Excitability changes in human forearm corticospinal projections and spinal reflex pathways during rhythmic voluntary movement of the opposite limb

Rhythmic movements brought about by the contraction of muscles on one side of the body give rise to phase-locked changes in the excitability of the homologous motor pathways of the opposite limb. Such crossed facilitation should favour patterns of  bimanual coordination in which homologous muscles are engaged simultaneously, and disrupt those in which the muscles are activated in an alternating fashion. In order to examine these issues, we obtained responses to transcranial magnetic stimulation (TMS), to stimulation of the cervicomedullary junction (cervicomedullary-evoked potentials, CMEPs), to peripheral nerve stimulation (H-reflexes and f-waves), and elicited stretch reflexes in the relaxed right flexor carpi radialis (FCR) muscle during rhythmic (2 Hz) flexion and extension movements of the opposite (left) wrist. The potentials evoked by TMS in right FCR were potentiated during the phases of movement in which the left FCR was most strongly engaged. In contrast, CMEPs were unaffected by the movements of the opposite limb. These results suggest that there was systematic variation of the excitability of the motor cortex ipsilateral to the moving limb. H-reflexes and stretch reflexes recorded in right FCR were modulated in phase with the activation of left FCR. As the f-waves did not vary in corresponding fashion, it appears that the phasic modulation of the H-reflex was mediated by presynaptic inhibition of Ia afferents. The observation that both H-reflexes and f-waves were depressed markedly during movements of the opposite indicates that there may also have been postsynaptic inhibition or disfacilitation of the largest motor units. Our findings indicate that the patterned modulation of excitability in motor pathways that occurs during rhythmic movements of the opposite limb is mediated primarily by interhemispheric interactions between cortical motor areas.     

Visual feedback alters the variations in corticospinal excitability that arise from rhythmic movements of the opposite limb

Augmented visual feedback can have a profound bearing on the stability of bimanual coordination. Indeed, this has been used to render tractable the study of patterns of coordination that cannot otherwise be produced in a stable fashion. In previous investigations (Carson et al. 1999), we have shown that rhythmic movements, brought about by the contraction of muscles on one side of the body, lead to phase-locked changes in the excitability of homologous motor pathways of the opposite limb. The present study was conducted to assess whether these changes are influenced by the presence of visual feedback of the moving limb. Eight participants performed rhythmic flexion–extension movements of the left wrist to the beat of a metronome (1.5 Hz). In 50% of trials, visual feedback of wrist displacement was provided in relation to a target amplitude, defined by the mean movement amplitude generated during the immediately preceding no feedback trial. Motor potentials (MEPs) were evoked in the quiescent muscles of the right limb by magnetic stimulation of the left motor cortex. Consistent with our previous observations, MEP amplitudes were modulated during the movement cycle of the opposite limb. The extent of this modulation was, however, smaller in the presence of visual feedback of the moving limb (FCR ²=0.41; ECR ²=0.29) than in trials in which there was no visual feedback (FCR ²=0.51; ECR ²=0.48). In addition, the relationship between the level of FCR activation and the excitability of the homologous corticospinal pathway of the opposite limb was sensitive to the vision condition; the degree of correlation between the two variables was larger when there was no visual feedback of the moving limb. The results of the present study support the view that increases in the stability of bimanual coordination brought about by augmented feedback may be mediated by changes in the crossed modulation of excitability in homologous motor pathways.     

Instabilities during antiphase bimanual movements: are ipsilateral pathways involved?

The spatial and temporal coupling between the hands is known to be very robust during movements which use homologous muscles (in-phase or symmetric movements). In contrast, movements using nonhomologous muscles (antiphase or asymmetric movements) are less stable and exhibit a tendency to undergo a phase transition to in-phase movements as movement frequency increases. The instability during antiphase movements has been modeled in terms of signal interference mediated by the ipsilateral corticospinal pathways. In this study we report that participants in whom distal ipsilateral motor-evoked potentials could be elicited with transcranial magnetic stimulation (TMS), exhibited higher variability during a bimanual circling task than participants whose ipsilateral pathways could not be transcranially activated. These results suggest that ipsilateral control of the limb affects the level of bimanual coupling, and may contribute to uncoupling phenomena observed during asymmetric coordination.     

Disinhibition in the human motor cortex is enhanced by synchronous upper limb movements

The phasic modulation of wrist flexor corticomotor disinhibition has previously been demonstrated during the flexion phase of rhythmical passive flexion-extension of the human wrist. Here we ask if rhythmical bimanual flexion-extension movements of the wrists of neurologically intact subjects, modulate inhibitory activity in the motor cortex. In the first experiment intracortical inhibition was assessed when one wrist was passively flexed and extended on its own, with the addition of the opposite limb voluntarily moving synchronously in a mirror symmetric pattern, and also in a near-symmetric asynchronous pattern. Two subsequent experiments investigated firstly the modulation of spinal reflex pathway activity during the same three movement conditions, and secondly the effect of contralateral wrist movement alone on the excitability of corticomotoneuronal pathways to a static test limb. When the wrist flexors of both upper limbs were shortening simultaneously (i.e. synchronously), intracortical inhibition associated with flexor representations was suppressed to a greater extent than when the two muscles were shortening asynchronously. The results of the three experiments indicate that modulation of inhibitory activity was taking place at the cortical level. These findings may have further application in the study of rehabilitation procedures where the effects of simultaneous activation of affected and unaffected upper limbs in hemiparetic patients are to be investigated.     

A guide to performing difficult bimanual coordination tasks: just follow the yellow brick road

Both discrete and continuous bimanual coordination patterns are difficult to effectively perform when the two limbs are required to perform different movements patterns, move at different velocities and/or move different amplitudes unless some form of integrated feedback is provided. The purpose of the present experiment was to determine the degree to which a complex bimanual coordination pattern could be performed when integrated feedback and movement template are provided. The complex bimanual coordination pattern involved reciprocal movements of the two limbs under different difficulty requirements. As defined by Fitts’ index of difficulty (ID), the left arm (ID = 3, A = 16°, W = 4°) task was of lower difficulty than the right arm task (ID = 5, A = 32°, W = 2°). Note that the left and right limb movements are also different in terms of movement time, movement velocity, accuracy requirements and amplitude as well as one movement was continuous and the other intermittent. Participants were provided 2 blocks of 9 trials in the bimanual condition (30 s/trial). Following the bimanual phase, participants performed two unimanual test trials—one with each limb. The results demonstrated that the performance for each limb in the bimanual condition was similar to the performance for the same limb and conditions in the unimanual control conditions. The similarity was indicated by the same movement speed, movement structure, endpoint variability and hit rates for the bimanual and unimanual conditions. The results support our hypothesis that people can overcome the intrinsic difficulties associated with performing complex bimanual coordination patterns when provided appropriate perceptual information feedback that allows them to detect and correct coordination errors.     

Coordinative and limb-specific control of bimanual movements in patients with Parkinson's disease and cerebellar degeneration

The present study examined the effects of basal ganglia and cerebellar pathology on bimanual coordination using patients with Parkinson's disease (PD) and cerebellar dysfunction (CD). Twenty patients with idiopathic PD (10 untreated early and 10 advanced PD), 10 patients with cerebellar degeneration, and 11 normal subjects were instructed to perform in-phase and anti-phase bimanual coordination movements. The results indicated that while the quality of coordinated bimanual movements in untreated early PD and CD patients was not significantly different from that of normal controls, advanced PD patients exhibited reduced synchronized coordination during the faster anti-phase mode. This suggests that the observed bimanual coordination abnormalities in PD are not an early sign of the pathophysiology of the disease, and cerebellar degeneration may have minimal consequences on synchronized coordination between the limbs. In terms of the parameterization of individual limb movements, CD patients showed a tendency for hypermetric impairments with more irregular movements, while PD patients exhibited relatively slower limb movements and lower amplitudes than normal controls. Overall, the current data provide evidence of the specific functions of different neural structures involved in the pathological process of PD and CD on bimanual coordination.     

Perceptual and motor contributions to bimanual coordination

Following earlier work by Mechsner et al. (Nature 414 (2001) 69), the purpose of this experiment was to determine the perceptual and motoric contributions to bimanual coordination. Twenty right-handed, healthy, young adults performed continuous, horizontal, linear movements of both upper limbs at frequencies of 1.5 and 2.0 Hz. The goal was to control the spatial-temporal displacement of two flags by coordinating upper limb movements in two perceptual conditions. In a congruent condition, the movement of the flags matched the movement of the upper limbs. In an incongruent condition, the movement of the flags was opposite to the movement of the upper limbs. Measures of error in coordination provided support primarily for a motor view of bimanual coordination, and failed to replicate the earlier findings of Mechsner et al.     

Dynamical changes in corticospinal excitability during imagery of unimanual and bimanual wrist movements in humans: a transcranial magnetic stimulation study

This study explored the dynamical changes in corticospinal excitability during the imagination of cyclical unimanual and bimanual wrist flexion-extension movements. Transcranial magnetic stimulation was applied over the left motor cortex to evoke motor evoked potentials in the right wrist flexor and extensor muscles. Findings provided evidence for increased reciprocal excitability changes during imagery of symmetrical in-phase movements as compared to asymmetrical (anti-phase) or unimanual movements. This suggests that in-phase movements may reinforce whereas anti-phase movements may reduce the temporal representation of the task in the corticospinal motor networks of the brain.     

Resource-demanding versus cost-effective bimanual interaction in the brain

When two hands require different information in bimanual asymmetric movements, interference can occur via callosal connections and ipsilateral corticospinal pathways. This interference could potentially work as a cost-effective measure in symmetric movements, allowing the same information to be commonly available to both hands at once. Using functional magnetic resonance imaging, we investigated supra-additive and sub-additive neural interactions in bimanual movements during the initiation and continuation phases of movement. We compared activity during bimanual asymmetric and symmetric movements with the sum of activity during unimanual right and left finger-tapping. Supra-additive continuation-related activation was found in the right dorsal premotor cortex and left cerebellum (lobule V) during asymmetric movements. In addition, for unimanual movements, the right dorsal premotor cortex and left cerebellum (lobule V) showed significant activation only for left-hand (non-dominant) movements, but not for right-hand movements. These results suggest that resource-demanding interactions in bimanual asymmetric movements are involved in a non-dominant hand motor network that functions to keep non-dominant hand movements stable. We found sub-additive continuation-related activation in the supplementary motor area (SMA), bilateral cerebellum (lobule VI) in symmetric movements, and the SMA in asymmetric movements. This suggests that no extra demands were placed on these areas in bimanual movements despite the conventional notion that they play crucial roles in bimanual coordination. Sub-additive initiation-related activation in the left anterior putamen suggests that symmetric movements place lower demands on motor programming. These findings indicate that, depending on coordination patterns, the neural substrates of bimanual movements either exhibit greater effort to keep non-dominant hand movements stable, or save neural cost by sharing information commonly to both hands.     

Age-related differences in corticospinal excitability and inhibition during coordination of upper and lower limbs

The ability to coordinate upper and lower limbs--a prerequisite for many everyday activities--is known to decline with age. Here we report 2 experiments in which transcranial magnetic stimulation (TMS) was used to assess corticospinal excitatory and inhibitory processes in younger and older adults during cyclical hand-foot movements. In experiment 1, motor evoked potentials (MEP) and silent period (SP) durations were measured from the active right extensor carpi radialis (ECR) muscle while it executed rhythmic oscillations in conjunction with the right or left foot. Younger adults exhibited increased SP with ipsilateral limb combinations and decreased SP with contralateral limb combinations, relative to a baseline hand only condition. Strikingly, older adults exhibited a reduced SP when ipsilateral limbs moved in opposite directions. This effect was found to be most pronounced in those older adults who exhibited poor coordination performance, suggesting that the inability to regulate inhibitory processes may underlie age-related degradation of task performance. Experiment 2 examined motor evoked potentials and SP duration in the left extensor carpi radialis which maintained a tonic contraction while the coordination task was undertaken by the right arm and right or left foot. For younger adults, coordination of ipsilateral limbs was accompanied by increased inhibition in the ipsilateral motor cortex than during the coordination of contralateral limbs. No differences in SP between conditions were noted for the older adults. In summary, older adults' reduced ability to coordinate upper and lower limbs may be related to the capacity to regulate inhibitory function in both hemispheres. This study suggests for the first time a direct link between age-related differences in interlimb coordination and the control of corticospinal inhibitory processes.     

Head movements destabilize cyclical in-phase but not anti-phase homologous limb coordination in humans

The present study addressed the role of head movements in the coordination of the homologous upper or lower limbs in supine normal subjects. Consistent with previous research, in-phase mirror symmetrical movements were performed more accurately and consistently than anti-phase movements. However, inclusion of head movements destabilized in-phase but not anti-phase homologous limb coordination, in contrast to previous work demonstrating a higher vulnerability of anti-phase than in-phase coordination to various experimental perturbations. It was observed that the head moved in the same direction as the limbs during anti- but not during in-phase coordination. Furthermore, the interlimb patterns also affected the head rotations that were lower in spatiotemporal consistency and less consistently coupled with the limbs during in-phase than during anti-phase coordination. These findings provide new insights into the coalition of egocentric and allocentric constraints during interlimb coordination.     

Neuromuscular-skeletal constraints upon the dynamics of unimanual and bimanual coordination

In the first of three experiments, 11 participants generated pronation and supination movements of the forearm. in time with an auditory metronome. The metronome frequency was increased in eight steps (0.25 Hz) from a base frequency of 1.75 Hz. On alternating trials, participants were required to coordinate either maximum pronation or maximum supination with each beat of the metronome. In each block of trials, the axis of rotation was either coincident with the long axis of the forearm, above this axis, or below this axis. The stability of the pronate-on-the-beat pattern, as indexed by the number of pattern changes, and the time of onset of pattern change, was greatest when the axis of rotation of the movement was below the long axis of the forearm. In contrast, the stability of the supinate-on-the-beat pattern was greatest when the axis of rotation of the movement was above the long axis of the forearm. In a second experiment, we examined how changes in the position of the axis of rotation alter the activation patterns of muscles that contribute to pronation and supination of the forearm. Variations in the relative dominance of the pronation and supination phases of the movement cycle across conditions were accounted for primarily by changes in the activation profile of flexor carpi radialis (FCR) and extensor carpi radialis longus (ECR). In the final experiment we examined how these constraints impact upon the stability of bimanual coordination. Thirty-two participants were assigned at random to one of four conditions, each of which combined an axis of rotation configuration (bottom or top) for each limb. The participants generated both inphase (both limbs pronating simultaneously, and supinating simultaneously) and antiphase (left limb pronating and right limb supinating simultaneously, and vice versa) patterns of coordination. When the position of the axis of rotation was equivalent for the left and the right limb, transitions from antiphase to inphase patterns of coordination were frequently observed. In marked contrast, when the position of the axis of rotation for the left and right limb was contradistinct, transitions from inphase to antiphase patterns of coordination occurred. The results demonstrated that when movements are performed in an appropriate mechanical context, inphase patterns of coordination are less stable than antiphase patterns.     

The coalition of constraints during coordination of the ipsilateral and heterolateral limbs

Previous work on the coordination between the upper and lower limbs has invariably shown that its accuracy/stability is primarily determined by the mutual direction between limbs in extrinsic space and not by muscle relationships. Here we show that muscle grouping does play a critical role in coordination of the arm and leg, in addition to direction. More specifically, the simultaneous activation of isofunctional muscles and/or limb movements proceeding in the same direction, results in more successful performance than the alternated activation of isofunctional muscles and/or movements occurring in different directions. In the absence of isofunctional muscle coupling, the mutual direction between the limbs plays a more prominent role in determining coordinative accuracy. These coordination constraints can largely account for the observed differences between ipsilateral and heterolateral limb coordination. The findings are discussed in view of the coalition of coordination constraints.     

Effects of movement stability and congruency on the emergence of spontaneous interpersonal coordination

The current project evaluated the relationship between the stability of intrapersonal coordination and the emergence of spontaneous interpersonal coordination. Participants were organized into pairs, and each participant was instructed to produce either an inphase or antiphase pattern of intrapersonal bimanual coordination using two hand-held pendulums, while simultaneously performing an interpersonal puzzle task. At issue was whether the emergence and stability of spontaneous interpersonal rhythmic coordination is influenced by ("Experiment 1") the stability of the intrapersonal coordination patterns produced by co-actors and ("Experiment 2") the congruency of the intrapersonal coordination patterns produced by co-actors. The stability of intrapersonal movement coordination did not affect the emergence of spontaneous interpersonal coordination. The degree of interpersonal coordination observed was similar when both participants in a pair produced either inphase or antiphase patterns of intrapersonal bimanual coordination. Moreover, the congruency of the intrapersonal coordination patterns only slightly affected the emergence of interpersonal coordination, with only marginally lower inphase interpersonal entrainment when participants produced incongruent patterns of intrapersonal coordination (e.g., inphase-antiphase). Interestingly, movement observation and the emergence of interpersonal coordination did not affect the stability of intrapersonal bimanual coordination. The results suggest that interlimb rhythmic bimanual coordination reflects a single intrapersonal perceptual-motor synergy and that these bimanual synergies (not individual limbs) are what become spontaneously entrained interpersonally.     

Central motor conduction in hereditary motor and sensory neuropathy and hereditary spastic paraplegia.

Conduction of the central motor pathways (CMCT) by magnetic stimulation of the motor cortex (TMS) was performed in 17 patients with hereditary motor sensory neuropathy (HMSN) and 2 siblings with hereditary spastic paraplegia (HSP). CMCT was prolonged in two patients with HMSN I with associated pyramidal features and in two subjects with HMSN II without clinical pyramidal signs. CMCT may be abnormal in HMSN due to central motor pathways involvement or altered spinal excitability with increased synaptic delay. CMCT was normal in the upper limbs in patients with HSP but increased in the legs. Diagnostic yield of TMS increased in less disabled cases with HSP when selective conduction at the spinal level (C7-S1) was calculated. Abnormal spinal conduction in HSP is consistent with degeneration of the crossed corticospinal tracts at the thoracic level found in neuropathologic observations.     

Using scanning trials to assess intrinsic coordination dynamics

Bimanual 1:1 coordination patterns other than in-phase (0°) and anti-phase (180°) have proven difficult to perform even with extended practice. The difficulty has been attributed to phase attraction that draws the coordination between the limbs towards the bimanual patterns of in-phase and anti-phase and variability associated with the activation of non-homologous muscles via crossed and uncrossed cortical pathways. We found participants could very effectively produce a large range of supposedly unstable coordination patterns (between 0° and 180° in 30° increments) after only 3 min of practice when integrated feedback (Lissajous plots) was provided and other perceptual and attentional distractions were minimized. These findings clearly indicate that the perception-action system is fully capable of producing a wide range of bimanual coordination patterns and that the reason for the failure to produce these patterns in previous experiments reside in the perceptual information and attentional requirements typically found in experimental testing environments.     

Bilateral phase entrainment by movement-elicited afference contributes equally to the stability of in-phase and antiphase coordination

This study examined if and how phase entrainment by movement-related afference-- induced by passive movements of the contralateral hand-- contributes to the coordinative stability of rhythmic bimanual movements. The results revealed that phase-shifted passive movements of the dominant or the nondominant hand induced similar entrainment effects on the active movements of the contralateral hand. In terms of the phase relations between the hands only two attractors of equal strength were present, corresponding to relative phase shifts of 0 degrees and 180 degrees , respectively, i.e., to in-phase and antiphase coordination. The attractors were separated by two repellors located at relative phase shifts of +90 degrees and -90 degrees . EMG analysis indicated that the entrainment effects indeed resulted from contralateral afference, because no related changes in muscle activation were observed in the passively moved hand. It was concluded that phase entrainment by contralateral afference contributed equally to the stable performance of the bimanual in-phase and antiphase patterns, thereby enhancing the stability of these patterns relative to other phase relations between the limbs.     

Increasingly complex bimanual multi-frequency coordination patterns are equally easy to perform with on-line relative velocity feedback

An experiment was conducted to determine whether multi-frequency continuous bimanual circling movements of varying difficulty (1:2. 2:3, 3:4, and 4:5) could be effectively performed following relatively little practice when on-line continuous relative velocity feedback is provided. The between-subjects results indicate extremely effective bimanual multi-frequency performance for all coordination patterns with relatively stable and continuous movements of both limbs. The findings suggest that the previous performance effects using Lissajous feedback with reciprocal movement can be extended to circling movements using on-line relative velocity feedback. Contrary to the long-held position that these coordination patterns result in increasing difficulty, we failed to find systematic relative velocity error, variability, or bias differences between the participants performing the various multi-frequency coordination patterns. Indeed, coordination error, variability, and biases were remarkably low for each of the tasks. The results clearly indicate the ease with which participants are able to produce bimanual coordination patterns typically considered difficult if not impossible when salient visual information is provided that allows the participants to detect and correct their coordination errors.     

Combined effect of motor imagery and peripheral nerve electrical stimulation on the motor cortex

Although motor imagery enhances the excitability of the corticospinal tract, there are no peripheral afferent inputs during motor imagery. In contrast, peripheral nerve electrical stimulation (ES) can induce peripheral afferent inputs; thus, a combination of motor imagery and ES may enhance the excitability of the corticospinal tract compared with motor imagery alone. Moreover, the level of stimulation intensity may also be related to the modulation of the excitability of the corticospinal tract during motor imagery. Here, we evaluated whether a combination of motor imagery and peripheral nerve ES influences the excitability of the corticospinal tract and measured the effect of ES intensity on the excitability induced during motor imagery. The imagined task was a movement that involved touching the thumb to the little finger, whereas ES involved simultaneous stimulation of the ulnar and median nerves at the wrist. Two different ES intensities were used, one above the motor threshold and another above the sensory threshold. Further, we evaluated whether actual movement with afferent input induced by ES modulates the excitability of the corticospinal tract as well as motor imagery. We found that a combination of motor imagery and ES enhanced the excitability of the motor cortex in the thenar muscle compared with the other condition. Furthermore, we established that the modulation of the corticospinal tract was related to ES intensity. However, we found that the excitability of the corticospinal tract induced by actual movement was enhanced by peripheral nerve ES above the sensory threshold.     

Interactions between interlimb and intralimb coordination during the performance of bimanual multijoint movements

The simultaneous performance of movements involving different effectors gives rise to neural and biomechanical interactions between and within limbs. The present study addressed the role of interlimb and intralimb constraints during the control of bimanual multijoint movements. Thirteen participants performed eight tasks involving the bilateral elbows and wrists under different coordination conditions. With respect to interlimb coordination, coordination patterns referred to the in-phase and anti-phase coordination modes, involving the simultaneous timing of homologous versus non-homologous muscles, respectively. With respect to inter-segmental (intralimb) coordination, the isodirectional mode referred to simultaneous flexions and extensions in the ipsilateral wrist and elbow joints, whereas the non-isodirectional mode involved simultaneous flexion in one joint together with extension in the other joint, or vice versa. The analysis of the data focused upon measures of relative phasing between proximal and distal joints within a limb as well as between the homologous joints of both limbs. With respect to interlimb coordination, findings revealed that adoption of the in-phase mode resulted in a higher quality of interlimb coordination than the anti-phase mode. However, the mode adopted in the distal joints had a larger impact on the quality of interlimb coordination than the mode adopted in the proximal joints. More specifically, in-phase coordination of the distal joints had a positive, and anti-phase coordination a negative, influence on the global coordinative behavior of the system. Minor effects of intralimb coordination modes on interlimb coordination were observed. With respect to intralimb coordination between the ipsilateral elbow and wrist, the isodirectional mode was performed with higher stability than the non-isodirectional mode. The mode of interlimb coordination also affected the quality of intralimb coordination, such that generating anti-phase coordination patterns in the distal joints had a negative influence on the accuracy and stability of intralimb coordination. Taken together, the present findings suggest a hierarchical structure whereby interlimb coordination constraints have a stronger impact on the global coordinative behavior of the system than intralimb coordination constraints. Moreover, the global coordinative state of the system is more affected by the coordination between the distal than between the proximal joints. Overall, the findings suggest that the mirror-image symmetry constraint has a powerful influence on bimanual multijoint coordination.