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International audience; Visuospatial attention has an inherent asymmetry: the leftward bias called pseudoneglect. In typical line bisection tasks, healthy individuals tend to judge the center of a line leftward of the true center, an effect attributed to the right hemisphere dominance in visuospatial attention. Since it has been shown that information perceived by the dominant eye strongly activates the ipsilateral visual cortex, we hypothesized that eye dominance may modulate visuospatial attention bias. Because activation of the left hemisphere induced by left eye dominance should mitigate the right hemisphere dominance in attention, we predicted that right-handed individuals with left dominant eye would show smaller amount of pseudoneglect than right-handed individuals with right dominant eye. We compared the performance at both the perceptual (Landmark) and manual line bisection task of forty right-handed healthy individuals, half of whom had a right dominant eye and the other half a left dominant eye. As predicted, the left eyed dominant group showed smaller, actually not significant pseudoneglect, which was thus greater in the right eye dominant group. The influence of eye dominance on visuospatial attention was present in the Landmark but not the manual line bisection task, in which the amount of visuospatial bias correlated with participants' degree of (right) handedness. This is the first report of the effect of eye dominance on visuospatial attention within a right-handed population. This finding, by showing the influence of eye dominance on visuospatial cognition, not only helps in better defining intact visuospatial cognition mechanism but also encourages further research to pinpoint the neural basis of such interaction.

Sensorimotor reorganization is believed to play an important role in the development and maintenance of phantom limb pain, but pain itself might modulate sensorimotor plasticity induced by deafferentation. Clinical and basic research support this idea, as pain prior to amputation increases the risk of developing post-amputation pain. The aim of this study was to examine the influence of experimental tonic cutaneous hand pain on the plasticity induced by temporary ischemic hand deafferentation. Sixteen healthy subjects participated in two experimental sessions ( Pain, No Pain ) in which transcranial magnetic stimulation was used to assess corticospinal excitability in two forearm muscles (flexor carpi radialis and flexor digitorum superficialis) before (T0, T10, T20, and T40) and after (T60 and T75) inflation of a cuff around the wrist. The cuff was inflated at T45 in both sessions and in the Pain session capsaicin cream was applied on the dorsum of the hand at T5. Corticospinal excitability was significantly greater during the Post-inflation phase ( p = 0.002) and increased similarly in both muscles ( p = 0.861). Importantly, the excitability increase in the Post-inflation phase was greater for the Pain than the No-Pain condition ( p = 0.006). Post-hoc analyses revealed a significant difference between the two conditions during the Post-inflation phase ( p = 0.030) but no difference during the Pre-inflation phase ( p = 0.601). In other words, the corticospinal facilitation was greater when pain was present prior to cuff inflation. These results indicate that pain can modulate the plasticity induced by another event, and could partially explain the sensorimotor reorganization often reported in chronic pain populations.

Background Motor imagery (MI) training is often used to improve physical practice (PP), and the functional equivalence between imagined and practiced movements is widely considered essential for positive training outcomes. Objective We previously showed that a 5-week MI training program improved tenodesis grasp in individuals with C6–C7 quadriplegia. Here we investigated whether functional equivalence changed during the course of this training program. Methods In this descriptive pilot study, we retrospectively analyzed data for 6 individuals with C6–C7 quadriplegia (spinal cord injured [SCI]) and 6 healthy age-matched controls who trained for 5 weeks in visual and kinesthetic motor imagery or visualization of geometric shapes (controls). Before training, we assessed MI ability by using the Kinesthetic and Visual Imagery Questionnaire (KVIQ). We analyzed functional equivalence by vividness measured on a visual analog scale (0–100) and MI/PP time ratios computed from imagined and physically practiced movement durations measured during MI training. These analyses were re-run considering that half of the participants with quadriplegia were good imagers and the other half were poor imagers based on KVIQ scores. To investigate generalization of training effects, we analyzed MI/PP ratios for an untrained pointing task before (3 baseline measures), immediately after, and 2 months after training. Results During MI training, imagery vividness increased significantly. Only the good imagers evolved toward temporal equivalence during training. Good imagers were also the only participants who showed changes in temporal equivalence on the untrained pointing task. Conclusion This is the first study reporting improvement in functional equivalence during an MI training program that improved tenodesis grasp in individuals with C6–C7 quadriplegia. We recommend that clinical MI programs focus primarily on vividness and suggest that feedback about movement duration could potentially improve temporal equivalence, which could in turn lead to further improvement in PP.

Rightward prism adaptation has been shown to ameliorate visuospatial biases in right brain-damaged patients with neglect, and a single session of prism adaptation can lead to improvements that last up to several hours. Leftward prism adaptation in neurologically healthy individuals induces neglect-like biases in visuospatial tasks. The duration of these effects in healthy individuals, typically assumed to be ephemeral, has never been investigated. Here we assessed the time-course of the adaptation-induced modifications in a classical perceptual line bisection task that was repeatedly administered for approximately 40 min after a single session of adaptation to either a leftward or rightward prismatic deviation. Consistent with previous reports, only adaptation to leftward-deviating prisms induced a visuospatial shift on perceptual line bisection judgments. The typical pattern of pseudoneglect was counteracted by a rightward shift in midline judgments, which became significant between 5 and 10 min after adaptation, fluctuated between being significant or not several times in the 40 min following adaptation, and was present as late as 35 min. In contrast, the sensorimotor aftereffect was present immediately after adaptation to both rightward and leftward deviating prisms, decayed initially then remained stable until 40 min. These results demonstrate that both the sensorimotor and visuospatial effects last for at least 35 min, but that the visuospatial shift needs time to fully develop and fluctuates. By showing that the effects of prism adaptation in the undamaged brain are not ephemeral, these findings reveal the presence of another, so-far neglected dimension in the domain of the cognitive effects induced by prism adaptation, namely time. The prolonged duration of the induced visuospatial shift, previously considered to be a feature of prism adaptation unique to brain-damaged subjects, also applies to the normal brain.

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It is well established that permanent or transient reduction of somatosensory inputs, following hand deafferentation or anesthesia, induces plastic changes across the hand-face border, supposedly responsible for some altered perceptual phenomena such as tactile sensations being referred from the face to the phantom hand. It is also known that transient increase of hand somatosensory inputs, via repetitive somatosensory stimulation (RSS) at a fingertip, induces local somatosensory discriminative improvement accompanied by cortical representational changes in the primary somatosensory cortex (SI). We recently demonstrated that RSS at the tip of the right index finger induces similar training-independent perceptual learning across the hand-face border, improving somatosensory perception at the lips (Muret D, Dinse HR, Macchione S, Urquizar C, Farnè A, Reilly KT. Curr Biol 24: R736–R737, 2014). Whether neural plastic changes across the hand-face border accompany such remote and adaptive perceptual plasticity remains unknown. Here we used magnetoencephalography to investigate the electrophysiological correlates underlying RSS-induced behavioral changes across the hand-face border. The results highlight significant changes in dipole location after RSS both for the stimulated finger and for the lips. These findings reveal plastic changes that cross the hand-face border after an increase, instead of a decrease, in somatosensory inputs.

Neglect patients typically show a rightward attentional orienting bias and a strong disengagement deficit, such that they are especially slow in responding to left-sided targets after right-sided cues (Posner et al., 1984). Prism adaptation (PA) can reduce diverse debilitating neglect symptoms and it has been hypothesized that PA's effects are so generalized that they might be mediated by attentional mechanisms (Pisella et al., 2006; Redding and Wallace, 2006). In neglect patients, performance on spatial attention tasks improves after rightward-deviating PA (Jacquin-Courtois et al., 2013). In contrast, in healthy subjects, although there is evidence that leftward-deviating PA induces neglect-like performance on some visuospatial tasks, behavioral studies of spatial attention tasks have mostly yielded negative results (Morris et al., 2004; Bultitude et al., 2013). We hypothesized that these negative behavioral findings might reflect the limitations of behavioral measures in healthy subjects. Here we exploited the sensitivity of event-related potentials to test the hypothesis that electrophysiological markers of attentional processes in the healthy human brain are affected by PA. Leftward-deviating PA generated asymmetries in attentional orienting (reflected in the cue-locked N1) and in attentional disengagement for invalidly cued left targets (reflected in the target-locked P1). This is the first electrophysiological demonstration that leftward-deviating PA in healthy subjects mimics attentional patterns typically seen in neglect patients.SIGNIFICANCE STATEMENTPrism adaptation (PA) is a promising tool for ameliorating many deficits in neglect patients and inducing neglect-like behavior in healthy subjects. The mechanisms underlying PA's effects are poorly understood but one hypothesis suggests that it acts by modulating attention. To date, however, there has been no successful demonstration of attentional modulation in healthy subjects. We provide the first electrophysiological evidence that PA acts on attention in healthy subjects by mimicking the attentional pattern typically reported in neglect patients: both a rightward attentional orienting bias (reflected in the cue-locked N1) and a deficit in attentional disengagement from the right hemispace (reflected in the target-locked P1). This study makes an important contribution to refining current models of the mechanisms underlying PA's cognitive effects.

Rightward prism adaptation ameliorates neglect symptoms while leftward prism adaptation (LPA) induces neglect-like biases in healthy individuals. Similarly, inhibitory repetitive transcranial magnetic stimulation (rTMS) on the right posterior parietal cortex (PPC) induces neglect-like behavior, whereas on the left PPC it ameliorates neglect symptoms and normalizes hyperexcitability of left hemisphere parietal-motor (PPC-M1) connectivity. Based on this analogy we hypothesized that LPA increases PPC-M1 excitability in the left hemisphere and decreases it in the right one. In an attempt to shed some light on the mechanisms underlying LPA’s effects on cognition, we investigated this hypothesis in healthy individuals measuring PPC-M1 excitability with dual-site paired-pulse TMS (ppTMS). We found a left hemisphere increase and a right hemisphere decrease in the amplitude of motor evoked potentials elicited by paired as well as single pulses on M1. While this could indicate that LPA biases interhemispheric connectivity, it contradicts previous evidence that M1-only MEPs are unchanged after LPA. A control experiment showed that input-output curves were not affected by LPAper se. We conclude that LPA combined with ppTMS on PPC-M1 differentially alters the excitability of the left and right M1.

Predicting intentions from observing another agent’s behaviours is often thought to depend on motor resonance – i.e., the motor system’s response to a perceived movement by the activation of its stored motor counterpart, but observers might also rely on prior expectations, especially when actions take place in perceptually uncertain situations. Here we assessed motor resonance during an action prediction task using transcranial magnetic stimulation to probe corticospinal excitability (CSE) and report that experimentally-induced updates in observers’ prior expectations modulate CSE when predictions are made under situations of perceptual uncertainty. We show that prior expectations are updated on the basis of both biomechanical and probabilistic prior information and that the magnitude of the CSE modulation observed across participants is explained by the magnitude of change in their prior expectations. These findings provide the first evidence that when observers predict others’ intentions, motor resonance mechanisms adapt to changes in their prior expectations. We propose that this adaptive adjustment might reflect a regulatory control mechanism that shares some similarities with that observed during action selection. Such a mechanism could help arbitrate the competition between biomechanical and probabilistic prior information when appropriate for prediction.

Human motor cortex is capable of rapid and long-lasting reorganization, evident globally, as shifts in body part representations, and at the level of individual muscles as changes in corticospinal excitability. Representational shifts provide an overview of how various body parts reorganize relative to each other but do not tell us whether all muscles in a given body part reorganize in the same manner and to the same extent. Transcranial magnetic stimulation (TMS) provides information about individual muscles and can therefore inform us about the uniformity of plastic changes within a body part. We used TMS to investigate changes in corticospinal excitability of forearm flexors and extensors after inflation of a tourniquet around the wrist. Motor evoked potential (MEP) amplitudes and input/output (I/O) curves were obtained from wrist flexors and extensors simultaneously before and during block. TMS was delivered to the optimal site for eliciting MEPs in flexors in experiment 1, extensors in experiment 2, and both flexors and extensors in experiment 3. In all experiments flexor MEP amplitude increased during block while extensor MEP amplitude showed no systematic change, and the slope of flexor but not extensor I/O curves increased. Flexor H-reflex amplitude normalized to maximal M wave showed negligible changes during block, suggesting that the increase in corticospinal excitability in the flexors cannot be completely explained by increased excitability at the spinal cord level. These findings show that forearm flexors and extensors differ in their potential for plastic changes, highlight the importance of investigating how experimentally induced plasticity affects anatomically close, but functionally distinct, muscle groups, and suggest that rehabilitation interventions aiming to alter cortical organization should consider the differential sensitivity of various muscle groups to plasticity processes.

Amputees who have a phantom limb often report the ability to move this phantom voluntarily. In the literature, phantom limb movements are generally considered to reflect motor imagery rather than motor execution. The aim of this study was to investigate whether amputees distinguish between executing a movement of the phantom limb and imagining moving the missing limb. We examined the capacity of 19 upper-limb amputees to execute and imagine movements of both their phantom and intact limbs. Their behaviour was compared with that of 18 age-matched normal controls. A global questionnaire-based assessment of imagery ability and timed tests showed that amputees can indeed distinguish between motor execution and motor imagery with the phantom limb, and that the former is associated with activity in stump muscles while the latter is not. Amputation reduced the speed of voluntary movements with the phantom limb but did not change the speed of imagined movements, suggesting that the absence of the limb specifically affects the ability to voluntarily move the phantom but does not change the ability to imagine moving the missing limb. These results suggest that under some conditions, for example amputation, the predicted sensory consequences of a motor command are sufficient to evoke the sensation of voluntary movement. They also suggest that the distinction between imagined and executed movements should be taken into consideration when designing research protocols to investigate the analgesic effects of sensorimotor feedback.

Purpose: The primary motor cortex is capable of rapid, reversible plastic changes and longer-term, more permanent reorganization. Ischemic nerve block (INB) is a model of deafferentation-induced short-term plasticity. We used transcranial magnetic stimulation to examine whether changes in the excitability of short- and/or long-interval intracortical inhibitory (SICI, LICI) or short-interval intracortical facilitatory (SICF) circuits underlie the corticospinal excitability increases observed during INB. Methods: SICI and LICI recruitment curves, obtained by varying conditioning stimulus intensity, and SICF were measured at multiple inter-stimulus intervals (ISIs). Results: Forearm flexor MEP amplitude increased during INB at the wrist; this was not accompanied by changes in SICI at ISIs of 1 or 2 ms, in SICF at ISIs of 1.2, 2.7, or 4.4 ms, or in LICI at an ISI of 80 ms, but was accompanied by an increase in LICI at an ISI of 150 ms. Conclusions: The results suggest that (1) the increased excitability of forearm flexors is not due to reduced SICI or LICI or increased SICF, and (2) LICI measured at ISIs of 80 and 150 ms are distinct processes. We discuss the importance of identifying distinct processes of LICI and speculate regarding other mechanisms that could potentially underlie INB-induced plasticity.

It is generally considered that hand amputation changes primary motor cortex (M1) stump muscle representations. Transcranial magnetic stimulation (TMS) studies show that the corticospinal excitability of a stump muscle and its homologous muscle on the intact side is not equivalent, and that the resting level of excitability is higher in the stump muscle. Since changes in M1 stump muscle map characteristics (e.g., size and location) are identified by comparing stump and intact muscle maps, such changes might reflect between‐side differences in corticospinal excitability rather than a true reorganization of the stump muscle's map. In eight above‐elbow amputees we used TMS to map the M1 representation of a stump muscle and its homologous muscle on the intact side during rest and contraction. Importantly, the same relative stimulation intensity was used to construct each map; stimulation was performed at 120% of the motor threshold of each muscle (intact/amputated limb) measured in each condition (rest/active contraction). Resting motor threshold was lower in the stump muscle, but active motor thresholds did not differ. Motor‐evoked potential amplitudes increased between the rest and muscle contraction conditions, but this increase was smaller for the stump muscle because its at‐rest corticospinal excitability was higher than that of the intact muscle. When the between‐side difference in excitability was considered no interhemispheric difference was found for map areas or for their medio‐lateral locations. The present results challenge the view that after an upper limb amputation the stump representation moves laterally and occupies a larger M1 territory. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.

Recent evidence shows that the primary motor cortex continues to send motor commands when amputees execute phantom movements. These commands are retargeted toward the remaining stump muscles as a result of motor system reorganization. As amputation-induced reorganization in the primary motor cortex has been associated with phantom limb pain we hypothesized that the motor control of the phantom limb would differ between amputees with and without phantom limb pain. Eight above-elbow amputees with or without pain were included in the study. They were asked to produce cyclic movements with their phantom limb (hand, wrist, and elbow movements) while simultaneously reproducing the same movement with the intact limb. The time needed to complete a movement cycle and its amplitude were derived from the kinematics of the intact limb. Electromyographic (EMG) activity from different stump muscles and from the homologous muscles on the intact side was recorded. Different EMG patterns were recorded in the stump muscles depending on the movement produced, showing that different phantom movements are associated with distinct motor commands. Phantom limb pain was associated with some aspects of phantom limb motor control. The time needed to complete a full cycle of a phantom movement was systematically shorter in subjects without phantom limb pain. Also, the amount of EMG modulation recorded in a stump muscle during a phantom hand movement was positively correlated with the intensity of phantom limb pain. Since phantom hand movement-related EMG patterns in above-elbow stump muscles can be considered as a marker of motor system reorganization, this result indirectly supports the hypothesis that amputation-induced plasticity is associated with phantom limb pain severity. The discordance between the (amputated) hand motor command and the feedback from above-elbow muscles might partially explain why subjects exhibiting large EMG modulation during phantom hand movement have more phantom limb pain.

Neural activity in the motor cortex and its descending projections is modulated in a task‐related manner. Several TMS studies have shown that when normal human subjects execute different manual tasks requiring similar contraction levels in first dorsal interroseous (FDI) there is a task‐related modulation of the amplitude of FDI motor evoked potentials (MEPs). Not all studies of task‐related changes show the same pattern of results, however. One reason for this might be methodological. Studies have assessed task‐related changes by stimulating a single site, which can provide information about task‐related changes in the excitability of the cortex at that site, but which is not sensitive to excitability changes throughout the muscle's cortical representation. We investigated how the execution of an individuated versus a nonindividuated isometric grasping task affected the excitability of FDI's entire cortical representation. We examined FDI MEP amplitudes while subjects grasped an object between their thumb and index finger, or when they grasped the same object between their thumb and all four fingers, keeping the background level of EMG in FDI constant for the two tasks. We found no overall task‐related change in the excitability of FDI or its cortical topography, possibly due to behavioral differences of individual subjects. The stability of FDI's cortical representation during two different manual tasks expands the possibilities for studying cortical reorganization in the context of active muscle contraction, which will enable us to better understand whether changes in the motor system observed when muscles are at rest are also present during voluntary muscle recruitment. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.

Limb amputation results in plasticity of connections between the brain and muscles; the cortical motor representation of the missing limb seemingly disappears. The disappearance of the hand's motor representation is, however, difficult to reconcile with evidence that a perceptual representation of the missing limb persists in the form of a phantom limb endowed with sensory and motor qualities. Here, we argue that despite considerable reorganization within the motor cortex of upper-limb amputees, the representation of the amputated hand does not disappear. We hypothesize that two levels of hand-movement representation coexist within the primary motor cortex; at one level, limb movements are specified in terms of arm and hand motor commands, and at another level, limb movements are specified as muscles synergies. We propose that primary motor cortex reorganization after amputation concerns primarily the upper limb's muscular map but not its motor command map and that the integrity of the motor command map underlies the existence of the phantom limb. NEUROSCIEN-TIST 14(2):195—202, 2008. DOI: 10.1177/1073858407309466

Purpose Grasp recovery after C6-C7-spinal cord injury (SCI) requires learning "tenodesis grasp" whereby active wrist extension elicits passive thumb-to-forefinger and finger-to-palm flexion. Evidence that motor imagery (MI) promotes upper limb function after tetraplegia is growing, but whether MI potentiates grasp recovery in C6-C7-SCI individuals who have successfully learned the "tenodesis grasp" remains unknown. Methods Six chronic stable C6-C7-SCI inpatients and six healthy control participants were included. C6-C7-SCI participants imagined grasping movements and controls visualized geometric forms for 45 minutes, three times a week for five weeks. Three separate measures taken over a five week period before the intervention formed the baseline. Intervention effects were assessed immediately after the intervention and eight weeks later. Each testing session consisted of kinematic recordings during reach-to-grasp and magnetoencephalographic (MEG) recordings during wrist extension. Results During baseline, kinematic wrist extension angle during "tenodesis grasp" and MEG contralateral sensorimotor cortex (cSMC) activity during wrist extension were stable. Moreover, SCI participants exhibited a greater number of voxels within cSMC than controls. After MI sessions, wrist extension angle increased during "tenodesis grasp" and the number of voxels within cSMC during wrist extension decreased and became similar to controls. Conclusion These findings provide further support for the use of MI to reinforce a compensatory grasping movement (tenodesis) and induce brain plasticity.

Rightward prismatic adaptation (RPA) can reduce neglect symptoms in patients whereas adaptation to leftward deviating prisms (LPA) can induce neglect-like behavior in healthy subjects. One influential anatomo-functional model of prismatic adaptation (PA) postulates that it inhibits activity of the posterior parietal cortex (PPC) contralateral to the prismatic deviation. By hypo-activating the PPC and thus eventually acting on interhemispheric balance, both LPA and RPA could possibly affect visuospatial perception in healthy subjects, however, such behavioral modulation has seldom been reported after RPA. In the light of recent evidence showing that LPA-induced visuospatial shift need time to develop we hypothesized that RPA might induce significant changes in visuospatial cognition on a longer time scale. We thus assessed the Landmark task, as well as sensorimotor aftereffects, several times over 8 h after a single session of either LPA or RPA. In agreement with previous reports, sensorimotor effects were symmetrical and long-lasting, with both LPA and RPA inducing shifts of comparable amplitudes in the direction opposite to the deviation that lasted up to 8 h. Visuospatial cognition assessed by Landmark performance, was also significantly modulated for up to 8 h, but only after LPA. Interestingly, the timing and direction of this modulation differed according to participants' baseline bias. An initial leftward bias led to a rapid, but short-lasting rightward shift, whereas an initial rightward bias led to a slower-developing and longer-lasting leftward shift. These findings shed new light on a so-far relatively overlooked feature of spatial cognition that may interact with the effect of PA: the state of the visuospatial system prior to PA should be taken into account when attempting to understand and modulate visuospatial cognition in healthy and brain-damaged populations. This highlights the need for refining current models of PA's mechanisms of action.

A substantial body of evidence documents massive reorganization of primary sensory and motor cortices following hand amputation, the extent of which is correlated with phantom limb pain. Many therapies for phantom limb pain are based upon the idea that plastic changes after amputation are maladaptive and attempt to normalize representations of cortical areas adjacent to the hand area. Recent data suggest, however, that higher levels of phantom pain are associated with stronger local activity and more structural integrity in the missing hand area rather than with reorganization of neighbouring body parts. While these models appear to be mutually exclusive they could co-exist, and one reason for the apparent discrepancy between them might be that no single study has examined the organisation of lip, elbow, and hand movements in the same participants. In this study we thoroughly examined the 3D anatomy of the central sulcus and BOLD responses during movements of the hand, elbow, and lips using MRI techniques in 11 upper-limb amputees and 17 healthy control subjects. We observed different reorganizational patterns for all three body parts as the former hand area showed few signs of reorganization, but the lip and elbow representations reorganized and shifted towards the hand area. We also found that poorer voluntary control and higher levels of pain in the phantom limb were powerful drivers of the lip and elbow topological changes. In addition to providing further support for the maladaptative plasticity model, we demonstrate for the first time that motor capacities of the phantom limb correlate with post-amputation reorganization, and that this reorganization is not limited to the face and hand representations but also includes the proximal upper-limb.

Moving and interacting with the world requires that the sensory and motor systems share information, but while some information about tactile events is preserved during sensorimotor transfer the spatial specificity of this information is unknown. Afferent inhibition studies, in which corticospinal excitability is inhibited when a single tactile stimulus is presented before a transcranial magnetic stimulation pulse over the motor cortex, offer contradictory results regarding the sensory-to-motor transfer of spatial information. Here, we combined the techniques of afferent inhibition and tactile repetition suppression (RS: the decreased neurophysiological response following double stimulation of the same vs. different fingers) to investigate whether topographic information is preserved in the sensory-to-motor transfer in humans. We developed a double afferent inhibition paradigm to examine both spatial (same vs. different finger) and temporal (short vs. long delay) aspects of sensorimotor interactions. Two consecutive electrocutaneous stimuli (separated by either 30 or 125 ms) were delivered to either the same or different fingers on the left hand (i.e., index finger stimulated twice or middle finger stimulated before index finger). Information about which fingers were stimulated was reflected in the size of the motor responses in a time-constrained manner: corticospinal excitability was modulated differently by same and different finger stimulation only when the two stimuli were separated by the short delay (p=.004). We demonstrate that the well-known response of the somatosensory cortices following repetitive stimulation is mirrored in the motor cortex and that corticospinal excitability is modulated as a function of the temporal and spatial relationship between afferent stimuli.

The loss of a limb leads to sensorimotor modifications that are frequently accompanied by the vivid experience that the missing limb is still present, and that it can be moved at will. Furthermore, amputees can clearly distinguish between phantom movements of the fingers and of more proximal joints, like movements of the elbow. This phenomenon raises the question of whether these specific phantom movement experiences are translated into differentiated activity within the remaining muscles. We recorded stump muscle activity when above-elbow amputees voluntarily moved their phantom limb. Voluntary movements of the phantom hand triggered specific patterns of stump muscle activity, which differed from activity recorded in the same muscle groups during movements of the proximal limb. This result indicates that the brain's motor areas can be differentially activated according to the phantom movement the patient intends to perform, and suggests that hand motor commands are preserved after amputation. To further understand the interaction between central commands and sensory feedback in the perception of phantom movement we also measured stump muscle EMG activity in an amputee experiencing a frozen phantom limb, and in three below-elbow amputees with vivid phantom movements after inducing an ischaemic block. Failed attempts to move the paralysed phantom limb always resulted in the same EMG pattern, no matter what type of phantom movement was attempted, while ischaemic nerve block reduced or eliminated the ability to voluntarily move the phantom limb and produced a dramatic reduction in the amplitude of stump muscle EMG activity. Our data suggest that the experience of phantom hand movement involves the activation of hand motor commands. We propose that preserved hand movement representations re-target the stump muscles to express themselves and that when these representations are voluntarily accessible they can instruct the remaining muscles to move in such a way as if the limb is still there.

Although the superior dexterity of one hand is an almost ubiquitous human experience, it is unclear which characteristics of the motor system controlling the preferred hand produce this superior dexterity. Between-species studies show that greater dexterity is associated with a motor system that permits more independent movements of the digits. If between-hand dexterity differences are mediated by the same mechanism as between-species dexterity differences, then there should be asymmetries within the corticospinal tracts of humans that would result in between-hand independence differences. The evidence for asymmetries in the corticospinal tracts is sparse, and if an asymmetry does exist, it appears to be limited to the control of intrinsic hand muscles. We wondered, therefore, whether there might be a difference in the degree of independent control on the two hands during performance of a task that primarily uses intrinsic hand muscles. We examined digit individuation when subjects produced abduction or adduction forces with a single digit in isolation. Consistent with previous studies in which forces or movements in single digits were generated primarily by extrinsic hand muscles, we found no difference between the individuation of the digits on the preferred and non-preferred hands. We suggest that whereas independence differences underlie large dexterity differences between species, they do not underlie the more subtle dexterity differences between the preferred and non-preferred hands. Instead, the neural substrate for handedness might be asymmetrical connectivity within M1, with more profuse connections within the dominant than non-dominant M1 imparting a greater potential for excitatory and inhibitory interactions between movement representations which might then result in the more efficient coordination of hand and arm movements of the preferred hand.

In non-human primates, comparative studies show that greater dexterity is associated with greater independent control over the digits. Studies of humans, however, show no difference in the degree of independent control of single digits on the more dexterous preferred hand and its less dexterous partner. We wondered whether there might be a difference in the degree of independent control on the two hands during performance of functionally relevant tasks. Many object manipulation tasks require the ability to produce and control forces with more than one finger at the same time. We hypothesized that asymmetrical independence, with greater independence on the preferred than the non-preferred hand, would be evident with a task that requires the simultaneous production of force in two digits. We examined digit individuation when subjects produced flexion forces with a single digit in isolation, and simultaneous flexion forces in all ten combinations of two digits. Consistent with previous studies, we found no difference between the individuation of the digits on the preferred and non-preferred hands during force production with single digits in isolation. Similarly, no asymmetry was present when forces were produced by two digits. However, separation of two-digit forces into thumb-to-digit opposition forces and non-opposition forces showed that although there was no difference in individuation between the two hands for non-opposition forces, the digits on the preferred hand were more independent than those on the non-preferred hand for opposition forces. We suggest that this independence asymmetry is not itself the underlying cause of the dexterity differences between the hands, but rather arises from a difference in the capacity for use-dependent reorganization of the motor cortical circuits controlling each hand, and that this difference might underlie the dexterity differences between the hands.

The aim of this study was to verify the short-term reliability of transcranial magnetic stimulation (TMS) parameters for a damaged stump muscle in upper-limb amputees (n = 6). The motor threshold, response latency and map center of gravity in the mediolateral plane showed good reliability, whereas the map volume measure was less stable. The stability of most TMS measures across time supports the use of TMS in studying cortical plasticity in amputees.

Amputees can move their phantom limb at will. These 'movements without movements' have generally been considered as motor imagery rather than motor execution, but amputees can in fact perform both executed and imagined movements with their phantom and they report distinct perceptions during each task. Behavioural evidence for this dual ability comes from the fact that executed movements are associated with stump muscle contractions whereas imagined movements are not, and that phantom executed movements are slower than intact hand executed movements whereas the speed of imagined movements is identical for both hands. Since neither execution nor imagination produces any visible movement, we hypothesized that the perceptual difference between these two motor tasks relies on the activation of distinct cerebral networks. Using functional magnetic resonance imaging and changes in functional connectivity (dynamic causal modelling), we examined the activity associated with imagined and executed movements of the intact and phantom hands of 14 upper-limb amputees. Distinct but partially overlapping cerebral networks were active during both executed and imagined phantom limb movements (both performed at the same speed). A region of interest analysis revealed a 'switch' between execution and imagination; during execution there was more activity in the primary somatosensory cortex, the primary motor cortex and the anterior lobe of the cerebellum, while during imagination there was more activity in the parietal and occipital lobes, and the posterior lobe of the cerebellum. In overlapping areas, task-related differences were detected in the location of activation peaks. The dynamic causal modelling analysis further confirmed the presence of a clear neurophysiological distinction between imagination and execution, as motor imagery and motor execution had opposite effects on the supplementary motor area-primary motor cortex network. This is the first imaging evidence that the neurophysiological network activated during phantom limb movements is similar to that of executed movements of intact limbs and differs from the phantom limb imagination network. The dual ability of amputees to execute and imagine movements of their phantom limb and the fact that these two tasks activate distinct cortical networks are important factors to consider when designing rehabilitation programmes for the treatment of phantom limb pain.

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.

Consciousness and Intention Where in the brain are our intentions formed and how do we become aware of these intentions? Desmurget et al. (p. 811 ; see the Perspective by Haggard ) investigated the effect of direct cortical stimulation of parietal and premotor regions in patients undergoing brain surgery for tumor removal. Stimulation of the parietal lobe provoked the conscious experience of wanting to move the upper limb, lips, or tongue without any concomitant motor activity. When stimulation intensity was increased, patients believed that they had actually moved or talked, but again no muscle activity was detected. When, however, the premotor region of the frontal lobes was stimulated, real complex multijoint movements were induced. However, patients did not experience these movements as produced by a conscious internal act of will. Indeed, they were not even aware that they had moved. Increasing stimulation intensity increased the amplitude or complexity of the movement but never made it reach consciousness.

The human primary motor cortex (M1) undergoes considerable reorganization in response to traumatic upper limb amputation. The representations of the preserved arm muscles expand, invading portions of M1 previously dedicated to the hand, suggesting that former hand neurons are reassigned to the control of remaining proximal upper limb muscles. Hand allograft offers a unique opportunity to study the reversibility of such long-term cortical changes. We used transcranial magnetic stimulation in patient LB, who underwent bilateral hand transplantation 3 years after a traumatic amputation, to longitudinally track both the emergence of intrinsic (from the donor) hand muscles in M1 as well as changes in the representation of stump (upper arm and forearm) muscles. The same muscles were also mapped in patient CD, the first bilateral hand allograft recipient. Newly transplanted intrinsic muscles acquired a cortical representation in LB's M1 at 10 months postgraft for the left hand and at 26 months for the right hand. The appearance of a cortical representation of transplanted hand muscles in M1 coincided with the shrinkage of stump muscle representations for the left but not for the right side. In patient CD, transcranial magnetic stimulation performed at 51 months postgraft revealed a complete set of intrinsic hand-muscle representations for the left but not the right hand. Our findings show that newly transplanted muscles can be recognized and integrated into the patient's motor cortex.

Individuated finger movements of the human hand require selective activation of particular sets of muscles. Such selective activation is controlled primarily by the motor cortex via the corticospinal tract. Is this selectivity therefore lost when lesions damage the corticospinal tract? Or when the motor cortex reorganizes after amputation? We studied finger movements in normal human subjects and in patients who had recovered substantially from pure motor hemiparesis caused by lacunar strokes, which damage the corticospinal tract without affecting other pathways. Even after substantial recovery from these strokes, individuation of finger movements remained reduced-both for flexion/extension and for adduction/ abduction motion of the fingers. Stroke subjects regained the ability to move the instructed digit through a normal range, but unintentional motion of other digits was increased. This increase did not result from a change in the passive biomechanical coupling of the fingers. Rather, voluntary contractions of muscles that move the intended digit were accompanied by inappropriate contractions in muscles acting on additional digits. These observations suggest that the normal corticospinal system produces individuated finger movements not only by selectively activating certain muscles, but also by suppressing activation of other muscles during voluntary effort to move a given digit. In a separate experiment, reversible amputation of the hand was produced in normal subjects by ischemic nerve block at the wrist. Motor output to the intrinsic muscles and sensory input both become blocked under these conditions, effectively amputating the hand from the nervous system. But the long extrinsic muscles that flex and extend the digits remain normally innervated, and thus flexion forces still can be generated at the fingertips. During reversible amputation of the hand produced by ischemic nerve block, the ability of subjects to activate subdivisions of extrinsic muscles and to exert flexion force at individual fingertips continued to show essentially normal selectivity. Voluntary activation of the remaining muscles thus continues to be selective after amputation, in spite of both the loss of sensory input from the amputated hand, and reorganization within the primary motor cortex. During cortical reorganization after amputation, then, voluntary patterns of motor output intended for finger muscles may not be lost. We therefore examined activity in the stump muscles of above-elbow amputees, who have no remaining hand muscles. Different movements of the phantom hand were accompanied by different patterns of EMG in remaining proximal muscles, distinct from the EMG patterns associated with movement of the phantom elbow. We infer that voluntary motor output patterns that normally control finger movements after amputation may become diverted to remaining proximal muscles.

During ischemic nerve block of an extremity, the cortical representations of muscles proximal to the block are known to expand, increasing the overlap of different muscle representations. Such reorganization mimics that seen in actual amputees. We investigated whether such changes degrade voluntary control of muscles proximal to the block. Nine subjects produced brief, isometric flexion force selectively with each fingertip before, during, and after ischemic block at the wrist. We recorded the isometric force exerted at the distal phalanx of each digit, along with electromyographic (EMG) activity from intrinsic and extrinsic finger muscles. Despite paralysis of the intrinsic hand muscles, and associated decrements in the flexion forces exerted by the thumb, index, and little fingers, the selectivity of voluntary finger flexion forces and of EMG activity in the extrinsic finger muscles that generated these forces remained unchanged. Our observations indicate that during ischemic nerve block, reorganization does not eliminate or degrade motor representations of the temporarily deafferented and paralyzed fingers.

Limb amputation results in plasticity of connections between the brain and muscles, with the cortical motor representation of the missing limb seemingly shrinking, to the presumed benefit of remaining body parts that have cortical representations adjacent to the now-missing limb. Surprisingly, the corresponding perceptual representation does not suffer a similar fate but instead persists as a phantom limb endowed with sensory and motor qualities. How can cortical reorganization after amputation be reconciled with the maintenance of a motor representation of the phantom limb in the brain? In an attempt to answer this question we explored the relationship between the cortical representation of the remaining arm muscles and that of phantom movements. Using transcranial magnetic stimulation (TMS) we systematically mapped phantom movement perceptions while simultaneously recording stump muscle activity in three above-elbow amputees. TMS elicited sensations of movement in the phantom hand when applied over the presumed hand area of the motor cortex. In one subject the amplitude of the perceived movement was positively correlated with the intensity of stimulation. Interestingly, phantom limb movements that the patient could not produce voluntarily were easily triggered by TMS, suggesting that the inability to voluntarily move the phantom is not equivalent to a loss of the corresponding movement representation. We suggest that hand movement representations survive in the reorganized motor area of amputees even when these cannot be directly accessed. The activation of these representations is probably necessary for the experience of phantom movement.

The human flexor digitorum profundus (FDP) sends tendons to all 4 fingers. One might assume that this multitendoned muscle consists of 4 discrete neuromuscular compartments each acting on a different finger, but recent anatomical and physiological studies raise the possibility that the human FDP is incompletely subdivided. To investigate the functional organization of the human FDP, we recorded electromyographic (EMG) activity by bipolar fine-wire electrodes simultaneously from 2 or 4 separate intramuscular sites as normal human subjects performed isometric, individuated flexion, and extension of each left-hand digit. Some recordings showed EMG activity during flexion of only one of the 4 fingers, indicating that the human FDP has highly selective core regions that act on single fingers. The majority of recordings, however, showed a large amount of EMG activity during flexion of one finger and lower levels of EMG activity during flexion of an adjacent finger. This lesser EMG activity during flexion of adjacent fingers was unlikely to have resulted from recording motor units in neighboring neuromuscular compartments, and instead suggests incomplete functional subdivision of the human FDP. In addition to the greatest agonist EMG activity during flexion of a given finger, most recordings also showed EMG activity during extension of adjacent fingers, apparently serving to stabilize the given finger against unwanted extension. Paradoxically, the functional organization of the human FDP—with both incomplete functional subdivision and highly selective core regions—may contribute simultaneously to the inability of humans to produce completely independent finger movements, and to the greater ability of humans (compared with macaques) to individuate finger movements.

The effects of acoustic stimuli whose onsets and durations were controlled to vary their transient and sustained features on the size of a subsequently elicited blink reflex were examined in humans. Prestimuli both with and without transient features inhibited the reflex when they preceded the eliciting stimulus by brief lead intervals, showing that acoustic transients are sufficient, but not necessary, for reflex inhibition. Inhibition evoked by transient and sustained stimulus features showed partial summation, and inhibition evoked by stimuli with only transient and with transient and sustained features showed similar decay functions with increasing lead intervals. Blink augmentation was found at longer lead intervals early but not late in a session, and was more evident in women than men. Prestimuli with only transient features were more effective than those with both transient and sustained features, showing that sustained stimulus energy at the time of reflex elicitation is not only not necessary for blink augmentation, but also diminishes it.

The hypothesis that handedness stems from a greater ability to produce independent forces in the digits of the preferred than the non-preferred hand was investigated in 20 right-handed males who made a sustained isometric flexion of the distal phalanx of a single digit (the instructed digit). Instructed flexion forces were accompanied by non-instructed forces in all other digits. Mean non-instructed force was least when the thumb was the instructed digit, and increased progressively when the index, middle, ring, and little finger was the instructed digit. Both flexion and extension were recorded in non-instructed digits. There was no asymmetry in production of non-instructed force, and hence no evidence for greater independence of force production in the digits of the preferred than the non-preferred hand.

Summary The hand–face border is one of the most prominent features of the primate somatosensory cortex. A reduction of somatosensory input, following amputation or anesthesia, induces perceptual changes across this border that are explained by plastic competitive mechanisms [1–4]. Whether cross-border plasticity can be induced by learning processes relying on increased somatosensory input has been unclear. Here we report that training-independent learning [5] improves tactile perception, not only at the stimulated index finger, but also at the unstimulated face. These findings demonstrate that learning-induced tactile improvement can cross the hand–face border, suggesting that facilitation-based plasticity may operate in the healthy human brain.