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.     

Cortical Mechanisms of Central Fatigue and Sense of Effort

The purpose of this study was to investigate cortical mechanisms upstream to the corticospinal motor neuron that may be associated with central fatigue and sense of effort during and after a fatigue task. We used two different isometric finger abduction protocols to examine the effects of muscle activation and fatigue the right first dorsal interosseous (FDI) of 12 participants. One protocol was intended to assess the effects of muscle activation with minimal fatigue (control) and the other was intended to elicit central fatigue (fatigue). We hypothesized that high frequency repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area (SMA) would hasten recovery from central fatigue and offset a fatigue-induced increase in sense of effort by facilitating the primary motor cortex (M1). Constant force-sensation contractions were used to assess sense of effort associated with muscle contraction. Paired-pulse TMS was used to assess intracortical inhibition (ICI) and facilitation (ICF) in the active M1 and interhemispheric inhibitory (IHI) was assessed to determine if compensation occurs via the resting M1. These measures were made during and after the muscle contraction protocols. Corticospinal excitability progressively declined with fatigue in the active hemisphere. ICF increased at task failure and ICI was also reduced at task failure with no changes in IHI found. Although fatigue is associated with progressive reductions in corticospinal excitability, compensatory changes in inhibition and facilitation may act within, but not between hemispheres of the M1. rTMS of the SMA following fatigue enhanced recovery of maximal voluntary force and higher levels of ICF were associated with lower sense of effort following stimulation. rTMS of the SMA may have reduced the amount of upstream drive required to maintain motor output, thus contributing to a lower sense of effort and increased rate of recovery of maximal force.     

Cortical control of grasp in non-human primates

The skilled use of the hand for grasping and manipulation of objects is a fundamental feature of the primate motor system. Grasping movements involve transforming the visual information about an object into a motor command appropriate for the coordinated activation of hand and finger muscles. The cerebral cortex and its descending projections to the spinal cord are known to play a crucial role for the control of grasp. Recent studies in non-human primates have provided some striking new insights into the respective contribution of the parietal and frontal motor cortical areas to the control of grasp. Also, new approaches allowed investigating the coupling of grasp-related activity in different cortical areas for the control of the descending motor command.     

Neuronal adaptation of corticospinal mechanisms of muscle contraction regulation in athletes

Physiological mechanisms of neuronal adaptation of the human corticospinal pathways in response to long-term intense motor activity have been studied insufficiently. In this work, we investigated adaptational changes in corticospinal mechanisms of muscular contraction control in athletes. We measured parameters of motor evoked potentials of lower limb skeletal muscles under voluntary static loads of various intensity and duration, using the transcranial magnetic stimulation method. Elite athletes, as compared to the reference group, in the course of increased intensity and duration of isometric muscular contractions demonstrated more expressed increase in the maximum amplitude of the motor evoked potentials of lower limb skeletal muscles, smaller decrease in the time of central motor conduction of nervous pulses and the peripheral period in electromyograms, and less expressed increase in the cortical and segmental silent periods. Mechanisms of adaptation of corticospinal regulation of human muscular contraction to specific conditions of extreme motor activities are discussed.     

Influence of the sensorimotor cortex on single neurons of the nucleus gracilis in the cat

The aim of this study was to investigate the functional role of the cortical projections to gracile nucleus. In unanesthetized cats single nuclear units projecting to the thalamus were tested for microstimulation of cortical foci (area 4) able to evoke single joint movements in contralateral hindlimb. A very significant percentage of gracile cells was influenced, very often in excitatory manner, if their receptive field was overlaying or very close to the joint controlled by a given cortical focus. Conversely, when the location of the receptive field was more distant, the percentage of responses and the incidence of excitatory effects decreased, inhibitions occurring more frequently. From a functional point of view, such an organization of the cortico-gracile control could be effective in modulating transmission of exteroceptive information from the region of the motor target (facilitation) as well as from adjacent ones (suppression). This arrangement could provide an higher resolution of afferent messages, in relation with the cortically induced movements.     

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.     

Relation between changes in the preparatory brain potential and excitability of the H-reflex, and localization of a focal ischaemic brain lesion

In the sample of 15 hemiparetics, ischaemic focus was localized cortically 8 times, deep subcortically 7 times. Use was made of a method that permits simultaneously to record both the cortical potential changes associated with preparation for voluntary movement, and excitability changes of the H-reflex. A slightly depressed amplitude of the preparatory brain potential and a relatively satisfactory facilitation of the H-reflex was observed in the light cortical focal brain ischaemia. A striking deformation up to disorganization of the preparatory brain potential and the absence of facilitation of the H-reflex in subjects with deeper subcortical ischaemic foci may be related to an impairment of the generator of the slow preparatory potential (thalamus, mesencephalon) and to a discruption of cooperation in the complex cerebral cortex - middle thalamus.     

Homologous Muscle Contraction during Unilateral Movement Does Not Show a Dominant Effect on Leg Representation of the Ipsilateral Primary Motor Cortex

Co-activation of homo- and heterotopic representations in the primary motor cortex (M1) ipsilateral to a unilateral motor task has been observed in neuroimaging studies. Further analysis showed that the ipsilateral M1 is involved in motor execution along with the contralateral M1 in humans. Additionally, transcranial magnetic stimulation (TMS) studies have revealed that the size of the co-activation in the ipsilateral M1 has a muscle-dominant effect in the upper limbs, with a prominent decline of inhibition within the ipsilateral M1 occurring when a homologous muscle contracts. However, the homologous muscle-dominant effect in the ipsilateral M1 is less clear in the lower limbs. The present study investigates the response of corticospinal output and intracortical inhibition in the leg representation of the ipsilateral M1 during a unilateral motor task, with homo- or heterogeneous muscles. We assessed functional changes within the ipsilateral M1 and in corticospinal outputs associated with different contracting muscles in 15 right-handed healthy subjects. Motor tasks were performed with the right-side limb, including movements of the upper and lower limbs. TMS paradigms were measured, consisting of short-interval intracortical inhibition (SICI) and recruitment curves (RCs) of motor evoked potentials (MEPs) in the right M1, and responses were recorded from the left rectus femoris (RF) and left tibialis anterior (TA) muscles. TMS results showed that significant declines in SICI and prominent increases in MEPs of the left TA and left RF during unilateral movements. Cortical activations were associated with the muscles contracting during the movements. The present data demonstrate that activation of the ipsilateral M1 on leg representation could be increased during unilateral movement. However, no homologous muscle-dominant effect was evident in the leg muscles. The results may reflect that functional coupling of bilateral leg muscles is a reciprocal movement.     

Corticospinal control of soleus motoneurons in man

Electrical or magnetic stimulation of the human motor cortex causes a strong, short latency facilitation of tibialis anterior (TA) motoneurons but only weak, longer latency changes in the excitability of soleus (SOL) motoneurons. The facilitation of TA motoneurons has been attributed to the monosynaptic action of the "fast" corticospinal pathway. The present study further investigates the cortical control of soleus motoneurons in man. In tests of reaction time to auditory stimuli, normal subjects took significantly longer to activate soleus motoneurons than tibialis anterior motoneurons. Thus we could not demonstrate the existence of a "fast" pathway from the brain to SOL motoneurons that, for some reason, is not activated by magnetic stimulation. The hypothesis that the cortex might control soleus motoneurons indirectly by modulation of the Ia input from muscle spindles was tested. Magnetic stimulation of the cortex was used to condition the facilitation of soleus motoneurons resulting from the stimulation of group I fibres in the tibial nerve. There were no consistent changes in Ia facilitation. We conclude (i) that there is no evidence so far that SOL motoneurons are excited by a direct pathway from the cortex (similar to that projecting to TA motoneurons) and (ii) that the observed changes in firing probability of soleus motoneurons produced by magnetic stimulation over the motor cortex do not result from modulation of presynaptic inhibition of Ia afferents.     

Excitability of the motor cortex ipsilateral to the moving body side depends on spatio-temporal task complexity and hemispheric specialization

Unilateral movements are mainly controlled by the contralateral hemisphere, even though the primary motor cortex ipsilateral (M1(ipsi)) to the moving body side can undergo task-related changes of activity as well. Here we used transcranial magnetic stimulation (TMS) to investigate whether representations of the wrist flexor (FCR) and extensor (ECR) in M1(ipsi) would be modulated when unilateral rhythmical wrist movements were executed in isolation or in the context of a simple or difficult hand-foot coordination pattern, and whether this modulation would differ for the left versus right hemisphere. We found that M1(ipsi) facilitation of the resting ECR and FCR mirrored the activation of the moving wrist such that facilitation was higher when the homologous muscle was activated during the cyclical movement. We showed that this ipsilateral facilitation increased significantly when the wrist movements were performed in the context of demanding hand-foot coordination tasks whereas foot movements alone influenced the hand representation of M1(ipsi) only slightly. Our data revealed a clear hemispheric asymmetry such that MEP responses were significantly larger when elicited in the left M1(ipsi) than in the right. In experiment 2, we tested whether the modulations of M1(ipsi) facilitation, caused by performing different coordination tasks with the left versus right body sides, could be explained by changes in short intracortical inhibition (SICI). We found that SICI was increasingly reduced for a complex coordination pattern as compared to rest, but only in the right M1(ipsi). We argue that our results might reflect the stronger involvement of the left versus right hemisphere in performing demanding motor tasks.     

Inter-individual variation in reciprocal Ia inhibition is dependent on the descending volleys delivered from corticospinal neurons to Ia interneurons

IntroductionWe investigated the extent to which the corticospinal inputs delivered to Ia inhibitory interneurons influence the strength of disynaptic reciprocal Ia inhibition.MethodsSeventeen healthy subjects participated in this study. The degree of reciprocal Ia inhibition was determined via short-latency (condition-test interval: 1–3 ms) suppression of Sol H-reflex by conditioning stimulation of common peroneal nerve. The effect of corticospinal descending inputs on Ia inhibitory interneurons was assessed by evaluating the conditioning effect of transcranial magnetic stimulation (TMS) on the Sol H-reflex. Then, we determined the relationship between the degree of reciprocal Ia inhibition and the conditioning effect of TMS on the Sol H-reflex.ResultWe found that the degree of reciprocal Ia inhibition and the extent of change in the amplitude of the TMS-conditioned H-reflex, which was measured from short latency facilitation to inhibition, displayed a strong correlation (r = 0.76, p < 0.01) in the resting conditions.ConclusionThe extent of reciprocal Ia inhibition is affected by the corticospinal descending inputs delivered to Ia inhibitory interneurons, which might explain the inter-individual variations in reciprocal Ia inhibition.     

alpha2-Chimaerin is an essential EphA4 effector in the assembly of neuronal locomotor circuits

The assembly of neuronal networks during development requires tightly controlled cell-cell interactions. Multiple cell surface receptors that control axon guidance and synapse maturation have been identified. However, the signaling mechanisms downstream of these receptors have remained unclear. Receptor signals might be transmitted through dedicated signaling lines defined by specific effector proteins. Alternatively, a single cell surface receptor might couple to multiple effectors with overlapping functions. We identified the neuronal RacGAP alpha2-chimaerin as an effector for the receptor tyrosine kinase EphA4. alpha2-Chimaerin interacts with activated EphA4 and is required for ephrin-induced growth cone collapse in cortical neurons. alpha2-Chimaerin mutant mice exhibit a rabbit-like hopping gait with synchronous hindlimb movements that phenocopies mice lacking EphA4 kinase activity. Anatomical and functional analyses of corticospinal and spinal interneuron projections reveal that loss of alpha2-chimaerin results in impairment of EphA4 signaling in vivo. These findings identify alpha2-chimaerin as an indispensable effector for EphA4 in cortical and spinal motor circuits.     

Influence of mental motor imagery on the execution of a finger-to-thumb opposition task

The present fMRI study compares regional distribution of the cortical activity during the execution of unilateral hand movements (finger-to-thumb opposition) preceded or not by their motor simulation (S + E and E condition, respectively). The results show that, overall, the number and the spatial distribution of activated voxels are both increased in the S + E with respect to the E condition. The motor performance preceded by mental rehearsal is related to selective increase of the cortical activity. Among the motor areas that are found active during the simple motor execution a significant enhancement of functional activation during the S + E condition ipsilateral primary motor regions (M1). The activity increase may be accounted by a sort of neural recruiting that is made possible by the overlapping of cortical networks involved in both motor output and motor imagery. The beneficial effects of "mental practice" on the physical performance may rely to the close temporal association between motor rehearsal and actual performance.     

Evolution of Premotor Cortical Excitability after Cathodal Inhibition of the Primary Motor Cortex: A Sham-Controlled Serial Navigated TMS Study

Background

Premotor cortical regions (PMC) play an important role in the orchestration of motor function, yet their role in compensatory mechanisms in a disturbed motor system is largely unclear. Previous studies are consistent in describing pronounced anatomical and functional connectivity between the PMC and the primary motor cortex (M1). Lesion studies consistently show compensatory adaptive changes in PMC neural activity following an M1 lesion. Non-invasive brain modification of PMC neural activity has shown compensatory neurophysiological aftereffects in M1. These studies have contributed to our understanding of how M1 responds to changes in PMC neural activity. Yet, the way in which the PMC responds to artificial inhibition of M1 neural activity is unclear. Here we investigate the neurophysiological consequences in the PMC and the behavioral consequences for motor performance of stimulation mediated M1 inhibition by cathodal transcranial direct current stimulation (tDCS).

Purpose

The primary goal was to determine how electrophysiological measures of PMC excitability change in order to compensate for inhibited M1 neural excitability and attenuated motor performance.

Hypothesis

Cathodal inhibition of M1 excitability leads to a compensatory increase of ipsilateral PMC excitability.

Methods

We enrolled 16 healthy participants in this randomized, double-blind, sham-controlled, crossover design study. All participants underwent navigated transcranial magnetic stimulation (nTMS) to identify PMC and M1 corticospinal projections as well as to evaluate electrophysiological measures of cortical, intracortical and interhemispheric excitability. Cortical M1 excitability was inhibited using cathodal tDCS. Finger-tapping speeds were used to examine motor function.

Results

Cathodal tDCS successfully reduced M1 excitability and motor performance speed. PMC excitability was increased for longer and was the only significant predictor of motor performance.

Conclusion

The PMC compensates for attenuated M1 excitability and contributes to motor performance maintenance.     

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.     

Neuronal adaptation of corticospinal mechanisms of muscle contraction regulation in athletes

Adaptation changes in the corticospinal mechanisms of muscle contraction control in athletes were investigated. Using the transcranial magnetic stimulation method, the parameters of motor evoked potentials of skeletal muscles of the lower limbs during voluntary static loads of various intensities and durations were measured. Athletes, as compared to the reference group, exhibited a greater increase in the maximal amplitude of the motor evoked potentials of the skeletal muscles of the lower limbs, a smaller decrease in the central motor conduction time of nerve pulses and the peripheral period in electromyograms, and a smaller increase in the cortical and segmental silent periods with increasing intensity and duration of isometric muscle contractions. The mechanisms of adaptation of corticospinal regulation of human muscle contraction to specific conditions of extreme motor activities are discussed.     

Effects of ageing on motor unit activation patterns and reflex sensitivity in dynamic movements

Both contraction type and ageing may cause changes in H-reflex excitability. H reflex is partly affected by presynaptic inhibition that may also be an important factor in the control of MU activation. The purpose of the study was to examine age related changes in H-reflex excitability and motor unit activation patterns in dynamic and in isometric contractions. Ten younger (YOUNG) and 13 elderly (OLD) males performed isometric (ISO), concentric (CON) and eccentric (ECC) plantarflexions with submaximal activation levels (20% and 40% of maximal soleus surface EMG). Intramuscular EMG data was analyzed utilizing an intramuscular spike amplitude frequency histogram method. Average H/M ratio was always lowest in ECC (n.s.). Mean spike amplitude increased with activation level (P < .05), whereas no significant differences were found between contraction types. Both H-reflex excitability, which may be due to an increase in presynaptic inhibition, and mean spike frequency were higher in YOUNG compared to OLD. In OLD the mean spike frequency was significantly smaller in CON compared to ISO. Lack of difference in mean spike amplitude and frequency across contraction types in YOUNG would imply a similar activation strategy, whereas the lower frequency in dynamic contractions in OLD could be related to synergist muscle behavior.     

Corticospinal Excitability of Trunk Muscles during Different Postural Tasks

Evidence suggests that the primary motor cortex (M1) is involved in both voluntary, goal-directed movements and in postural control. Trunk muscles are involved in both tasks, however, the extent to which M1 controls these muscles in trunk flexion/extension (voluntary movement) and in rapid shoulder flexion (postural control) remains unclear. The purpose of this study was to investigate this question by examining excitability of corticospinal inputs to trunk muscles during voluntary and postural tasks. Twenty healthy adults participated. Transcranial magnetic stimulation was delivered to the M1 to examine motor evoked potentials (MEPs) in the trunk muscles (erector spinae (ES) and rectus abdominis (RA)) during dynamic shoulder flexion (DSF), static shoulder flexion (SSF), and static trunk extension (STE). The level of background muscle activity in the ES muscles was matched across tasks. MEP amplitudes in ES were significantly larger in DSF than in SSF or in STE; however, this was not observed for RA. Further, there were no differences in levels of muscle activity in RA between tasks. Our findings reveal that corticospinal excitability of the ES muscles appears greater during dynamic anticipatory posture-related adjustments than during static tasks requiring postural (SSF) and goal-directed voluntary (STE) activity. These results suggest that task-oriented rehabilitation of trunk muscles should be considered for optimal transfer of therapeutic effect to function.     

Polarity Specific Effects of Transcranial Direct Current Stimulation on Interhemispheric Inhibition

Transcranial direct current stimulation (tDCS) has been used as a useful interventional brain stimulation technique to improve unilateral upper-limb motor function in healthy humans, as well as in stroke patients. Although tDCS applications are supposed to modify the interhemispheric balance between the motor cortices, the tDCS after-effects on interhemispheric interactions are still poorly understood. To address this issue, we investigated the tDCS after-effects on interhemispheric inhibition (IHI) between the primary motor cortices (M1) in healthy humans. Three types of tDCS electrode montage were tested on separate days; anodal tDCS over the right M1, cathodal tDCS over the left M1, bilateral tDCS with anode over the right M1 and cathode over the left M1. Single-pulse and paired-pulse transcranial magnetic stimulations were given to the left M1 and right M1 before and after tDCS to assess the bilateral corticospinal excitabilities and mutual direction of IHI. Regardless of the electrode montages, corticospinal excitability was increased on the same side of anodal stimulation and decreased on the same side of cathodal stimulation. However, neither unilateral tDCS changed the corticospinal excitability at the unstimulated side. Unilateral anodal tDCS increased IHI from the facilitated side M1 to the unchanged side M1, but it did not change IHI in the other direction. Unilateral cathodal tDCS suppressed IHI both from the inhibited side M1 to the unchanged side M1 and from the unchanged side M1 to the inhibited side M1. Bilateral tDCS increased IHI from the facilitated side M1 to the inhibited side M1 and attenuated IHI in the opposite direction. Sham-tDCS affected neither corticospinal excitability nor IHI. These findings indicate that tDCS produced polarity-specific after-effects on the interhemispheric interactions between M1 and that those after-effects on interhemispheric interactions were mainly dependent on whether tDCS resulted in the facilitation or inhibition of the M1 sending interhemispheric volleys.     

Somatic and motor components of action simulation

Seminal studies in monkeys report that the viewing of actions performed by other individuals activates frontal and parietal cortical areas typically involved in action planning and execution. That mirroring actions might rely on both motor and somatosensory components is suggested by reports that action observation and execution increase neural activity in motor and in somatosensory areas. This occurs not only during observation of naturalistic movements but also during the viewing of biomechanically impossible movements that tap the afferent component of action, possibly by eliciting strong somatic feelings in the onlooker. Although somatosensory feedback is inherently linked to action execution, information on the possible causative role of frontal and parietal cortices in simulating motor and sensory action components is lacking. By combining low-frequency repetitive and single-pulse transcranial magnetic stimulation, we found that virtual lesions of ventral premotor cortex (vPMc) and primary somatosensory cortex (S1) suppressed mirror motor facilitation contingent upon observation of possible and impossible movements, respectively. In contrast, virtual lesions of primary motor cortex did not influence mirror motor facilitation. The reported double dissociation suggests that vPMc and S1 play an active, differential role in simulating efferent and afferent components of observed actions.