M1 Hand Research Articles

The importance of the cortico-motoneuronal system for control of grasp.

Our recent work has revealed new evidence of the importance of direct cortico-motoneuronal (CM) connections for voluntary control of the hand. Most of these connections are derived from corticospinal neurons located in the M1 hand area, although there are some much smaller contributions from other secondary motor areas, such as the supplementary motor area (SMA). Intracellular recordings show that 75% of upper limb motoneurons in the chloralose-anaesthetized macaque monkey receive a monosynaptic projection from the corticospinal tract; evidence for non-monosynaptic, propriospinal excitatory influences from the corticospinal tract was conspicuously lacking in these anaesthetized preparations. Moreover, in the conscious monkey, hand and arm muscle motor unit responses to corticospinal tract input are dominated by single, brief peaks compatible with monosynaptic excitation. CM excitatory post-synaptic potentials, recorded from a comparable sample of hand and arm motoneurons in anaesthetized macaque and squirrel monkeys, were found to be larger and faster rising in the macaque, which is by far the more dexterous of the two species. CM cells facilitating a given muscle in the conscious macaque are distributed over a wide region of M1 cortex, and each contributes a particular pattern of discharge during a skilled task. In addition to their direct effects on target muscles there may be weaker but potentially important effects that derive from the synchronous binding of assemblies of output neurons. Synchronous oscillations between these neurons are particularly prevalent during steady grip, but disappear during digit movement.

Neuronal HIF-1α Protein and VEGFR-2 Immunoreactivity in Functionally Related Motor Areas following a Focal M1 Infarct

Clinical and experimental data support a role for the intact cortex in recovery of function after stroke, particularly ipsilesional areas interconnected to the infarct. There is, however, little understanding of molecular events in the intact cortex, as most studies focus on the infarct and peri-infarct regions. This study investigated neuronal immunoreactivity for hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2) in remote cortical areas 3 days after a focal ischemic infarct, as both HIF-1alpha and VEGFR-2 have been implicated in peri-infarct neuroprotection. For this study, intracortical microstimulation techniques defined primary motor (M1) and premotor areas in squirrel monkeys (genus Saimiri). An infarct was induced in the M1 hand representation, and immunohistochemical techniques identified neurons, HIF-1alpha and VEGFR-2. Stereologic techniques quantified the total neuronal populations and the neurons immunoreactive for HIF-1alpha or VEGFR-2. The results indicate that HIF-1alpha upregulation is confined to the infarct and peri-infarct regions. Increases in VEGFR-2 immunoreactivity occurred; however, in two remote regions: the ventral premotor hand representation and the M1 hindlimb representation. Neurons in these representations were previously shown to undergo significant increases in VEGF protein immunoreactivity, and comparison of the two data sets showed a significant correlation between levels of VEGF and VEGFR-2 immunoreactivity. Thus, while remote areas undergo a molecular response to the infarct, we hypothesize that there is a delay in the initiation of the response, which ultimately may increase the 'window of opportunity' for neuroprotective interventions in the intact cortex.

Decoding M1 Neurons During Multiple Finger Movements

We tested several techniques for decoding the activity of primary motor cortex (M1) neurons during movements of single fingers or pairs of fingers. We report that single finger movements can be decoded with >99% accuracy using as few as 30 neurons randomly selected from populations of task-related neurons recorded from the M1 hand representation. This number was reduced to 20 neurons or less when the neurons were not picked randomly but selected on the basis of their information content. We extended techniques for decoding single finger movements to the problem of decoding the simultaneous movement of two fingers. Movements of pairs of fingers were decoded with 90.9% accuracy from 100 neurons. The techniques we used to obtain these results can be applied, not only to movements of single fingers and pairs of fingers as reported here, but also to movements of arbitrary combinations of fingers. The remarkably small number of neurons needed to decode a relatively large repertoire of movements involving either one or two effectors is encouraging for the development of neural prosthetics that will control hand movements.

VEGF Protein Associates to Neurons in Remote Regions following Cortical Infarct

Vascular endothelial growth factor (VEGF) is thought to contribute to both neuroprotection and angiogenesis after stroke. While increased expression of VEGF has been demonstrated in animal models after experimental ischemia, these studies have focused almost exclusively on the infarct and peri-infarct regions. The present study investigated the association of VEGF to neurons in remote cortical areas at three days after an infarct in primary motor cortex (M1). Although these remote areas are outside of the direct influence of the ischemic injury, remote plasticity has been implicated in recovery of function. For this study, intracortical microstimulation techniques identified primary and premotor cortical areas in a non-human primate. A focal ischemic infarct was induced in the M1 hand representation, and neurons and VEGF protein were identified using immunohistochemical procedures. Stereological techniques quantitatively assessed neuronal-VEGF association in the infarct and peri-infarct regions, M1 hindlimb, M1 orofacial, and ventral premotor hand representations, as well as non-motor control regions. The results indicate that VEGF protein significantly increased association to neurons in specific remote cortical areas outside of the infarct and peri-infarct regions. The increased association of VEGF to neurons was restricted to cortical areas that are functionally and/or behaviorally related to the area of infarct. There was no significant increase in M1 orofacial region or in non-motor control regions. We hypothesize that enhancement of neuronal VEGF in these functionally related remote cortical areas may be involved in recovery of function after stroke, through either neuroprotection or the induction of remote angiogenesis.

Effects of a Rostral Motor Cortex Lesion on Primary Motor Cortex Hand Representation Topography in Primates

Background. Small lesions to rostral versus caudal portions of the hand representation in the primary motor cortex (M1) produce different behavioral deficits. The goal of the present study was to determine if rehabilitative training has similar effects on functional topography of the spared M1 after rostral versus previously reported caudal M1 lesions. Methods. Following a lesion to the rostral M1 hand area, monkeys were trained for 1 h/day for 30 days to retrieve food pellets from small wells using their impaired hand. Electrophysiological maps of the M1 were derived in anesthetized monkeys before infarct and after rehabilitative training using intracortical microstimulation. Results. After a lesion to the rostral M1 and rehabilitative training, the size of the spared hand representation decreased 1.2%. This change is not statistically different from the 9% increase seen after caudal M1 lesion and rehabilitative training (P > 0.2). Conclusion. Postlesion training spares peri-infarct hand area regardless of whether the lesion is in the rostral or caudal M1.

Extensive Cortical Rewiring after Brain Injury

Previously, we showed that the ventral premotor cortex (PMv) underwent neurophysiological remodeling after injury to the primary motor cortex (M1). In the present study, we examined cortical connections of PMv after such lesions. The neuroanatomical tract tracer biotinylated dextran amine was injected into the PMv hand area at least 5 months after ischemic injury to the M1 hand area. Comparison of labeling patterns between experimental and control animals demonstrated extensive proliferation of novel PMv terminal fields and the appearance of retrogradely labeled cell bodies within area 1/2 of the primary somatosensory cortex after M1 injury. Furthermore, evidence was found for alterations in the trajectory of PMv intracortical axons near the site of the lesion. The results suggest that M1 injury results in axonal sprouting near the ischemic injury and the establishment of novel connections within a distant target. These results support the hypothesis that, after a cortical injury, such as occurs after stroke, cortical areas distant from the injury undergo major neuroanatomical reorganization. Our results reveal an extraordinary anatomical rewiring capacity in the adult CNS after injury that may potentially play a role in recovery.

Intensity modulation of TMS-induced cortical excitation: primary motor cortex.

The intensity dependence of the local and remote effects of transcranial magnetic stimulation (TMS) on human motor cortex was characterized using positron-emission tomography (PET) measurements of regional blood flow (BF) and concurrent electromyographic (EMG) measurements of the motor-evoked potential (MEP). Twelve normal volunteers were studied by applying 3 Hz TMS to the hand region of primary motor cortex (M1(hand)). Three stimulation intensities were used: 75%, 100%, and 125% of the motor threshold (MT). MEP amplitude increased nonlinearly with increasing stimulus intensity. The rate of rise in MEP amplitude was greater above MT than below. The hemodynamic response in M1(hand) was an increase in BF. Hemodynamic variables quantified for M1(hand) included value-normalized counts (VNC), intensity (z-score), and extent (mm(3)). All three hemodynamic response variables increased nonlinearly with stimulus intensity, closely mirroring the MEP intensity-response function. VNC was the hemodynamic response variable which showed the most significant effect of TMS intensity. VNC correlated strongly with MEP amplitude, both within and between subjects. Remote regions showed varying patterns of intensity response, which we interpret as reflecting varying levels of neuronal excitability and/or functional coupling in the conditions studied.

Physical interactions between induced electrical fields can have substantial effects on neuronal excitation during simultaneous TMS of two brain areas

Objective To analyse the interactions between simultaneous or nearly simultaneous focal transcranial magnetic stimulation (TMS) of the motor cortex hand area (M1 hand) of both hemispheres. Methods In 7 healthy subjects, motor evoked potential (MEP) amplitude and cortical silent period (CSP) duration were elicited in the right hand by bihemispheric focal TMS of M1 hand (8-shaped coils, monophasic current waveform, stimulus intensity 120% above motor threshold, TMS of right M1 hand preceding TMS of left M1 hand by 0–1000 μs), or by unilateral TMS of left M1 hand alone. A dipole probe was used to measure the physical interactions between the two stimulating coils. Results Bihemispheric TMS markedly decreased MEP and CSP at intervals of 0 and 50 μs compared to unilateral TMS, whereas both measures increased at the interval of 150 μs. The dipole probe experiments showed that the physical interactions between the electrical fields of the two coils entirely explained the MEP and CSP findings, but only under the assumption that excitation of M1 hand is not point-focal but extends over several centimetres. Conclusions First, simultaneous focal TMS of distant brain sites may result in marked ‘distortion’ of brain excitation through physical interaction between the induced electrical fields. Second, these findings support the notion that excitation of human M1 hand is relatively non-focal, even if a ‘focal’ stimulating coil and low stimulus intensity are used. Significance Potentially marked physical interaction between induced electrical fields must be taken into account when testing or disrupting distant brain sites with simultaneous focal TMS.

Dissociation of Sensorimotor Deficits After Rostral Versus Caudal Lesions in the Primary Motor Cortex Hand Representation

Primary motor cortex (M1) has traditionally been considered a motor structure. Although neurophysiologic studies have demonstrated that M1 is also influenced by somatosensory inputs (cutaneous and proprioceptive), the behavioral significance of these inputs has yet to be fully defined in primates. The present study describes differential sensory-related deficits after small ischemic lesions in either the rostral or caudal subregion of the M1 hand area in a nonhuman primate. Squirrel monkeys retrieved food pellets out of different sized wells drilled into a Plexiglas board. Before the lesion, monkeys retrieved pellets by directing the hand to the well, inserting fingers directly into it, and extracting the pellet. After a lesion to the rostral portion of M1, monkeys frequently failed to direct the hand accurately to the well. Instead, fingers contacted the surface of the board outside the well before entering the well. These aiming errors are consistent with both the large amount of proximal motor outputs and the predominant proprioceptive inputs of rostral M1. Overall, these aiming errors are suggestive of dysfunctional processing of proprioceptive information or the failure to integrate proprioceptive information with motor commands. In contrast, after a lesion to the caudal portion of M1, monkeys frequently examined their palm visually for the presence of the pellet after an attempted retrieval. These errors are consistent with both the large amount of distal motor outputs and the predominant cutaneous inputs of caudal M1. Thus these errors are suggestive of a deficit in processing of cutaneous information or the failure to integrate cutaneous information with motor commands. Rostral and caudal M1 lesions result in different deficits in sensory-dependent motor control that appear to correlate with broad segregation of motor outputs and previously described sensory inputs of M1.

Effects of motor imagery on finger force responses to transcranial magnetic stimulation

The purpose of this study was to investigate whether characteristics of finger interaction seen in voluntary finger force production tasks could also be observed during motor imagery. Transcranial magnetic stimulation (TMS) was applied over the contralateral M1 hand area. Three conditions were tested in eight young healthy volunteers: At rest, during motor imagery of maximal force production by the index finger (ImIn), and during motor imagery of maximal force production by all four fingers simultaneously (ImAll). We obtained measures of motor threshold (MT), motor-evoked potentials (MEP) from the contralateral flexor digitorium superficialis, and TMS-induced forces from individual fingers. Increased MEP and decreased MT during motor imagery tasks suggested enhanced excitability of structures involved in the generation of TMS-induced responses. TMS-induced forces were larger during motor imagery tasks than at rest. This effect was present, albeit significantly smaller, in the middle, ring, and little fingers during ImIn as compared to ImAll. This finding has been interpreted as a correlate of the phenomenon of unintended finger force production (enslaving). The motor imagery effect on finger forces evoked by TMS was significantly larger during ImIn (4% MVC) than during ImAll (2.8% MVC) tasks, corresponding to the phenomenon of force deficit. These results provide direct evidence of the neural origin of the main phenomena of finger interaction. Furthermore, the similarities between characteristics of finger interaction during motor imagery and during voluntary movement suggest the involvement of similar neural structures (including M1).

Reorganization of remote cortical regions after ischemic brain injury: a potential substrate for stroke recovery.

Although recent neurological research has shed light on the brain's mechanisms of self-repair after stroke, the role that intact tissue plays in recovery is still obscure. To explore these mechanisms further, we used microelectrode stimulation techniques to examine functional remodeling in cerebral cortex after an ischemic infarct in the hand representation of primary motor cortex in five adult squirrel monkeys. Hand preference and the motor skill of both hands were assessed periodically on a pellet retrieval task for 3 mo postinfarct. Initial postinfarct motor impairment of the contralateral hand was evident in each animal, followed by a gradual improvement in performance over 1-3 mo. Intracortical microstimulation mapping at 12 wk after infarct revealed substantial enlargements of the hand representation in a remote cortical area, the ventral premotor cortex. Increases ranged from 7.2 to 53.8% relative to the preinfarct ventral premotor hand area, with a mean increase of 36.0 +/- 20.8%. This enlargement was proportional to the amount of hand representation destroyed in primary motor cortex. That is, greater sparing of the M1 hand area resulted in less expansion of the ventral premotor cortex hand area. These results suggest that neurophysiologic reorganization of remote cortical areas occurs in response to cortical injury and that the greater the damage to reciprocal intracortical pathways, the greater the plasticity in intact areas. Reorganization in intact tissue may provide a neural substrate for adaptive motor behavior and play a critical role in postinjury recovery of function.

Functional somatotopy of finger representations in human primary motor cortex.

To assess the degree of fine-scale somatotopy within the hand area of the human primary motor cortex (M1), functional mapping of individual movements of all fingers was performed in healthy young subjects (n = 7) using MRI at 0.8 x 0.8 mm2 resolution and 4 mm section thickness. The experimental design comprised both a direct paradigm contrasting single digit movements vs. motor rest and multiple differential paradigms contrasting single digit movements vs. the movement of another digit. Direct mapping resulted in largely overlapping activations. A somatotopic arrangement was only recognizable when considering the mean center-of-mass coordinates of individual digit representations averaged across subjects. In contrast, differential paradigms revealed more segregated and somatotopically ordered activations in single subjects. The use of center-of-mass coordinates yielded inter-digit distances ranging from 2.0 to 16.8 mm, which reached statistical significance for pairs of more distant digits. For the middle fingers, the functional somatotopy obtained by differential mapping was dependent on the choice of the digit used for control. These results confirm previous concepts that finger somatotopy in the human M1 hand area emerges as a functional predominance of individual digit representations sharing common areas in a distributed though ordered network.

Motor cortex and the distributed anatomy of finger movements.

Voluntary movements are thought to be controlled via a well-ordered, spatially discrete, somatotopic map in the primary motor cortex (M1). We examined this hypothesis in monkeys trained to perform visually-cued, individuated flexion and extension movements of each digit and of the wrist. Single neurone recordings in M1 during such finger movements revealed two unexpected features. First, single M1 neurones often discharge during instructed movements of multiple digits. Second, neurones active during any particular instructed movement are distributed widely throughout the same M1 territory as neurones active during any other movement. Reversible, partial inactivation of the M1 hand representation produced by injection of 5-10 microg muscimol at one site impaired the monkeys' ability to perform finger movements, but no relationship was evident between the particular finger movements that were affected and the mediolateral location of the injection site along the central sulcus. Thus each finger movement is represented by activity distributed widely in the M1 upper extremity representation. If not controlled from spatially segregated M1 regions, movements of different fingers might be controlled by groups of spatially scattered but physiologically similar neurones. Cluster analysis of M1 neurones demonstrated a large group that discharged during most finger movements, and a small group that paused during most movements. Distinct functional groups of M1 neurones that might control particular finger movements were identified inconsistently. We therefore hypothesize that M1 neurones are a very diverse network controlling finger movements.

Somatotopy in human primary motor and somatosensory hand representations revisited.

High-resolution functional magnetic resonance imaging of healthy volunteers was used to study the functional anatomy of the human primary motor (M1) and somatosensory (S1) cortical hand representations during simple movements of thumb, little finger and wrist and a sequential movement of the middle three fingers. Rest served as a control state. The results demonstrated an orderly somatotopy in both M1 and S1, even though the cortical areas active with individual movements significantly overlapped. Moreover, the activation patterns in M1 and S1 differed in three aspects: (i) S1 activation was distributed into significantly more clusters than M1 and the primary cluster was smaller; (ii) the overlaps of areas active with different movements were significantly larger in M1 than in S1; (iii) the difference between the three-finger sequential movement and the single-finger movements was more pronounced in S1 than in M1. The sequence-activated S1 cortex was distributed into significantly more clusters. There was also a trend for a bigger volume difference between sequence and the single finger movements in S1 than M1. These data suggest that while the distributed character dominates in M1 and S1, a somatotopic arrangement exists for both M1 and S1 hand representations, with the S1 somatotopy being more discrete and segregated, in contrast to the more integrated and overlapping somatotopy in M1.

Synchronization in monkey motor cortex during a precision grip task. I. Task-dependent modulation in single-unit synchrony.

Neural synchronization in the cortex, and its potential role in information coding, has attracted much recent attention. In this study, we have recorded long spike trains (mean, 33,000 spikes) simultaneously from multiple single neurons in the primary motor cortex (M1) of two conscious macaque monkeys performing a precision grip task. The task required the monkey to use its index finger and thumb to move two spring-loaded levers into a target, hold them there for 1 s, and release for a food reward. Synchrony was analyzed using a time-resolved cross-correlation method, normalized using an estimate of the instantaneous firing rate of the cell. This was shown to be more reliable than methods using trial-averaged firing rate. A total of 375 neurons was recorded from the M1 hand area; 235 were identified as pyramidal tract neurons. Synchrony was weak [mean k' = 1.05 +/- 0.04 (SD)] but widespread among pairs of M1 neurons (218/1359 pairs with above-chance synchrony), including output neurons. Synchrony usually took the form of a broad central peak [average width, 18.7 +/- 8.7 (SD) ms]. There were marked changes during different phases of the task. As a population, synchrony was greatest during the steady hold period in striking contrast to the averaged cell firing rate, which was maximal when the animal was moving the levers into target. However, the modulation of synchrony during task performance showed considerable variation across individual cell pairs. Two types of synchrony were identified: oscillatory (with periodic side lobes in the cross-correlation) and nonoscillatory. Their relative contributions were quantified by filtering the cross-correlations to exclude either frequencies from 18 to 37 Hz or all higher and lower frequencies. At the peak of population synchrony during the hold period, about half (51.7% in one monkey, 56.2% in the other) of the synchronization was within this oscillatory bandwidth. This study provides strong support for assemblies of neurons being synchronized during specific phases of a complex task with potentially important consequences for both information processing within M1 and for the impact of M1 commands on target motoneurons.

Subthreshold 5-Hz repetitive transcranial magnetic stimulation of the human primary motor cortex reduces intracortical paired-pulse inhibition

Paired-pulse transcranial magnetic stimulation (TMS) at short interstimulus intervals was employed to investigate short-term effects of 5-Hz repetitive TMS (rTMS) over the primary motor hand area (M1 HAND) on intracortical excitability. In ten healthy individuals, 1250 pulses of 5-Hz rTMS were applied at 90% of motor resting threshold over the left M1 HAND. Ten minutes after 5-Hz rTMS, paired-pulse inhibition was significantly reduced, whereas paired-pulse facilitation was not modified. Sham-rTMS had no lasting effect on intracortical excitability. These findings suggest that subthreshold 5-Hz rTMS causes a short-term modulation of the excitability of intracortical circuitry in the stimulated M1 HAND. The lasting effect of subthreshold 5-Hz rTMS on intracortical inhibition provides a useful probe for studying short-term plasticity of the human M1 HAND.

Limited functional grouping of neurons in the motor cortex hand area during individuated finger movements: A cluster analysis.

Primary motor cortex (M1) hand area neurons show patterns of discharge across a set of individuated finger and wrist movements so diverse as to preclude classifying the neurons into functional groups on the basis of simple inspection. We therefore applied methods of cluster analysis to search M1 neuronal populations for groups of neurons with similar patterns of discharge across the set of movements. Populations from each of three monkeys showed a large group of neurons the discharge of which increased for many or all of the movements and a second small group the discharge of which decreased for many or all movements. Two to three other small groups of neurons that discharged more specifically for one or two movements also were found in each monkey, but these groups were less consistent than the groups with broad movement fields. The limited functional grouping of M1 hand area neurons suggests that M1 neurons act as a network of highly diverse elements in controlling individuated finger movements.

Mechanisms of recovery of dexterity following unilateral lesion of the sensorimotor cortex in adult monkeys.

The mechanisms of recovery of manual dexterity after unilateral lesion of the sensorimotor cortex in adult primates remain a matter of debate. It has been proposed that the cortical zone adjacent to the lesion may take over part of the function of the damaged cortex. To investigate further this possibility, two adult (4-5 years old) macaque monkeys were trained to perform a natural precision-grip task to assess hand dexterity. Intracortical microstimulations (ICMS) were used to map the hand area in M1 on both hemispheres. Ibotenic acid was then injected intracortically to damage the representation in M1 of the preferred hand. Subsequent histological analysis indicated that the hand representation in M1 was indeed lesioned, but, due to a spread of ibotenic acid, the lesion encroached a significant extent of the hand representation in the primary somatosensory cortex. A few minutes after infusion of ibotenic acid, there was a complete loss of dexterity of the preferred hand, which lasted for 1-2 months. Later, a progressive functional recovery of the affected hand took place over a 3- to 4-month period, reaching a stable level corresponding to 30% of the pre-lesion behavioral score. ICMS remapping, conducted nine months after the lesion, revealed that stimulation of the intact or lesioned M1 did not induce any visible movement of the recovered hand. The M1 hand representation on the intact hemisphere was similar to that observed before the lesion. Transient inactivation of the M1 hand/arm areas or of the dorsal and ventral premotor cortical areas (PM) on both hemispheres was undertaken by using microinjections of the GABA-agonist muscimol. Inactivations of M1 had no effect. Inhibition of PM in the damaged hemisphere suppressed the recovered manual dexterity of the affected hand. These results suggest that PM plays a significant role in the incomplete functional recovery of hand dexterity following unilateral damage of the sensorimotor cortex in adult monkeys.

Partial Inactivation of the Primary Motor Cortex Hand Area: Effects on Individuated Finger Movements

After large lesions of the primary motor cortex (M1), voluntary movements of affected body parts are weak and slow. In addition, the relative independence of moving one body part without others is lost; attempts at individuated movements of a given body part are accompanied by excessive, unintended motion of contiguous body parts. The effects of partial inactivation of the M1 hand area are comparatively unknown, however. If the M1 hand area contains the somatotopically ordered finger representations implied by the classic homunculus or simiusculus, then partial inactivation might produce weakness, slowness, and loss of independence of one or two adjacent digits without affecting other digits. But if control of each finger movement is distributed in the M1 hand area as many studies suggest, then partial inactivation might produce dissociation of weakness, slowness, and relative independence of movement, and which fingers movements are impaired might be unrelated to the location of the inactivation along the central sulcus. To investigate the motoric deficits resulting from partial inactivation of the M1 hand area, we therefore made single intracortical injections of muscimol as trained monkeys performed visually cued, individuated flexion-extension movements of the fingers and wrist. We found little if any evidence that which finger movements were impaired after each injection was related to the injection location along the central sulcus. Unimpaired fingers could be flanked on both sides by impaired fingers, and the flexion movements of a given finger could be unaffected even though the extension movements were impaired, or vice versa. Partial inactivation also could produce dissociated weakness and slowness versus loss of independence in a given finger movement. These findings suggest that control of each individuated finger movement is distributed widely in the M1 hand area.

Dexterity in adult monkeys following early lesion of the motor cortical hand area: the role of cortex adjacent to the lesion.

Infant monkeys were subjected to unilateral lesions of the motor cortex (mainly its hand representation). After maturation, they showed normal use of the contralateral hand for global grip movements. However, as compared with the ipsilateral hand, precision grip tasks requiring relatively independent finger movements were performed with less dexterity, particularly if adjustments of the wrist position were necessary. The purpose of this study was to investigate mechanisms which may be responsible for the rather well, although not complete, preservation of manipulative behaviour of these adult monkeys. To this end, the hand representations were mapped bilaterally with intracortical microstimulation in the mature monkeys, and the dexterity of both hands assessed quantitatively in a precision grip task. The behavioural effects of reversible inactivations of the primary (M1) and supplementary (SMA) motor cortical areas were then tested. The following were found. (i) The hand contralateral to the lesion exhibited subtle but significant dexterity deficits, as compared with the ipsilateral hand; the deficit was essentially for complex movements requiring dissociation of the thumb-index finger pinch from the other digits, involving also an arm rotation. (ii) Reversible inactivation of the M1 hand representation in the intact hemisphere dramatically impaired dexterity of the opposite hand without affecting the ipsilateral hand (contralateral to the early lesion). (iii) A relatively complete hand representation was found to occupy a new territory, medial to the old lesion. (iv) The role of this new displaced representation was crucial for the preserved dexterity of the opposite hand, as evidenced by its functional inactivation. In contrast, inactivation of both SMA cortices did not interfere with the manipulative behaviour. It is thus concluded that the preserved functional capacity of manipulations with the hand opposite the early lesion can be essentially attributed to a cortical reorganization around the old lesion. Under the present experimental conditions, contributions from either the SMA or the intact M1 appear not to be crucial.