Effects of acetylcholine and succinylcholine on isolated frog neuromuscular spindle]

The mode of action of acetylcholine (ACh) and succinylcholine (SCh) on the isolated frog's muscle spindle has been studied. Receptor afferent nervous supply was maintained; the appropriate spinal roots were dissected for stimulating motor axons and recording from sensory fibres. Excitatory effects on the afferent activity, when the receptor was held still and during stretching, were found with ACh or SCh concentrations of 10(-8) to 10(-3); 10(-6) g/ml being usually effective. These effects are similar to those obtained by stimulating fusimotor nerve fibres. The contractile activity of intrafusal muscle fibres which occurred during these effects was observed. Seldom, and only for high concentrations of ACh and SCh, a decrease in afferent activity following the excitatory effects was found. Tubocurarine chloride (10(-5)-10(04) g/ml) in the bath prevented both motor fibres and drugs effects. Sometimes slight transient excitation occurred at very high concentrations of the two tested substances; however, this effect was prevented by stronger curarization. The observed blocking effects were always reversed by removing tubocurarine from the bath. No more excitatory effects by motor fibres stimulation and by ACh and SCh action could be found after destruction of intrafusal muscle fibres, by pinching them as close as possible to the ends of the spindle. It is suggested that ACh and SCh act indirectly by causing mechanical changes in intrafusal muscle fibres, and that a direct action on sensory nerve endings, if any, cannot, by itself, increase the afferent activity of the receptor.     

Participation of the primary motor cortex in programming of muscle activity during catching of falling object

Object fell into the cup that sitting subject held between thumb and index fingers. Transcranial magnetic stimulation (TMS) of the primary motor cortex was performed early before and during anticipatory grip force increasing. Comparison of current EMG activity of adductor pollicis brevis and first dorsal interosseous muscles and responses of these muscles on TMS showed that responses were increased before the raising of muscle activity. From the other side only slight augmentation of responses was observed during subsequent strong muscle activation. It is assumed that the increasing of the TMS responses that occurred before the initiation of muscle activity reflects the enhancement ofthe motor cortex excitability associated to specific processes related to the motor cortex participation in programming of the muscles activities.     

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.     

Study of motor cortex excitability in the load holding task

Changes in the amplitude of hand muscle responses to a series of ten stimuli applied to the motor cortex has been studied in subjects holding a small load for 3 min. The amplitude of muscle responses and the background activity decreased with time as compared to the initial level. Regression analysis showed that the muscle response amplitude decreased with the number of stimuli to a greater extent than the background activity. Comparison of the parameters of hand muscle activity during load holding in the stable and unstable equilibrium positions showed that the decrease in the muscle response to motor cortex stimulation during load holding in a state of unstable equilibrium is less pronounced than during load holding in a state of stable equilibrium. For the forearm muscles, the muscle response amplitude and background activity decreased less with the number of stimuli, and this decrease did not depend on the stability of the load position. It may be supposed that the evoked responses decreased more rapidly than the background activity because the motor cortex is involved in the adjustment of the level of muscle activity at the stage of the development of the program for the performance of motor tasks and then transfers the control to subcortical structures.     

Assessing the function of motor cortex: single-neuron models of how neural response is modulated by limb biomechanics

Do neurons in primary motor cortex encode the generative details of motor behavior, such as individual muscle activities, or do they encode high-level movement attributes? Resolving this question has proven difficult, in large part because of the sizeable uncertainty inherent in estimating or measuring the joint torques and muscle forces that underlie movements made by biological limbs. We circumvented this difficulty by considering single-neuron responses in an isometric task, where joint torques and muscle forces can be straightforwardly computed from limb geometry. The response for each neuron was modeled as a linear function of a "preferred" joint torque vector, and this model was fit to individual neural responses across variations in limb posture. The resulting goodness of fit suggests that neurons in motor cortex do encode the kinetics of motor behavior and that the neural response properties of "preferred direction" and "gain" are dual components of a unitary response vector.     

Use of motor cortex stimulation to measure simultaneously the changes in dynamic muscle properties and voluntary activation in human muscles.

Force responses to transcranial magnetic stimulation of motor cortex (TMS) during exercise provide information about voluntary activation and contractile properties of the muscle. Here, TMS-generated twitches and muscle relaxation during the TMS-evoked silent period were measured in fresh, heated, and fatigued muscle. Subjects performed isometric contractions of elbow flexors in two studies. Torque and EMG were recorded from elbow flexor and extensor muscles. One study (n = 6) measured muscle contraction times and relaxation rates during brief maximal and submaximal contractions in fresh and fatigued muscle. Another study (n = 7) aimed to 1) assess the reproducibility of muscle contractile properties during brief voluntary contractions in fresh muscle, 2) validate the technique for contractile properties in passively heated muscle, and 3) apply the technique to study contractile properties during sustained maximal voluntary contractions. In both studies, muscle contractile properties during voluntary contractions were compared with the resting twitch evoked by motor nerve stimulation. Measurement of muscle contractile properties during voluntary contractions is reproducible in fresh muscle and reveals faster and slower muscle relaxation rates in heated and fatigued muscle, respectively. The technique is more sensitive to altered muscle state than the traditional motor nerve resting twitch. Use of TMS during sustained maximal contractions reveals slowing of muscle contraction and relaxation with different time courses and a decline in voluntary activation. Voluntary output from the motor cortex becomes insufficient to maintain complete activation of muscle, although slowing of muscle contraction and relaxation indicates that lower motor unit firing rates are required for fusion of force.     

Influence of Vibration on Motor Responses in the Upper Arm Muscles under Stationary Conditions and during Voluntary and Evoked Arm Movements under Limb Unloading Conditions

Locomotion of mammals, including humans, is based on the rhythmic activity of spinal cord circuitries. The functioning of these circuitries depends on multimodal afferent information and on supraspinal influences from the motor cortex. Using the method of transcranial magnetic stimulation (TMS) of arm muscle areas in the motor cortex, we studied the motor evoked potentials (MEP) in the upper arm muscles in stationary conditions and during voluntary and vibration-evoked arm movements. The study included 13 healthy subjects under arm and leg unloading conditions. In the first series of experiments, with motionless limbs, the effect of vibration of left upper arm muscles on motor responses in these muscles was evaluated. In the second series of experiments, MEP were compared in the same muscles during voluntary and rhythmic movements generated by left arm m. triceps brachii vibration (the right arm was stationary). Motionless left arm vibration led to an increase in MEP values in both vibrated muscle and in most of the non-vibrated muscles. For most target muscles, MEP was greater with voluntary arm movements than with vibration-evoked movements. At the same time, a similar MEP modulation in the cycle of arm movements was observed in the same upper arm muscles during both types of arm movements. TMS of the motor cortex significantly potentiated arm movements generated by vibration, but its effect on voluntary movements was weaker. These results indicate significant differences in the degree of motor cortex involvement in voluntary and evoked arm movements. We suppose that evoked arm movements are largely due to spinal rather than central mechanisms of generation of rhythmic movements.     

Comparison of Leg Muscle Responses to Transcranial Magnetic Stimulation upon Standing on Stable and Unstable Supports

The role of supraspinal structures in postural adjustment upon standing on stable and unstable supports was studied in healthy individuals. For this purpose, transcranial magnetic stimulation (TMS) of the motor cortex was used in the region of leg representation. The subject stood with the eyes closed on a firm floor or on an unstable support in the form of a paperweight (20 cm in height, with a base radius of 32 cm) with mobility in the sagittal direction. Electric responses of four muscles—the soleus muscle, the anterior tibial muscle, the femoral biceps muscle, and the femoral rectus muscle—were recorded. It was shown that, in all the muscles, the response to TMS upon standing on an unstable support increased by 1.8–2.7 times as compared with the response upon standing on a firm floor. Since the increase in the tonic activity of the muscles studied was statistically insignificant upon switching over from standing on a firm floor to standing on an unstable support, it is hypothesized that the increase in the amplitude of muscle responses is connected with an increased activity of the supraspinal structures or with an increase in the effectiveness of corticospinal connections. The results are discussed from the point of view of the role of the motor cortex in maintaining balance on an unstable support.     

Transformation of the afferent tactile signal into a motor command in the cat motor cortex

Activity of 112 neurons of the precruciate motor cortex in cats was studied during a forelimb placing reaction to tactile stimulation of its distal parts. The latent period of response of the limb to tactile stimulation was: for flexors of the elbow (biceps brachii) 30–40 msec, for the earliest reponses of cortical motor neurons about 20 msec. The biceps response was observed 5–10 msec after the end of stimulation of the cortex with a series of pulses lasting 25 msec. Two types of excitatory responses of the neurons were identified: responses of sensory type observed to each tactile stimulation of the limb and independent of the presence or absence of motion, and responses of motor type, which developed parallel with the motor response of the limb and were not observed in the absence of motion. The minimal latent period of the responses of motor type was equal to the latent period of the sensory responses to tactile stimulation (20±10 msec). Stimulation of the cortex through the recording microelectrode at the site of derivation of unit activity, which increased during active flexion of the forelimb at the elbow (11 stimuli at intervals of 2.5 msec, current not exceeding 25 µA), in 70% of cases evoked an electrical response in the flexor muscle of the elbow.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 9, No. 2, pp. 115–123, March–April, 1977.     

How Thoughts Give Rise to Action - Conscious Motor Intention Increases the Excitability of Target-Specific Motor Circuits

The present study shows evidence for conscious motor intention in motor preparation prior to movement execution. We demonstrate that conscious motor intention of directed movement, combined with minimally supra-threshold transcranial magnetic stimulation (TMS) of the motor cortex, determines the direction and the force of resulting movements, whilst a lack of intention results in weak and omni-directed muscle activation. We investigated changes of consciously intended goal directed movements by analyzing amplitudes of motor-evoked potentials of the forearm muscle, flexor carpi radialis (FCR), and extensor carpi radialis (ECR), induced by transcranial magnetic stimulation over the right motor cortex and their motor outcome. Right-handed subjects were asked to develop a strong intention to move their left wrist (flexion or extension), without any overt motor output at the wrist, prior to brain stimulation. Our analyses of hand acceleration and electromyography showed that during the strong motor intention of wrist flexion movement, it evoked motor potential responses that were significantly larger in the FCR muscle than in the ECR, whilst the opposite was true for an extension movement. The acceleration data on flexion/extension corresponded to this finding. Under no-intention conditions again, which served as a reference for motor evoked potentials, brain stimulation resulted in undirected and minimally simultaneous extension/flexion innervation and virtually no movement. These results indicate that conscious intentions govern motor function, which in turn shows that a neuronal activation representing an “intention network” in the human brain pre-exists, and that it functionally represents target specific motor circuits. Until today, it was unclear whether conscious motor intention exists prior to movement, or whether the brain constructs such an intention after movement initiation. Our study gives evidence that motor intentions become aware before any motor execution.     

Sensing with the motor cortex

The primary motor cortex is a critical node in the network of brain regions responsible for voluntary motor behavior. It has been less appreciated, however, that the motor cortex exhibits sensory responses in a variety of modalities including vision and somatosensation. We review current work that emphasizes the heterogeneity in sensorimotor responses in the motor cortex and focus on its implications for cortical control of movement as well as for brain-machine interface development.     

Modulation of motor cortex excitability by physical similarity with an observed hand action

The passive observation of hand actions is associated with increased motor cortex excitability, presumably reflecting activity within the human mirror neuron system (MNS). Recent data show that in-group ethnic membership increases motor cortex excitability during observation of culturally relevant hand gestures, suggesting that physical similarity with an observed body part may modulate MNS responses. Here, we ask whether the MNS is preferentially activated by passive observation of hand actions that are similar or dissimilar to self in terms of sex and skin color. Transcranial magnetic stimulation-induced motor evoked potentials were recorded from the first dorsal interosseus muscle while participants viewed videos depicting index finger movements made by female or male participants with black or white skin color. Forty-eight participants equally distributed in terms of sex and skin color participated in the study. Results show an interaction between self-attributes and physical attributes of the observed hand in the right motor cortex of female participants, where corticospinal excitability is increased during observation of hand actions in a different skin color than that of the observer. Our data show that specific physical properties of an observed action modulate motor cortex excitability and we hypothesize that in-group/out-group membership and self-related processes underlie these effects.     

Participation of primary motor cortex in the programming of muscle activity during catching of a falling object

A sitting person has been exposed to transcranial magnetic stimulation (TMS) of the primary motor cortex shortly before and during increasing anticipatory grip force, while an object was falling into a cup held between the thumb and index finger of the subject. Comparison of the changes in the electrical activity of adductor pollicis brevis and the first dorsal interosseous muscles and of TMS response in these muscles revealed, on the one hand, a strong increase in TMS response not long before enhancement of muscle activity and, on the other hand, an insignificant increase in the response amplitude during substantial increase in muscle activity. An increase in the TMS response prior to initiation of motor activity suggests that the excitability of the primary motor cortex is enhanced due to specific processes caused by the direct involvement of the cortex in the programming of motor activity.     

Rate-coding of spinal motoneurons with high-frequency magnetic stimulation of human motor cortex

Rate-coding in spinal motoneurons was studied using high-frequency magnetic stimulation of the human motor cortex. The subject made a weak contraction to cause rhythmic (i.e., tonic) discharge of a single motor unit in flexor (or extensor) carpi radialis or tibialis anterior, while the motor cortical representation of that muscle was stimulated with brief trains of pulses from a Pyramid stimulator (4 Magstim units connected by 3 BiStim modules). An "m@n" stimulus train consisted of m number of pulses (1-4), with an interpulse interval (IPI) of n ms (1-6). Peristimulus time histograms were constructed for each stimulus condition of a given motor unit, and related to the average rectified surface electromyography (EMG) from that muscle. Surface EMG responses showed markedly more facilitation than single-pulse stimulation, with increasing numbers of pulses in the train; responses also tended to increase in magnitude for the longer IPI values (4 and 6 ms) tested. Motor-unit response probability increased in a manner comparable to that of surface EMG. In particular, motoneurons frequently responded twice to a given stimulus train. In addition to recruitment of new motor units, the increased surface EMG responses were, in part, a direct consequence of short-term rate-coding within the tonically discharging motoneuron. Our results suggest that human corticomotoneurons are capable of reliably following high-frequency magnetic stimulation rates, and that this activity pattern is carried over to the spinal motoneuron, enabling it to discharge at extremely high rates for brief periods of time, a pattern known to be optimal for force generation at the onset of a muscle contraction.     

Motor cortex excitability does not increase during sustained cycling exercise to volitional exhaustion

The excitability of the motor cortex increases as fatigue develops during sustained single-joint contractions, but there are no previous reports on how corticospinal excitability is affected by sustained locomotor exercise. Here we addressed this issue by measuring spinal and cortical excitability changes during sustained cycling exercise. Vastus lateralis (VL) and rectus femoris (RF) muscle responses to transcranial magnetic stimulation of the motor cortex (motor evoked potentials, MEPs) and electrical stimulation of the descending tracts (cervicomedullary evoked potentials, CMEPs) were recorded every 3 min from nine subjects during 30 min of cycling at 75% of maximum workload (W(max)), and every minute during subsequent exercise at 105% of W(max) until subjective task failure. Responses were also measured during nonfatiguing control bouts at 80% and 110% of W(max) prior to sustained exercise. There were no significant changes in MEPs or CMEPs (P > 0.05) during the sustained cycling exercise. These results suggest that, in contrast to sustained single-joint contractions, sustained cycling exercise does not increase the excitability of motor cortical neurons. The contrasting corticospinal responses to the two modes of exercise may be due to differences in their associated systemic physiological consequences.     

Comparative analysis of the facilitating effects induced on muscular periphery by the microstimulation of various cerebellar nuclei

The facilitatory effects evoked on the motor periphery by the activation of neuronal pools in cerebellar nuclei were analized in 13 cats. The aim of the work was to compare the frequency and the characteristics of the motor facilitations induced on the ipsilateral forelimb by the microstimulation of cerebellar foci in the fastigial (CBM or in the interposital (NIA) nucleus. CBM or NIA sites, previously identified for the motor effects, were microstimulated, together with the contralateral motor cortex, to give evidence of the facilitations. It was observed that 51% of the NIA motor sites, 46% of the rostral and 33% of the caudal CBM ones, were able, when activated, to evoke facilitatory effects on at least one muscle. The most frequent motor pattern observed following NIA microstimulation was the contraction of a proximal muscle and simultaneously the facilitation of a distal one. Similar responses were detected upon activation of neuronal pools in both zones of CBM. A good number of CBM foci (39% in the rostral division and 33% in the caudal one), however, was unable to induce facilitation, eliciting, upon stimulation, only massive axial movements. Distal muscles were involved by facilitatory effects in a higher number of cases following NIA stimulation (61% of all the facilitatory responses) than CBM rostral (39%) or caudal (43%) one. Furthermore, a particular characteristic of a good percentage of CBM facilitating foci (36% in rostral and 28% in caudal CBM) was the capability to elicit motor activity in the contralateral side and simultaneously facilitation in the ipsilateral one.(ABSTRACT TRUNCATED AT 250 WORDS)     

Altered Rolandic Gamma-Band Activation Associated with Motor Impairment and Ictal Network Desynchronization in Childhood Epilepsy

Epilepsy is associated with an abnormal expression of neural oscillations and their synchronization across brain regions. Oscillatory brain activation and synchronization also play an important role in cognition, perception and motor control. Childhood epilepsy is associated with a variety of cognitive and motor deficits, but the relationship between altered functional brain responses in various frequency ranges and functional impairment in these children remains poorly understood. We investigated functional magnetoencephalographic (MEG) responses from motor cortex in multiple functionally relevant frequency bands following median nerve stimulation in twelve children with epilepsy, including four children with motor impairments. We demonstrated that children with motor impairments exhibit an excessive gamma-band response from Rolandic cortex, and that the magnitude of this Rolandic gamma response is negatively associated with motor function. Abnormal responses from motor cortex were also associated with ictal desynchronization of oscillations within Rolandic cortex measured using intracranial EEG (iEEG). These results provide the evidence that ictal disruption of motor networks is associated with an altered functional response from motor cortex, which is in turn associated with motor impairment.     

Muscle afferent modulation by stimulation of motor and supplementary motor cortex in cats

Local stimulation in the zone of motor representation of the cat hind limb in the postcruciate cortex (area 4) modulates afferent activity of flexor spindles of the foot. An initial pause, connected with contraction of extrafusal fibers, is observed in this activity. After the muscle has returned to its original length, a sharp rise of discharge frequency develops followed by a return to its initial level. Similar phases, but less marked, are observed in secondary afferents. Stimulation of contralateral and ipsilateral regions of the medial precruciate cortex (area 6) causes selective, intensive, and prolonged facilitation of discharge of type Ia units followed by an after-effect, without involving extrafusal muscle fibers. Since influences of the premotor supplementary cortex on lumbar gamma motoneurons are relatively independent of influences coupled with activation of the alpha system on muscle afferents from the motor cortex, a specific role of area 6 in the regulation of segmental excitability of the gamma system can be postulated.     

Effect of neuromuscular electrical stimulation on motor cortex excitability upon release of tonic muscle contraction

The aim of the present study was to investigate the neurophysiological triggers underlying muscle relaxation from the contracted state, and to examine the mechanisms involved in this process and their subsequent modification by neuromuscular electrical stimulation (NMES). Single-pulse transcranial magnetic stimulation (TMS) was used to produce motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) in 23 healthy participants, wherein motor cortex excitability was examined at the onset of voluntary muscle relaxation following a period of voluntary tonic muscle contraction. In addition, the effects of afferent input on motor cortex excitability, as produced by NMES during muscle contraction, were examined. In particular, two NMES intensities were used for analysis: 1.2 times the sensory threshold and 1.2 times the motor threshold (MT). Participants were directed to execute constant wrist extensions and to release muscle contraction in response to an auditory “GO” signal. MEPs were recorded from the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, and TMS was applied at three different time intervals (30, 60, and 90?ms) after the “GO” signal. Motor cortex excitability was greater during voluntary ECR and FCR relaxation using high-intensity NMES, and relaxation time was decreased. Each parameter differed significantly between 30 and 60?ms. Moreover, in both muscles, SICI was larger in the presence than in the absence of NMES. Therefore, the present findings suggest that terminating a muscle contraction triggers transient neurophysiological mechanisms that facilitate the NMES-induced modulation of cortical motor excitability in the period prior to muscle relaxation. High-intensity NMES might facilitate motor cortical excitability as a function of increased inhibitory intracortical activity, and therefore serve as a transient trigger for the relaxation of prime mover muscles in a therapeutic context.     

Sensitivity to dicholines of membranes from vertebrate and invertebrate muscles

1. The depolarizing effectiveness of azelainylcholine (AzCh, a 7-C-chain dicholine) is about 10 times higher than that of succinylcholine (SCh, a 2-C-chain dicholine) in skeletal muscles of chick, frog and fish, and in body muscles of the earthworm. 2. In the chicken anterior latissimus dorsi (ALD) muscle, AzCh is about 100 times more effective than SCh. 3. In contrast to that in mammalian muscles, the AzCh-SCh sensitivity difference is not increased by denervation in frog muscles. 4. d-Tubocurarine is equally effective in the ALD and in other chicken muscles; its effectiveness is not decreased by denervation in frog muscles. 5. Cells containing muscarinic acetylcholine receptors are weakly sensitive to dicholines or not at all.