The cortical control of movement revisited

Recently, we found that electrical stimulation of motor cortex caused monkeys to make coordinated, complex movements. These evoked movements were arranged across the cortex in a map of spatial locations to which the hand moved. We suggest that some of the subdivisions previously described within primary motor and premotor cortex may represent different types of actions that monkeys tend to make in different regions of space. According to this view, primary and premotor cortex may fit together into a larger map of manual space.     

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.     

Concatenation of Observed Grasp Phases with Observer’s Distal Movements: A Behavioural and TMS Study

The present study aimed at determining how actions executed by two conspecifics can be coordinated with each other, or more specifically, how the observation of different phases of a reaching-grasping action is temporary related to the execution of a movement of the observer. Participants observed postures of initial finger opening, maximal finger aperture, and final finger closing of grasp after observation of an initial hand posture. Then, they opened or closed their right thumb and index finger (experiments 1, 2 and 3). Response times decreased, whereas acceleration and velocity of actual finger movements increased when observing the two late phases of grasp. In addition, the results ruled out the possibility that this effect was due to salience of the visual stimulus when the hand was close to the target and confirmed an effect of even hand postures in addition to hand apparent motion due to the succession of initial hand posture and grasp phase. In experiments 4 and 5, the observation of grasp phases modulated even foot movements and pronunciation of syllables. Finally, in experiment 6, transcranial magnetic stimulation applied to primary motor cortex 300 ms post-stimulus induced an increase in hand motor evoked potentials of opponens pollicis muscle when observing the two late phases of grasp. These data suggest that the observation of grasp phases induced simulation which was stronger during observation of finger closing. This produced shorter response times, greater acceleration and velocity of the successive movement. In general, our data suggest best concatenation between two movements (one observed and the other executed) when the observed (and simulated) movement was to be accomplished. The mechanism joining the observation of a conspecific’s action with our own movement may be precursor of social functions. It may be at the basis for interactions between conspecifics, and related to communication between individuals.     

Reaching for answers

The exact function of motor cortex continues to be an enigma. In this issue of Neuron, present provocative data showing that microstimulation of the precentral cortex evokes complex movements, and conclude that the motor and premotor cortex together may form a single map of complex postures.     

The role of ventral premotor cortex in action execution and action understanding

The human ventral premotor cortex overlaps, at least in part, with Broca's region in the dominant cerebral hemisphere, that is known to mediate the production of language and contributes to language comprehension. This region is constituted of Brodmann's areas 44 and 45 in the inferior frontal gyrus. We summarize the evidence that the motor related part of Broca's region is localized in the opercular portion of the inferior frontal cortex, mainly in area 44 of Brodmann. According to our own data, there seems to be a homology between Brodmann area 44 in humans and the monkey area F5. The non-language related motor functions of Broca's region comprise complex hand movements, associative sensorimotor learning and sensorimotor integration. Brodmann's area 44 is also a part of a specialized parieto-premotor network and interacts significantly with the neighbouring premotor areas. In the ventral premotor area F5 of monkeys, the so called mirror neurons have been found which discharge both when the animal performs a goal-directed hand action and when it observes another individual performing the same or a similar action. More recently, in the same area mirror neurons responding not only to the observation of mouth actions, but also to sounds characteristic to actions have been found. In humans, through an fMRI study, it has been shown that the observation of actions performed with the hand, the mouth and the foot leads to the activation of different sectors of Broca's area and premotor cortex, according to the effector involved in the observed action, following a somatotopic pattern which resembles the classical motor cortex homunculus. On the other hand the evidence is growing that human ventral premotor cortex, especially Brodmann's area 44, is involved in polymodal action processing. These results strongly support the existence of an execution-observation matching system (mirror neuron system). It has been proposed that this system is involved in polymodal action recognition and might represent a precursor of language processing. Experimental evidence in favour of this hypothesis both in the monkey and humans is shortly reviewed.     

Effect of Microstimulation of Movement-Evoking Cortical Foci on the Activity of Neurons on the Dorsal Column Nuclei

Cortical foci in which stimulation produced movement in either the forelimb or hindlimb were isolated in rats. In each experiment, two foci were selected: one for movement in the forelimb, and the other in the hindlimb. Stimulation was subsequently reduced in order to avoid eliciting a movement, and the effects of this stimulation on activity of gracile and cuneate neurons were examined. Both excitation and inhibition were observed and were found to be arranged in a somatotopic manner. Excitation was almost exclusively obtained when the receptive field (RF) of a given neuron corresponded to the body surfaces overlying the joints involved in the cortically evoked movement. A high percentage of neurons with RFs on body surfaces corresponding to, or adjacent to, the region of cortically induced movement were inhibited, while the activity of neurons with RFs distant to the site of movement was seldom modified. These results suggest that cortical influences exerted on the dorsal column nuclei (DCN) in rats are organized in a somatotopic manner.     

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

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

Distinct cortical circuit mechanisms for complex forelimb movement and motor map topography

Cortical motor maps are the basis of voluntary movement, but they have proven difficult to understand in the context of their underlying neuronal circuits. We applied light-based motor mapping of Channelrhodopsin-2 mice to reveal a functional subdivision of the forelimb motor cortex based on the direction of movement evoked by brief (10?ms) pulses. Prolonged trains of electrical or optogenetic stimulation (100-500?ms) targeted to anterior or posterior subregions of motor cortex evoked reproducible complex movements of the forelimb to distinct positions in space. Blocking excitatory cortical synaptic transmission did not abolish basic motor map topography, but the site-specific expression of complex movements was lost. Our data suggest that the topography of?movement maps arises from their segregated output projections, whereas complex movements evoked by prolonged stimulation require intracortical synaptic transmission.     

Central Projection of Pain Arising from Delayed Onset Muscle Soreness (DOMS) in Human Subjects

Delayed onset muscle soreness (DOMS) is a subacute pain state arising 24–48 hours after a bout of unaccustomed eccentric muscle contractions. Functional magnetic resonance imaging (fMRI) was used to examine the patterns of cortical activation arising during DOMS-related pain in the quadriceps muscle of healthy volunteers evoked by either voluntary contraction or physical stimulation. The painful movement or physical stimulation of the DOMS-affected thigh disclosed widespread activation in the primary somatosensory and motor (S1, M1) cortices, stretching far beyond the corresponding areas somatotopically related to contraction or physical stimulation of the thigh; activation also included a large area within the cingulate cortex encompassing posteroanterior regions and the cingulate motor area. Pain-related activations were also found in premotor (M2) areas, bilateral in the insular cortex and the thalamic nuclei. In contrast, movement of a DOMS-affected limb led also to activation in the ipsilateral anterior cerebellum, while DOMS-related pain evoked by physical stimulation devoid of limb movement did not.     

Medial wall motor areas and skeletomotor control

The results of recent studies in primates provide convincing evidence that the cortex on the medial wall of the hemisphere contains multiple areas concerned with the generation and control of body movement. Highlights of these findings include the demonstration that each of these motor areas has substantial direct projections to the spinal cord, somatotopically organized projections to the primary motor cortex, a 'motor' map, revealed by intracortical stimulation, and neuronal activity that precedes trained hand movements.     

The modulation of corticospinal excitability during motor imagery of actions with objects

We investigated whether corticospinal excitability during motor imagery of actions (the power or the pincer grip) with objects was influenced by actually touching objects (tactile input) and by the congruency of posture with the imagined action (proprioceptive input). Corticospinal excitability was assessed by monitoring motor evoked potentials (MEPs) in the first dorsal interosseous following transcranial magnetic stimulation over the motor cortex. MEPs were recorded during imagery of the power grip of a larger-sized ball (7 cm) or the pincer grip of a smaller-sized ball (3 cm)--with or without passively holding the larger-sized ball with the holding posture or the smaller-sized ball with the pinching posture. During imagery of the power grip, MEPs amplitude was increased only while the actual posture was the same as the imagined action (the holding posture). On the other hand, during imagery of the pincer grip while touching the ball, MEPs amplitude was enhanced in both postures. To examine the pure effect of touching (tactile input), we recorded MEPs during imagery of the power and pincer grip while touching various areas of an open palm with a flat foam pad. The MEPs amplitude was not affected by the palmer touching. These findings suggest that corticospinal excitability during imagery with an object is modulated by actually touching an object through the combination of tactile and proprioceptive inputs.     

Interdependency of the maximum range of flexion–extension of hand metacarpophalangeal joints

Mobility of the fingers metacarpophalangeal (MCP) joints depends on the posture of the adjacent ones. Current Biomechanical hand models consider fixed ranges of movement at joints, regardless of the posture, thus allowing for non-realistic postures, generating wrong results in reach studies and forward dynamic analyses. This study provides data for more realistic hand models. The maximum voluntary extension (MVE) and flexion (MVF) of different combinations of MCP joints were measured covering their range of motion. Dependency of the MVF and MVE on the posture of the adjacent MCP joints was confirmed and mathematical models obtained through regression analyses (RMSE 7.7°).     

Human Left Ventral Premotor Cortex Mediates Matching of Hand Posture to Object Use

Visuomotor transformations for grasping have been associated with a fronto-parietal network in the monkey brain. The human homologue of the parietal monkey region (AIP) has been identified as the anterior part of the intraparietal sulcus (aIPS), whereas the putative human equivalent of the monkey frontal region (F5) is located in the ventral part of the premotor cortex (vPMC). Results from animal studies suggest that monkey F5 is involved in the selection of appropriate hand postures relative to the constraints of the task. In humans, the functional roles of aIPS and vPMC appear to be more complex and the relative contribution of each region to grasp selection remains uncertain. The present study aimed to identify modulation in brain areas sensitive to the difficulty level of tool object - hand posture matching. Seventeen healthy right handed participants underwent fMRI while observing pictures of familiar tool objects followed by pictures of hand postures. The task was to decide whether the hand posture matched the functional use of the previously shown object. Conditions were manipulated for level of difficulty. Compared to a picture matching control task, the tool object – hand posture matching conditions conjointly showed increased modulation in several left hemispheric regions of the superior and inferior parietal lobules (including aIPS), the middle occipital gyrus, and the inferior temporal gyrus. Comparison of hard versus easy conditions selectively modulated the left inferior frontal gyrus with peak activity located in its opercular part (Brodmann area (BA) 44). We suggest that in the human brain, vPMC/BA44 is involved in the matching of hand posture configurations in accordance with visual and functional demands.     

Role of motor cortex in coordinating multi-joint movements: is it time for a new paradigm?

Reaching movements to spatial targets require motor patterns at the shoulder to be coordinated carefully with those at the elbow to smoothly move the hand through space. While the motor cortex is involved in this volitional task, considerable debate remains about how this cortical region participates in planning and controlling movement. This article reviews two opposing interpretations of motor cortical function during multi-joint movements. On the one hand, studies performed predominantly on single-joint movement generally support the notion that motor cortical activity is intimately involved in generating motor patterns at a given joint. In contrast, studies on reaching demonstrate correlations between motor cortical activity and features of movement related to the hand, suggesting that the motor cortex may be involved in more global features of the task. Although this latter paradigm involves a multi-joint motor task in which neural activity is correlated with features of movement related to the hand, this neural activity is also correlated to other movement variables. Therefore it is difficult to assess if and how the motor cortex contributes to the coordination of motor patterns at different joints. In particular, present paradigms cannot assess whether motor cortical activity contributes to the control of one joint or multiple joints during whole-arm tasks. The final point discussed in this article is the development of a new experimental device (KINARM) that can both monitor and manipulate the mechanics of the shoulder and elbow independently during multi-joint motor tasks. It is hoped that this new device will provide a new approach for examining how the motor cortex is involved in motor coordination.     

Interaction between the premotor processes of eye and hand movements: Possible mechanism underlying eye–hand coordination

Interaction between the execution process of eye movement and that of hand movement must be indispensable for eye–hand coordination. The present study investigated corticospinal excitability in the hand muscles during the premotor processes of eye and/or hand movement to elucidate interaction between these processes. Healthy humans performed a precued reaction task of eye and/or finger movement and motor-evoked potentials in the hand muscles were evoked in the reaction time. Leftward eye movement suppressed corticospinal excitability in the right abductor digiti minimi muscle only when little finger abduction was simultaneously executed. Corticospinal excitability in the first dorsal interosseous muscle was not suppressed by eye movement regardless of whether or not it was accompanied by finger movement. Suppression of corticospinal excitability in the hand muscles induced by eye movement in the premotor period depends on the direction of eye movement, the muscle tested, and the premotor process of the tested muscle. The suppression may reflect interaction between the motor process of eye movement and that of hand movement particularly active during eye–hand coordination tasks during which both processes proceed.     

Empathy and the somatotopic auditory mirror system in humans

How do we understand the actions of other individuals if we can only hear them? Auditory mirror neurons respond both while monkeys perform hand or mouth actions and while they listen to sounds of similar actions . This system might be critical for auditory action understanding and language evolution . Preliminary evidence suggests that a similar system may exist in humans . Using fMRI, we searched for brain areas that respond both during motor execution and when individuals listened to the sound of an action made by the same effector. We show that a left hemispheric temporo-parieto-premotor circuit is activated in both cases, providing evidence for a human auditory mirror system. In the left premotor cortex, a somatotopic pattern of activation was also observed: A dorsal cluster was more involved during listening and execution of hand actions, and a ventral cluster was more involved during listening and execution of mouth actions. Most of this system appears to be multimodal because it also responds to the sight of similar actions. Finally, individuals who scored higher on an empathy scale activated this system more strongly, adding evidence for a possible link between the motor mirror system and empathy.     

Abnormal Movement Preparation in Task-Specific Focal Hand Dystonia

Electrophysiological and behavioral studies in primary dystonia suggest abnormalities during movement preparation, but this crucial phase preceding movement onset has not yet been studied specifically with functional magnetic resonance imaging (fMRI). To identify abnormalities in brain activation during movement preparation, we used event-related fMRI to analyze behaviorally unimpaired sequential finger movements in 18 patients with task-specific focal hand dystonia (FHD) and 18 healthy subjects. Patients and controls executed self-initiated or externally cued prelearnt four-digit sequential movements using either right or left hands. In FHD patients, motor performance of the sequential finger task was not associated with task-related dystonic posturing and their activation levels during motor execution were highly comparable with controls. On the other hand reduced activation was observed during movement preparation in the FHD patients in left premotor cortex / precentral gyrus for all conditions, and for self-initiation additionally in supplementary motor area, left mid-insula and anterior putamen, independent of effector side. Findings argue for abnormalities of early stages of motor control in FHD, manifesting during movement preparation. Since deficits map to regions involved in the coding of motor programs, we propose that task-specific dystonia is characterized by abnormalities during recruitment of motor programs: these do not manifest at the behavioral level during simple automated movements, however, errors in motor programs of complex movements established by extensive practice (a core feature of FHD), trigger the inappropriate movement patterns observed in task-specific dystonia.     

Influence of long-term intracortical microstimulation on the motor cortex

Long-term (0.5–1 s) stimulation of the hand region of the motor cortex in both macaque and human through a microelectrode by a series of biphasic current pulses of small amplitude evokes different complex, coordinated movements of the hand. There are two different opinions on how these movements are produced. The first hypothesis associates the movements with the presence of specific subregions in the motor cortex, which reflect different ethologically relevant categories of movement. According to the second hypothesis, these evoked complex movements are the artifacts of electrical stimulation. This article discusses the results of a number of studies in favor of each of the hypotheses. The conclusion about the validity of the first hypothesis is based on the analysis of the results of microstimulation and their comparison with the data obtained by the latest methods without the use of electric current. Moreover, this finding suggests the possibility of testing the condition changes of the monkey motor cortex through analysis the characteristics of the movements caused by long-term microstimulation.     

Motor cortex representation of the upper-limb in individuals born without a hand

The body schema is an action-related representation of the body that arises from activity in a network of multiple brain areas. While it was initially thought that the body schema developed with experience, the existence of phantom limbs in individuals born without a limb (amelics) led to the suggestion that it was innate. The problem with this idea, however, is that the vast majority of amelics do not report the presence of a phantom limb. Transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1) of traumatic amputees can evoke movement sensations in the phantom, suggesting that traumatic amputation does not delete movement representations of the missing hand. Given this, we asked whether the absence of a phantom limb in the majority of amelics means that the motor cortex does not contain a cortical representation of the missing limb, or whether it is present but has been deactivated by the lack of sensorimotor experience. In four upper-limb amelic subjects we directly stimulated the arm/hand region of M1 to see 1) whether we could evoke phantom sensations, and 2) whether muscle representations in the two cortices were organised asymmetrically. TMS applied over the motor cortex contralateral to the missing limb evoked contractions in stump muscles but did not evoke phantom movement sensations. The location and extent of muscle maps varied between hemispheres but did not reveal any systematic asymmetries. In contrast, forearm muscle thresholds were always higher for the missing limb side. We suggest that phantom movement sensations reported by some upper limb amelics are mostly driven by vision and not by the persistence of motor commands to the missing limb within the sensorimotor cortex. We propose that prewired movement representations of a limb need the experience of movement to be expressed within the primary motor cortex.     

Set-related neuronal activity in the premotor cortex of rhesus monkeys: effects of changes in motor set

Previous studies have suggested that the premotor cortex plays a role in motor preparation. We have tested this hypothesis in macaque monkeys by examining neuronal activity during an enforced, 1.5-3.0 s delay period between the presentation of an instruction for movement and the onset of that movement. Two targets for movement were available to the monkey, one on the left and one on the right. Illumination of one of the targets served as the instruction for a forelimb movement. It is known that there are cells in the premotor cortex that have directionally specific, sustained activity increases or decreases following such instructions. If the premotor cortex is involved in the preparation for movement in a particular direction, then changing the target from one to the opposite side during the delay period should lead to a pronounced change in sustained neuronal activity. Further, removing the instruction, while still requiring movement to the target, should have little or no sustained effect. Seventy cells showed the predicted activity patterns, thus supporting the view that the premotor cortex plays a role in motor preparation.