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Background: Intermittent theta-burst stimulation (i) (TBS) is a transcranial magnetic stimulation (TMS) plasticity protocol. Conventionally, TBS is applied using biphasic pulses due to hardware limitations. However, monophasic pulses are hypothesised to recruit cortical neurons more selectively than biphasic pulses, predicting stronger plasticity effects. Monophasic and biphasic TBS can be generated using a custom-made pulse-width modulation-based TMS device (pTMS). Objective: Using pTMS, we tested the hypothesis that monophasic iTBS would induce a stronger plasticity effect than biphasic, measured as induced increases in motor corticospinal excitability. Methods: In a repeated-measures design, thirty healthy volunteers participated in three separate sessions, where monophasic and biphasic iTBS was applied to the primary motor cortex (M1 condition) or the vertex (control condition). Plasticity was quantified as increases in motor corticospinal excitability after versus before iTBS, by comparing peak-to-peak amplitudes of motor evoked potentials (MEP) measured at baseline and over 60 min after iTBS. Results: Both monophasic and biphasic M1 iTBS led to significant increases in MEP amplitude. As predicted, linear mixed effects (LME) models showed that the iTBS condition had a significant effect on the MEP amplitude (χ2 (1) = 27.615, p

Intermittent theta-burst stimulation (i) (TBS) is a transcranial magnetic stimulation (TMS) plasticity protocol. Conventionally, TBS is applied using biphasic pulses due to hardware limitations. However, monophasic pulses are hypothesised to recruit cortical neurons more selectively than biphasic pulses, predicting stronger plasticity effects. Monophasic and biphasic TBS can be generated using a custom-made pulse-width modulation-based TMS device (pTMS). Using pTMS, we tested the hypothesis that monophasic iTBS would induce a stronger plasticity effect than biphasic, measured as induced increases in motor corticospinal excitability. In a repeated-measures design, thirty healthy volunteers participated in three separate sessions, where monophasic and biphasic iTBS was applied to the primary motor cortex (M1 condition) or the vertex (control condition). Plasticity was quantified as increases in motor corticospinal excitability after versus before iTBS, by comparing peak-to-peak amplitudes of motor evoked potentials (MEP) measured at baseline and over 60 min after iTBS. Both monophasic and biphasic M1 iTBS led to significant increases in MEP amplitude. As predicted, linear mixed effects (LME) models showed that the iTBS condition had a significant effect on the MEP amplitude (χ2 (1) = 27.615, p < 0.001) with monophasic iTBS leading to significantly stronger plasticity than biphasic iTBS (t (693) = 2.311, p = 0.021). Control vertex iTBS had no effect. In this study, monophasic iTBS induced a stronger motor corticospinal excitability increase than biphasic within participants. This greater physiological effect suggests that monophasic iTBS may also have potential for greater functional impact, of interest for future fundamental and clinical applications of TBS. • Plasticity induction via pulse-width modulation-based TMS. • Both mono- and biphasic theta burst stimulation induced motor plasticity. • Monophasic intermittent TBS induced a larger plasticity effect than biphasic. [ABSTRACT FROM AUTHOR]

Recent research has investigated whether the representation of space around the body, in terms of reach–action (imagining of reaching another person) and comfort–social (tolerance of the other's proximity) spaces, may reflect a shared sensorimotor basis. Some studies exploiting motor plasticity induced by tool use have not observed sensorimotor identity (i.e., the same mechanisms that underlie, based on sensory information, the representation of proximal space in terms of action possibilities, goal-directed motor actions, and anticipation of the sensorimotor consequences), whereas evidence to the contrary has also emerged. Since the data are not fully convergent, here we wondered whether or not the combination of motor plasticity induced by tool use and the processing of the role of social context might reflect a similar modulation in both spaces. To this end, we conducted a randomized control trial with three groups of participants (N = 62) in which reaching and comfort distances were measured in Pre- and Post-tool-use sessions. The tool-use sessions were conducted under different conditions: (i) in the presence of a social stimulus (determining the social context) (Tool plus Mannequin group); (ii) without any stimulus (Only Tool group); (iii) in the presence of a box (Tool plus Object group) as a control condition. Results showed an extension of comfort distance in the Post-tool session of the Tool plus Mannequin group compared with the other conditions. Conversely, the reaching distance was larger after tool use than at the Pre-tool-use session, independently of the experimental conditions. Our findings suggest that motor plasticity impacts reaching and comfort spaces to different degrees; while reaching space is markedly sensitive to motor plasticity, comfort space needs qualification of social context information. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether a common polymorphism (Val66Met) in the gene for brain-derived neurotrophic factor (BDNF)—a gene thought to influence plasticity—contributes to inter-individual variability in responses to continuous theta-burst stimulation (cTBS), and explore whether variability in stimulation-induced plasticity among Val66Met carriers relates to differences in stimulation intensity (SI) used to probe plasticity.Methods: Motor evoked potentials (MEPs) were collected from 33 healthy individuals (11 Val66Met) prior to cTBS (baseline) and in 10 min intervals immediately following cTBS for a total of 30 min post-cTBS (0 min post-cTBS, 10 min post-cTBS, 20 min post cTBS, and 30 min post-cTBS) of the left primary motor cortex. Analyses assessed changes in cortical excitability as a function of BDNF (Val66Val vs. Val66Met) and SI.Results: For both BDNF groups, MEP-suppression from baseline to post-cTBS time points decreased as a function of increasing SI. However, the effect of SI on MEPs was more pronounced for Val66Met vs. Val66Val carriers, whereby individuals probed with higher vs. lower SIs resulted in paradoxical cTBS aftereffects (MEP-facilitation), which persisted at least 30 min post-cTBS administration.Conclusions: cTBS aftereffects among BDNF Met allele carriers are more variable depending on the SI used to probe cortical excitability when compared to homozygous Val allele carriers, which could, to some extent, account for the inconsistency of previously reported cTBS effects.Significance: These data provide insight into the sources of cTBS response variability, which can inform how best to stratify and optimize its use in investigational and clinical contexts.

Objective : To evaluate whether a common polymorphism (Val66Met) in the gene for brain-derived neurotrophic factor (BDNF)—a gene thought to influence plasticity—contributes to inter-individual variability in responses to continuous theta-burst stimulation (cTBS), and explore whether variability in stimulation-induced plasticity among Val66Met carriers relates to differences in stimulation intensity (SI) used to probe plasticity. Methods : Motor evoked potentials (MEPs) were collected from 33 healthy individuals (11 Val66Met) prior to cTBS (baseline) and in 10 min intervals immediately following cTBS for a total of 30 min post-cTBS (0 min post-cTBS, 10 min post-cTBS, 20 min post cTBS, and 30 min post-cTBS) of the left primary motor cortex. Analyses assessed changes in cortical excitability as a function of BDNF (Val66Val vs. Val66Met) and SI. Results : For both BDNF groups, MEP-suppression from baseline to post-cTBS time points decreased as a function of increasing SI. However, the effect of SI on MEPs was more pronounced for Val66Met vs. Val66Val carriers, whereby individuals probed with higher vs. lower SIs resulted in paradoxical cTBS aftereffects (MEP-facilitation), which persisted at least 30 min post-cTBS administration. Conclusions : cTBS aftereffects among BDNF Met allele carriers are more variable depending on the SI used to probe cortical excitability when compared to homozygous Val allele carriers, which could, to some extent, account for the inconsistency of previously reported cTBS effects. Significance : These data provide insight into the sources of cTBS response variability, which can inform how best to stratify and optimize its use in investigational and clinical contexts. [ABSTRACT FROM AUTHOR]

Background: Perinatal stroke often leads to lifelong motor impairment. Two common subtypes differ in timing, location, and mechanism of injury: periventricular venous infarcts (PVI) are fetal white matter lesions while most arterial ischemic strokes (AIS) are cortical injuries acquired near term birth. Both alter motor system development and primary motor cortex (M1) plasticity, often with retained ipsilateral corticospinal fibers from the non-lesioned motor cortex (M1').Methods: Task-based functional magnetic resonance imaging was used to define patterns of motor cortex activity during paretic and unaffected hand movement. Peak coordinates of M1, M1', and the supplementary motor area in the lesioned and intact hemispheres were compared to age-matched controls. Correlations between displacements and clinical motor function were explored.Results: Forty-nine participants included 14 PVI (12.59 ± 3.7 years), 13 AIS (14.91 ± 3.9 years), and 22 controls (13.91 ± 3.4 years). AIS displayed the greatest M1 displacement from controls in the lesioned hemisphere while PVI locations approximated controls. Peak M1' activations were displaced from the canonical hand knob in both PVI and AIS. Extent of M1 and M1' displacement were correlated (r = 0.50, P = 0.025) but were not associated with motor function. Supplementary motor area activity elicited by paretic tapping was displaced in AIS compared to controls (P = 0.003).Conclusion: Motor network components may be displaced in both hemispheres after perinatal stroke, particularly in AIS and those with ipsilateral control of the affected limb. Modest correlations with clinical function may support that more complex models of developmental plasticity are needed to inform targets for individualized neuromodulatory therapies in children with perinatal stroke. [ABSTRACT FROM AUTHOR]

Before primary motor cortex (M1) develops its motor functions, it functions like a somatosensory area. Here, by recording from neurons in the forelimb representation of M1 in postnatal day (P) 8–12 rats, we demonstrate a rapid shift in its sensory responses. At P8-10, M1 neurons respond overwhelmingly to feedback from sleep-related twitches of the forelimb, but the same neurons do not respond to wake-related movements. By P12, M1 neurons suddenly respond to wake movements, a transition that results from opening the sensory gate in the external cuneate nucleus. Also at P12, fewer M1 neurons respond to individual twitches, but the full complement of twitch-related feedback observed at P8 is unmasked through local disinhibition. Finally, through P12, M1 sensory responses originate in the deep thalamorecipient layers, not primary somatosensory cortex. These findings demonstrate that M1 initially establishes a sensory framework upon which its later-emerging role in motor control is built.

The present study tested whether remapping of visuomotor correspondence alters automatic motor responses induced by visual stimuli. We hypothesized that the congruency effect, an automatic modulation of motor responses based on stimulus-response congruency, changes in accordance with a new visuomotor correspondence acquired through an adaptation task. To induce visuomotor adaptation, participants performed a tracking task with 30° or 150° rotation of the visual feedback. The congruency effect was evaluated multiple times by a visual response task where participants moved their finger left or right. We predicted that the congruency effect, as a measure of automatic responses, would be almost reversed after adaptation to the 150° rotation, because a visual stimulus spatially opposite to the participant's own action would become a "congruent" stimulus in a 150°-rotated environment but not in a 30°-rotation environment. The results show that visuomotor adaptation to the 150° rotation did modulate the congruency effect in accordance with the acquired visuomotor correspondence, but did not completely reverse the effect. When the effect was assessed after the manipulation, which was assumed to switch an internal model back to its normal state, there was no change in automatic motor responses. Furthermore, we found that after effects developed as the training proceeded but decreased over time. These findings suggest that the visuomotor system subserving automatic modulation in motor responses is based on the currently active internal model and, therefore, highly adaptive. In addition, the mechanism underlying after effects in a visuomotor task is discussed in terms of a switching function of internal models. [ABSTRACT FROM AUTHOR]

Abstract: In relapsing‐remitting MS (RRMS), the symptoms of a clinical relapse subside over time. Neuroplasticity is believed to play an important compensatory role. In this study, we assessed excitability‐decreasing plasticity during an acute relapse of MS and 12 weeks afterwards. Motor plasticity was examined in 19 patients with clinically isolated syndrome or RRMS during a steroid‐treated relapse (t1) and 12 weeks afterwards (t2) using paired‐associative stimulation (PAS10). This method combines repetitive electric nerve stimulation with transcranial magnetic stimulation of the contralateral motor cortex to model long‐term synaptic depression in the human cortex. Additionally, 19 age‐matched healthy controls were assessed. Motor‐evoked potentials of the abductor pollicis brevis muscle were recorded before and after intervention. Clinical disability was assessed by the multiple sclerosis functional composite and the subscore of the nine‐hole peg test taken as a measure of hand function. The effect of PAS10 was significantly different between controls and patients; at t1, but not at t2, baseline‐normalized postinterventional amplitudes were significantly higher in patients (106 [IQR 98–137] % post10–15 and 111 [IQR 88–133] % post20–25) compared to controls (92 [IQR 85–111] % and 90 [IQR 75–102] %). Additional exploratory analysis indicated a potentially excitability‐enhancing effect of PAS10 in patients as opposed to controls. Significant clinical improvement between t1 and t2 was not correlated with PAS10 effects. Our results indicate an alteration of PAS10‐induced synaptic plasticity during relapse, presumably reflecting a polarity shift due to metaplastic processes within the motor cortex. Further studies will need to elucidate the functional significance of such changes for the clinical course of MS. [ABSTRACT FROM AUTHOR]

The idea that the damaged brain can functionally reorganize itself ⎯ so when one part fails, there lies the possibility for another to substitute ⎯ is an exciting discovery of the twentieth century. We now know that motor circuits once presumed to be hardwired are not, and motor-skill learning, exercise, and even mental rehearsal of motor tasks can turn genes on or off to shape brain architecture, function and, consequently, behavior. This is a very significant alteration from our previously static view of the brain, and has profound implications for the rescue of function after a motor injury. Presentation of the right cues, applied in relevant spatiotemporal geometries, is required to awaken the dormant plastic forces essential for repair. The focus of this review is to highlight some of the recent progress in neural interfaces designed to harness motor plasticity, and the role of miniaturization in development of strategies that engage diverse elements of the neuronal machinery to synergistically facilitate recovery of function after motor damage.

Breathing is a vital homeostatic behavior and must be precisely regulated throughout life. Clinical conditions commonly associated with inflammation, undermine respiratory function may involve plasticity in respiratory control circuits to compensate and maintain adequate ventilation. Alternatively, other clinical conditions may evoke maladaptive plasticity. Yet, we have only recently begun to understand the effects of inflammation on respiratory plasticity. Here, we review some of common models used to investigate the effects of inflammation and discuss the impact of inflammation on nociception, chemosensory plasticity, medullary respiratory centers, motor plasticity in motor neurons and respiratory frequency, and adaptation to high altitude. We provide new data suggesting glial cells contribute to CNS inflammatory gene expression after 24 h of sustained hypoxia and inflammation induced by 8 h of intermittent hypoxia inhibits long-term facilitation of respiratory frequency. We also discuss how inflammation can have opposite effects on the capacity for plasticity, whereby it is necessary for increases in the hypoxic ventilatory response with sustained hypoxia, but inhibits phrenic long term facilitation after intermittent hypoxia. This review highlights gaps in our knowledge about the effects of inflammation on respiratory control (development, age, and sex differences). In summary, data to date suggest plasticity can be either adaptive or maladaptive and understanding how inflammation alters the respiratory system is crucial for development of better therapeutic interventions to promote breathing and for utilization of plasticity as a clinical treatment. [ABSTRACT FROM AUTHOR]

Summary During REM sleep, skeletal muscles are paralyzed in one moment but twitch and jerk in the next. REM sleep twitches are traditionally considered random motor events that result from momentary lapses in REM sleep paralysis [ 1–3 ]. However, recent evidence indicates that twitches are not byproducts of REM sleep, but are in fact self-generated events that could function to promote motor learning and development [ 4–6 ]. If REM twitches are indeed purposefully generated, then they should be controlled by a coordinated and definable mechanism. Here, we used behavioral, electrophysiological, pharmacological, and neuroanatomical methods to demonstrate that an inhibitory drive onto skeletal motoneurons produces a temporally coordinated pattern of muscle twitches during REM sleep. First, we show that muscle twitches in adult rats are not uniformly distributed during REM sleep, but instead follow a well-defined temporal trajectory. They are largely absent during REM initiation but increase steadily thereafter, peaking toward REM termination. Next, we identify the transmitter mechanism that controls the temporal nature of twitch activity. Specifically, we show that a GABA and glycine drive onto motoneurons prevents twitch activity during REM initiation, but progressive weakening of this drive functions to promote twitch activity during REM termination. These results demonstrate that REM twitches are not random byproducts of REM sleep, but are instead rather coherently generated events controlled by a temporally variable inhibitory drive. [ABSTRACT FROM AUTHOR]

After watching sports, people often feel as if their sports skills might have been improved, even without any actual training. On some occasions, this motor skill learning through observation actually occurs. This phenomenon may be due to the fact that both action and action observation ( AO) can activate shared cortical areas. However, the neural basis of performance gain through AO has not yet been fully clarified. In the present study, we used transcranial magnetic stimulation to investigate whether primary motor cortex (M1) plasticity is a physiological substrate of AO-induced performance gain and whether AO itself is sufficient to change motor performance. The excitability of M1, especially that of its intracortical excitatory circuit, was enhanced after and during AO with kinesthetic illusion but not in interventions without this illusion. Moreover, behavioral improvement occurred only after AO with kinesthetic illusion, and a significant correlation existed between the performance gain and the degree of illusion. Our findings indicated that kinesthetic illusion is an essential component of the motor learning and M1 plasticity induced by AO, and this insight may be useful for the strategic rehabilitation of stroke patients. [ABSTRACT FROM AUTHOR]

Action-related sounds are known to increase the excitability of motoneurones within the primary motor cortex (M1), but the role of this auditory input remains unclear. We investigated repetition priming-induced plasticity, which is characteristic of semantic representations, in M1 by applying transcranial magnetic stimulation pulses to the hand area. Motor evoked potentials (MEPs) were larger while subjects were listening to sounds related versus unrelated to manual actions. Repeated exposure to the same manual-action-related sound yielded a significant decrease in MEPs when right, hand area was stimulated; no repetition effect was observed for manual-action-unrelated sounds. The shared repetition priming characteristics suggest that auditory input to the right primary motor cortex is part of auditory semantic representations. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess whether the simultaneous application of slow-oscillation transcranial direct current stimulation enhances the neuroplastic response to transcranial magnetic theta burst stimulation. Motor evoked potential amplitude was assessed at baseline and at regular intervals up to 60 min following continuous theta burst stimulation, slow-oscillation transcranial direct current stimulation, and the simultaneous application of these paradigms. In addition, the electroencephalographic power spectra of slow and fast delta, and theta frequency bands recorded over the motor cortex were analyzed prior to and up to 5 min following each intervention. There was longer-lasting motor evoked potential suppression following the simultaneous application of continuous theta burst stimulation and slow-oscillation transcranial direct current stimulation compared with when continuous theta burst stimulation was applied alone. Slow-oscillation transcranial direct current stimulation applied alone did not modulate the motor evoked potential amplitude. No significant changes in spectral power were observed following slow-oscillation transcranial direct current stimulation. Simultaneous application of continuous theta burst stimulation and slow-oscillation transcranial direct current stimulation may provide an approach to prolong the induction of neuroplastic changes in motor cortical circuits by repetitive transcranial magnetic brain stimulation. [ABSTRACT FROM AUTHOR]

Background: Compensation of brain injury in multiple sclerosis (MS) may in part work through mechanisms involving neuronal plasticity on local and interregional scales. Mechanisms limiting excessive neuronal activity may have special significance for retention and (re-)acquisition of lost motor skills in brain injury. However, previous neurophysiological studies of plasticity in MS have investigated only excitability enhancing plasticity and results from neuroimaging are ambiguous. Thus, the aim of this study was to probe long-term depression-like central motor plasticity utilizing continuous theta-burst stimulation (cTBS), a non-invasive brain stimulation protocol. Because cTBS also may trigger behavioral effects through local interference with neuronal circuits, this approach also permitted investigating the functional role of the primary motor cortex (M1) in force control in patients with MS. Methods: We used cTBS and force recordings to examine long-term depression-like central motor plasticity and behavioral consequences of a M1 lesion in 14 patients with stable mild-to-moderate MS (median EDSS 1.5, range 0 to 3.5) and 14 age-matched healthy controls. cTBS consisted of bursts (50 Hz) of three subthreshold biphasic magnetic stimuli repeated at 5 Hz for 40 s over the hand area of the left M1. Corticospinal excitability was probed via motor-evoked potentials (MEP) in the abductor pollicis brevis muscle over M1 before and after cTBS. Force production performance was assessed in an isometric right thumb abduction task by recording the number of hits into a predefined force window. Results: cTBS reduced MEP amplitudes in the contralateral abductor pollicis brevis muscle to a comparable extent in control subjects (69 ± 22% of baseline amplitude, p < 0.001) and in MS patients (69 ± 18%, p < 0.001). In contrast, postcTBS force production performance was only impaired in controls (2.2 ± 2.8, p = 0.011), but not in MS patients (2.0 ± 4.4, p = 0.108). The decline in force production performance following cTBS correlated with corticomuscular latencies (CML) in MS patients, but did not correlate with MEP amplitude reduction in patients or controls. Conclusions: Long-term depression-like plasticity remains largely intact in mild-to-moderate MS. Increasing brain injury may render the neuronal networks less responsive toward lesion-induction by cTBS. [ABSTRACT FROM AUTHOR]

Summary Neuromuscular adaptations during skill acquisition have been extensively investigated for skeletal muscles. Motor rehabilitation is the main target for application of motor training. Such measures are also relevant for the musculature of the jaw, but few data are available for motor adaptation of the masticatory system. The objective of this study was to evaluate and compare long-term training effects of different motor tasks on masseter and temporal muscles. In 20 healthy subjects, the electromyographic response to unilateral and bilateral maximum voluntary tooth clenching, balancing the mandible on a hydrostatic system under force-feedback-controlled conditions, and unilateral chewing was investigated in an initial session and then in two follow-up sessions separated by 2 and 10 weeks from baseline. Motor tasks were repeated three times for chewing, nine times for maximum biting (MB) and 24 times for the coordination tasks (CT). The sequences of the various motor tasks were applied once in the first session and twice in the second and third sessions. No effects of training were observed for MB tasks except for MB in intercuspation, for which significant yet transient avoidance behaviour occurred in the second session. No significant effects were found for chewing tests. For the CT, however, a robust significant long-term training effect was detected which reduced the electric muscle activity in session 2 by approximately 20% and in session 3 by approximately 40% compared with the initial measurements. The study showed that the masticatory muscles are remarkably prone to motor adaptation if demanding CT must be accomplished. [ABSTRACT FROM AUTHOR]

Abstract: Our actions need constant calibration to arrive accurately at locations of their intended goals; errors in execution must drive rapid adjustments. As an example, saccadic eye movements are vital for bringing objects of interest into the high-acuity center of vision and they must be continually tuned to compensate for ongoing changes in body, muscle strength and neural variability. This adaptation of eye movement responses can be induced artificially by systematically displacing the saccade targets by a constant proportion during each saccade. Observers do not notice these shifts and yet the oculomotor system does, rapidly compensating for the landing error until the saccades finally land close to the artificially displaced target. This recalibration has been described as spatially selective, dropping off with distance in direction and amplitude from the adapted saccade vector. However, we now report that this local adaptation property is a consequence of adapting to only one direction at a time, the method generally used in previous studies. When we induced adaptation in all directions, using a quasi-random walk where each target was displaced 25% back toward to the previous fixation, we found strong, spatially generalized adaptation that could not be accounted for by an accumulation of many vector-specific adaptations. This global adaptation is a plausible strategy for calibration given the absence of any obvious growth changes or muscle deficits that would lead to vector specific losses and it provides a robust model for testing motor calibration. [ABSTRACT FROM AUTHOR]

Abstract: Structural equation modeling (SEM) and fMRI were used to test whether changes in the regional activity are accompanied by changes in the inter-regional connectivity as motor practice progresses. Ten healthy subjects were trained to perform finger movement task daily for 4 weeks. Three sessions of fMRI images were acquired within 4 weeks. The changes in inter-regional connectivity were evaluated by measuring the effective connectivity between the primary motor area (M1), supplementary motor area (SMA), dorsal premotor cortex (PMd), basal ganglia (BG), cerebellum (CB), and posterior ventrolateral prefrontal cortex (pVLPFC). The regional activities in M1 and SMA increased from pre-training to week 2 and decreased from week 2 to week 4. The inter-regional connectivity generally increased in strength (with SEM path coefficients becoming more positive or negative) as practice progressed. The increases in the strength of the inter-regional connectivity may reflect long-term reorganization of the skilled motor network. We suggest that the performance gain was achieved by dynamically tuning the inter-regional connectivity in the motor network. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Human motor development is thought to result from a complex interaction between genes and experience. The well-known somatotopic organization of the primate primary motor cortex (M1) emerges postnatally. Although adaptive changes in response to learning and use occur throughout life, somatotopy is maintained as reorganization is restricted to modifications within major body part representations. We report of a unique opportunity to evaluate the influence of experience on the genetically determined somatotopic organization of motor cortex in human. We examined the motor "foot" representation in subjects with congenitally compromised hand function and compensatory skillful foot use. Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) of M1 revealed that the foot was represented in the classical medial foot area of M1 and was several centimetres away in nonadjacent cortex in the vicinity of the lateral "hand" area. Both areas had direct output to the spinal motor neurons innervating foot muscles and were behaviorally relevant because experimental disruption of either area by TMS altered reaction times. We demonstrate a unique, nonsomatotopically organized M1 in humans, which emerged as a function of grossly altered motor behavior from the earliest stages of development. Our results imply that during early motor development experience may play a more critical role in the shaping of genetically determined neural networks than previously assumed. [ABSTRACT FROM AUTHOR]

Blindness leads to a major reorganization of neural pathways associated with touch. Because incoming somatosensory information influences motor output, it is plausible that motor plasticity occurs in the blind. In this work, we evaluated this issue at the peripheral level in enucleated rats. Whisker muscles in enucleated rats 160 days of age or older showed increased cytochrome oxidase activity, capillary density, motor plate size, and amplitude of evoked field potentials as compared with their control counter- parts. Such differences were not observed at ages 10 and 60 days, the capillary density was the exception being greater in the enucleated rat at the latter age. Interestingly, there was a trend to increased neurotrophin-3 concentrations in the whisker pads of enucleated rats throughout postnatal development. Our results show that neonatal enucleation leads to late onset plasticity of the whisker's motor system. [ABSTRACT FROM AUTHOR]

Circling training during rat striatum postnatal critical period (PN30 to 37 days) induces a life-lasting co-reduction of muscarinic acetylcholine receptors (mAChR) and dopamine D2 receptors (D2R) binding. Here, we evaluated the expression of D1R and D2R under similar experimental conditions. Trained rats showed a decrease of 40% in D2R binding sites (p<0.01) and of 45% in the D2R mRNA expression which involve short (p<0.05) and long (p<0.01) isoforms. In contrast, D1R binding sites nor its mRNA expression levels were affected by training, indicating a differential synaptic refinement during this ontogenetically fixed period. [Copyright &y& Elsevier]

A review of the research on anatomical and functional asymmetries in human primary motor cortex suggests that the area of hand representation is greater in the dominant than in the non-dominant hemisphere and that there is a greater dispersion of elementary movement representations with more profuse horizontal connections between them. The more profuse interconnections in motor cortex (M1) of the dominant hemisphere might form a neural substrate which favors the formation of experience-dependent excitatory and inhibitory interactions between elementary movement representations. Motor practice might lead to more precise spatiotemporal coordination of the activity of the elementary movement representations in M1 of the dominant than that of the non-dominant hemisphere, thus leading to more dexterous behavior of the dominant than that of the non-dominant hand. [Copyright &y& Elsevier]

After damage to the central nervous system, caused by traumatic injury or ischemia, plasticity becomes critically important for functional recovery. When this inherent capacity to adapt is limited despite training, external stimulation may support this process. Vagus nerve stimulation (VNS) is an effective method to enhance the effect of motor rehabilitation training on functional recovery. However, the mechanisms by which VNS exerts beneficial effects on cortical plasticity are not completely understood. Experimental work suggests that VNS fosters a neurochemical milieu that facilitates synaptic plasticity and supports reinforcement mechanisms. Animal studies, furthermore, suggest that VNS delivery is time-critical and that optima in the parameter space need to be titrated for effect maximization. Human studies suggest that VNS modifies corticospinal excitability. First studies in stroke patients show positive results for invasive, and also promising findings for non-invasive VNS. [ABSTRACT FROM AUTHOR]

In humans, limb amputation or brachial plexus avulsion (BPA) often results in phantom pain sensation. Actively observing movements made by a substitute of the injured limb can reduce phantom pain , Proc. R. Soc. London B Biol. Sci. 263, 377–386). The neural basis of phantom limb sensation and its amelioration remains unclear. Here, we studied the effects of visuomotor training on motor cortex (M1) activity in three patients with BPA. Functional magnetic resonance imaging scans were obtained before and after an 8-week training program during which patients learned to match voluntary “movements” of the phantom limb with prerecorded movements of a virtual hand. Before training, phantom limb movements activated the contralateral premotor cortex. After training, two subjects showed increased activity in the contralateral primary motor area. This change was paralleled by a significant reduction in phantom pain. The third subject showed no increase in motor cortex activity and no improvement in phantom pain. We suggest that successful visuomotor training restores a coherent body image in the M1 region and, as a result, directly affects the experience of phantom pain sensation. Artificial visual feedback on the movements of the phantom limb may thus “fool” the brain and reestablish the original hand/arm cortical representation. [Copyright &y& Elsevier]