Can local vibration alter the contribution of persistent inward currents to human motoneuron firing?

The response of spinal motoneurons to synaptic input greatly depends on the activation of persistent inward currents (PICs), which in turn are enhanced by the neuromodulators serotonin and noradrenaline. Local vibration (LV) induces excitatory Ia input onto motoneurons and may alter neuromodulatory inputs. Therefore, we investigated whether LV influences the contribution of PICs to motoneuron firing. This was assessed in voluntary contractions with concurrent, ongoing LV, as well as after a bout of prolonged LV. High-density surface electromyograms (HD-EMG) of the tibialis anterior were recorded with a 64-electrode matrix. Twenty males performed isometric, triangular, dorsiflexion contractions to 20% and 50% of maximal torque at baseline, during LV of the tibialis anterior muscle, and after 30-min of LV. HD-EMG signals were decomposed, and motor units tracked across time points to estimate PICs through a paired motor unit analysis, which quantifies motor unit recruitment-derecruitment hysteresis (ΔF). During ongoing LV, ΔF was lower for both 20% and 50% ramps. Although significant changes in ΔF were not observed after prolonged LV, a differential effect across the motoneuron pool was observed. This study demonstrates that PICs can be non-pharmacologically modulated by LV. Given that LV leads to reflexive motor unit activation, it is postulated that lower PIC contribution to motoneuron firing during ongoing LV results from decreased neuromodulatory inputs associated with lower descending corticospinal drive. A differential effect in motoneurons of different recruitment thresholds after prolonged LV is provocative, challenging the interpretation of previous observations and motivating future investigations. KEY POINTS: Neuromodulatory inputs from the brainstem influence motoneuron intrinsic excitability through activation of persistent inward currents (PICs). PICs make motoneurons more responsive to excitatory input. We demonstrate that vibration applied on the muscle modulates the contribution of PICs to motoneuron firing, as observed through analysis of the firing of single motor units. The effects of PICs on motoneuron firing were lower when vibration was concurrently applied during voluntary ramp contractions, likely due to lower levels of neuromodulation. Additionally, prolonged exposure to vibration led to differential effects of lower- vs. higher-threshold motor units on PICs, with lower-threshold motor units tending to present an increased and higher-threshold motor units a decreased contribution of PICs to motoneuron firing. These results demonstrate that muscle vibration has the potential to influence the effects of neuromodulation on motoneuron firing. The potential of using vibration as a non-pharmacological neuromodulatory intervention should be further investigated.

Influence of biceps brachii tendon mechanical properties on elbow flexor force steadiness in young and old males.

Elbow flexor force steadiness (FS) depends on strength and decreases with age. Achilles tendon mechanics effect standing balance and isometric plantarflexion FS. This study investigated the influence of distal biceps brachii (BB) tendon mechanics and elbow flexor strength on age-related decline in FS. Nine young (23 ± 2 years) and nine old (77 ± 5 years) males performed submaximal isometric elbow flexion tasks at low (2.5%, 5%, 10% maximal voluntary contraction (MVC)) and high (20%, 40%, 60%, 80%MVC) forces in a neutral forearm position. Distal BB tendon elongation and cross-sectional area (CSA) were recorded on ultrasound to calculate mechanics of strain, stress, and stiffness. Coefficient of variation (CV) of force was used to assess relationship of FS to tendon mechanics and strength. Young were 22% stronger and 41% steadier than old (P < .05). Tendon stiffness (170.1 ± 132.9 N/mm; 113.0 ± 55.1 N/mm) did not differ with age (P > .05). Young had 40% less strain compared to old at 5% MVC, but 42% greater strain at 60% and 80% MVC (P ≤ .05). Stress was ~18% greater in young at 10%, 20%, and 80% MVC (P ≤ .05). At low forces, CV of force was predicted by stress (r2  = 0.56) in young, and stress and MVC (r2  = 0.641) in old. At high forces for both age groups, CV of force was predicted by MVC and stress (r2  = 0.39-0.43). Stress and strain is greater in young compared with old males. Because strength influences tendon mechanics and is also associated with FS, absolute strength is a large and modifiable contributor to age-related decline in FS.

Anodal transcranial direct current stimulation enhances time to task failure of a submaximal contraction of elbow flexors without changing corticospinal excitability.

BACKGROUND: The increase in corticospinal excitability in response to anodal transcranial direct current stimulation (a-tDCS) may contribute to decrease neuromuscular fatigability. OBJECTIVE: This study investigated the effects of a-tDCS on neuromuscular fatigability in relation with changes in corticospinal excitability. METHODS: Eleven adults participated in two experimental sessions consisting of two submaximal voluntary contractions (35% maximal torque) performed to failure, one hour apart with the right elbow flexor muscles. Sham stimulation (90 s) and a-tDCS (10 min) were applied in two separate sessions 10 min prior to the second fatiguing contraction. Corticospinal excitability was assessed by recording motor-evoked potential (MEP), elicited by transcranial magnetic stimulation (TMS) of the motor cortex, in biceps brachii, brachioradialis and triceps brachii during the first (C1) and second (C2) fatiguing contractions. The silent period (SP) in electromyogramme (EMG) that followed MEP was also recorded for biceps brachii and brachioradialis. RESULTS: Time to failure was briefer for C2 than C1 in both experimental sessions, but the decrease was less pronounced after a-tDCS (-14.4±12.7%) than sham stimulation (-23.3±11.9%; p=0.04). MEP amplitude (+9.7±4.0%) and SP duration (+22.5±12.8%) in biceps brachii and brachioradialis increased significantly (p<0.05) during C1 and C2, but to a similar extent in both sessions (p>0.05). A similar result was observed for MEP amplitude in triceps brachii. No association was found between changes in time to task failure of C2 and corticospinal excitability. CONCLUSION: The reduced neuromuscular fatigability induced by a-tDCS does not rely on changes in the excitability of the corticospinal pathway of both agonist and antagonist muscles.

Changes in Kidney Functions during Middle-distance Triathlon in Male Athletes.

Strenuous exercise induces proteinuria which is related to the intensity of exercise. However, renal responses to each type of exercise during a middle-distance triathlon have not been reported. The present study, carried out on 7 healthy athletes, investigated renal function at rest and after each exercise of a half-triathlon race. Blood and urine samples were collected at rest and after each specific event. Protein excretion and renal clearances were determined on each sample. Compared with resting values, albuminuria was increased by a factor of 30 (p<0.05) after swimming but did not differ from the resting value after cycling and running (p>0.05). Rates of ß2-microglobulin and retinol-binding protein excretion did not change throughout the triathlon (p>0.05). Glomerular filtration rate (expressed as creatinine clearance) remained stable after each exercise event, whereas tubular reabsorption rate (expressed as urea clearance) was reduced by 50, 40 and 65% after swimming, cycling and running, respectively, compared to pre-exercise values (p<0.05). Glomerular membrane permeability (expressed as albumin clearance) was significantly increased by the swimming event (13 times, p<0.05). These results suggest that middle-distance triathlon has a noticeable impact on the glomerular membrane permeability (albumin clearance) and elimination of protein waste (urea clearance) depending on exercise type.

Presynaptic inhibition of soleus Ia afferents does not vary with center of pressure displacements during upright standing.

The present work was designed to investigate the presynaptic modulation of soleus Ia afferents with the position and the direction of the displacement of the center of pressure (CoP) during unperturbed upright standing and exaggerated CoP displacements in young adults. Hoffmann (H) reflex was evoked in the soleus by stimulating the tibial nerve at the knee level. Modulation of Ia presynaptic inhibition was assessed by conditioning the H reflex with fibular nerve (D1 inhibition) and femoral nerve (heteronymous facilitation) stimulation. Leg muscle activity was assessed by electromyography (EMG). The results indicate that in unperturbed standing and exaggerated CoP displacements, the H-reflex amplitude was greater during forward than backward CoP direction (p<0.05). However, the amplitude of the conditioned H reflex (expressed relative to unconditioned H reflex) did not vary with CoP displacement, regardless of the experimental condition. The soleus EMG was greater during forward than backward CoP direction and during anterior than posterior position in both experimental conditions (p<0.05). The modulation of the unconditioned H reflex with CoP direction was positively associated with the corresponding changes in soleus EMG (r(2)>0.34). The tibialis anterior EMG did not change during unperturbed standing, but was greater for backward than forward CoP direction during exaggerated CoP displacements. In this experimental condition, soleus EMG was negatively associated with tibialis anterior EMG (r(2)=0.81). These results indicate that Ia presynaptic inhibition is not modulated with CoP direction and position, but rather suggest that CoP displacements induced changes in excitability of the soleus motor neuron pool.

Independent modulation of corticospinal and group I afferents pathways during upright standing.

Balance control during upright standing is accompanied by an increased amplitude of motor-evoked potentials (MEP) induced by transcranial magnetic stimulation and a decreased amplitude of the Hoffmann (H) reflex in the soleus muscle. Nonetheless, whether these observations reflect reciprocal adjustments between corticospinal and group I afferents pathways during upright standing remains unknown. To further investigate this question, cathodal transcranial direct current stimulation (c-tDCS) applied over the motor cortex and vibration of Achilles tendons were used to modify the excitability of corticospinal and group I afferent pathways, respectively. MEPs and H reflexes were recorded in the soleus muscle during upright standing with or without bilateral Achilles tendon vibration, these recordings being performed before and after 20 min of c-tDCS (1.5 mA) or sham stimulation applied over the sensorimotor cortex. The results indicate that tendon vibration increased MEP amplitude (+28%) and decrease (-68%) the H-reflex amplitude (p<0.05). After c-tDCS, MEP amplitude was reduced by 13% and 26% without and with tendon vibration (p<0.05), respectively. In contrast, no significant change occurred in H-reflex amplitude after c-tDCS. Regardless of the conditions (c-tDCS and tendon vibration), no significant correlation was observed between changes in MEP and H-reflex amplitudes. The results failed to demonstrate close reciprocal changes in soleus MEP and H-reflex amplitudes during upright standing. These original findings suggest independent adjustments in corticospinal and group I afferents pathways during upright standing.

Vision and proprioception do not influence the excitability of the corticomotoneuronal pathway during upright standing in young and elderly adults.

This study investigated the influence of vision and proprioception on the excitability of direct corticospinal (corticomotoneuronal) pathway to the soleus in young and elderly adults during upright standing. Ten young and 10 elderly adults stood upright on a rigid surface with eyes open or closed, and on foam mat with eyes open. The corticomotoneuronal excitability was investigated by assessing facilitation of the soleus H-reflex induced by subthreshold transcranial magnetic stimulation (TMS). The torque produced by the plantar flexor muscles during a maximal voluntary contraction was also measured. The maximal plantar flexion torque was significantly lower in elderly than in young adults (p<0.05). The activity of leg muscles, recorded by electromyography (EMG) was greater in elderly than in young adults regardless of balance conditions (p<0.05), and greater when standing on foam than in the other conditions (p<0.05), regardless of age. The H-reflex facilitation was greater for elderly [182.9 (45)%] than young adults [130.5 (33.1)%; p<0.05] but did not differ across sensory conditions (p>0.05). However, the amplitude of the H reflex conditioned by TMS relative to the amplitude of the test H reflex ratio was positively associated with EMG activity of the plantar flexor muscles during upright standing (r(2)=0.47; p<0.001). These results indicate that regardless of age the excitability of the corticomotoneuronal pathway is not modulated with changes in the sensory conditions during upright standing. Nonetheless, the corticomotoneural drive to control leg muscle during upright standing increases with the level of soleus muscle activity.

Input-output characteristics of soleus homonymous Ia afferents and corticospinal pathways during upright standing differ between young and elderly adults.

AIM: This study investigated the effects of ageing on the excitability of soleus homonymous Ia afferents and corticospinal pathways during bipedal upright standing. METHODS: The input-output relations for the Hoffmann (H) reflex and motor-evoked potential (MEP) were computed for the soleus in response to electrical nerve stimulation and transcranial magnetic stimulation, respectively, in young (n = 16) and elderly (n = 16) adults. In subsets of subjects, the input-output relations were compared between normal and supported upright standing, and corticomotoneuronal excitability was assessed during upright standing with an H-reflex conditioning method. For the H-reflex and MEP threshold, maximal amplitude (Hmax , MEPmax ) and the slope of the input-output relation (Hslope , MEPslope ) were measured and normalized to the corresponding M-wave value. RESULTS: In normal standing, the Hmax /Mmax [mean (SD); young: 48.3 (14.2)%; elderly: 17.3 (6.4)%] and Hslope /Mslope were significantly (P < 0.05) lower in elderly than in young adults, whereas the MEPmax /Mmax [young: 13.6 (7.5)%; elderly: 24.5 (12.8)%] and MEPslope /Mslope were greater in elderly adults (P < 0.05). The Hslope /Mslope and MEPslope /Mslope decreased and increased, respectively, from supported to normal standing for both age groups but more so in elderly adults. Furthermore, the conditioned H reflex was greater (P < 0.05) in elderly [175.1 (34.3)%] than in young adults [141.8 (29.8)%] during normal standing. CONCLUSION: This is the first study that clearly indicates lower efficacy of Ia afferents to discharge spinal motor neurones accompanied by greater corticospinal excitability in elderly adults, suggesting an increased contribution of the descending drive in controlling soleus activity during upright standing with ageing.

Workplace bullying and psychotropic drug use: the mediating role of physical and mental health status.

OBJECTIVES: The association between workplace bullying and psychotropic drug use is not well established. This study was aimed at exploring the association between workplace bullying, and its characteristics, and psychotropic drug use and studying the mediating role of physical and mental health. METHODS: The study population consisted of a random sample of 3132 men and 4562 women of the working population in the south-east of France. Workplace bullying, evaluated using the validated instrument elaborated by Leymann, and psychotropic drug use, as well as covariates, were measured using a self-administered questionnaire. Covariates included age, marital status, presence of children, education, occupation, working hours, night work, physico-chemical exposures at work, self-reported health, and depressive symptoms. Statistical analysis was performed using logistic regression analysis and was carried out separately for men and women. RESULTS: Workplace bullying was strongly associated with psychotropic drug use. Past exposure to bullying increased the risk for this use. The more frequent and the longer the exposure to bullying, the stronger the association with psychotropic drug use. Observing bullying on someone else at the workplace was associated with psychotropic drug use. Adjustment for covariates did not modify the results. Additional adjustment for self-reported health and depressive symptoms reduced the magnitude of the associations, especially for men. CONCLUSIONS: The association between bullying and psychotropic drug use was found to be significant and strong and was partially mediated by physical and mental health.

Influence of rest duration on muscle activation during submaximal intermittent contractions with the elbow flexor muscles.

AIM: The purpose of the study was to compare the influence of two intervals between consecutive intermittent contractions with the elbow flexors on time to failure and the accompanying changes in electromyographic (EMG) activity and excitation-contraction coupling. METHODS: Subjects performed 6-s intermittent isometric contractions at 50% of the maximal voluntary contraction (MVC) force to task failure in two sessions. The recovery period between consecutive contractions was 4-s (short recovery protocol, SRP) in one and 14-s (long recovery protocol, LRP) in the other session. RESULTS: The number of contractions performed to task failure was greater for the LRP (99 + or - 24) compared with the SRP (46 + or - 18; P<0.05). The amplitude and duration of the maximal compound action potential (M-wave) did not change during either protocol. EMG activity (% peak MVC) for the elbow flexors and the force fluctuations increased more rapidly during the SRP compared with the LRP (P<0.05) and was greater at task failure for the SRP protocol (P<0.05). These changes were accompanied by a faster decline in twitch force. CONCLUSIONS: The results indicate that a briefer interval between consecutive contractions was associated with a more rapid impairment of the excitation-contraction coupling and a faster increase in muscle activation, despite a similar net muscle force for the two protocols.

Workplace bullying and sleep disturbances: findings from a large scale cross-sectional survey in the French working population.

STUDY OBJECTIVES: The purpose of this study was to explore the associations between workplace bullying, the characteristics of workplace bullying, and sleep disturbances in a large sample of employees of the French working population. DESIGN: Workplace bullying, evaluated using the validated instrument developed by Leymann, and sleep disturbances, as well as covariates, were measured using a self-administered questionnaire. Covariates included age, marital status, presence of children, education, occupation, working hours, night work, physical and chemical exposures at work, self-reported health, and depressive symptoms. Statistical analysis was performed using logistic regression analysis and was carried out separately for men and women. SETTING: General working population. PARTICIPANTS: The study population consisted of a random sample of 3132 men and 4562 women of the working population in the southeast of France. RESULTS: Workplace bullying was strongly associated with sleep disturbances. Past exposure to bullying also increased the risk for this outcome. The more frequent the exposure to bullying, the higher the risk of experiencing sleep disturbances. Observing someone else being bullied in the workplace was also associated with the outcome. Adjustment for covariates did not modify the results. Additional adjustment for self-reported health and depressive symptoms diminished the magnitude of the associations that remained significant. CONCLUSIONS: The prevalence of workplace bullying (around 10%) was found to be high in this study as well was the impact of this major job-related stressor on sleep disturbances. Although no conclusion about causality could be drawn from this cross-sectional study, the findings suggest that the contribution of workplace bullying to the burden of sleep disturbances may be substantial.

Diffusion tensor imaging (DTI) and tractography of the cerebellar projections to prefrontal and posterior parietal cortices: a study at 3T.

OBJECTIVES: Previous diffusion tensor imaging (DTI) studies have identified cerebellar pathways and supratentorial connections, but none of them have isolated cerebellar projections to prefrontal and posterior parietal cortices using tractography. The aim of our study was to identify and visualize on 3D projections, as well as on 2D cross-sectional images, the cerebellar projections to prefrontal (PF) and posterior parietal (PP) cortices. MATERIAL AND METHODS: The study included 10 healthy volunteers, four males and six females aged 25 to 45 years (mean age 31 years). A DTI sequence was applied at 3 Tesla using diffusion sensitizing gradients in 32 directions. White matter tracts were reconstructed by applying a multiple ROI (region of interest) tractography technique. RESULTS: PF projections were obtained in all subjects. PP projections were obtained in six over 10 subjects. On 2D cross-sectional images, the tracts showed the same anatomical location in each ROI in all subjects. CONCLUSION: This DTI study at 3T resulted in a selective and full visualization of cerebellar projections to PF and PP cortices for the first time and is introductive for further optimized and quantitative DTI study of these tracts.

Stereoselective passage of mefloquine through the blood-brain barrier in the rat.

The pharmacokinetics of the enantiomers of mefloquine were studied in the rat after administration of a racemic mixture and of the separate enantiomers (+)-mefloquine and (-)-mefloquine. When 50 mg kg-1 racemic mixture was administered orally for 22 days, plasma concentrations of the (+) enantiomer were 2-3 times higher than those of the (-) enantiomer whereas the opposite was true in every part of the brain (cerebellum, cortex, hippocampus, hypothalamus and striatum). Different concentrations of mefloquine were found in the different regions of the brain; the lowest concentrations of (+/-)-mefloquine (27.0 nmol g-1) were in the cerebellum and the highest (110.0 nmol g-1) in the hippocampus. The main metabolite, carboxymefloquine, was detected in plasma but not in the brain. The results indicate the mefloquine crosses the blood-brain barrier stereoselectively.