Central nervous adaptations following 1 wk of wrist and hand immobilization.

Plastic neural changes have been documented in relation to different types of physical activity, but little is known about central nervous system plasticity accompanying reduced physical activity and immobilization. In the present study we investigated whether plastic neural changes occur in relation to 1 wk of immobilization of the nondominant wrist and hand and a corresponding period of recovery in 10 able-bodied volunteers. After immobilization, maximal voluntary contraction torque decreased and the variability of submaximal static contractions increased significantly without evidence of changes in muscle contractile properties. Hoffmann (H)-reflex amplitudes and the ratios of H-slope to M-slope increased significantly in flexor carpi radialis and abductor pollicis brevis at rest and during contraction without changes in corticospinal excitability, estimated from motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation. Corticomuscular coherence measures were derived from EEG and EMG obtained during static contractions. After immobilization, corticomuscular coherence in the 15- to 35-Hz range associated with maximum negative cumulant values at lags corresponding to MEP latencies decreased. One week after cast removal, all measurements returned to preimmobilization levels. The increased H-reflex amplitudes without changes in MEPs may suggest that presynaptic inhibition or postactivation depression of Ia afferents is reduced following immobilization. Reduced corticomuscular coherence may be caused by changes in afferent input at spinal and cortical levels or by changes in the descending drive from motor cortex. Further studies are needed to elucidate the mechanisms underlying the observed increased spinal excitability and reduced coupling between motor cortex and spinal motoneuronal activity following immobilization.     

Influence of acute inspiratory loading upon diaphragm motor-evoked potentials in healthy humans.

Acute prior activity of the inspiratory muscles can enhance inspiratory muscle strength and reduce effort perception during subsequent inspiratory efforts. However, the mechanisms subserving these changes are poorly understood. Responses to magnetic stimulation in 10 subjects were studied after an acute bout of nonfatiguing inspiratory muscle loading (IML), corresponding to 40% of subjects' initial maximal inspiratory pressure (MIP), and after an acute bout of nonloaded, forced inspiration (NLF). Motor-evoked potentials elicited by cortical stimulation (MEP(c)) and by phrenic nerve stimulation (MEP(p)) were recorded transcutaneously from the diaphragm before, immediately after, and 15 min after two sets of 30 inspiratory efforts, at rest and during an MIP effort. After IML, MIP increased to 113 +/- 3% (SE) of baseline and diaphragm MEP(p) (during MIP) significantly increased (129 +/- 10% of baseline). Diaphragmatic MEP(c) (during MIP), expressed as a percentage of maximal MEP(p), decreased after IML (from 29 +/- 9% to 20 +/- 6%; P = 0.017) and after NLF (from 43 +/- 5% to 31 +/- 5%; P = 0.032). Observations from the biceps brachi demonstrated that changes after IML and NLF were specific to the inspiratory muscle, since no significant changes were observed in biceps force generation or in MEP(p) or MEP(c) amplitudes. These data indicate that after IML increased global inspiratory strength is accompanied by increased peripheral excitability and by a dampening of corticospinal excitability of the diaphragm.     

Central excitability does not limit postfatigue voluntary activation of quadriceps femoris.

After fatigue, motor evoked potentials (MEP) elicited by transcranial magnetic stimulation and cervicomedullary evoked potentials elicited by stimulation of the corticospinal tract are depressed. These reductions in corticomotor excitability and corticospinal transmission are accompanied by voluntary activation failure, but this may not reflect a causal relationship. Our purpose was to determine whether a decline in central excitability contributes to central fatigue. We hypothesized that, if central excitability limits voluntary activation, then a caffeine-induced increase in central excitability should offset voluntary activation failure. In this repeated-measures study, eight men each attended two sessions. Baseline measures of knee extension torque, maximal voluntary activation, peripheral transmission, contractile properties, and central excitability were made before administration of caffeine (6 mg/kg) or placebo. The amplitude of vastus lateralis MEPs elicited during minimal muscle activation provided a measure of central excitability. After a 1-h rest, baseline measures were repeated before, during, and after a fatigue protocol that ended when maximal voluntary torque declined by 35% (Tlim). Increased prefatigue MEP amplitude (P=0.055) and cortically evoked twitch (P<0.05) in the caffeine trial indicate that the drug increased central excitability. In the caffeine trial, increased MEP amplitude was correlated with time to task failure (r=0.74, P<0.05). Caffeine potentiated the MEP early in the fatigue protocol (P<0.05) and offset the 40% decline in placebo MEP (P<0.05) at Tlim. However, this was not associated with enhanced maximal voluntary activation during fatigue or recovery, demonstrating that voluntary activation is not limited by central excitability.     

Transpinal and Transcortical Stimulation Alter Corticospinal Excitability and Increase Spinal Output

The objective of this study was to assess changes in corticospinal excitability and spinal output following noninvasive transpinal and transcortical stimulation in humans. The size of the motor evoked potentials (MEPs), induced by transcranial magnetic stimulation (TMS) and recorded from the right plantar flexor and extensor muscles, was assessed following transcutaneous electric stimulation of the spine (tsESS) over the thoracolumbar region at conditioning-test (C-T) intervals that ranged from negative 50 to positive 50 ms. The size of the transpinal evoked potentials (TEPs), induced by tsESS and recorded from the right and left plantar flexor and extensor muscles, was assessed following TMS over the left primary motor cortex at 0.7 and at 1.1× MEP resting threshold at C-T intervals that ranged from negative 50 to positive 50 ms. The recruitment curves of MEPs and TEPs had a similar shape, and statistically significant differences between the sigmoid function parameters of MEPs and TEPs were not found. Anodal tsESS resulted in early MEP depression followed by long-latency MEP facilitation of both ankle plantar flexors and extensors. TEPs of ankle plantar flexors and extensors were increased regardless TMS intensity level. Subthreshold and suprathreshold TMS induced short-latency TEP facilitation that was larger in the TEPs ipsilateral to TMS. Noninvasive transpinal stimulation affected ipsilateral and contralateral actions of corticospinal neurons, while corticocortical and corticospinal descending volleys increased TEPs in both limbs. Transpinal and transcortical stimulation is a noninvasive neuromodulation method that alters corticospinal excitability and increases motor output of multiple spinal segments in humans.     

Direct corticospinal pathways contribute to neuromuscular control of perturbed stance.

The antigravity soleus muscle (Sol) is crucial for compensation of stance perturbation. A corticospinal contribution to the compensatory response of the Sol is under debate. The present study assessed spinal, corticospinal, and cortical excitability at the peaks of short- (SLR), medium- (MLR), and long-latency responses (LLR) after posterior translation of the feet. Transcranial magnetic stimulation (TMS) and peripheral nerve stimulation were individually adjusted so that the peaks of either motor evoked potential (MEP) or H reflex coincided with peaks of SLR, MLR, and LLR, respectively. The influence of specific, presumably direct, corticospinal pathways was investigated by H-reflex conditioning. When TMS was triggered so that the MEP arrived in the Sol at the same time as the peaks of SLR and MLR, EMG remained unaffected. Enhanced EMG was observed when the MEP coincided with the LLR peak (P < 0.001). Similarly, conditioning of the H reflex by subthreshold TMS facilitated H reflexes only at LLR (P < 0.001). The earliest facilitation after perturbation occurred after 86 ms. The TMS-induced H-reflex facilitation at LLR suggests that increased cortical excitability contributes to the augmentation of the LLR peaks. This provides evidence that the LLR in the Sol muscle is at least partly transcortical, involving direct corticospinal pathways. Additionally, these results demonstrate that approximately 86 ms after perturbation, postural compensatory responses are cortically mediated.     

Differences in Supraspinal and Spinal Excitability during Various Force Outputs of the Biceps Brachii in Chronic- and Non-Resistance Trained Individuals

Motor evoked potentials (MEP) and cervicomedullary evoked potentials (CMEP) may help determine the corticospinal adaptations underlying chronic resistance training-induced increases in voluntary force production. The purpose of the study was to determine the effect of chronic resistance training on corticospinal excitability (CE) of the biceps brachii during elbow flexion contractions at various intensities and the CNS site (i.e. supraspinal or spinal) predominantly responsible for any training-induced differences in CE. Fifteen male subjects were divided into two groups: 1) chronic resistance-trained (RT), (n = 8) and 2) non-RT, (n = 7). Each group performed four sets of ∼5 s elbow flexion contractions of the dominant arm at 10 target forces (from 10%–100% MVC). During each contraction, subjects received 1) transcranial magnetic stimulation, 2) transmastoid electrical stimulation and 3) brachial plexus electrical stimulation, to determine MEP, CMEP and compound muscle action potential (M_max) amplitudes, respectively, of the biceps brachii. All MEP and CMEP amplitudes were normalized to M_max. MEP amplitudes were similar in both groups up to 50% MVC, however, beyond 50% MVC, MEP amplitudes were lower in the chronic RT group (p<0.05). CMEP amplitudes recorded from 10–100% MVC were similar for both groups. The ratio of MEP amplitude/absolute force and CMEP amplitude/absolute force were reduced (p<0.012) at all contraction intensities from 10–100% MVC in the chronic-RT compared to the non-RT group. In conclusion, chronic resistance training alters supraspinal and spinal excitability. However, adaptations in the spinal cord (i.e. motoneurone) seem to have a greater influence on the altered CE.     

Differential effects of ballistic versus sensorimotor training on rate of force development and neural activation in humans

Balancing exercises on instable bases (sensorimotor training [SMT]) are often used in the rehabilitation process of an injured athlete to restore joint function. Recently it was shown that SMT was able to enhance rate of force development (RFD) in a maximal voluntary muscle contraction. The purpose of this study was to compare adaptations on strength capacity following ballistic strength training (BST) with those following an SMT during a training period of 1 microcycle (4 weeks). Maximum voluntary isometric strength (MVC), maximum RFD (RFDmax) and the corresponding neural activation of M. soleus (SOL), M. gastrocnemius (GAS), and M. tibialis anterior (TIB) were measured during plantar flexion in 33 healthy subjects. The subjects were randomly assigned to a SMT, BST, or control group. RFDmax increased significantly stronger following BST (48 +/- 16%; p < 0.01) compared to SMT (14 +/- 5%; p < 0.05), whereas MVC remained unchanged in both groups. Median frequencies of the electromyographic power spectrum during the first 200 ms of contraction for GAS increased following both BST (45 +/- 21%; p < 0.05) and SMT (45 +/- 22%; p < 0.05), but median frequencies for SOL increased only after SMT (13 +/- 4%; p < 0.05). Additionally, mean amplitude voltage increased following BST for SOL (38 +/- 12%; p < 0.01) and for GAS (73 +/- 23%; p < 0.01) during the first 100 ms, whereas it remained unchanged after SMT. It is concluded that BST and SMT may induce different neural adaptations that specifically affect recruitment and discharge rates of motor units at the beginning of voluntary contraction. Specific neural adaptations indicate that SMT might be used complementarily to BST, especially in sports that require contractile explosive properties in situations with high postural demands, e.g., during jumps in ball sports.     

Age-related differences in corticospinal control during functional isometric contractions in left and right hands.

The purpose of the study was to examine age-related differences in electromyographic (EMG) responses to transcranial magnetic stimulation (TMS) during functional isometric contractions in left and right hands. EMG responses were recorded from the first dorsal interosseus muscle following TMS in 10 young (26.6 +/- 1.3 yr) and 10 old (67.6 +/- 2.3 yr) right-handed subjects. Muscle evoked potentials (MEPs) and silent-period durations were obtained in the left and right hands during index finger abduction, a precision grip, a power grip, and a scissor grip, while EMG was held constant at 5% of maximum. For all tasks, MEP area was 30% (P < 0.001) lower in the left hand of old compared with young subjects, whereas there was no age difference in the right hand. The duration of the EMG silent period was 14% (P < 0.001) shorter in old (150.3 +/- 2.9 ms) compared with young (173.9 +/- 3.0 ms) subjects, and the age differences were accentuated in the left hand (19% shorter, P < 0.001). For all subjects, the largest MEP area (10-12% larger) and longest EMG silent period (8-19 ms longer) were observed for the scissor grip compared with the other three tasks, and the largest task-dependent change in these variables was observed in the right hand of older adults. These differences in corticospinal control in the left and right hands of older adults may reflect neural adaptations that occur throughout a lifetime of preferential hand use for skilled (dominant) and unskilled (nondominant) motor tasks.     

Neurophysiological responses after short-term strength training of the biceps brachii muscle

The neural adaptations that mediate the increase in strength in the early phase of a strength training program are not well understood; however, changes in neural drive and corticospinal excitability have been hypothesized. To determine the neural adaptations to strength training, we used transcranial magnetic stimulation (TMS) to compare the effect of strength training of the right elbow flexor muscles on the functional properties of the corticospinal pathway. Motor-evoked potentials (MEPs) were recorded from the right biceps brachii (BB) muscle from 23 individuals (training group; n = 13 and control group; n = 10) before and after 4 weeks of progressive overload strength training at 80% of 1-repetition maximum (1RM). The TMS was delivered at 10% of the root mean square electromyographic signal (rmsEMG) obtained from a maximal voluntary contraction (MVC) at intensities of 5% of stimulator output below active motor threshold (AMT) until saturation of the MEP (MEPmax). Strength training resulted in a 28% (p = 0.0001) increase in 1RM strength, and this was accompanied by a 53% increase (p = 0.05) in the amplitude of the MEP at AMT, 33% (p = 0.05) increase in MEP at 20% above AMT, and a 38% increase at MEPmax (p = 0.04). There were no significant differences in the estimated slope (p = 0.47) or peak slope of the stimulus-response curve for the left primary motor cortex (M1) after strength training (p = 0.61). These results demonstrate that heavy-load isotonic strength training alters neural transmission via the corticospinal pathway projecting to the motoneurons controlling BB and in part underpin the strength changes observed in this study.     

Change in the Ipsilateral Motor Cortex Excitability Is Independent from a Muscle Contraction Phase during Unilateral Repetitive Isometric Contractions

The aim of this study was to investigate the difference in a muscle contraction phase dependence between ipsilateral (ipsi)- and contralateral (contra)-primary motor cortex (M1) excitability during repetitive isometric contractions of unilateral index finger abduction using a transcranial magnetic stimulation (TMS) technique. Ten healthy right-handed subjects participated in this study. We instructed them to perform repetitive isometric contractions of the left index finger abduction following auditory cues at 1 Hz. The force outputs were set at 10, 30, and 50% of maximal voluntary contraction (MVC). Motor evoked potentials (MEP) were obtained from the right and left first dorsal interosseous muscles (FDI). To examine the muscle contraction phase dependence, TMS of ipsi-M1 or contra-M1 was triggered at eight different intervals (0, 20, 40, 60, 80, 100, 300, or 500 ms) after electromyogram (EMG) onset when each interval had reached the setup triggering level. Furthermore, to demonstrate the relationships between the integrated EMG (iEMG) in the active left FDI and the ipsi-M1 excitability, we assessed the correlation between the iEMG in the left FDI for the 100 ms preceding TMS onset and the MEP amplitude in the resting/active FDI for each force output condition. Although contra-M1 excitability was significantly changed after the EMG onset that depends on the muscle contraction phase, the modulation of ipsi-M1 excitability did not differ in response to any muscle contraction phase at the 10% of MVC condition. Also, we found that contra-M1 excitability was significantly correlated with iEMG in all force output conditions, but ipsi-M1 excitability was not at force output levels of below 30% of MVC. Consequently, the modulation of ipsi-M1 excitability was independent from the contraction phase of unilateral repetitive isometric contractions at least low force output.     

Increased rate of force development and neural drive of human skeletal muscle following resistance training.

The maximal rate of rise in muscle force [rate of force development (RFD)] has important functional consequences as it determines the force that can be generated in the early phase of muscle contraction (0-200 ms). The present study examined the effect of resistance training on contractile RFD and efferent motor outflow ("neural drive") during maximal muscle contraction. Contractile RFD (slope of force-time curve), impulse (time-integrated force), electromyography (EMG) signal amplitude (mean average voltage), and rate of EMG rise (slope of EMG-time curve) were determined (1-kHz sampling rate) during maximal isometric muscle contraction (quadriceps femoris) in 15 male subjects before and after 14 wk of heavy-resistance strength training (38 sessions). Maximal isometric muscle strength [maximal voluntary contraction (MVC)] increased from 291.1 +/- 9.8 to 339.0 +/- 10.2 N. m after training. Contractile RFD determined within time intervals of 30, 50, 100, and 200 ms relative to onset of contraction increased from 1,601 +/- 117 to 2,020 +/- 119 (P < 0.05), 1,802 +/- 121 to 2,201 +/- 106 (P < 0.01), 1,543 +/- 83 to 1,806 +/- 69 (P < 0.01), and 1,141 +/- 45 to 1,363 +/- 44 N. m. s(-1) (P < 0.01), respectively. Corresponding increases were observed in contractile impulse (P < 0.01-0.05). When normalized relative to MVC, contractile RFD increased 15% after training (at zero to one-sixth MVC; P < 0.05). Furthermore, muscle EMG increased (P < 0.01-0.05) 22-143% (mean average voltage) and 41-106% (rate of EMG rise) in the early contraction phase (0-200 ms). In conclusion, increases in explosive muscle strength (contractile RFD and impulse) were observed after heavy-resistance strength training. These findings could be explained by an enhanced neural drive, as evidenced by marked increases in EMG signal amplitude and rate of EMG rise in the early phase of muscle contraction.     

Changes in canine latissimus dorsi muscle during 24 wk of continuous electrical stimulation.

To study functional, structural, and biochemical adaptations to electrical stimulation of striated muscle in a large animal, the canine latissimus dorsi (LD) muscle was conditioned continuously for 24 wk with an increasing number of pulse bursts (burst duration 250 ms, burst frequency 30 Hz). Force measurements in vivo after 12 wk showed a significant decrease in the ripple, the ratio of interstimulus to peak force amplitude, from 0.94 +/- 0.03 to 0.13 +/- 0.08 (SE; n = 8, P less than 0.05), indicating reduction in contractile speed. Also the steep part of the force-frequency relation shifted to lower frequencies. A significant change in fiber-type composition was seen with both enzyme- and immunohistochemistry, manifested by an increase of type I fibers from 29.5 +/- 2.9 to 83 +/- 8% (SE; n = 8, P less than 0.05). During this period a transient rise in the number of type IIc/Ic fibers (from 3 to 10%) was seen. In the stimulated muscle, capillary-to-fiber ratio increased from 1.9 +/- 0.4 to 2.7 +/- 0.1 (P less than 0.05). A significant increase in mitochondrial volume was also seen, especially in the peripheral part of the fiber. Both creatine kinase and lactate dehydrogenase revealed a significant decline in activity within 12 wk. At the same time a shift in lactate dehydrogenase-isozyme pattern was observed toward the cardiac composition. No additional changes occurred after 12 wk of stimulation, indicating that conversion of the canine LD muscle was complete within this period.     

Age and Muscle-Dependent Variations in Corticospinal Excitability during Standing Tasks

In this study, we investigated how modulation in corticospinal excitability elicited in the context of standing tasks varies as a function of age and between muscles. Changes in motor evoked potentials (MEPs) recorded in tibialis anterior (TA) and gastrocnemius lateralis (GL) were monitored while participants (young, n = 10; seniors, n = 11) either quietly stood (QS) or performed a heel raise (HR) task. In the later condition, transcranial magnetic stimulation (TMS) pulses were delivered at three specific time points during the task: 1) 250 ms before the “go” cue (preparatory (PREP) phase), 2) 100 ms before the heel rise (anticipatory postural adjustment (APA) phase), and 3) 200 ms after heel rise (execution (EXEC) phase). In each task and each phase, variations in MEP characteristics were analysed for age and muscle-dependent effects. Variations in silent period (SP) duration were also examined for certain phases (APA and EXEC). Our analysis revealed no major difference during QS, as participants exhibited very similar patterns of modulation in both TA and GL, irrespective of their age group. During the HR task, young adults exhibited a differential modulation in the PREP phase with enhanced responses in TA relative to GL, which was not seen in seniors. Finally, besides differences in MEP latency, age had little influence on MEP modulation during the APA and EXEC phases, where amplitude was largely a function of background muscle activity associated with each phase (i.e., APA: TA; EXEC: GL). No age or muscle effects were detected for SP measurements. Overall, our results revealed no major differences between young adults and healthy seniors in the ability to modulate corticospinal facilitation destined to ankle muscles during standing tasks, with maybe the exception of the ability to prime muscle synergies in the preparatory phase of action.     

Muscle Na-K-pump and fatigue responses to progressive exercise in normoxia and hypoxia

To investigate the effects of hypoxia and incremental exercise on muscle contractility, membrane excitability, and maximal Na(+)-K(+)-ATPase activity, 10 untrained volunteers (age = 20 +/- 0.37 yr and weight = 80.0 +/- 3.54 kg; +/- SE) performed progressive cycle exercise to fatigue on two occasions: while breathing normal room air (Norm; Fi(O(2)) = 0.21) and while breathing a normobaric hypoxic gas mixture (Hypox; Fi(O(2)) = 0.14). Muscle samples extracted from the vastus lateralis before exercise and at fatigue were analyzed for maximal Na(+)-K(+)-ATPase (K(+)-stimulated 3-O-methylfluorescein phosphatase) activity in homogenates. A 32% reduction (P < 0.05) in Na(+)-K(+)-ATPase activity was observed (90.9 +/- 7.6 vs. 62.1 +/- 6.4 nmol.mg protein(-1).h(-1)) in Norm. At fatigue, the reductions in Hypox were not different (81 +/- 5.6 vs. 57.2 +/- 7.5 nmol.mg protein(-1).h(-1)) from Norm. Measurement of quadriceps neuromuscular function, assessed before and after exercise, indicated a generalized reduction (P < 0.05) in maximal voluntary contractile force (MVC) and in force elicited at all frequencies of stimulation (10, 20, 30, 50, and 100 Hz). In general, no differences were observed between Norm and Hypox. The properties of the compound action potential, amplitude, duration, and area, which represent the electromyographic response to a single, supramaximal stimulus, were not altered by exercise or oxygen condition when assessed both during and after the progressive cycle task. Progressive exercise, conducted in Hypox, results in an inhibition of Na(+)-K(+)-ATPase activity and reductions in MVC and force at different frequencies of stimulation; these results are not different from those observed with Norm. These changes occur in the absence of reductions in neuromuscular excitability.     

Training-induced changes in muscle CSA, muscle strength, EMG, and rate of force development in elderly subjects after long-term unilateral disuse.

The ability to develop muscle force rapidly may be a very important factor to prevent a fall and to perform other tasks of daily life. However, information is still lacking on the range of training-induced neuromuscular adaptations in elderly humans recovering from a period of disuse. Therefore, the present study examined the effect of three types of training regimes after unilateral prolonged disuse and subsequent hip-replacement surgery on maximal muscle strength, rapid muscle force [rate of force development (RFD)], muscle activation, and muscle size. Thirty-six subjects (60-86 yr) were randomized to a 12-wk rehabilitation program consisting of either 1) strength training (3 times/wk for 12 wk), 2) electrical muscle stimulation (1 h/day for 12 wk), or 3) standard rehabilitation (1 h/day for 12 wk). The nonoperated side did not receive any intervention and thereby served as a within-subject control. Thirty subjects completed the trial. In the strength-training group, significant increases were observed in maximal isometric muscle strength (24%, P < 0.01), contractile RFD (26-45%, P < 0.05), and contractile impulse (27-32%, P < 0.05). No significant changes were seen in the two other training groups or in the nontrained legs of all three groups. Mean electromyogram signal amplitude of vastus lateralis was larger in the strength-training than in the standard-rehabilitation group at 5 and 12 wk (P < 0.05). In contrast to traditional physiotherapy and electrical stimulation, strength training increased muscle mass, maximal isometric strength, RFD, and muscle activation in elderly men and women recovering from long-term muscle disuse and subsequent hip surgery. The improvement in both muscle mass and neural function is likely to have important functional implications for elderly individuals.     

Whole-Body Water Flow Stimulation to the Lower Limbs Modulates Excitability of Primary Motor Cortical Regions Innervating the Hands: A Transcranial Magnetic Stimulation Study

Whole-body water immersion (WI) has been reported to change sensorimotor integration. However, primary motor cortical excitability is not affected by low-intensity afferent input. Here we explored the effects of whole-body WI and water flow stimulation (WF) on corticospinal excitability and intracortical circuits. Eight healthy subjects participated in this study. We measured the amplitude of motor-evoked potentials (MEPs) produced by single transcranial magnetic stimulation (TMS) pulses and examined conditioned MEP amplitudes by paired-pulse TMS. We evaluated short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) using the paired-TMS technique before and after 15-min intervention periods. Two interventions used were whole-body WI with water flow to the lower limbs (whole-body WF) and whole-body WI without water flow to the lower limbs (whole-body WI). The experimental sequence included a baseline TMS assessment (T0), intervention for 15 min, a second TMS assessment immediately after intervention (T1), a 10 min resting period, a third TMS assessment (T2), a 10 min resting period, a fourth TMS assessment (T3), a 10 min resting period, and the final TMS assessment (T4). SICI and ICF were evaluated using a conditioning stimulus of 90% active motor threshold and a test stimulus adjusted to produce MEPs of approximately 1–1.2 mV, and were tested at intrastimulus intervals of 3 and 10 ms, respectively. Whole-body WF significantly increased MEP amplitude by single-pulse TMS and led to a decrease in SICI in the contralateral motor cortex at T1, T2 and T3. Whole-body WF also induced increased corticospinal excitability and decreased SICI. In contrast, whole-body WI did not change corticospinal excitability or intracortical circuits.     

Neuromuscular Fatigue Is Not Different between Constant and Variable Frequency Stimulation

This study compared fatigue development of the triceps surae induced by two electrical stimulation protocols composed of constant and variable frequency trains (CFTs, VFTs, 450 trains, 30 Hz, 167 ms ON, 500 ms OFF and 146 ms ON, 500 ms OFF respectively). For the VFTs protocol a doublet (100 Hz) was used at the beginning of each train. The intensity used evoked 30% of a maximal voluntary contraction (MVC) and was defined using CFTs. Neuromuscular tests were performed before and after each protocol. Changes in excitation-contraction coupling were assessed by analysing the M-wave [at rest (M_max) and during MVC (M_sup)] and associated peak twitch (Pt). H-reflex [at rest (H_max) and during MVC (H_sup)] and the motor evoked potential (MEP) during MVC were studied to assess spinal and corticospinal excitability of the soleus muscle. MVC decrease was similar between the protocols (−8%, P<0.05). M_max, M_sup and Pt decreased after both protocols (P<0.01). H_max/M_max was decreased (P<0.05), whereas H_sup/M_sup and MEP/M_sup remained unchanged after both protocols. The results indicate that CFTs and VFTs gave rise to equivalent neuromuscular fatigue. This fatigue resulted from alterations taking place at the muscular level. The finding that cortical and spinal excitability remained unchanged during MVC indicates that spinal and/or supraspinal mechanisms were activated to compensate for the loss of spinal excitability at rest.     

Motor skill training and strength training are associated with different plastic changes in the central nervous system.

Changes in corticospinal excitability induced by 4 wk of heavy strength training or visuomotor skill learning were investigated in 24 healthy human subjects. Measurements of the input-output relation for biceps brachii motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation were obtained at rest and during voluntary contraction in the course of the training. The training paradigms induced specific changes in the motor performance capacity of the subjects. The strength training group increased maximal dynamic and isometric muscle strength by 31% (P < 0.001) and 12.5% (P = 0.045), respectively. The skill learning group improved skill performance significantly (P < 0.001). With one training bout, the only significant change in transcranial magnetic stimulation parameters was an increase in skill learning group maximal MEP level (MEP(max)) at rest (P = 0.02) for subjects performing skill training. With repeated skill training three times per week for 4 wk, MEP(max) increased and the minimal stimulation intensity required to elicit MEPs decreased significantly at rest and during contraction (P < 0.05). In contrast, MEP(max) and the slope of the input-output relation both decreased significantly at rest but not during contraction in the strength-trained subjects (P < or = 0.01). No significant changes were observed in a control group. A significant correlation between changes in neurophysiological parameters and motor performance was observed for skill learning but not strength training. The data show that increased corticospinal excitability may develop over several weeks of skill training and indicate that these changes may be of importance for task acquisition. Because strength training was not accompanied by similar changes, the data suggest that different adaptive changes are involved in neural adaptation to strength training.     

Excitability decreasing central motor plasticity is retained in multiple sclerosis patients

ABSTRACT: BACKGROUND: Compensation of brain injury in multiple sclerosis (MS) may in part work through mechanisms involving neuronal plasticity on local and interregional scales. Mechanisms limiting excessive neuronal activity may have special significance for retention and (re-)acquisition of lost motor skills in brain injury. However, previous neurophysiological studies of plasticity in MS have investigated only excitability enhancing plasticity and results from neuroimaging are ambiguous. Thus, the aim of this study was to probe long-term depression-like central motor plasticity utilizing continuous theta-burst stimulation (cTBS), a non-invasive brain stimulation protocol. Because cTBS also may trigger behavioral effects through local interference with neuronal circuits, this approach also permitted investigating the functional role of the primary motor cortex (M1) in force control in patients with MS. METHODS: We used cTBS and force recordings to examine long-term depression-like central motor plasticity and behavioral consequences of a M1 lesion in 14 patients with stable mild-to-moderate MS (median EDSS 1.5, range 0 to 3.5) and 14 age-matched healthy controls. cTBS consisted of bursts (50 Hz) of three subthreshold biphasic magnetic stimuli repeated at 5 Hz for 40 s over the hand area of the left M1. Corticospinal excitability was probed via motor-evoked potentials (MEP) in the abductor pollicis brevis muscle over M1 before and after cTBS. Force production performance was assessed in an isometric right thumb abduction task by recording the number of hits into a predefined force window. RESULTS: cTBS reduced MEP amplitudes in the contralateral abductor pollicis brevis muscle to a comparable extent in control subjects (69 +/- 22 % of baseline amplitude, p < 0.001) and in MS patients (69 +/- 18 %, p < 0.001). In contrast, post-cTBS force production performance was only impaired in controls (2.2 +/- 2.8, p = 0.011), but not in MS patients (2.0 +/- 4.4, p = 0.108). The decline in force production performance following cTBS correlated with corticomuscular latencies (CML) in MS patients, but did not correlate with MEP amplitude reduction in patients or controls. CONCLUSIONS: Long-term depression-like plasticity remains largely intact in mild-to-moderate MS. Increasing brain injury may render the neuronal networks less responsive toward lesion-induction by cTBS.     

Inactivation of human muscle Na+-K+-ATPase in vitro during prolonged exercise is increased with hypoxia.

This study investigated the effects of prolonged exercise performed in normoxia (N) and hypoxia (H) on neuromuscular fatigue, membrane excitability, and Na+-K+ -ATPase activity in working muscle. Ten untrained volunteers [peak oxygen consumption (Vo2peak) = 42.1 +/- 2.8 (SE) ml x kg(-1) x min(-1)] performed 90 min of cycling during N (inspired oxygen fraction = 0.21) and during H (inspired oxygen fraction = 0.14) at approximately 50% of normoxic Vo2peak. During N, 3-O-methylfluorescein phosphatase activity (nmol x mg protein(-1) x h(-1)) in vastus lateralis, used as a measure of Na+-K+-ATPase activity, decreased (P < 0.05) by 21% at 30 min of exercise compared with rest (101 +/- 53 vs. 79.6 +/- 4.3) with no further reductions observed at 90 min (72.8 +/- 8.0). During H, similar reductions (P < 0.05) were observed during the first 30 min (90.8 +/- 5.3 vs. 79.0 +/- 6.3) followed by further reductions (P < 0.05) at 90 min (50.5 +/- 3.9). Exercise in N resulted in reductions (P < 0.05) in both quadriceps maximal voluntary contractile force (MVC; 633 +/- 50 vs. 477 +/- 67 N) and force at low frequencies of stimulation, namely 10 Hz (142 +/- 16 vs. 86.7 +/- 10 N) and 20 Hz (283 +/- 32 vs. 236 +/- 31 N). No changes were observed in the amplitude, duration, and area of the muscle compound action potential (M wave). Exercise in H was without additional effect in altering MVC, low-frequency force, and M-wave properties. It is concluded that, although exercise in H resulted in a greater inactivation of Na+-K+-ATPase activity compared with N, neuromuscular fatigue and membrane excitability are not differentially altered.