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.     

The discontinuous nature of motor execution

Human movement control requires adequate coordination of different movements, which is particularly important when different motor tasks are simultaneously executed by the same effector(s) (e.g. a muscle or a joint). The process of movement execution involves a series of highly nonlinear elements; for instance, a motor unit of a muscle produces force only in the direction of muscle shortening, thus representing a threshold operator that transforms the bipolar (i.e. excitatory or inhibitory) information at its spinal input into a purely unipolar signal (i.e. muscle force). This tripartite research report addresses the contribution of the nonlinearity of neuromuscular elements to the coordination of different motor tasks simultaneously executed by the same limb. In this first part of the series, a new hypothesis for such a single-muscle multiple-task coordination is presented which suggests an essentially threshold-linear coordination mechanism. Control signals generated by the central nervous system for each individual movement independently and feedback information from peripheral receptors are linearly superimposed. This compound control/feedback signal is processed by a nonlinear limiter element reflecting the discontinuous properties of the muscle and its reflex circuitry. It is shown that threshold-linear interaction of descending commands and afferent feedback information can lead to complex interdependent patterns of compound motor action. This includes the possibility of gating (i.e. the ability of one movement pattern to constrain or even impede the execution of another pattern) and of delayed response initiation when simultaneously performing more than one voluntary motor task. A theoretical analysis of the threshold-linear coordination mechanism and an extensive experimental validation of the model is provided in part II and part III of the report. Received: 6 October 1998 / Accepted in revised form: 2 June 1999     

Roles of the Caudate Nuclei, Cerebellum, and Caudato-Cerebellar Interconnections in the Control and Coordination of Ballistic Food-Procuring Movements

We studied the roles of the cerebellum and caudate nuclei in the programming and control of ballistic movements. An experimental model of operant food-procuring movements of the rats was used; the activity of single neurons of the above structures was recorded in the course of these motor performances. To evaluate the impact of the cerebellar–caudate interaction on the process of control of the ballistic (centrally programmed) components of food-procuring motor performance, we also recorded modifications of the neuronal activity in one of the above-mentioned structures induced by electrical extrastimulation of another structure in the course of realization of the above components. It is demonstrated that the cerebellum and, in particular, its dentate nuclei are involved in the programming of ballistic food-procuring movements. Neurons of the caudate nuclei play a significant role in the immediate preparation for and subsequent current control of stereotyped ballistic movements. The high plastic properties of the cerebellar neurons manifested in the process of control of ballistic food-procuring movements are proved.     

Control of targeted flexor movements of the human arm at different levels of the possibility for their preprograming

Contribution of the processes of central preprograming of an equilibrium target position of the limb link was studied by testing two variants of motor task in humans. In the first variant, the tested person could obtain visual information about the target position before the movement initiation. In the second variant, such information initially was absent and was presented only in the course of the movement performance. It has been shown that in both variants the pattern of EMG activity of flexor muscles, which realize the movement (and, respectively, the pattern of motor commands, i.e., efferent activity of spinal motoneurons) demonstrated no fundamental differences. Therefore, it can be supposed that the attainment of a target level in both cases was preprogramed only to a limited extent; more probably, it was provided by successive current control of the limb link position. This control is based, first of all, on dynamic changes of the control signals. In general, data of the experiments are in agreement with the impulse—temporal hypothesis of control of targeted movements.     

Learning to predict the future: the cerebellum adapts feedforward movement control

The role of the cerebellum in motor control and learning has been largely inferred from the effects of cerebellar damage. Recent work shows that cerebellar damage produces greater impairment of movements that require predictive as opposed to reactive control. This dissociation is consistent across many different types of movement. Predictive control is crucial for fast and ballistic movements, but impaired prediction can also affect slow movements, because of increased reliance on time-delayed feedback signals. The new findings are compatible with theories of cerebellar function, but still do not resolve whether the cerebellum operates by predicting the optimal motor commands or future sensory states. Prediction mechanisms must be learned and maintained through comparisons between predicted and observed outcomes. New results show that not all such error information is equivalent in driving cerebellar learning.     

Mental representations of movements. Brain potentials associated with imagination of hand movements

The present study was designed in order to contribute towards the understanding of the physiology of motor imagery. DC potentials were recorded when subjects either imagined or executed a sequence of unilateral or bilateral hand movements. The sequence consisted of hand movements in 4 directions, forwards, backwards, to the right and to the left, and varied from trial to trial. The sequence had been cued by visual targets on a computer screen and had to be memorized before the trial was initiated. Changes of DC potentials between task execution and imagination were localized in central recordings (C3, Cz, C4) with larger amplitudes when executing the task than when imagining to do so. Stimulation of peripheral receptors associated with task execution or a different level of activation of the cortico-motoneural system could account for this finding. The main result of the present study was that with unilateral performance, the side of the performing hand (right, left) had localized effects in recordings over the sensorimotor hand area (C3, C4) which were qualitatively the same with imagination and execution and quantitatively similar (i.e., without significant difference). Performance of the right hand augmented negative DC potentials in C3, performance of the left hand augmented amplitudes in C4. This result is consistent with the assumption that the primary motor cortex is active with motor imagery. Finally, the question has been addressed whether motor imagery may involve the left hemisphere to a larger extent than the execution of the movement. It is shown that a particular contribution of the left hemisphere associated with motor imagery may only show up under strictly controlled conditions.     

Activity of precentral neurons during torque-triggered hand movements in awake primates.

In monkeys performing a handle-repositioning task involving primarily wrist flexion-extension (F-E) movements after a torque perturbation was delivered to the handle, single units were recorded extracellularly in the contralateral precentral cortex. Precentral neurons were identified by passive somatosensory stimulation, and were classified into five somatotopically organized populations. Based on electromyographic recordings, it was observed that flexors and extensors about the wrist joint were specifically involved in the repositioning of the handle, while many other muscles which act at the wrist and other forelimb joints were involved in the task in a supportive role. In precentral cortex, all neuronal responses observed were temporally correlated to both the sensory stimuli and the motor responses. Visual stimuli, presented simultaneously with torque perturbations, did not affect the early portion of cortical responses to such torque perturbations. In each of the five somatotopically organized neuronal populations, task-related neurons as well as task-unrelated ones were observed. A significantly larger proportion of wrist (F-E) neurons was related to the task, as compared with the other, nonwrist (F-E) populations. The above findings were discussed in the context of a hypothesis for the function of precentral cortex during voluntary limb movement in awake primates. This hypothesis incorporates a relationship between activities of populations of precentral neurons, defined with respect to their responses to peripheral events at or about single joints, and movements about the same joint.     

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.     

Role of the motor cortex in the control of axial and proximal muscles in learning

Involvement of the motor cortex in the control of the shoulder and the scapula muscles was studied during acquisition of the novel head-forelimb coordination in dogs. The dogs were trained to raise the forelimb fixed to the lever in order to lift a food-containing cup and keep it elevated during eating with the head tilted down to the feeder. At the early stage of learning, the movement of raising the limb occurred with an anticipatory upward head tilt, whereas the head tilt to the feeder was associated with the lowering of the raised limb. Food consumption required a new coordination, i.e., maintaining the raised limb in a posture with the head lowered. This coordination could only be achieved by learning. This new coordination was critically dependent on the intact motor cortex. It was found that in the natural coordination, raise of the limb involved regular activation of the main flexors of shoulder, i.e., deltoid and teres major muscles, and inconstant participation of teres minor, supra- and infraspinatus, trapezius muscles. Muscles of the latter group were often active during standing but ceased their activity before limb raise. The learned limb raise with the head tilted down occurred with activation of all the mentioned muscles, and some of them changed their activity for the opposite pattern. Lesions in the motor cortex (inclusive the main part of the projection area of the "working" limb) led to a restoration of the natural head-fore- limb coordination and the innate muscle pattern of the limb raise. Thus, in the course of learning, the motor cortex rearranges the innate pattern of coordination of phylogenetically old axial and proximal muscles, which begin to work in a new manner.     

Are we ready for a natural history of motor learning?

Here we argue that general principles with regard to the contributions of the cerebellum, basal ganglia, and primary motor cortex to motor learning can begin to be inferred from explicit comparison across model systems and consideration of phylogeny. Both the cerebellum and the basal ganglia have highly conserved circuit architecture in vertebrates. The cerebellum has consistently been shown to be necessary for adaptation of eye and limb movements. The precise contribution of the basal ganglia to motor learning remains unclear but one consistent finding is that they are necessary for early acquisition of novel sequential actions. The primary motor cortex allows independent control of joints and construction of new movement synergies. We suggest that this capacity of the motor cortex implies that it is a necessary locus for motor skill learning, which we argue is the ability to execute selected actions with increasing speed and precision.     

Neurofeedback using real-time near-infrared spectroscopy enhances motor imagery related cortical activation

Accumulating evidence indicates that motor imagery and motor execution share common neural networks. Accordingly, mental practices in the form of motor imagery have been implemented in rehabilitation regimes of stroke patients with favorable results. Because direct monitoring of motor imagery is difficult, feedback of cortical activities related to motor imagery (neurofeedback) could help to enhance efficacy of mental practice with motor imagery. To determine the feasibility and efficacy of a real-time neurofeedback system mediated by near-infrared spectroscopy (NIRS), two separate experiments were performed. Experiment 1 was used in five subjects to evaluate whether real-time cortical oxygenated hemoglobin signal feedback during a motor execution task correlated with reference hemoglobin signals computed off-line. Results demonstrated that the NIRS-mediated neurofeedback system reliably detected oxygenated hemoglobin signal changes in real-time. In Experiment 2, 21 subjects performed motor imagery of finger movements with feedback from relevant cortical signals and irrelevant sham signals. Real neurofeedback induced significantly greater activation of the contralateral premotor cortex and greater self-assessment scores for kinesthetic motor imagery compared with sham feedback. These findings suggested the feasibility and potential effectiveness of a NIRS-mediated real-time neurofeedback system on performance of kinesthetic motor imagery. However, these results warrant further clinical trials to determine whether this system could enhance the effects of mental practice in stroke patients.     

Impairment of gradual muscle adjustment during wrist circumduction in Parkinson's disease

Purposeful movements are attained by gradually adjusted activity of opposite muscles, or synergists. This requires a motor system that adequately modulates initiation and inhibition of movement and selectively activates the appropriate muscles. In patients with Parkinson''s disease (PD) initiation and inhibition of movements are impaired which may manifest itself in e.g. difficulty to start and stop walking. At single-joint level, impaired movement initiation is further accompanied by insufficient inhibition of antagonist muscle activity. As the motor symptoms in PD primarily result from cerebral dysfunction, quantitative investigation of gradually adjusted muscle activity during execution of purposeful movement is a first step to gain more insight in the link between impaired modulation of initiation and inhibition at the levels of (i) cerebrally coded task performance and (ii) final execution by the musculoskeletal system. To that end, the present study investigated changes in gradual adjustment of muscle synergists using a manipulandum that enabled standardized smooth movement by continuous wrist circumduction. Differences between PD patients (N = 15, off-medication) and healthy subjects (N = 16) concerning the relation between muscle activity and movement performance in these groups were assessed using kinematic and electromyographic (EMG) recordings. The variability in the extent to which a particular muscle was active during wrist circumduction – defined as muscle activity differentiation - was quantified by EMG. We demonstrated that more differentiated muscle activity indeed correlated positively with improved movement performance, i.e. higher movement speed and increased smoothness of movement. Additionally, patients employed a less differentiated muscle activity pattern than healthy subjects. These specific changes during wrist circumduction imply that patients have a decreased ability to gradually adjust muscles causing a decline in movement performance. We propose that less differentiated muscle use in PD patients reflects impaired control of modulated initiation and inhibition due to decreased ability to selectively and jointly activate muscles.     

Interference in ballistic motor learning: specificity and role of sensory error signals

Humans are capable of learning numerous motor skills, but newly acquired skills may be abolished by subsequent learning. Here we ask what factors determine whether interference occurs in motor learning. We speculated that interference requires competing processes of synaptic plasticity in overlapping circuits and predicted specificity. To test this, subjects learned a ballistic motor task. Interference was observed following subsequent learning of an accuracy-tracking task, but only if the competing task involved the same muscles and movement direction. Interference was not observed from a non-learning task suggesting that interference requires competing learning. Subsequent learning of the competing task 4 h after initial learning did not cause interference suggesting disruption of early motor memory consolidation as one possible mechanism underlying interference. Repeated transcranial magnetic stimulation (rTMS) of corticospinal motor output at intensities below movement threshold did not cause interference, whereas suprathreshold rTMS evoking motor responses and (re)afferent activation did. Finally, the experiments revealed that suprathreshold repetitive electrical stimulation of the agonist (but not antagonist) peripheral nerve caused interference. The present study is, to our knowledge, the first to demonstrate that peripheral nerve stimulation may cause interference. The finding underscores the importance of sensory feedback as error signals in motor learning. We conclude that interference requires competing plasticity in overlapping circuits. Interference is remarkably specific for circuits involved in a specific movement and it may relate to sensory error signals.     

Responses of the red nucleus neurons to stimulation of the paw pads of forelimbs before and after cerebellar lesions.

Cerebellar cortex ablation releases deep cerebellar nuclei of monosynaptic inhibition from Purkinje cells. Therefore, it strengthens excitatory influence from Interpositus Nucleus (IN) upon Red Nucleus (RN), which results in much higher facilitation of the rubro-spinal neurons. This causes a big increase of spontaneous discharge rate, and eliminates brakes of discharges from responses generated by somatosensory stimuli. These two changes destroy content and timing of feedback information flowing through the spino-cerebello-rubro-spinal loop. This false bias of the feedback information, very important for fast postural adjustment and coordination of ongoing movements executed by central motor program, may at least in part be responsible for abnormal motor behavior evoked by cerebellar damage. Hemicerebellectomy resulted in dramatically reduced spontaneous activity and responses to limb stimulation because of severing a major input to the red nucleus from deep cerebellar nuclei. Due to direct somatosensory input to magnocellular Red Nucleus (mcRN) from the spinal cord that bypassed the cerebellum, the latency of response to limb stimulation was not changed and the narrower receptive fields were still present.     

Consolidation of dynamic motor learning is not disrupted by rTMS of primary motor cortex

Motor skills, once learned, are often retained over a long period of time. However, such learning first undergoes a period of consolidation after practice. During this time, the motor memory is susceptible to being disrupted by the performance of another motor-learning task. Recently, it was shown that repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex could disrupt the retention of a newly learned ballistic task in which subjects had to oppose their index finger and thumb as rapidly as possible. Here we investigate whether the motor cortex is similarly involved during the consolidation that follows learning novel dynamics. We applied rTMS to primary motor cortex shortly after subjects had either learned to compensate for a dynamic force field applied to their index finger or learned a ballistic finger abduction task. rTMS severely degraded the retention of the learning for the ballistic task but had no effect on retention of the dynamic force-field learning. This suggests that, unlike learning of simple ballistic skills, learning of dynamics may be stored in a more distributed manner, possibly outside the primary motor cortex.     

The role of the cerebellum in modulating voluntary limb movement commands

We recorded the activity of cerebellar Purkinje cells (PCs), primary motor cortical (M1) neurons, and limb EMG signals while monkeys executed a sequential reaching and button pressing task. PC simple spike discharge generally correlated well with the activity of one or more forelimb muscles. Surprisingly, given the inhibitory projection of PCs, only about one quarter of the correlations were negative. The largest group of neurons burst during movement and were positively correlated with EMG signals, while another significant group burst and were negatively correlated. Among the PCs that paused during movement most were negatively correlated with EMG. The strength of these various correlations was somewhat weaker, on average, than equivalent correlations between M1 neurons and EMG signals. On the other hand, there were no significant differences in the timing of the onset of movement related discharge among these groups of PCs, or between the PCs and M1 neurons. PC discharge was modulated largely in phase, or directly out of phase, with muscle activity. The nearly synchronous activation of PCs and muscles yielded positive correlations, despite the fact that the synaptic effect of the PC discharge is inhibitory. The apparent function of this inhibition is to restrain activity in the limb premotor network, shaping it into a spatiotemporal pattern that is appropriate for controlling the many muscles that participate in this task. The observed timing suggests that the cerebellar cortex learns to modulate PC discharge predictively. Through the cerebellar nucleus, this PC signal is combined with an underlying cerebral cortical signal. In this manner the cerebellum refines the descending command as compared with the relatively crude version generated when the cerebellum is damaged.     

Spinal cord atrophy and reorganization of motoneuron connections following long-standing limb loss in primates

Primates with long-standing therapeutic amputations of a limb at a young age were used to investigate the possibility that deefferented motor nerves sprout to new muscle targets. Injections of anatomical tracers into the muscles proximal to the amputated stump labeled a larger extent of motoneurons than matched injections on the intact side or in normal animals, including motoneurons that would normally supply only the missing limb muscles. Although the total numbers of distal limb motoneurons remained normal, some distal limb motoneurons on the amputated side were smaller in size and simpler in form. These results suggest that deprived motoneurons survive and retain function by reinnervating new muscle targets. The sprouted motor efferents may account for some of the reorganization of primary motor cortex that follows long-standing amputation.     

Cross-Limb Interference during Motor Learning

It is well known that following skill learning, improvements in motor performance may transfer to the untrained contralateral limb. It is also well known that retention of a newly learned task A can be degraded when learning a competing task B that takes place directly after learning A. Here we investigate if this interference effect can also be observed in the limb contralateral to the trained one. Therefore, five different groups practiced a ballistic finger flexion task followed by an interfering visuomotor accuracy task with the same limb. Performance in the ballistic task was tested before the training, after the training and in an immediate retention test after the practice of the interference task for both the trained and the untrained hand. After training, subjects showed not only significant learning and interference effects for the trained limb but also for the contralateral untrained limb. Importantly, the interference effect in the untrained limb was dependent on the level of skill acquisition in the interfering motor task. These behavioural results of the untrained limb were accompanied by training specific changes in corticospinal excitability, which increased for the hemisphere ipsilateral to the trained hand following ballistic training and decreased during accuracy training of the ipsilateral hand. The results demonstrate that contralateral interference effects may occur, and that interference depends on the level of skill acquisition in the interfering motor task. This finding might be particularly relevant for rehabilitation.     

Illusory sensation of movement induced by repetitive transcranial magnetic stimulation

Human movement sense relies on both somatosensory feedback and on knowledge of the motor commands used to produce the movement. We have induced a movement illusion using repetitive transcranial magnetic stimulation over primary motor cortex and dorsal premotor cortex in the absence of limb movement and its associated somatosensory feedback. Afferent and efferent neural signalling was abolished in the arm with ischemic nerve block, and in the leg with spinal nerve block. Movement sensation was assessed following trains of high-frequency repetitive transcranial magnetic stimulation applied over primary motor cortex, dorsal premotor cortex, and a control area (posterior parietal cortex). Magnetic stimulation over primary motor cortex and dorsal premotor cortex produced a movement sensation that was significantly greater than stimulation over the control region. Movement sensation after dorsal premotor cortex stimulation was less affected by sensory and motor deprivation than was primary motor cortex stimulation. We propose that repetitive transcranial magnetic stimulation over dorsal premotor cortex produces a corollary discharge that is perceived as movement.     

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.