Age-related changes in brain deactivation but not in activation after motor learning.

It is poorly understood how healthy aging affects neural mechanisms underlying motor learning. We used blood-oxygen-level dependent (BOLD) contrasts to examine age-related changes in brain activation after acquisition and consolidation (24 h) of a visuomotor tracking skill. Additionally, structural magnetic resonance imaging and diffusion tensor imaging were used to examine age-related structural changes in the brain. Older adults had reduced gray matter volume (628 ±â€¯57 ml) and mean white matter anisotropy (0.18 ±â€¯0.03) compared with young adults (741 ±â€¯59 ml and 0.22 ±â€¯0.02, respectively). Although motor performance was 53% lower in older (n = 15, mean age 63.1 years) compared with young adults (n = 15, mean age 25.5 years), motor practice improved motor performance similarly in both age groups. While executing the task, older adults showed in general greater brain activation compared with young adults. BOLD activation decreased in parietal and occipital areas after skill acquisition but activation increased in these areas after consolidation in both age groups, indicating more efficient visuospatial processing immediately after skill acquisition. Changes in deactivation in specific areas were age-dependent after consolidating the motor skill into motor memory. Young adults showed greater deactivations from post-test to retention in parietal, occipital and temporal cortices, whereas older adults showed smaller deactivation in the frontal cortex. Since learning rate was similar between age groups, age-related changes in activation patterns may be interpreted as a compensatory mechanism for age-related structural decline.

Direct and crossed effects of somatosensory electrical stimulation on motor learning and neuronal plasticity in humans.

PURPOSE: Sensory input can modify voluntary motor function. We examined whether somatosensory electrical stimulation (SES) added to motor practice (MP) could augment motor learning, interlimb transfer, and whether physiological changes in neuronal excitability underlie these changes. METHODS: Participants (18-30 years, n = 31) received MP, SES, MP + SES, or a control intervention. Visuomotor practice included 300 trials for 25 min with the right-dominant wrist and SES consisted of weak electrical stimulation of the radial and median nerves above the elbow. Single- and double-pulse transcranial magnetic stimulation (TMS) metrics were measured in the intervention and non-intervention extensor carpi radialis. RESULTS: There was 27 % motor learning and 9 % (both p < 0.001) interlimb transfer in all groups but SES added to MP did not augment learning and transfer. Corticospinal excitability increased after MP and SES when measured at rest but it increased after MP and decreased after SES when measured during contraction. No changes occurred in intracortical inhibition and facilitation. MP did not affect the TMS metrics in the transfer hand. In contrast, corticospinal excitability strongly increased after SES with MP + SES showing sharply opposite of these effects. CONCLUSION: Motor practice and SES each can produce motor learning and interlimb transfer and are likely to be mediated by different mechanisms. The results provide insight into the physiological mechanisms underlying the effects of MP and SES on motor learning and cortical plasticity and show that these mechanisms are likely to be different for the trained and stimulated motor cortex and the non-trained and non-stimulated motor cortex.

Neuronal mechanisms of motor learning and motor memory consolidation in healthy old adults.

It is controversial whether or not old adults are capable of learning new motor skills and consolidate the performance gains into motor memory in the offline period. The underlying neuronal mechanisms are equally unclear. We determined the magnitude of motor learning and motor memory consolidation in healthy old adults and examined if specific metrics of neuronal excitability measured by magnetic brain stimulation mediate the practice and retention effects. Eleven healthy old adults practiced a wrist extension-flexion visuomotor skill for 20 min (MP, 71.3 years), while a second group only watched the templates without movements (attentional control, AC, n = 11, 70.5 years). There was 40 % motor learning in MP but none in AC (interaction, p < 0.001) with the skill retained 24 h later in MP and a 16 % improvement in AC. Corticospinal excitability at rest and during task did not change, but when measured during contraction at 20 % of maximal force, it strongly increased in MP and decreased in AC (interaction, p = 0.002). Intracortical inhibition at rest and during the task decreased and facilitation at rest increased in MP, but these metrics changed in the opposite direction in AC. These neuronal changes were especially profound at retention. Healthy old adults can learn a new motor skill and consolidate the learned skill into motor memory, processes that are most likely mediated by disinhibitory mechanisms. These results are relevant for the increasing number of old adults who need to learn and relearn movements during motor rehabilitation.

Direct and crossed effects of somatosensory stimulation on neuronal excitability and motor performance in humans.

This analytic review reports how prolonged periods of somatosensory electric stimulation (SES) with repetitive transcutaneous nerve stimulation can have 'direct' and 'crossed' effects on brain activation, corticospinal excitability, and motor performance. A review of 26 studies involving 315 healthy and 78 stroke and dystonia patients showed that the direct effects of SES increased corticospinal excitability up to 40% (effect size: 0.2 to 6.1) and motor performance up to 14% (effect size: 0.3 to 3.1) but these two features did not correlate. SES did not affect measures of intracortical excitability. Most likely, a long-term potentiation-like mechanism in the excitatory glutamatergic connections between the primary sensory and motor cortices mediates the direct effects of SES on corticospinal excitability and motor performance. We propose two models for the untested hypothesis that adding SES to unilateral motor practice could magnify the magnitude of inter-limb transfer. If tenable, the hypothesis would expand the evolving repertoire of sensory augmentation of cross-education using mirrors and add SES as an alternative to conventional rehabilitation strategies such as constraint-induced movement therapy.

Human spinal cord injury: motor unit properties and behaviour.

Spinal cord injury (SCI) results in widespread variation in muscle function. Review of motor unit data shows that changes in the amount and balance of excitatory and inhibitory inputs after SCI alter management of motoneurons. Not only are units recruited up to higher than usual relative forces when SCI leaves few units under voluntary control, the force contribution from recruitment increases due to elevation of twitch/tetanic force ratios. Force gradation and precision are also coarser with reduced unit numbers. Maximal unit firing rates are low in hand muscles, limiting voluntary strength, but are low, normal or high in limb muscles. Unit firing rates during spasms can exceed voluntary rates, emphasizing that deficits in descending drive limit force production. SCI also changes muscle properties. Motor unit weakness and fatigability seem universal across muscles and species, increasing the muscle weakness that arises from paralysis of units, motoneuron death and sensory impairment. Motor axon conduction velocity decreases after human SCI. Muscle contractile speed is also reduced, which lowers the stimulation frequencies needed to grade force when paralysed muscles are activated with patterned electrical stimulation. This slowing does not necessarily occur in hind limb muscles after cord transection in cats and rats. The nature, duration and level of SCI underlie some of these species differences, as do variations in muscle function, daily usage, tract control and fibre-type composition. Exploring this diversity is important to promote recovery of the hand, bowel, bladder and locomotor function most wanted by people with SCI.

Mechanisms underlying muscle fatigue differ between multiple sclerosis patients and controls: a combined electrophysiological and neuroimaging study.

Increased sense of fatigue is an important and conspicuous symptom in multiple sclerosis (MS). Muscle fatigue is associated with increased sense of fatigue in MS (Steens et al., 2011). The aim of this study was to investigate mechanisms that can explain muscle fatigue in MS patients and controls. We assessed changes in cortical activation (BOLD), voluntary activation (twitch interpolation) and muscle force during a sustained maximal voluntary contraction (MVC) in twenty MS patients and twenty healthy controls. In control participants, individual differences in force decline (mean 65% MVC, 8 SD) during the sustained maximal contraction could be accounted for by differences in maximal voluntary force (R(2): 0.49, p = 0.001); stronger participants presented a larger force decline. The small decline in voluntary activation (mean 7.8%, 11.8 SD) did not contribute significantly to the force decline. During the sustained contraction, the force decline was accompanied by an increase in cortical activation in the main motor areas. In MS patients, the differences in the decline in force (mean 67% MVC, 9 SD) were significantly associated (R(2): 0.51, p = 0.001) with a decline in voluntary activation (mean 20.1%, 20.6 SD) and not with maximal force or decline in rest twitch. The corresponding cortical activation in motor areas showed an increase in the first two intervals of the sustained contraction but declined during the last interval. Our data indicate that muscle fatigue during a sustained contraction in MS patients is associated with changes in the voluntary activation that are not sufficiently compensated by increased cortical activation. Control participants, however, show increased cortical activation to compensate for these fatigue-related changes in voluntary activation and the major cause of force decline is therefore to be found in the periphery (muscles).

Secondary sensory area SII is crucially involved in the preparation of familiar movements compared to movements never made before.

Secondary sensorimotor regions are involved in sensorimotor integration and movement preparation. These regions take part in parietal-premotor circuitry that is not only active during motor execution but also during movement observation and imagery. This activation particularly occurs when observed movements belong to one's own motor repertoire, consistent with the finding that motor imagery only improves performance when one can actually make such movement. We aimed to investigate whether imagery or observation of a movement that was never made before causes parietal-premotor activation or that the ability to perform this movement is indeed a precondition. Nine subjects [group Already Knowing It (AKI)] could abduct their hallux (moving big toe outward). Seven subjects initially failed to make such movement (Absolute Zero A0 group). They had to imagine, observe, or execute this movement, whereas fMRI data were obtained both before and after training. Contrasting abduction observation between the AKI-group and A0-group showed increased left SII and supplementary motor area activation. Comparing the observation of hallux flexion with abduction showed increased bilateral SII activation in the A0 and not in the AKI group. Prolonged training resulted in equal performance and similar cerebral activation patterns in the two groups. Thereby, conjunction analysis of the correlations on subject's range of abduction during execution, imagery, and observation of hallux abduction showed exclusive bilateral SII activation. The reduced SII involvement in A0 may imply that effective interplay between sensory predictions and feedback does not take place without actual movement experience. However, this can be acquired by training.

Spontaneous motor unit behavior in human thenar muscles after spinal cord injury.

Our first aim was to characterize spontaneous motor unit activity in thenar muscles influenced by chronic cervical spinal cord injury. Thenar surface electromyography (EMG), intramuscular EMG, and abduction and flexion forces were recorded. Subjects were instructed to relax for 2 min. Units still firing after 10 s were considered spontaneously active. Two distinct patterns of spontaneous unit activity were recorded. Units either fired tonically at a mean frequency of 6.1 HZ or were active sporadically (2.2 HZ). Stimuli (e.g., light touch of nearby skin) were then used to influence tonic spontaneous unit activity. Most stimuli produced a change in firing frequency, usually a temporary increase, but sometimes unit frequency decreased or new activity was initiated. Inputs to these motoneurons clearly make important contributions to changes in unit activity. However, the difficulty that subjects had in stopping unit activity, and the initiation of activity when subjects relaxed, suggest that the source of spontaneity may be the motoneuron itself.

Bilateral interactions during contractions of intrinsic hand muscles.

During demanding voluntary contractions (e.g., high force or fatigue), activation is not restricted to the target muscle but extends to other ipsilateral muscles; even contralateral muscles become activated. The contralateral "irradiation" of activity was measured in five subjects during submaximal and maximal voluntary contractions (MVCs) of the first dorsal interosseous (FDI) (index finger abduction) and during unfatigued and fatigued conditions. All subjects were tested five times with at least one week between tests. Unilateral MVCs were associated with a substantial amount of contralateral FDI activation [mean = 7.9 +/- 6.7% (SD) MVC prior to fatigue]. The amount of such contralateral irradiation was significantly different between different individuals and was positively correlated between dominant and nondominant hands. During fatigue tests, the contractile activity of the contralateral "nontarget" index finger showed progressive increase (force, electromyogram) as was measured during both the submaximal task and interspersed MVCs of the target finger. In addition, a superimposed saw-tooth pattern of intermittently waxing and waning contractions commonly appeared contralaterally. The expression of contralateral irradiation force was itself fatigue-sensitive: less irradiation was seen in a recently fatigued muscle than was seen before the fatigue test. These fatigue effects could not be explained as having been caused by changes in muscle properties. Possible anatomical sites of contralateral irradiation are briefly discussed.

Muscle fatigue induced by stimulation with and without doublets.

Muscles are usually stimulated by shocks delivered at some constant rate. However, human thenar motor units generate optimum force per pulse when excited by impulse trains that begin with one or two short interpulse intervals ("doublets"), followed by longer intervals. Our aim was to determine whether the rate of force and force-time integral reduction during fatigue of thenar muscles is influenced by an initial doublet, and/or the number of pulses per train. We first matched thenar force-time integral using two different pulse patterns, one of which began with a doublet. Fatigue induced by trains that contained a doublet resulted in slower rates of force and force-time integral reduction and smaller increases in half-relaxation time than that evoked by bursts of 40-HZ stimulation. When the force was measured in each protocol after equal numbers of pulses had been delivered, the force loss was still significantly less for pulse trains containing a doublet. These results have useful implications when designing stimulation to strengthen weak muscles or to drive paralyzed muscles.

Potentiating and fatiguing cortical reactions in a voluntary fatigue test of a human hand muscle.

Fatigue-associated changes in the excitability of central motor mechanisms were investigated using transcranial magnetic stimulation (TMS) of the motor cortex. Test stimuli were applied before, during and after a voluntary fatigue test of the first dorsal interosseus muscle (FDI). Subjects were required to maintain 50% of their maximum voluntary force (MVC) for at least 2 min (1/2-MVC test) and electromyographic (EMG) reactions of FDI were measured with surface electrodes. Prior to the test, TMS pulses of 70% maximum output (about 1.4 T) produced muscle-evoked potentials (MEPs) of widely different amplitudes in different subjects, ranging from 13% to 55% of the maximum compound action potential (M-wave) evoked by ulnar nerve stimulation. During the test, MEPs of all subjects showed a potentiation; this effect was markedly greater in subjects with a small initial MEP. After the test, the differential degrees of contraction-evoked potentiation still influenced the MEP amplitudes; small pre-test MEPs showed a post-test net potentiation and larger pre-test MEPs showed a net post-test depression. The results underline that the net outcome of motor activation on motor cortex excitability, as studied with TMS, depends on a complex balance of fatiguing and potentiating effects.

Fatigue-associated changes in the electromyogram of the human first dorsal interosseous muscle.

Muscle fatigue is a clinically important symptom, often analyzed using electromyography (EMG). We analyzed fatigue reactions of the first dorsal interosseous muscle (FDI) during a maintained contraction at half-maximal force ((1/2)-MVC test). EMGs were recorded with large surface electrodes and, simultaneously, with intramuscular fine-wire electrodes. Compound muscle action potentials (M waves) were evoked by electrical ulnar nerve stimulation. During the first half of the test, an almost direct proportionality was found between the variations in voluntary rectified and smoothed EMG (rsEMG) and in M-wave area as recorded with surface electrodes. This indicated that much of the variation in voluntary EMG reflected changes in the spike-generating properties of the muscle fibers. The changes in the fatigue-associated rsEMG were often quantitatively markedly different for the "wide-angle" recording from the surface and the more local intramuscular recording. This suggests that fatigue-associated EMG-responses of the FDI have a markedly heterogeneous intramuscular distribution.

Influence of a voluntary fatigue test on the contralateral homologous muscle in humans?

Influences of a submaximal endurance test in the right first dorsal interosseus on force and fatigue-related parameters of activating the contralateral muscle were studied. The test consisted of a 30% maximum voluntary contraction (MVC), regularly interrupted by maximal contractions and brief rest periods. Despite the induced central fatigue, as tested with the MVC-superimposed twitch technique, and substantial peripheral fatigue, only minor effects of the previous fatigue test were seen for the contralateral hand. No significant influence was found on endurance time, the perceived effort for maintaining 30% MVC force or the MVC-superimposed twitch. Thus, our fatigue protocol induced both central and peripheral fatigue but only minor cross-over effects of fatigue were found for the homologous contralateral muscle.

Task-related variations in motoneuronal drive to a human intrinsic hand muscle.

Maximal electromyogram (EMG) levels of the first dorsal interosseus muscle (FDI) were studied during maximal pinching between index finger and thumb at two different wrist angles. Despite the fact that there was no change in the biomechanical conditions for the FDI, the maximal EMG levels of the FDI differed significantly; typically EMG levels were higher while pinching at a maximally flexed wrist angle compared to a maximally extended wrist angle. The stability of the EMG recordings was checked with supramaximal peripheral nerve stimulation. Significant changes in the area of the compound muscle actions potentials (M-waves) were obtained. However, these changes could not explain the observed differences in the maximal EMG levels. Our results suggest that the ease of producing a maximal drive to the FDI muscle depends on the motor task.

Spatial differences in fatigue-associated electromyographic behaviour of the human first dorsal interosseus muscle.

1. Fatigue-associated electromyographic (EMG) reactions of intrinsic hand muscles were studied during maintained isometric voluntary contractions of normal subjects. Most measurements concerned actions of the first dorsal interosseus (FDI). In a smaller number of subjects, complementary measurements were obtained for adductor pollicis (AP). 2. Measurements were made of isometric force (thumb adduction, index finger abduction and flexion) and of surface EMG amplitudes (AP and FDI) after rectification and smoothing (rsEMG). 3. In the analysis of fatigue, the subjects were required to maintain a steady isometric force (index finger abduction or thumb adduction) of half their maximum voluntary contraction (1/2MVC test) for as long as possible. Average endurance times were 88 +/- 19 s (mean +/- S.D.) for FDI and 119 +/- 29 s for AP (Student's t test, P < 0.02). 4. Pronounced differences in fatigue-associated EMG behaviour were observed between AP and FDI. In AP the reaction was as expected: a rise of EMG during maintained force (mean rsEMG at end of fatigue test/mean rsEMG at start of test (rsEMG-FI): 181 +/- 64%). In FDI this reaction was seen in half of the recorded cases, the remainder displaying bidirectional changes or a more or less marked decrease of EMG during the endurance task (mean for all cases together: rsEMG-FI, 103 +/- 15%; difference between AP vs. FDI significant, P < 0.01). 5. The unexpected EMG variability of the FDI reactions was further analysed with multiple bipolar recordings of surface EMG. For all the four thoroughly studied subjects, recordings were obtained which showed simultaneously occurring EMG changes in opposite directions (decrease and increase) at different sites of FDI while force was kept constant at 50% of the maximum voluntary contraction (MVC). 6. Further observations on FDI showed that EMGs simultaneously obtained from different recording sites could show dramatic differences in their responses depending on 'synergistic context' (e.g. in relation to changes in index finger extension force during maintained abduction at 50% MVC). Evidence for 'task switching' (shift in rsEMG distribution, shift in hand muscle synergy) was frequently observed during the performance of the 1/2MVC test. 7. The results indicate that FDI is not handled in a topographically homogeneous manner during the execution of an isometric constant force endurance test. Furthermore, the results suggest that this seemingly simple motor performance can be executed in several alternative manners associated with the activation of different muscle synergies and with different distributions of activity within the FDI.

Fatigue associated EMG behavior of the first dorsal interosseous and adductor pollicis muscles in different groups of subjects.

We have studied the fatigue-associated behavior of surface EMG in two histochemically different muscles of the hand: first dorsal interosseous (FDI) and adductor pollicis (AP; relatively more type I fibers in AP than in FDI). During a fatigue test evoked by electrical stimulation of the ulnar nerve, the mean amplitudes of compound muscle action potentials (M-waves) exhibited the same overall pattern for both muscles: a rapid phase of potentiation followed by a gradual decline. However, if the group of subjects was subdivided on the basis of hand length, significant differences emerged in the reactions of AP: in large hands, no fatigue-associated M-wave decline was seen, whereas in small hands a distinct decline was observed. A possible explanation for this phenomenon might be the presence of a greater amount of EMG contamination from other muscles in smaller hands. In the supposedly "cleaner" recordings from larger hands, significant differences between FDI and AP were observed with regard to their fatigue-associated EMG reactions (M-wave depression in FDI but not in AP). The direction of these differences was in accordance with expectations on the basis of known differences in histochemical fiber type composition.

Index finger position and force of the human first dorsal interosseus and its ulnar nerve antagonist.

In normal subjects, maximum voluntary contraction (MVC) and electrical ulnar nerve stimulation (UNS; 30-Hz bursts of 0.33 s) were systematically compared with regard to the forces generated in different directions (abduction/adduction and flexion) and at different degrees of index finger abduction. With a "resting" hand position in which there was no index finger abduction, UNS produced about one-half of the abduction force elicited by an MVC (mean ratio 51%). Qualitatively, such a discrepancy would be expected, because UNS activates two index finger muscles with opposing actions in the abduction/adduction plane of torques: the first dorsal interosseus (FDI) and the first palmar interosseus (FPI). The abduction forces produced by MVC and UNS were very sensitive to index finger abduction angle: at a maximum degree of abduction, the UNS-generated force even reversed its direction of action to adduction (with FPI dominating) and the abduction MVC declined to 37% of that in the resting hand position. Inasmuch as these declines in MVC- and UNS-generated abduction force could not be explained by a change in moment arm, the main alternative seemed to be abduction-associated alterations in FDI fiber length (analysis by previously published biomechanical data). The FDI and FPI were further compared by application of a UNS-generated fatigue test (5-min burst stimulation), with the index finger kept at a "neutral" angle, i.e., the abduction angle at which, in the unfatigued state, the forces of the FDI and FPI were in balance (zero net UNS-generated abduction/adduction force).(ABSTRACT TRUNCATED AT 250 WORDS)