Short-term beetroot juice supplementation improves muscle speed and power but does not reduce blood pressure or oxidative stress in 65-79 y old men and women.

We have previously demonstrated that acute ingestion of inorganic nitrate (NO3-)-rich beetroot juice (BRJ), a source of nitric oxide (NO) via the NO3- → nitrite (NO2-) → NO pathway, can improve muscle speed and power in older individuals. It is not known, however, whether this effect is maintained or perhaps even enhanced with repeated ingestion, or if tolerance develops as with organic nitrates, e.g., nitroglycerin. Using a double-blind, placebo-controlled, crossover design, we therefore studied 16 community-dwelling older (age 71 ± 5 y) individuals after both acute and short-term (i.e., daily for 2 wk) BRJ supplementation. Blood samples were drawn and blood pressure was measured periodically during each ∼3 h experiment, with muscle function determined using isokinetic dynamometry. Acute ingestion of BRJ containing 18.2 ± 6.2 mmol of NO3- increased plasma NO3- and NO2- concentrations 23 ± 11 and 2.7 ± 2.1-fold over placebo, respectively. This was accompanied by 5 ± 11% and 7 ± 13% increases in maximal knee extensor speed (Vmax) and power (Pmax), respectively. After daily supplementation for 2 wk, BRJ ingestion elevated NO3- and NO2- levels 24 ± 12 and 3.3 ± 4.0-fold, respectively, whereas Vmax and Pmax were 7 ± 9% and 9 ± 11% higher than baseline. No changes were observed in blood pressure or in plasma markers of oxidative stress with either acute or short-term NO3- supplementation. We conclude that both acute and short-term dietary NO3- supplementation result in similar improvements in muscle function in older individuals. The magnitudes of these improvements are sufficient to offset the decline resulting from a decade or more of aging and are therefore likely to be clinically significant.

The influence of acute dietary nitrate supplementation on skeletal muscle fatigue and recovery in older women.

Older individuals fatigue more rapidly during, and recover more slowly from, dynamic exercise. Women are particularly vulnerable to these deleterious effects of aging, which increases their risk of falling. We have shown that dietary nitrate (NO3 - ), a source of nitric oxide (NO) via the NO3 - → nitrite (NO2 - ) → NO pathway, enhances muscle speed and power in older individuals in the non-fatigued state; however, it is unclear if it reduces fatigability and/or improves recoverability in this population. Using a double-blind, placebo-controlled, crossover design, we studied 18 older (age 70 ± 4 years) women who were administered an acute dose of beetroot juice (BRJ) containing either 15.6 ± 3.6 or <0.05 mmol of NO3 - . Blood samples were drawn throughout each ~3 h visit for plasma NO3 - and NO2 - analysis. Peak torque was measured during, and periodically for 10 min after, 50 maximal knee extensions performed at 3.14 rad/s on an isokinetic dynamometer. Ingestion of NO3 - -containing BRJ increased plasma NO3 - and NO2 - concentrations by 21 ± 8 and 4 ± 4 fold, respectively. However, there were no differences in muscle fatigue or recovery. Dietary NO3 - increases plasma NO3 - and NO2 - concentrations but does not reduce fatigability during or enhance recoverability after high intensity exercise in older women.

The influence of acute dietary nitrate supplementation on skeletal muscle fatigue and recovery in older women.

Older individuals fatigue more rapidly during, and recover more slowly from, dynamic exercise. Women are particularly vulnerable to these deleterious effects of aging, which increases their risk of falling. We have shown that dietary nitrate (NO 3 - ), a source of nitric oxide (NO) via the NO 3 - → nitrite (NO 2 - ) → NO pathway, enhances muscle speed and power in older individuals in the non-fatigued state; however, it is unclear if it reduces fatigability and/or improves recoverability in this population. Using a double-blind, placebo-controlled, crossover design, we studied 18 older (age 70 ± 4 y) women who were administered an acute dose of beetroot juice (BRJ) containing either 15.6±3.6 or <0.05 mmol of NO 3 - . Blood samples were drawn throughout each ∼3 h visit for plasma NO 3 - and NO 2 - analysis. Peak torque was measured during, and periodically for 10 min after, 50 maximal knee extensions performed at 3.14 rad/s on an isokinetic dynamometer. Ingestion of NO 3 - -containing BRJ increased plasma NO 3 - and NO 2 - concentrations by 21±8 and 4±4 fold, respectively. However, there were no differences in muscle fatigue or recovery. Dietary NO 3 - increases plasma NO 3 - and NO 2 - concentrations but does not reduce fatigability during or enhance recoverability after high intensity exercise in older women.

Dose-Response Effect of Dietary Nitrate on Muscle Contractility and Blood Pressure in Older Subjects: A Pilot Study.

We have recently demonstrated that dietary nitrate, a source of nitric oxide (NO) via the nitrate → nitrite → NO enterosalivary pathway, can improve muscle contractility in healthy older men and women. Nitrate ingestion has also been shown to reduce blood pressure in some, but not all, studies of older individuals. However, the optimal dose for eliciting these beneficial effects is unknown. A pilot randomized, double-blind, placebo-controlled crossover study was therefore performed to determine the effects of ingesting 3.3 mL/kg of concentrated beetroot juice containing 0, 200, or 400 µmol/kg of nitrate in 9 healthy older subjects (mean age 70 ± 1 years). Maximal knee extensor power (Pmax) and speed (Vmax) were measured ~2.5 hours after nitrate ingestion using isokinetic dynamometry. Blood pressure was monitored periodically throughout each study. Pmax (in W/kg) was higher (p < .05) after the lower dose (3.9 ± 0.4) compared to the placebo (3.7 ± 0.4) or higher dose (3.7 ± 0.4). Vmax (in rad/s) also tended to be higher (p = .08) after the lower dose (11.9 ± 0.7) compared to the placebo (10.8 ± 0.8) or higher dose (11.2 ± 0.8). Eight out of 9 subjects achieved a higher Pmax and Vmax after the lower versus the higher dose. These dose-related changes in muscle contractility generally paralleled changes in breath NO levels. No significant changes were found in systolic, diastolic, or mean arterial blood pressure. A lower dose of nitrate increases muscle speed and power in healthy older individuals, but these improvements are lost at a higher dose. Blood pressure, on the other hand, is not reduced even with a higher dose.

A Single Dose of Dietary Nitrate Increases Maximal Knee Extensor Angular Velocity and Power in Healthy Older Men and Women.

BACKGROUND: Aging results in reductions in maximal muscular strength, speed, and power, which often lead to functional limitations highly predictive of disability, institutionalization, and mortality in elderly adults. This may be partially due to reduced nitric oxide (NO) bioavailability. We, therefore, hypothesized that dietary nitrate (NO3-), a source of NO via the NO3- → nitrite (NO2-) → NO enterosalivary pathway, could increase muscle contractile function in older subjects. METHODS: Twelve healthy older (age 71 ± 5 years) men and women were studied using a randomized, double-blind, placebo-controlled, crossover design. After fasting overnight, subjects were tested 2 hours after ingesting beetroot juice containing or devoid of 13.4 ± 1.6 mmol NO3-. Plasma NO3- and NO2- and breath NO were measured periodically, and muscle function was determined using isokinetic dynamometry. RESULTS: N O 3 - ingestion increased (p < .001) plasma NO3-, plasma NO2-, and breath NO by 1,051% ± 433%, 138% ± 149%, and 111% ± 115%, respectively. Maximal velocity of knee extension increased (p < .01) by 10.9% ± 12.1%. Maximal knee extensor power increased (p < .05) by 4.4% ± 7.8%. CONCLUSIONS: Acute dietary NO3- intake improves maximal knee extensor angular velocity and power in older individuals. These findings may have important implications for this population, in whom diminished muscle function can lead to functional limitations, dependence, and even premature death.

Cortical and spinal mechanisms of task failure of sustained submaximal fatiguing contractions.

In this and the subsequent companion paper, results are presented that collectively seek to delineate the contribution that supraspinal circuits have in determining the time to task failure (TTF) of sustained submaximal contractions. The purpose of this study was to compare adjustments in supraspinal and spinal excitability taken concurrently throughout the performance of two different fatigue tasks with identical mechanical demands but different TTF (i.e., force-matching and position-matching tasks). On separate visits, ten healthy volunteers performed the force-matching or position-matching task at 15% of maximum strength with the elbow flexors to task failure. Single-pulse transcranial magnetic stimulation (TMS), paired-pulse TMS, paired cortico-cervicomedullary stimulation, and brachial plexus electrical stimulation were delivered in a 6-stimuli sequence at baseline and every 2-3 minutes throughout fatigue-task performance. Contrary to expectations, the force-matching task TTF was 42% shorter (17.5 ± 7.9 min) than the position-matching task (26.9 ± 15.11 min; p<0.01); however, both tasks caused the same amount of muscle fatigue (p = 0.59). There were no task-specific differences for the total amount or rate of change in the neurophysiologic outcome variables over time (p>0.05). Therefore, failure occurred after a similar mean decline in motorneuron excitability developed (p<0.02, ES = 0.35-0.52) coupled with a similar mean increase in measures of corticospinal excitability (p<0.03, ES = 0.30-0.41). Additionally, the amount of intracortical inhibition decreased (p<0.03, ES = 0.32) and the amount of intracortical facilitation (p>0.10) and an index of upstream excitation of the motor cortex remained constant (p>0.40). Together, these results suggest that as fatigue develops prior to task failure, the increase in corticospinal excitability observed in relationship to the decrease in spinal excitability results from a combination of decreasing intracortical inhibition with constant levels of intracortical facilitation and upstream excitability that together eventually fail to provide the input to the motor cortex necessary for descending drive to overcome the spinal cord resistance, thereby contributing to task failure.

Reliability of a modified motor unit number index (MUNIX) technique.

INTRODUCTION: The purpose of this study was to examine the relative and absolute between-day reliability of the motor unit number index (MUNIX). METHODS: Young, healthy adults (n=19) attended two testing sessions separated by 4-weeks where their maximal pinch-grip strength, MUNIX, and motor unit size index (MUSIX) were assessed in the abductor pollicis brevis muscle. Reliability was assessed by intraclass correlation coefficients (ICC), coefficient of variation (CV) and limits of agreement (LOA). RESULTS: No mean differences were observed for MUNIX or MUSIX. The CV for the MUNIX and MUSIX measures were between 13.5% and 17.5%. The ICC for both measures were moderate to moderately-high (0.73-0.76), The LOA for both indicated a homoscedastic relationship. DISCUSSION: Our findings indicate moderate to moderately-high reliability for both MUNIX and MUSIX. Future work is needed to ensure both measures are reliable in other muscles and cohorts, and further investigations are required to examine the validity of MUNIX.

Preliminary evidence that anodal transcranial direct current stimulation enhances time to task failure of a sustained submaximal contraction.

The purpose of this study was to determine whether anodal transcranial direct current stimulation (tDCS) delivered while performing a sustained submaximal contraction would increase time to task failure (TTF) compared to sham stimulation. Healthy volunteers (n = 18) performed two fatiguing contractions at 20% of maximum strength with the elbow flexors on separate occasions. During fatigue task performance, either anodal or sham stimulation was delivered to the motor cortex for up to 20 minutes. Transcranial magnetic stimulation (TMS) was used to assess changes in cortical excitability during stimulation. There was no systematic effect of the anodal tDCS stimulation on TTF for the entire subject set (n = 18; p = 0.64). Accordingly, a posteriori subjects were divided into two tDCS-time groups: Full-Time (n = 8), where TTF occurred prior to the termination of tDCS, and Part-Time (n = 10), where TTF extended after tDCS terminated. The TTF for the Full-Time group was 31% longer with anodal tDCS compared to sham (p = 0.04), whereas TTF for the Part-Time group did not differ (p = 0.81). Therefore, the remainder of our analysis addressed the Full-Time group. With anodal tDCS, the amount of muscle fatigue was 6% greater at task failure (p = 0.05) and the amount of time the Full-Time group performed the task at an RPE between 8-10 ("very hard") increased by 38% (p = 0.04) compared to sham. There was no difference in measures of cortical excitability between stimulation conditions (p = 0.90). That the targeted delivery of anodal tDCS during task performance both increased TTF and the amount of muscle fatigue in a subset of subjects suggests that augmenting cortical excitability with tDCS enhanced descending drive to the spinal motorpool to recruit more motor units. The results also suggest that the application of tDCS during performance of fatiguing activity has the potential to bolster the capacity to exercise under conditions required to derive benefits due to overload.

Interrelationship between muscle strength, motor units, and aging.

The interrelationship between muscle strength, motor unit (MU) number, and age is poorly understood, and in this study we sought to determine whether age-related differences in muscle strength are moderated by estimates of functioning MU number and size. Eighteen older adults (OA; 67 ± 1.20 years) and 24 young adults (YA; 22 ± 0.74 years) participated in this study. Maximum voluntary pinch-grip strength of the nondominant hand was determined and estimates of MU number were obtained from the abductor pollicis brevis muscle using the noninvasive motor unit number index (MUNIX) technique. The MUNIX technique was also utilized to derive a motor unit size index (MUSIX). An analysis of covariance (Age Group × MUNIX or MUSIX) was used to test heterogeneity of regression slopes, with body mass and gender serving as covariates. We observed that the slope of pinch-grip strength on the estimated number of MUs between YA and OA differed, indicated by an Age Group × MUNIX interaction (p = 0.04). Specifically, after controlling for the effect of body mass and gender, the slope in OA was significantly positive (0.14 ± 0.06 N/MUs, p = 0.03), whereas no such relationship was found in YA (-0.08 ± 0.09 N/MUs, p = 0.35). A significant Age Group × MUSIX interaction was also observed for strength (p < 0.01). In contrast to MUNIX, the slope in younger adults was significantly positive (0.48 ± 0.11 N/µV, p < 0.01), whereas no such relationship was found in older adults (-0.30 ± 0.22 N/µV, p = 0.18). These findings indicate that there is an interrelationship between muscle strength, MU numbers, and aging, which suggests that a portion of muscle weakness in seniors may be attributable to the loss of functioning motor units.

Effects of persistent Mal de debarquement syndrome on balance, psychological traits, and motor cortex exctiability.

Mal de debarquement syndrome (MdDS) is a poorly characterized and understood disorder of perceived motion. We sought to characterize postural control and the psychological impact of MdDS. Additionally, we explored whether patients with MdDS exhibit altered corticospinal and intracortical excitability. In a case-control study we compared patients with MdDS to age- and sex-matched controls (n=8/group). Postural stability (σr) was quantified from plane phase plots based on center or pressure, and psychological indices of depression, fatigue and kinesiophobia were obtained. Transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability by quantifying the motor evoked potential (MEP) amplitude of the flexor carpi radialis, and intracortical excitability was assessed by quantifying indices of intracortical facilitation (ICF), and short-interval and long-interval intracortical inhibition using a paired-pulse TMS paradigm. The patients with MdDS exhibited greater mean (±standard error of the mean) σr during semi-tandem stance (10.9 ± 1.5 compared to 7.1 ± 0.7, p=0.04), higher levels of kinesiophobia (41.6 ± 2.8 compared to 27.3 ± 2.2), and higher levels of fatigue (27.0 ± 4.1 compared to 48.4 ± 1.0). Patients with MdDS exhibited a higher mean motor threshold (MT) (58.1 ± 2.5 compared to 47.4 ± 2.7% of stimulator output), and larger MEP (13.1 ± 3.1 compared to 5.1 ± 1.2% of maximal compound muscle action potential) but there was no difference in measures of intracortical excitability. These findings suggest that patients with MdDS exhibit impaired postural stability, and high levels of kinesiophobia and fatigue. Additionally, we observed that patients with MdDS exhibit higher MT and large MEP amplitudes, but do not exhibit differences in measures of intracortical excitability, compared to controls. These findings help characterize MdDS, and provide insight into the physiology of MdDS.

Utilizing transcranial magnetic stimulation to study the human neuromuscular system.

Transcranial magnetic stimulation (TMS) has been in use for more than 20 years, and has grown exponentially in popularity over the past decade. While the use of TMS has expanded to the study of many systems and processes during this time, the original application and perhaps one of the most common uses of TMS involves studying the physiology, plasticity and function of the human neuromuscular system. Single pulse TMS applied to the motor cortex excites pyramidal neurons transsynaptically (Figure 1) and results in a measurable electromyographic response that can be used to study and evaluate the integrity and excitability of the corticospinal tract in humans. Additionally, recent advances in magnetic stimulation now allows for partitioning of cortical versus spinal excitability. For example, paired-pulse TMS can be used to assess intracortical facilitatory and inhibitory properties by combining a conditioning stimulus and a test stimulus at different interstimulus intervals. In this video article we will demonstrate the methodological and technical aspects of these techniques. Specifically, we will demonstrate single-pulse and paired-pulse TMS techniques as applied to the flexor carpi radialis (FCR) muscle as well as the erector spinae (ES) musculature. Our laboratory studies the FCR muscle as it is of interest to our research on the effects of wrist-hand cast immobilization on reduced muscle performance, and we study the ES muscles due to these muscles clinical relevance as it relates to low back pain. With this stated, we should note that TMS has been used to study many muscles of the hand, arm and legs, and should iterate that our demonstrations in the FCR and ES muscle groups are only selected examples of TMS being used to study the human neuromuscular system.

Neurophysiologic effects of spinal manipulation in patients with chronic low back pain.

BACKGROUND: While there is growing evidence for the efficacy of SM to treat LBP, little is known on the mechanisms and physiologic effects of these treatments. Accordingly, the purpose of this study was to determine whether SM alters the amplitude of the motor evoked potential (MEP) or the short-latency stretch reflex of the erector spinae muscles, and whether these physiologic responses depend on whether SM causes an audible joint sound. METHODS: We used transcranial magnetic stimulation to elicit MEPs and electromechanical tapping to elicit short-latency stretch reflexes in 10 patients with chronic LBP and 10 asymptomatic controls. Neurophysiologic outcomes were measured before and after SM. Changes in MEP and stretch reflex amplitude were examined based on patient grouping (LBP vs. controls), and whether SM caused an audible joint sound. RESULTS: SM did not alter the erector spinae MEP amplitude in patients with LBP (0.80±0.33 vs. 0.80±0.30 µV) or in asymptomatic controls (0.56±0.09 vs. 0.57±0.06 µV). Similarly, SM did not alter the erector spinae stretch reflex amplitude in patients with LBP (0.66±0.12 vs. 0.66±0.15 µV) or in asymptomatic controls (0.60±0.09 vs. 0.55±0.08 µV). Interestingly, study participants exhibiting an audible response exhibited a 20% decrease in the stretch reflex (p<0.05). CONCLUSIONS: These findings suggest that a single SM treatment does not systematically alter corticospinal or stretch reflex excitability of the erector spinae muscles (when assessed~10-minutes following SM); however, they do indicate that the stretch reflex is attenuated when SM causes an audible response. This finding provides insight into the mechanisms of SM, and suggests that SM that produces an audible response may mechanistically act to decrease the sensitivity of the muscle spindles and/or the various segmental sites of the Ia reflex pathway.

Cast immobilization increases long-interval intracortical inhibition.

Immobilization reduces muscle performance, and despite these performance losses being associated with neural impairments little is known regarding adaptations in cortical properties. We utilized transcranial magnetic stimulation to assess changes in flexor carpi radialis (FCR) intracortical facilitation (ICF), and short- and long-interval intracortical inhibition (SICI and LICI) in healthy humans undergoing 3 weeks of immobilization. Measurements were obtained at rest and during contraction (15% intensity). Central activation and the Hoffman reflex (H-reflex) were also assessed. Strength decreased 43.2% +/- 6.1% following immobilization, and central activation also decreased (97.5% +/- 2.4% to 73.2% +/- 8.3%). No changes in ICF, SICI, or LICI were observed at rest; however, LICI was increased during contraction (67.5% +/- 6.9% to 53.1% +/- 6.7% of unconditioned response). The increase in LICI correlated with the loss of strength (r = -0.63). The H-reflex increased following immobilization. These findings suggest that immobilization increases intracortical inhibition during contraction, and this increase is primarily mediated by GABA(B) receptors.

Older adults exhibit more intracortical inhibition and less intracortical facilitation than young adults.

BACKGROUND: Aging results in decreased neuromuscular function, which is likely associated with neurologic alterations. At present little is known regarding age-related changes in intracortical properties. METHODS: In this study we used transcranial magnetic stimulation (TMS) to measure intracortical facilitation (ICF), short- and long-interval intracortical inhibition (SICI and LICI), motor evoked potential amplitude, and silent period duration in young and older adults (21.4+/-0.8years and 70.9+/-1.8years). These variables were assessed from the flexor carpi radialis muscle of the non-dominant arm under resting conditions, and during a submaximal contraction (intensity 15% maximum strength). RESULTS: Older adults exhibited increased SICI and LICI in comparison to young adults (SICI: 29.0+/-9.2% vs. 46.2+/-4.8% of unconditioned pulse; LICI: 6.5+/-1.7% vs. 15.8+/-3.3% of unconditioned pulse; P=0.04), and less ICF under resting conditions (74.6+/-8.7% vs. 104.9+/-6.9% of unconditioned pulse; P=0.02). These age-related differences disappeared during contraction, although the older adults did exhibit a longer silent period during contraction (112.5+/-6.5 vs. 84.0+/-3.9ms; P<0.01). CONCLUSIONS: Collectively, these findings suggest increased GABA mediated intracortical inhibition with age.

Men and women exhibit a similar time to task failure for a sustained, submaximal elbow extensor contraction.

Sex differences in muscle fatigue-resistance have been observed in a variety of muscles and under several conditions. This study compared the time to task failure (TTF) of a sustained isometric elbow extensor (intensity 15% of maximal strength) contraction in young men (n = 12) and women (n = 11), and examined if their neurophysiologic adjustments to fatigue differed. Motor-evoked potential amplitude (MEP), silent period duration, interference electromyogram (EMG) amplitude, maximal muscle action potential (M (max)), heart rate, and mean arterial pressure were measured at baseline, during the task, and during a 2-min ischemia period. Men and women did not differ in TTF (478.2 +/- 31.9 vs. 500.4 +/- 41.3 s; P = 0.67). We also performed an exploratory post hoc cluster analysis, and classified subjects as low (n = 15) or high endurance (n = 8) based on TTF (415.3 +/- 16.0 vs. 626.7 +/- 25.8 s, respectively). The high-endurance group exhibited a lower MEP and EMG at baseline (MEP 16.3 +/- 4.1 vs. 37.2 +/- 3.0% M (max), P < 0.01; EMG 0.98 +/- 0.18 vs. 1.85 +/- 0.26% M (max), P = 0.03). These findings suggest no sex differences in elbow extensor fatigability, in contrast to observations from other muscle groups. The cluster analyses results indicated that high- and low-endurance groups displayed neurophysiologic differences at baseline (before performing the fatigue task), but that they did not differ in fatigue-induced changes in their neurophysiologic adjustments to the task.

Delayed-onset muscle soreness induced by low-load blood flow-restricted exercise.

We performed two experiments to describe the magnitude of delayed-onset muscle soreness (DOMS) associated with blood flow restriction (BFR) exercise and to determine the contribution of the concentric (CON) versus eccentric (ECC) actions of BFR exercise on DOMS. In experiment 1, nine subjects performed three sets of unilateral knee extension BFR exercise at 35% of maximal voluntary contraction (MVC) to failure with a thigh cuff inflated 30% above brachial systolic pressure. Subjects repeated the protocol with the contralateral limb without flow restriction. Resting soreness (0-10 scale) and algometry (pain-pressure threshold; PPT) were assessed before and 24, 48 and 96 h post-exercise. Additionally, MVC and vastus lateralis cross-sectional area (CSA) were measured as indices of exercise-induced muscle damage. At 24-h post-exercise, BFR exercise resulted in more soreness than exercise without BFR (2.8 +/- 0.3 vs 1.7 +/- 0.5) and greater reductions in PPT (15.2 +/- 1.7 vs. 20 +/- 2.3 N) and MVC (14.1 +/- 2.5% decrease vs. 1.5 +/- 4.5% decrease) (p

Restoration of voluntary muscle strength after 3 weeks of cast immobilization is suppressed in women compared with men.

OBJECTIVE: To investigate sex-related differences in the loss and recovery of voluntary muscle strength after immobilization. DESIGN: Longitudinal, repeated measures. SETTING: Research laboratory. PARTICIPANTS: Healthy men (n=5) and healthy women (n=5). INTERVENTION: Three weeks of forearm immobilization. MAIN OUTCOME MEASURES: Voluntary wrist flexion muscle strength was assessed at baseline and weekly during the immobilization protocol and 1 week after cast removal. Central activation was assessed before and after immobilization and after 1 week of recovery to determine what percentage of the muscle could be activated voluntarily. RESULTS: Men and women lost voluntary strength at a similar rate during immobilization. However, after 1 week of recovery voluntary strength had returned to within 1% of baseline in the men, but remained approximately 30% less than baseline in the women (P=0.03). Both sexes displayed reduced central activation after immobilization (P=0.02), but the decrease was similar in both sexes (P=0.82). CONCLUSIONS: These findings suggest sex-dependent adaptations to and recovery from limb immobilization, with voluntary strength recovering slower in women. As such, sex-specific rehabilitation protocols may be warranted, with women requiring additional or more intensive rehabilitation programs after periods of disuse. Future work is needed to determine the extent and mechanisms of these differences.

Immobilization-induced increase in fatigue resistance is not explained by changes in the muscle metaboreflex.

Immobilization has been reported to enhance fatigability, which is paradoxical in light of the metabolic and molecular alterations that occur in atrophied muscles. We examined whether the immobilization-induced enhancement in fatigability was associated with attenuation in the muscle metaboreflex response. Ten subjects were examined after 3 weeks of hand-forearm immobilization. The time to task failure of a handgrip contraction (20% intensity) was determined along with heart rate (HR) and mean arterial pressure (MAP) at rest, during the task and during a 2-min postexercise muscle ischemia (PEMI) test that continues to stimulate the metaboreflex. Immobilization decreased strength by 25% (P<0.01) and increased the time to task failure by 21% (P=0.03). However, no changes were observed for the HR and MAP responses to the exercise task or during PEMI (P>0.05). These findings indicate that the augmentation of time to task failure with immobilization is not associated with changes in the pressor or metaboreflex responses.

Neuromuscular plasticity during and following 3 wk of human forearm cast immobilization.

Prolonged reductions in muscle activity results in alterations in neuromuscular properties; however, the time course of adaptations is not fully understood, and many of the specific adaptations have not been identified. This study evaluated the temporal evolution of adaptations in neuromuscular properties during and following 3 wk of immobilization. We utilized a combination of techniques involving nerve stimulation and transcranial magnetic stimulation to assess changes in central activation of muscle, along with spinal (H reflex) and corticospinal excitability [i.e., motor-evoked potential (MEP) amplitude, silent period (SP)] and contractile properties in 10 healthy humans undergoing 3 wk of forearm immobilization and 9 control subjects. Immobilization induced deficits in central activation (85 +/- 3 to 67 +/- 7% ) that returned to baseline levels 1 wk after cast removal. The flexor carpii radialis MEP amplitude increased greater than twofold after the first week of immobilization and remained elevated throughout immobilization and 1 wk after cast removal. Additionally, we observed a prolongation of the SP 1 wk after cast removal compared with baseline (78.5 +/- 7.1 to 98.2 +/- 8.7 ms). The contractile properties were also altered, since the rate of evoked force relaxation was slower following immobilization (-14.5 +/- 1.4 to -11.3 +/- 1.0% peak force/ms), and remained depressed 1 wk after cast removal (-10.5 +/- 0.8% peak force/ms). These observations detail the time course of adaptations in corticospinal and contractile properties associated with disuse and illustrate the profound effect of immobilization on the human neuromuscular system as evidenced by the alterations in corticospinal excitability persisting 1 wk following cast removal.

Quantification of the corticospinal silent period evoked via transcranial magnetic stimulation.

A magnetic pulse to the cortex during a muscle contraction produces a motor evoked potential (MEP) followed by electrical quiescence before activity resumes that is indicative of corticospinal inhibition and commonly referred to as the corticospinal slient period (SP). The purpose of the present study was to determine the effect of stimulus intensity and quantification method on the between-visit variability of the SP in healthy individuals. On two occasions we recorded the SP from 9 humans at 3 stimulus intensities (10, 20 and 30% above active motor threshold [AMT]) and quantified the SP based on 8 common criteria. We evaluated the effect of stimulus intensity on reliability by using the limits of agreement, and this analysis revealed that the lower stimulus intensities (10 and 20% AMT) exhibited heteroscedasticity, which indicates the amount of random error increases as the silent period increases. The 30% AMT intensity was homoscedastic. We used both visual and mathematical approaches to quantify the SP, and observed that the between-visit coefficient of variation (CV) was less for the visual methods, and that the CV was reduced when the SP onset was earliest in the temporal occurrence of events (i.e. MEP onset to EMG return CV=12%). Inter-rater reliability for the visual analyses were high (r=0.91-0.99). These results suggest that SPs evoked with a stimulus intensity >or=30% AMT and quantified visually by defining the start of the SP at stimulus delivery or the start of the MEP be utilized to decrease the between visit variability.