Reproducible measurement of voluntary activation of human elbow flexors with motor cortical stimulation.

Voluntary activation of muscle is commonly quantified by comparison of the extra force added by motor nerve stimulation during a contraction [superimposed twitch (SIT)] with that produced at rest by the same stimulus (resting twitch). An inability to achieve 100% voluntary activation implies that failure to produce maximal force output from the muscle must have occurred at a site at or above the level of the motoneurons. We have used cortical stimulation to quantify voluntary activation. Here, incomplete activation implies a failure at or above the level of motor cortical output. With cortical stimulation, it is inappropriate to compare extra force evoked during a contraction with the twitch evoked in resting muscle because motor cortical and spinal cord excitability both increase with activity. However, an appropriate "resting twitch" can be estimated. We previously estimated its amplitude by extrapolation of the linear relation between SIT amplitude and voluntary torque calculated from 35 contractions of >50% maximum (Todd G, Taylor JL, and Gandevia SC. J Physiol 551: 661-671, 2003). In this study, we improved the utility of this method to enable evaluation of voluntary activation when it may be changing over time, such as during the development of fatigue, or in patients who may be unable to perform large numbers of contractions. We have reduced the number of contractions required to only three. Estimation of the resting twitch from three contractions was reliable over time with low variability. Furthermore, its reliability and variability were similar to the resting twitch estimated from 30 contractions and to that evoked by conventional motor nerve stimulation.     

Theta burst stimulation of the human motor cortex

It has been 30 years since the discovery that repeated electrical stimulation of neural pathways can lead to long-term potentiation in hippocampal slices. With its relevance to processes such as learning and memory, the technique has produced a vast literature on mechanisms of synaptic plasticity in animal models. To date, the most promising method for transferring these methods to humans is repetitive transcranial magnetic stimulation (rTMS), a noninvasive method of stimulating neural pathways in the brain of conscious subjects through the intact scalp. However, effects on synaptic plasticity reported are often weak, highly variable between individuals, and rarely last longer than 30 min. Here we describe a very rapid method of conditioning the human motor cortex using rTMS that produces a controllable, consistent, long-lasting, and powerful effect on motor cortex physiology and behavior after an application period of only 20-190 s.     

Comparison of techniques to determine human skeletal muscle voluntary activation

Determining volitional activation (VA) can provide insights on the cause of muscle weakness in orthopedic and neurological populations. Two electrical stimulation techniques are traditionally used to quantify VA: interpolation (IT) and superimposition (CAR). IT allows for a more accurate VA estimation, however it requires individuals to be stimulated twice, compared to once for CAR, and thus increases stimulation associated discomfort. To date, there is no agreement on what is the best practical technique for calculating quadriceps VA. This paper aims to address this problem by determining what reference force (i.e., using either peak force or force at the time of stimulation) and type of stimulation (train of pulses (burst), doublet, and twitch) is the best technique to use. Our findings showed that the IT with the force at the time of stimulation as a reference should be used to determine VA and that when a burst was used, the VA ratio computations were more accurate. Additionally, using a twitch with a 2 ms pulse duration produced reliable VA calculations and may be an acceptable alternative for pain-sensitive subjects. Accurate assessment of VA deficits can help clinicians design rehabilitation programs that are based on subject-specific strength impairments and are more effective.     

Multivariate analysis of simultaneously active motor units in human skeletal muscle

The joint activity of simultaneously active motor units was analyzed, using several methods including interunit interval and expectation density functions. The results show that there is no significant interaction between any motor units and, except for a slight coupling, the units fire independently of one another. The coupling is weak but pervasive and affects motor units overlapping and disjoint territories. Synchronous action potentions were recorded at sites whose distance is greater than the acknowledged diameter of motor unit territories. It is proposed that these expansive motor units and the viscoelastic properties of muscle are responsible for smooth contractions in human muscle.This work was supported in part by the Social Rehabilitation Service through the Krusen Research Center, Temple University, Philadelphia, Pennsylvania, while Dr. Shiavi was with the Biomedical Engineering and Science Program, Drexel University, Philadelphia, Pennsylvania, and the Krusen Research Center.     

Magnetic stimulation of the human motor cortex evokes skin sympathetic nerve activity.

Single-pulse magnetic coil stimulation (Cadwell MES 10) over the cranium induces without pain an electric pulse in the underlying cerebral cortex. Stimulation over the motor cortex can elicit a muscle twitch. In 10 subjects, we tested whether motor cortical stimulation could also elicit skin sympathetic nerve activity (SSNA; n = 8) and muscle sympathetic nerve activity (MSNA; n = 5) in the peroneal nerve. Focal motor cortical stimulation predictably elicited bursts of SSNA but not MSNA; with successive stimuli, the SSNA responses did not readily extinguish (94% of discharges to the motor cortex evoked SSNA responses) and had predictable latencies [739 +/- 33 (SE) to 895 +/- 13 ms]. The SSNA responses were similar after stimulation of dominant and nondominant sides. Focal stimulation posterior to the motor cortex elicited extinguishable SSNA responses. In three of six subjects, anterior cortical stimulation evoked SSNA responses similar to those seen with motor cortex stimulation but without detectable movement; in the other subjects, anterior stimulation evoked less SSNA discharge than that seen with motor cortex stimulation. Contrasting with motor cortical stimulation, evoked SSNA responses were more readily extinguished with 1) peripheral stimulation that directly elicited forearm muscle activation accompanied by electromyograms similar to those with motor cortical stimulation; 2) auditory stimulation by the click of the energized coil when off the head; and 3) in preliminary experiments, finger afferent stimulation sufficient to cause tingling. Our findings are consistent with the hypothesis that motor cortex stimulation can cause activation of both alpha-motoneurons and SSNA.     

Motor responses of the facial muscles to local stimulation of the motor cortex and facial nerve nucleus in the white mouse

The character of motor responses of the facial muscles evoked by stimulation of various regions of the frontal neocortex and of the nucleus of the facial nerve was studied in outbred mice. Motor responses of the vibrissae, of the upper lip and the jaw to monopolar microstimulation in the frontal cortical areas in 55 per cent of the cases had the latencies from 5 to 15 ms. The latencies of the responses to the facial nucleus stimulation ranged from 3 to 12 ms with maximal expressed interval of 4-6 ms. Excitation conduction velocities of the facial nerve estimated on the basis of latencies measurements, were from 1.5 to 12 m/s.     

Different motor learning effects on excitability changes of motor cortex in muscle contraction state

Abstract

We aimed to investigate whether motor learning induces different excitability changes in the human motor cortex (M1) between two different muscle contraction states (before voluntary contraction [static] or during voluntary contraction [dynamic]). For the same, using motor evoked potentials (MEPs) obtained by transcranial magnetic stimulation (TMS), we compared excitability changes during these two states after pinch-grip motor skill learning. The participants performed a force output tracking task by pinch grip on a computer screen. TMS was applied prior to the pinch grip (static) and after initiation of voluntary contraction (dynamic). MEPs of the following muscles were recorded: first dorsal interosseous (FDI), thenar muscle (Thenar), flexor carpi radialis (FCR), and extensor carpi radialis (ECR) muscles. During both the states, motor skill training led to significant improvement of motor performance. During the static state, MEPs of the FDI muscle were significantly facilitated after motor learning; however, during the dynamic state, MEPs of the FDI, Thenar, and FCR muscles were significantly decreased. Based on the results of this study, we concluded that excitability changes in the human M1 are differentially influenced during different voluntary contraction states (static and dynamic) after motor learning.     

Functional properties of efferent zones of the motor cortex which project to ipsilateral and contralateral face muscles

In both intact (4 animals) and lesioned (2 preparations with contralateral motor cortex ablation and 1 animal with transection of the rostral two thirds of the corpus callosum) cats, three different types of efferent zones were identified in the face motor cortex by the technique of microstimulation: contralateral, ipsilateral and bilateral efferent zones. The three types of efferent zones had different organizational features such as location, thresholds of effective sites and latencies of motor responses. Mean thresholds of effective sites from ipsilateral and bilateral efferent zones in lesioned animals were not significantly higher than those in intact preparations. In both intact and lesioned animals, neurons endowed with contralateral, bilateral and ipsilateral receptive fields were isolated from the three types of efferent zones.     

Spatial attention changes excitability of human visual cortex to direct stimulation

Conscious perception depends not only on sensory input, but also on attention [1, 2]. Recent studies in monkeys [3-6] and humans [7-12] suggest that influences of spatial attention on visual awareness may reflect top-down influences on excitability of visual cortex. Here we tested this specifically, by providing direct input into human visual cortex via cortical transcranial magnetic stimulation (TMS) to produce illusory visual percepts, called phosphenes. We found that a lower TMS intensity was needed to elicit a conscious phosphene when its apparent spatial location was attended, rather than unattended. Our results indicate that spatial attention can enhance visual-cortex excitability, and visual awareness, even when sensory signals from the eye via the thalamic pathway are bypassed.     

Mechanochemical coupling in muscle: attempts to measure simultaneously shortening and ATPase rates in myofibrils.

We studied the ATPase of shortening myofibrils at 4 degrees C by the rapid flow quench method. The progress curve has three phases: a P(i) burst, a fast linear phase kF of duration tB, and a deceleration to a slow kS. We propose that kF is the ATPase of myofibrils shortening under zero external load; at tB shortening and ATPase rates are reduced by passive resistance. The total ATP consumed during the rapid shortening is ATPc. Our purpose was to obtain information on the myofibrillar shortening velocity from their ATPase progress curves. We tested tB as an indicator of shortening velocity by determining the effects of different probes upon it and the other ATPase parameters. The dependence of tB upon the initial sarcomere length was linear, giving a shortening velocity close to that of muscle fibres (Vo). The Km of ATP was larger for tB than for kF, as found with fibers for Vo and their ATPase. ADP and 2,3-butanedione monoxime, but not P(i), inhibited tB to the same extent as Vo. The delta H for tB and Vo were similar. ATPc was independent of the sarcomere length, implying that the more the myofibrils shorten, the less ATP expended per myosin head per micron shortened. We propose that tB can be used as an indicator for myofibrillar shortening velocities.     

Effect of succinylcholine on responses of neurons in the motor cortex to natural activation of muscle spindle primary endings.

In locally anesthetized cats, the effects of intravenous administration of succinylcholine (SCh) in sub-paralytic dosages on the responses of single neurons in motor cortex to small dynamic muscle stretches were studied. A large transient enhancement of these cortical responses with a time course corresponding to the peripheral action of SCh on muscle spindles was observed. This finding is discussed in terms of the hypothesis that muscle spindle primary endings may activate projections to motor cortex.     

Differential changes in muscle oxygenation between voluntary and stimulated isometric fatigue of human dorsiflexors.

The purpose of this study was to compare fatigue and recovery of maximal voluntary torque [maximal voluntary contraction (MVC)] and muscle oxygenation after voluntary (Vol) and electrically stimulated (ES) protocols of equal torque production. On 1 day, 10 male subjects [25 yr (SD 4)] completed a Vol fatigue protocol and, on a separate day, an ES fatigue protocol of the right dorsiflexors. Each task involved 2 min of intermittent (2-s on, 1-s off) isometric contractions at 50% of MVC. For the ES protocol, stimulation was delivered percutaneously to the common peroneal nerve at a frequency of 25 Hz. Compared with the Vol protocol, the ES protocol caused a greater impairment in MVC (75 vs. 83% prefatigue value; Pre) and greater increase in 50-Hz half relaxation time (165 vs. 117% Pre) postexercise. After acute (1 min) recovery, MVC impairment was similar for both protocols, whereas 50- Hz half relaxation time was still greater in the ES than Vol protocol. Total hemoglobin decreased to a similar extent in both protocols during exercise, but it was elevated above the resting value to a significantly greater extent for the ES protocol in recovery (18 vs. 11 microM). Oxygen saturation was significantly lower in the ES than Vol protocol during exercise (46 vs. 57% Pre), but it was significantly greater during recovery (120 vs. 105% Pre). These findings suggest that despite, equal torque production, ES contractions impose a greater metabolic demand on the muscle that leads to a transient greater impairment in MVC. The enforced synchronization and fixed frequency of excitation inherent to ES are the most likely causes for the exacerbated changes in the ES compared with the Vol protocol.     

Effects of activation frequency on dynamic performance of human fresh and fatigued muscles.

The force-frequency relationship for an individual muscle depends on the fatigue state, the length at which it is activated, and the muscle's activation history. The relationship among stimulation frequency and dynamic (nonisometric) muscle performance measurements (e.g., excursion, work, peak power, and average power) has not been reported. The purpose of this study was to identify the relationship between stimulation frequency and dynamic performance measurements for fresh and fatigued muscles. Constant-frequency and catchlike-inducing trains (CFT and CIT, respectively) were tested. When fresh, interpulse intervals of 40-50 ms [20-25 pulses/s (pps)] produced maximum performance for CFTs. For CITs, maximum performance occurred at interpulse intervals of 50-60 ms ( approximately 16-20 pps). Generally, CFTs produced slightly greater performance than did CITs. When fatigued, however, CITs produced greater performance than did CFTs. Maximum performance for CFTs occurred at interpulse intervals of 20-40 ms (25-50 pps) and at 30-50 ms (20-33 pps) for CITs. Enhancement of performance by CITs when fatigued may be due to less susceptibility to impairments in excitation-contraction coupling and greater ability to maintain rates of rise of force than CFTs.     

The proprioceptive activation of stretch tension in pretibial flexor muscles induced by stimulation of antagonistic muscle afferents.

1. The effect of tetanic stimulation of ipsilateral group I afferents from the GS muscle on a synchronous stretch of the flexor EDL/TA muscles has been investigated in precollicular decerebrate cats. 2. The stretch-induced tension of the EDL/TA muscles increases remarkably during simultaneous stimulation of the GS nerve with maximal intensities corresponding to 1.5 times the threshold for the group 1 afferents. This increas appears above all in the dynamic part of stretch. 3. Under our experimental conditions there is no activation fo flexor-alpha-motoneurones during tetanic stimulation of the GS afferents without muscle stretch, as measured by the resting tension of the EDL/TA muscles. 4. Desptie an increase in the stretch-induced tension during fusimotor stimulation of antagonistic group I afferents, a transmission loss in the excitation via the psi-loop to the flexor-alpha-motoneurones occurs. This could be demonstrated by the ratio: increase in the tension T /increase in the number of Ia spikes. This is explained by snychronous convergence of the discharges of Ia inhibitory interneurones to the flexor-alpha-motoneurones. 5. The system studied demonstrates an input-output relation of the stretch reflex during conditions in which both reciprocal inhibition and autogenetic excitation via the psi-loop occur. It appears however, that the reciprocal inhibition is partly overwhelmed by the autogenetic excitation which results from the increase in the Ia discharge rate during fusimotor reflex. 6. It is postulated that static rather than dynamic psi-moto-neurones are involved in the investigated reflex arc.     

Relationship between mechanomyogram signals and changes in force of human forefinger flexor muscles during voluntary contraction

In previous studies on mechanomyogram (MMG) signals no analysis of these signals accompanying force generation has been performed. Therefore, we have recorded MMG signals (previously referred to as muscle sound or acoustomyographic signals) during voluntary contractions of forefinger flexor muscles in 31 young subjects. These subjects made contractions to produce force records of triangular or trapeziform shape. The peak target force amounted to 10, 20 or 40 N which represented less than 40% of maximal voluntary contraction. The MMG signals during the transient phases of force generation at three different rates were analysed. The MMG intensity level calculated for MMG records and the peak-to-peak amplitude of MMG signals correlated with both the velocity of force increase and the contraction force. The occurrence of the strongest MMG signals corresponded to changes in contractile force. Therefore, it is suggested that measurements of these parameters could be a useful tool in studies of changes in contractile force. Accepted: 11 March 1998     

Effect of voluntary vs. artificial activation on the relationship of muscle torque to speed

The speed-torque relationship of the right knee extensor muscle group was investigated in eight untrained subjects (28 +/- 2 yr old). Torque was measured at a specific knee angle during isokinetic concentric or eccentric actions at nine angular velocities (0.17-3.66 rad/s) and during isometric actions. Activation was by "maximal" voluntary effort or by transcutaneous tetanic electrical stimulation that induced an isometric torque equal to 60% (STIM 1) or 45% (STIM 2) of the voluntary isometric value. Torque increased (P less than 0.05) to 1.4 times isometric as the speed of eccentric actions increased to 1.57 rad/s for STIM 1 and STIM 2. Thereafter, increases in eccentric speed did not further increase torque. Torque did not increase (P greater than 0.05) above isometric for voluntary eccentric actions. As the speed of concentric actions increased from 0.00 to 3.66 rad/s, torque decreased (P less than 0.05) more (P less than 0.05) for both STIM 1 and STIM 2 (two-thirds) than for voluntary activation (one-half). As a result of these responses, torque changed three times as much (P less than 0.05) across speeds of concentric and eccentric actions with artificial (3.4-fold) than voluntary (1.1-fold) activation. The results indicate that with artificial activation the normalized speed-torque relationship of the knee extensors in situ is remarkably similar to that of isolated muscle. The relationship for voluntary activation, in contrast, suggests that the ability of the central nervous system to activate the knee extensors during maximal efforts depends on the speed and type of muscle action performed.     

A comparison of corticospinal activation by magnetic coil and electrical stimulation of monkey motor cortex

The effects of different orientations of a Cadwell round magnetic coil (MC) were compared with each other and with surface electrical stimulation of motor cortex in monkeys anesthetized with pentobarbital or urethane. Recordings were made from within the lateral corticospinal tract, either from axonal populations or with a microelectrode from individual axons. A lateral-sagittally orientated MC directly excited corticospinal neurons at lower stimulus intensity than was required for indirect, i.e., transsynaptic excitation via inputs to corticospinal neurons. By contrast, in 2 out of 3 macaques tested, a vertex-tangential orientation could excite corticospinal neurons indirectly at lower intensities than were required for direct excitation; at higher intensities, direct excitation also occurred.The site of direct corticospinal excitation by a lateral-sagitally oriented MC was inferred by comparing the response variability and latency to MC and surface electrical stimuli. Cathodal stimuli elicited more variable corticospinal population responses and later individual axonal responses than were obtained with anodal stimuli. The variability in response is attributed to interaction between nearby, on-going synaptic bombardment and the stimulus, implying that surface cathodal stimuli directly activate corticospinal neurons at the spike trigger zone (presumably the initial segment). By contrast, the consistency and reduced latency of the corticospinal responses to surface anodal stimuli are attributed to the direct excitation of corticospinal fibers within the white matter. When the stimulus intensity is clearly above threshold, surface anodal and cathodal stimuli can activate corticospinal neurons both directly and indirectly.Direct corticospinal excitation by the MC can resemble the effects of either surface anodal or surface cathodal stimuli. We conclude that the MC can activate corticospinal neurons at the spike trigger zone or their fibers deeper in white matter. The findings in the monkey are used to interpret the effects of different MC orientations in the human.