 50% of their maximum capacity. The relationship between MEP size and stimulus intensity at rest was sigmoidal (R2=0.97). Intra-class correlation coefficients (ICC) ranged between 0.47 and 0.81 for the parameters of the sigmoid function. For the active trials, the slope and intercept of regression equations of MEP size on level of background contraction were obtained more reliably for TES (ICC=0.63 and 0.78, respectively) than for TMS (ICC=0.50 and 0.53, respectively). These results suggest that input-output parameters of the cortico-spinal pathway may be reliably obtained via transcranial stimulation during longitudinal investigations of cortico-spinal plasticity.

Neural adaptations to resistance training: implications for movement control.

It has long been believed that resistance training is accompanied by changes within the nervous system that play an important role in the development of strength. Many elements of the nervous system exhibit the potential for adaptation in response to resistance training, including supraspinal centres, descending neural tracts, spinal circuitry and the motor end plate connections between motoneurons and muscle fibres. Yet the specific sites of adaptation along the neuraxis have seldom been identified experimentally, and much of the evidence for neural adaptations following resistance training remains indirect. As a consequence of this current lack of knowledge, there exists uncertainty regarding the manner in which resistance training impacts upon the control and execution of functional movements. We aim to demonstrate that resistance training is likely to cause adaptations to many neural elements that are involved in the control of movement, and is therefore likely to affect movement execution during a wide range of tasks. We review a small number of experiments that provide evidence that resistance training affects the way in which muscles that have been engaged during training are recruited during related movement tasks. The concepts addressed in this article represent an important new approach to research on the effects of resistance training. They are also of considerable practical importance, since most individuals perform resistance training in the expectation that it will enhance their performance in related functional tasks.

Neural influences on sprint running: training adaptations and acute responses.

Performance in sprint exercise is determined by the ability to accelerate, the magnitude of maximal velocity and the ability to maintain velocity against the onset of fatigue. These factors are strongly influenced by metabolic and anthropometric components. Improved temporal sequencing of muscle activation and/or improved fast twitch fibre recruitment may contribute to superior sprint performance. Speed of impulse transmission along the motor axon may also have implications on sprint performance. Nerve conduction velocity (NCV) has been shown to increase in response to a period of sprint training. However, it is difficult to determine if increased NCV is likely to contribute to improved sprint performance. An increase in motoneuron excitability, as measured by the Hoffman reflex (H-reflex), has been reported to produce a more powerful muscular contraction, hence maximising motoneuron excitability would be expected to benefit sprint performance. Motoneuron excitability can be raised acutely by an appropriate stimulus with obvious implications for sprint performance. However, at rest H-reflex has been reported to be lower in athletes trained for explosive events compared with endurance-trained athletes. This may be caused by the relatively high, fast twitch fibre percentage and the consequent high activation thresholds of such motor units in power-trained populations. In contrast, stretch reflexes appear to be enhanced in sprint athletes possibly because of increased muscle spindle sensitivity as a result of sprint training. With muscle in a contracted state, however, there is evidence to suggest greater reflex potentiation among both sprint and resistance-trained populations compared with controls. Again this may be indicative of the predominant types of motor units in these populations, but may also mean an enhanced reflex contribution to force production during running in sprint-trained athletes. Fatigue of neural origin both during and following sprint exercise has implications with respect to optimising training frequency and volume. Research suggests athletes are unable to maintain maximal firing frequencies for the full duration of, for example, a 100m sprint. Fatigue after a single training session may also have a neural manifestation with some athletes unable to voluntarily fully activate muscle or experiencing stretch reflex inhibition after heavy training. This may occur in conjunction with muscle damage. Research investigating the neural influences on sprint performance is limited. Further longitudinal research is necessary to improve our understanding of neural factors that contribute to training-induced improvements in sprint performance.

Changes in muscle recruitment patterns during skill acquisition.

The control of movement is predicated upon a system of constraints of musculoskeletal and neural origin. The focus of the present study was upon the manner in which such constraints are adapted or superseded during the acquisition of motor skill. Individuals participated in five experimental sessions, in which they attempted to produce abduction-adduction movements of the index finger in time with an auditory metronome. During each trial, the metronome frequency was increased in eight steps from an individually determined base frequency. Electromyographic (EMG) activity was recorded from first dorsal interosseous (FDI), first volar interosseous (FVI), flexor digitorum superficialis (FDS), and extensor digitorum communis (EDC) muscles. The movements produced on the final day of acquisition more accurately matched the required profile, and exhibited greater spatial and temporal stability, than those generated during initial performance. In the early stages of skill acquisition, an alternating pattern of activation in FDI and FVI was maintained, even at the highest frequencies. In contrast, as the frequency of movement was increased, activity in FDS and EDC was either tonic or intermittent. As learning proceeded, alterations in recruitment patterns were expressed primarily in the extrinsic muscles (EDC and FDS). These changes took the form of increases in the postural role of these muscles, shifts to phasic patterns of activation, or selective disengagement of these muscles. These findings suggest that there is considerable flexibility in the composition of muscle synergies, which is exploited by individuals during the acquisition of coordination.

Corticospinal responses to motor training revealed by transcranial magnetic stimulation.

Transcranial magnetic stimulation was recently used to investigate the nature of adaptations that occur in the central nervous system in response to motor training. In this report, we provide a brief description of trancranial magnetic stimulation and discuss its potential as a tool for identifying corticospinal response to exercise.

Let your feet do the walking: constraints on the stability of bipedal coordination.

In this paper we consider whether the behaviour of the neural circuitry that controls lower limb movements in humans is shaped primarily by the spatiotemporal characteristics of bipedal gait patterns, or by selective pressures that are sensitive to considerations of balance and energetics. During the course of normal locomotion, the full dynamics of the neural circuitry are masked by the inertial properties of the limbs. In the present study, participants executed bipedal movements in conditions in which their feet were either unloaded or subject to additional inertial loads. Two patterns of rhythmic coordination were examined. In the in-phase mode, participants were required to flex their ankles and extend their ankles in synchrony. In the out-of-phase mode, the participants flexed one ankle while extending the other and vice versa. The frequency of movement was increased systematically throughout each experimental trial. All participants were able to maintain both the in-phase and the out-of-phase mode of coordination, to the point at which they could no longer increase their frequency of movement. Transitions between the two modes were not observed, and the stability of the out-of-phase and in-phase modes of coordination was equivalent at all movement frequencies. These findings indicate that, in humans, the behaviour of the neural circuitry underlying coordinated movements of the lower limbs is not constrained strongly by the spatiotemporal symmetries of bipedal gait patterns.