Boosting focally-induced brain plasticity by dopamine

Dopamine (DA) simultaneously produces both excitation and inhibition in the human cortex. In order to shed light on the functional significance of these seemingly opposing effects, we administered the DA precursor levodopa (L-dopa) to healthy subjects in conjunction with 2 neuroplasticity-inducing motor cortex stimulation protocols. Transcranial direct current stimulation (tDCS) induces cortical excitability enhancement by anodal and depression by cathodal brain polarization, which is not restricted to specific subgroups of synapses. In contrast, paired associative stimulation (PAS) induces focal excitability enhancements of somatosensory and motor cortical neuronal synaptic connections. Here, we show that administering L-dopa turns the unspecific excitability enhancement caused by anodal tDCS into inhibition and prolongs the cathodal tDCS-induced excitability diminution. Conversely, it stabilizes the PAS-induced synapse-specific excitability increase. Most importantly, it prolongs all of these aftereffects by a factor of about 20. Hereby, DA focuses synapse-specific excitability-enhancing neuroplasticity in human cortical networks.     

Homeostatic metaplasticity of the motor cortex is altered during headache-free intervals in migraine with aura

Preconditioning of the human primary motor cortex (M1) with transcranial direct current stimulation (tDCS) can shape the magnitude and direction of excitability changes induced by a subsequent session of repetitive transcranial magnetic stimulation (rTMS). Here, we examined this form of metaplasticity in migraine patients with visual aura and healthy controls. In both groups, facilitatory preconditioning of left M1 with anodal tDCS increased the mean amplitudes of motor-evoked potentials (MEPs) elicited in the contralateral hand, whereas inhibitory preconditioning with cathodal tDCS produced a decrease in amplitude. Following cathodal tDCS, a short train of low-intensity 5-Hz rTMS antagonized the suppression of the mean MEP amplitude in both groups. In contrast, the homeostatic effects of 5-Hz rTMS differed between groups when rTMS was given after anodal tDCS. In controls 5-Hz rTMS induced a marked decrease in MEP amplitudes, whereas in migraineurs rTMS induced only a modest decrease in MEP amplitudes, which were still facilitated after rTMS when compared with baseline amplitudes. These findings indicate that short-term homeostatic plasticity is altered in patients with visual aura between the attacks.     

Catecholaminergic consolidation of motor cortical neuroplasticity in humans

Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptor-dependent long-lasting excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of excitability which lasted until the morning after tDCS, compared to approximately 1 h in the placebo condition. Prolongation of the excitability enhancement was most pronounced for long-term effects; the duration of short-term excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCS-driven excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a beta-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purpose-designed pharmacological interventions.     

Lie-specific involvement of dorsolateral prefrontal cortex in deception

Lies are intentional distortions of event knowledge. No experimental data are available on manipulating lying processes. To address this issue, we stimulated the dorsolateral prefrontal cortex (DLPFC) using transcranial direct current stimulation (tDCS). Fifteen healthy volunteers were tested before and after tDCS (anodal, cathodal, and sham). Two types of truthful (truthful selected: TS; truthful unselected: TU) and deceptive (lie selected: LS; lie unselected: LU) responses were evaluated using a computer-controlled task. Reaction times (RTs) and accuracy were collected and used as dependent variables. In the baseline task, the RT was significantly longer for lie responses than for true responses ([mean +/- standard error] 1153.4 +/- 42.0 ms vs. 1039.6 +/- 36.6 ms; F(1,14) = 27.25, P = 0.00013). At baseline, RT for selected pictures was significantly shorter than RT for unselected pictures (1051.26 +/- 39.0 ms vs. 1141.76 +/- 41.1 ms; F(1,14) = 34.85, P = 0.00004). Whereas after cathodal and sham stimulation, lie responses remained unchanged (cathodal 5.26 +/- 2.7%; sham 5.66 +/- 3.6%), after anodal tDCS, RTs significantly increased but did so only for LS responses (16.86 +/- 5.0%; P = 0.002). These findings show that manipulation of brain function with DLPFC tDCS specifically influences experimental deception and that distinctive neural mechanisms underlie different types of lies.     

Dissociating the roles of the cerebellum and motor cortex during adaptive learning: the motor cortex retains what the cerebellum learns

Adaptation to a novel visuomotor transformation has revealed important principles regarding learning and memory. Computational and behavioral studies have suggested that acquisition and retention of a new visuomotor transformation are distinct processes. However, this dissociation has never been clearly shown. Here, participants made fast reaching movements while unexpectedly a 30-degree visuomotor transformation was introduced. During visuomotor adaptation, subjects received cerebellar, primary motor cortex (M1) or sham anodal transcranial direct current stimulation (tDCS), a noninvasive form of brain stimulation known to increase excitability. We found that cerebellar tDCS caused faster adaptation to the visuomotor transformation, as shown by a rapid reduction of movement errors. These findings were not present with similar modulation of visual cortex excitability. In contrast, tDCS over M1 did not affect adaptation, but resulted in a marked increase in retention of the newly learnt visuomotor transformation. These results show a clear dissociation in the processes of acquisition and retention during adaptive motor learning and demonstrate that the cerebellum and primary motor cortex have distinct functional roles. Furthermore, they show that is possible to enhance cerebellar function using tDCS.     

Studying the neurobiology of social interaction with transcranial direct current stimulation--the example of punishing unfairness

Studying social behavior often requires the simultaneous interaction of many subjects. As yet, however, no painless, noninvasive brain stimulation tool existed that allowed the simultaneous affection of brain processes in many interacting subjects. Here we show that transcranial direct current stimulation (tDCS) can overcome these limits. We apply right prefrontal cathodal tDCS and show that subjects' propensity to punish unfair behavior is reduced significantly.     

A review of burn symptoms and potential novel neural targets for non-invasive brain stimulation for treatment of burn sequelae

Burn survivors experience myriad associated symptoms such as pain, pruritus, fatigue, impaired motor strength, post-traumatic stress, depression, anxiety, and sleep disturbance. Many of these symptoms are common and remain chronic, despite current standard of care. One potential novel intervention to target these post burn symptoms is transcranial direct current stimulation (tDCS). tDCS is a non-invasive brain stimulation (NIBS) technique that modulates neural excitability of a specific target or neural network. The aim of this work is to review the neural circuits of the aforementioned clinical sequelae associated with burn injuries and to provide a scientific rationale for specific NIBS targets that can potentially treat these conditions. We ran a systematic review, following the PRISMA statement, of tDCS effects on burn symptoms. Only three studies matched our criteria. One was a feasibility study assessing cortical plasticity in chronic neuropathic pain following burn injury, one looked at the effects of tDCS to reduce pain anxiety during burn wound care, and one assessed the effects of tDCS to manage pain and pruritus in burn survivors. Current literature on NIBS in burn remains limited, only a few trials have been conducted. Based on our review and results in other populations suffering from similar symptoms as patients with burn injuries, three main areas were selected: the prefrontal region, the parietal area and the motor cortex. Based on the importance of the prefrontal cortex in the emotional component of pain and its implication in various psychosocial symptoms, targeting this region may represent the most promising target. Our review of the neural circuitry involved in post burn symptoms and suggested targeted areas for stimulation provide a spring board for future study initiatives.     

Monocular visual deprivation suppresses excitability in adult human visual cortex

The adult visual cortex maintains a substantial potential for plasticity in response to a change in visual input. For instance, transcranial magnetic stimulation (TMS) studies have shown that binocular deprivation (BD) increases the cortical excitability for inducing phosphenes with TMS. Here, we employed TMS to trace plastic changes in adult visual cortex before, during, and after 48 h of monocular deprivation (MD) of the right dominant eye. In healthy adult volunteers, MD-induced changes in visual cortex excitability were probed with paired-pulse TMS applied to the left and right occipital cortex. Stimulus-response curves were constructed by recording the intensity of the reported phosphenes evoked in the contralateral visual field at range of TMS intensities. Phosphene measurements revealed that MD produced a rapid and robust decrease in cortical excitability relative to a control condition without MD. The cortical excitability returned to preinterventional baseline levels within 3 h after the end of MD. The results show that in contrast to the excitability increase in response to BD, MD acutely triggers a reversible decrease in visual cortical excitability. This shows that the pattern of visual deprivation has a substantial impact on experience-dependent plasticity of the human visual cortex.     

The perceptual and functional consequences of parietal top-down modulation on the visual cortex

The posterior parietal cortex (PPC) has been proposed to play a critical role in exerting top-down influences on occipital visual areas. By inducing activity in the PPC (angular gyrus) using transcranial magnetic stimulation (TMS), and using the phosphene threshold as a measure of visual cortical excitability, we investigated the functional role of this region in modulating the activity of the visual cortex. When triple-pulses of TMS were applied over the PPC unilaterally, the intensity of stimulation required to elicit a phosphene from the visual cortex (area V1/V2) was reduced, indicating an increase in visual cortical excitability. The increased excitability that was observed with unilateral TMS was abolished when TMS was applied over the PPC bilaterally. Our results provide a demonstration of the top-down modulation exerted by the PPC on the visual cortex and show that these effects are subject to interhemispheric competition.     

Effects of repetitive transcranial magnetic stimulation on movement-related cortical activity in humans

Several lines of evidence suggest that low-rate repetitive transcranial magnetic stimulation (rTMS) of the motor cortex at 1 Hz reduces the excitability of the motor cortex and produces metabolic changes under and at a distance from the stimulated side. Therefore, it has been suggested that rTMS may have beneficial effects on motor performance in patients with movement disorders. However, it is still unknown in what way these effects can be produced. The aim of the present study is to investigate whether rTMS of the motor cortex (15 min at 1 Hz) is able to modify the voluntary movement related cortical activity, as reflected in the Beretischaftspotential (BP), and if these changes are functionally relevant for the final motor performance. The cortical movement-related activity in a typical BP paradigm of five healthy volunteers has been recorded using 61 scalp electrodes, while subjects performed self-paced right thumb oppositions every 8-20 s. After a basal recording, the BP was recorded in three different conditions, counterbalanced across subjects: after rTMS stimulation of the left primary motor area (M1) (15 min, 1 Hz, 10% above motor threshold), after 15 min of sham rTMS stimulation and following 15 min of voluntary movements performed with spatio-temporal characteristics similar to those induced by TMS. The tapping test was used to assess motor performance before and after each condition. Only movement-related trials with similar electromyographic (onset from muscular 'silence') and accelerometric patterns (same initial direction and similar amplitudes) were selected for computing BP waveforms. TMS- evoked and self-paced thumb movements had the same directional accelerometric pattern but different amplitudes. In all subjects, the real rTMS, but neither sham stimulation nor prolonged voluntary movements, produced a significant amplitude decrement of the negative slope of the BP; there was also a shortening of the BP onset time in four subjects. The effect was topographically restricted to cortical areas which were active in the basal condition, irrespective of the basal degree of activation at every single electrode. No changes in the tapping test occurred. These findings suggest that rTMS of the motor cortex at 1 Hz may interfere with the movement related brain activity, probably through influence on cortical inhibitory networks.     

颈脊髓慢性压迫症的代谢组学研究

目的探讨应用磁共振波谱技术（magneticresonance spectroscopy,MRS）测量颈脊髓慢性压迫症患者脊髓代谢组改变的可行性,探讨脊髓代谢组学与脊髓功能的相关性。方法 2009年1月至2010年6月行减压手术的脊髓型颈椎病（cervical spondylotic myelopathy,CSM）患者13例作为实验组,男8例,女5例;年龄37～84岁,平均58.2岁。术前进行神经系统检查、神经功能评价（JOA评分）和MRS检查,将感兴趣区放置在脊髓受压最严重部位的相邻节段。通过MRS测得以下代谢物的浓度：氮-乙酰天门冬氨酸（NAA）、胆碱（Cho）、肌酸（Cr）、乳酸（Lac）、肌醇（Ins）、谷氨酰氨（Glx）。15名健康志愿者为正常对照组,年龄和性别与实验组无明显差异,同样用MRS测得脊髓代谢浓度。计算以下代谢浓度的比值：NAA/Cr、Cho/Cr、Lac/Cr、Ins/Cr、Glx/Cr。结果实验组的NAA/Cr和Glx/Cr比正常对照组明显降低（1.18 vs 2.58,P=0.023;0.56 vs 1.25,P=0.008）。实验组的NAA/Cr与脊髓JOA评分呈正相关。但是两组其他代谢物浓度比值如Cho/Cr,mI/Cr,Lac/Cr的差异均无统计学意义。实验组患者中有4例出现乳酸峰,而对照组中无一例出现乳酸峰。结论 MRS可以定量测量颈脊髓的代谢组学改变。慢性颈脊髓压迫症患者的NAA/Cr和Glx/Cr较健康志愿者明显降低,说明神经元和轴突的减少和损伤。NAA/Cr与脊髓功能的相关性,提示有评价脊髓功能的临床价值,但尚需大样本的研究来证实。     

Circadian modulation of GABA-mediated cortical inhibition

Circadian rhythms exert powerful influence on various aspects of human physiology and behavior. Here, we tested changes of human cerebral cortex excitability over the course of the day with transcranial magnetic stimulation (TMS). At different times of the day, intracortical and corticospinal excitability of the primary motor cortex (M1) was evaluated in 15 healthy subjects by TMS of left M1. While motor thresholds, short-interval intracortical inhibition and facilitation and input/output curves remained unchanged, we found that a specific form of γ-aminobutyric acid (GABA)-mediated intracortical inhibition, revealed by long-interval intracortical inhibition and cortical silent periods, progressively decreased during the course of the day. Additional experiments demonstrated that morning inhibition persisted irrespective of previous sleep or sleep deprivation. Corticotropin-releasing hormone (CRH) infusions in the evening lead to morning cortisol levels but did not restore levels of morning inhibition, whereas suppression of endogenous CRH release by repeated oral dexamethasone intake over 24 h prevented morning inhibition. The findings suggest a specific modulation of GABAergic motor cortex inhibition within the circadian cycle, possibly linked to the CRH system, and may indicate a neurobiological basis for variable neuroplasticity over the course of the day.     

Comparison Between Monopolar and Bipolar Electrical Stimulation of the Motor Cortex

Intra-operative neurophysiological techniques allow reliable identification of the sensorimotor region and make their anatomical and functional preservation feasible. Monopolar cortical stimulation has recently been described as a new mapping technique. In the present study this method was compared to the "traditional" technique of bipolar stimulation. Functional mapping of the motor cortex was performed in 35 patients during surgery in the central region. The central sulcus (CS) was identified by somatosensory evoked potential (SEP) phase reversal. Cortical motor mapping was first performed by monopolar anodal stimulation with a train of 500 Hz (7-10 pulses) followed by bipolar stimulation (pulses at 60 Hz with max. 4 sec train duration). Surgery was performed under general anaesthesia without muscle relaxants. Of 280 motor responses elicited by bipolar cortical stimulation, 54.23% [152] were located in the primary motor cortex (PMC), 37.85% 106[ outside the motor strip in the secondary motor cortex (SMC), and 8% 22[ posterior to the CS. Of 175 motor responses elicited by monopolar cortical stimulation. 68.57% 120[ were located in the SMC, 23.42% 41[ in the SMC and 8% 14[ posterior to the CS. Contrary to the general clinical view, there is considerable overlapping of primary motor units over a cortical area much broader than the "classical" narrow motor strip along the CS. Bipolar cortical stimulation is more sensitive than monopolar for mapping motor function in the premotor frontal cortex. Both methods are equally sensitive for mapping the primary motor cortex.     

Enhanced rapid-onset cortical plasticity in CADASIL as a possible mechanism of preserved cognition

Ischemic small vessel disease (SVD) may lead to cognitive impairment, but cognitive deficits with a given burden of SVD vary significantly. The underlying mechanisms of impaired or preserved cognition are unknown. Here, we investigated the impact of ischemic SVD on rapid-onset cortical plasticity, as induced with a paired-associative stimulation protocol. To exclude concomitant effects of aging, we examined 12 middle-aged patients (48.3 ± 8.3 years) with cerebral autosomal dominant arteriopathy with subcortical infarctions and leucoencephalopathy (CADASIL) who suffered from severe ischemic SVD and a group of 12 age-matched controls (49.9 ± 8.3 years). Cognitive status, motor performance and learning, and motor cortex excitability in response to cathodal transcranial direct current stimulation (ctDCS) were assessed. White matter integrity was analyzed by conventional magnetic resonance imaging and diffusion tensor imaging. We found that cognitive and motor functions were largely preserved in CADASIL patients, while rapid-onset cortical plasticity was significantly higher in the CADASIL group compared with controls (repeated measures analysis of variance [group × time] interaction: P = 0.03). This finding was even more pronounced in patients with higher white matter lesion load. ctDCS revealed no evidence of cortical dysplasticity. We conclude that increased rapid-onset cortical plasticity may contribute to largely preserved cognitive and motor function despite extensive ischemic SVD.     

A New Cortical Electrode for Neuronavigation-Guided Intraoperative Neurophysiological Monitoring: Technical Note

Intraoperative neurophysiological mapping and monitoring of eloquent brain areas can be combined with image-guided localisation to enhance the safety and efficacy of surgical procedures in the motor cortex. We designed a new type of cortical electrode which can be repeatedly placed on the cortical surface and allows accurate and reproducible stimulation by means of a navigation pointer. The newly designed device consists of a monopolar electrode contact for direct cortical stimulation, housed in a holder which allows placement, easy removal, and precise repeated placement of a surgical navigation pointer. It can be used for navigation-guided, high-frequency anodal monopolar cortical stimulation (MCS) for the mapping of eloquent cortex, and for monitoring of motor pathways. While the cortex is stimulated, compound muscle action potentials (CMAP) are recorded from muscles of the contralateral extremities and are assessed both qualitatively and quantitatively. When the device is used in combination with intraoperative navigation, the stimulation sites may optionally be registered or displayed on the system monitor. This allows repeated pinpointing and obviates the need for strip or grid electrodes in the operative field; although such electrodes may be useful for continuous monitoring, they often are in the surgeon's way. In addition, the primary and supplementary motor cortex can be mapped by determining the location of the sites of stimulation on surface-projected images of the cerebral cortex.     

Spinal cord responses to feline transcranial brain stimulation: evidence for involvement of cerebellar pathways

The physiological characteristics of spinal cord responses recorded from the spinal epidural space of the cat to transcranial brain stimulation were studied, in comparison with the spinal cord responses to direct stimulation of the motor cortex or cerebellum. The conduction velocity of the initial wave of the responses to transcranial brain stimulation (122.3 +/- 16.3 m/sec mean +/- SD, n = 5) was much faster than the conduction velocity of the initial wave of the responses to motor cortex stimulation (68.3 +/- 14.7, n = 5) and similar to the conduction velocity of the initial wave of the responses to cerebellar stimulation (120.2 +/- 16.2, n = 5). Furthermore, the conduction velocity of any component in the subsequent polyphasic waves at any intensity was not similar to the conduction velocity of the initial wave of the responses to motor cortex stimulation. All components of the responses to motor cortex stimulation disappeared after intercollicular transection. In contrast, the initial wave of the responses to cerebellar stimulation and transcranial brain stimulation remained unaffected by intercollicular transection. The initial wave caused by anodal transcranial brain stimulation was eliminated by ablation of the cerebellum. However, cathodal transcranial brain stimulation sometimes can produce an initial wave that can be eliminated only by transection at the medullospinal junction. The initial wave of the responses to cerebellar stimulation was largest in amplitude when the vicinity of the dentate nucleus was stimulated. These results suggest that responses to activation of the cerebellum, rather than corticospinal neurons arising from the motor cortex, represent a major component of the spinal cord responses to transcranial brain stimulation in cats. The data obtained indicate that it is difficult to activate the motor cortex selectively by transcranial brain stimulation in cats.     

Transcranial direct current stimulation (tDCS) paired with massed practice training to promote adaptive plasticity and motor recovery in chronic incomplete tetraplegia: A pilot study

Objective: Our goal was to determine if pairing transcranial direct current stimulation (tDCS) with rehabilitation for two weeks could augment adaptive plasticity offered by these residual pathways to elicit longer-lasting improvements in motor function in incomplete spinal cord injury (iSCI).

Design: Longitudinal, randomized, controlled, double-blinded cohort study.

Setting: Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Participants: Eight male subjects with chronic incomplete motor tetraplegia.

Interventions: Massed practice (MP) training with or without tDCS for 2 hrs, 5 times a week.

Outcome Measures: We assessed neurophysiologic and functional outcomes before, after and three months following intervention. Neurophysiologic measures were collected with transcranial magnetic stimulation (TMS). TMS measures included excitability, representational volume, area and distribution of a weaker and stronger muscle motor map. Functional assessments included a manual muscle test (MMT), upper extremity motor score (UEMS), action research arm test (ARAT) and nine hole peg test (NHPT).

Results: We observed that subjects receiving training paired with tDCS had more increased strength of weak proximal (15% vs 10%), wrist (22% vs 10%) and hand (39% vs. 16%) muscles immediately and three months after intervention compared to the sham group. Our observed changes in muscle strength were related to decreases in strong muscle map volume (r=0.851), reduced weak muscle excitability (r=0.808), a more focused weak muscle motor map (r=0.675) and movement of weak muscle motor map (r=0.935).

Conclusion: Overall, our results encourage the establishment of larger clinical trials to confirm the potential benefit of pairing tDCS with training to improve the effectiveness of rehabilitation interventions for individuals with SCI.

Trial Registration: NCT01539109     

Alteration of cortical but not spinal inhibitory circuits in idiopathic scoliosis

Background: The pathogenesis of adolescent idiopathic scoliosis (AIS), including the role of brain and spinal inhibitory circuits, is still poorly elucidated. The aim of this study was to identify which central inhibitory mechanisms are involved in the pathogenesis of AIS.Design: A prospective neurophysiological study, using a battery of neurophysiological tests, such as cutaneous (CuSP) and cortical (CoSP) silent periods, motor evoked potentials (MEP) and paired-pulse transcranial magnetic stimulation (ppTMS).Settings: Neurophysiological laboratory.Participants: Sixteen patients with AIS (14 females, median age 14.4) and healthy controls.Outcome measures: MEPs were obtained after transcranial magnetic stimulation (TMS) and recorded from the abductor pollicis muscle (APB). ppTMS was obtained at interval ratios (ISI) of 1, 2, 3, 6, 10, 15 and 20 ms. The cortical silent period (CoSP) was recorded from the APB. The cutaneous silent period (CuSP) was measured after painful stimuli delivered to the thumb while the subjects maintained voluntary contraction of the intrinsic hand muscles. The data were analyzed and compared with those from healthy subjects.Results: The CoSP duration was significantly prolonged in AIS patients. A significantly higher amplitude of ppTMS for ISI was found in all AIS patients, without remarkable left-right side differences. No significant difference in MEP latency or amplitude nor in the CuSP duration was obtained.Conclusion: Our observation demonstrates evidence of central nervous system involvement in adolescent idiopathic scoliosis (AIS). Lower intracortical inhibition, higher motor cortex excitability, and preserved spinal inhibitory circuits are the main findings of this study. A possible explanation of these changes could be attributed to impaired sensorimotor integration predominantly at the cortical level.     

Temporary occlusion of associative motor cortical plasticity by prior dynamic motor training

A novel Hebbian stimulation paradigm was employed to examine physiological correlates of motor memory formation in humans. Repetitive pairing of median nerve stimulation with transcranial magnetic stimulation over the contralateral motor cortex (paired associative stimulation, PAS) may decrease human motor cortical excitability at interstimulus intervals of 10 ms (PAS10) or increase excitability at 25 ms (PAS25). The properties of this plasticity have previously been shown to resemble associative timing-dependent long-term depression (LTD) and long-term potentiation (LTP) as established in vitro. Immediately after training a novel dynamic motor task, the capacity of the motor cortex to undergo plasticity in response to PAS25 was abolished. PAS10-induced plasticity remained unchanged. When retested after 6 h, PAS25-induced plasticity recovered to baseline levels. After training, normal PAS25-induced plasticity was observed in the contralateral training-naive motor cortex. Motor training did not reduce the efficacy of PAS25 to enhance cortical excitability when PAS10 was interspersed between the training and application of the PAS25 protocol. This indicated that the mechanism supporting PAS25-induced plasticity had remained intact immediately after training. Behavioral evidence was obtained for continued optimization of force generation at a time when PAS25-induced plasticity was blocked in the training motor cortex. Application of the PAS protocols after motor training did not prevent the consolidation of motor skills evident as performance gains at later retesting. The results are consistent with a concept of temporary suppression of associative cortical plasticity by neuronal mechanisms involved in motor training. Although it remains an open question exactly which element of motor training was responsible for this effect, our findings may link dynamic properties of LTP formation, as established in animal experiments, with human motor memory formation and possibly dynamic motor learning.