Practice-dependent Plasticity Research Articles

Does sonification of action simulation training impact corticospinal excitability and audiomotor plasticity?

Sonification is a sensory augmentation strategy whereby a sound is associated with, and modulated by, movement. Evidence suggests that sonification could be a viable strategy to maximize learning and rehabilitation. Recent studies investigated sonification of action observation, reporting beneficial effects, especially in Parkinson’s disease. However, research on simulation training—a training regime based on action observation and motor imagery, in which actions are internally simulated, without physical execution—suggest that action observation alone is suboptimal, compared to the combined use of action observation and motor imagery. In this study, we explored the effects of sonified action observation and motor imagery on corticospinal excitability, as well as to evaluate the extent of practice-dependent plasticity induced by this training. Nineteen participants were recruited to complete a practice session based on combined and congruent action observation and motor imagery (AOMI) and physical imitation of the same action. Prior to the beginning, participants were randomly assigned to one of two groups, one group (nine participants) completed the practice block with sonified AOMI, while the other group (ten participants) completed the practice without extrinsic auditory information and served as control group. To investigate practice-induced plasticity, participants completed two auditory paired associative stimulation (aPAS) protocols, one completed after the practice block, and another one completed alone, without additional interventions, at least 7 days before the practice. After the practice block, both groups significantly increased their corticospinal excitability, but sonification did not exert additional benefits, compared to non-sonified conditions. In addition, aPAS significantly increased corticospinal excitability when completed alone, but when it was primed by a practice block, no modulatory effects on corticospinal excitability were found. It is possible that sonification of combined action observation and motor imagery may not be a useful strategy to improve corticospinal, but further studies are needed to explore its relationship with performance improvements. We also confirm the neuromodulatory effect of aPAS, but its interaction with audiomotor practice remain unclear.

Practice-dependent motor cortex plasticity is reduced in non-disabled multiple sclerosis patients

ObjectivesSkill acquisition after motor training involves synaptic long-term potentiation (LTP) in primary motor cortex (M1). In multiple sclerosis (MS), LTP failure ensuing from neuroinflammation could contribute to worsen clinical recovery. We therefore addressed whether practice-dependent plasticity is altered in MS. MethodsEighteen relapsing-remitting (RR)-MS patients and eighteen healthy controls performed 600 fast abductions of index finger in 30 blocks of 20 movements. Before and after practice, transcranial magnetic stimulation (TMS) was delivered over the hot spot of the trained first dorsal interosseous muscle. Movements kinematics, measures of cortical excitability, and the input/output curves of motor evoked potentials (MEPs) were assessed. ResultsKinematic variables of movement improved with practice in patients and controls to a similar extent, although patients showed lower MEPs amplitude increase after practice. Practice did not change the difference in resting motor threshold values observed between patients and controls, nor did modulate short-interval intracortical inhibition. Clinical/radiological characteristics were not associated to practice-dependent effects. ConclusionsPractice-induced reorganization of M1 is altered in non-disabled RR-MS patients, as shown by impaired MEPs modulation after motor learning. SignificanceThese findings suggest that in RR-MS physiological mechanisms of practice-dependent plasticity are altered.

The effects of a single dose of fluoxetine on practice-dependent plasticity

ObjectiveTo determine whether a single dose of fluoxetine increases corticomotoneuronal excitability, motor performance and practice-dependent plasticity. MethodsTwelve healthy adults completed this placebo-controlled, pseudo-randomized, double-blind crossover study. Transcranial magnetic stimulation (TMS) was used to assess corticomotoneuronal excitability, and two uni-axial accelerometers measured kinetics of fastest possible ballistic voluntary thumb movements and TMS-evoked thumb movements. Six hours after administration of either 20 mg of the serotonin reuptake inhibitor fluoxetine or placebo, participants practiced ballistic thumb movements in the direction opposite to the TMS-evoked thumb movements. The primary outcome of this study was the proportion of thumb movements that fell within the target-training zone (TTZ) during and for 30 min after the practice. ResultsAll participants demonstrated practice-dependent plasticity evidenced by an increase of TMS-evoked thumb movements falling into the TTZ (P = 0.045), with no difference between drugs. There was a significant increase in peak acceleration of the practiced voluntary thumb movements (P = 0.002), but no DRUG by TIME interaction. Motor-evoked potential amplitudes were not changed by drug intake or practice. ConclusionsA single dose of 20 mg of fluoxetine did not enhance corticomotoneuronal excitability, performance of a ballistic thumb movement task, or practice-dependent plasticity in healthy adults. SignificanceLonger administration fluoxetine may be necessary to enhance motor performance and plasticity.

P093 Transcranial cortex stimulation, neuroplasticity and learning: An experimental and computational study

Question Noninvasive cortical stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) are capable of increasing and decreasing cortical excitability and thereby might be clinically relevant for rehabilitation of neurological and neuropsychiatric disorders. However, the induced after-effects are usually too short-lasting to be clinically relevant. In this study we investigated if combining rTMS with operant learning can induce long-lasting after-effects not achievable neither with rTMS alone nor with operant learning alone. Methods Experimental approach: Forty-six subjects were randomly assigned to three experimental groups. Experimental groups 1 & 2 received a psychophysical pretest of tactile discrimination abilities with the left ring finger, a training procedure to improve performance with this finger, and a posttest. In experimental group 1 the training procedure was combined with 15 Hz rTMS over the primary sensory cortex (SI) while in experimental group 2 the training was combined with sham rTMS. In the third experimental group, psychophysical pre- and posttests of tactile discrimination abilities were assessed. However, they received 15 Hz rTMS over SI without training. Computational approach: As a preliminary simulation trial we developed a neural model, which enabled us to discriminate between the encoding and decoding of particular input frequency represented in several scenarios. Results Combining rTMS with operant learning induced long-lasting after-effects not achievable neither with rTMS alone nor with operant learning alone. A conceptual framework for the efficiency of combining cortical stimulation with operant learning can be derived from the Bienenstock–Cooper–Munro theory of bidirectional synaptic plasticity. According to this theory the change of synaptic efficiency during learning processes is dependent on the preactivation level of the involved neural network, suggesting that high-frequency rTMS can transiently decrease the threshold for the induction of LTP-like effects and thereby gate practice-dependent plasticity. Conclusions Our findings provide important implications for the use of rTMS in combination with operant learning as a therapeutic tool for neurorehabilitation.

Combining Dopaminergic Facilitation with Robot-Assisted Upper Limb Therapy in Stroke Survivors

ABSTRACTDespite aggressive conventional therapy, lasting hemiplegia persists in a large percentage of stroke survivors. The aim of this article is to critically review the rationale behind targeting multiple sites along the motor learning network by combining robotic therapy with pharmacotherapy and virtual reality–based reward learning to alleviate upper extremity impairment in stroke survivors. Methods for personalizing pharmacologic facilitation to each individual’s unique biology are also reviewed. At the molecular level, treatment with levodopa was shown to induce long-term potentiation-like and practice-dependent plasticity. Clinically, trials combining conventional therapy with levodopa in stroke survivors yielded statistically significant but clinically unconvincing outcomes because of limited personalization, standardization, and reproducibility. Robotic therapy can induce neuroplasticity by delivering intensive, reproducible, and functionally meaningful interventions that are objective enough for the rigors of research. Robotic therapy also provides an apt platform for virtual reality, which boosts learning by engaging reward circuits. The future of stroke rehabilitation should target distinct molecular, synaptic, and cortical sites through personalized multimodal treatments to maximize motor recovery.

Recent History of Effector Use Modulates Practice-Dependent Changes in Corticospinal Excitability but Not Motor Learning.

The theory of homeostatic metaplasticity has significant implications for human motor cortical plasticity and motor learning. Previous work has shown that the extent of recent effector use before exogenously-induced plasticity can affect the direction, magnitude and variability of aftereffects. However, the impact of recent effector use on motor learning and practice-dependent plasticity is not known. We hypothesized that reducing effector use for 8 hours via hand/wrist immobilization would facilitate practice-dependent changes in corticospinal excitability and TMS-evoked thumb movement kinematics, while also promoting 24-hour retention of a ballistic motor skill. Subjects participated in a crossover study involving two conditions. During the immobilization condition, subjects wore a splint that restricted motion of the left hand and thumb for 8 hours. While wearing the splint, subjects were instructed to avoid using their left hand as much as possible. During the control condition, subjects did not wear a splint at any time nor were they instructed to avoid hand use. After either an 8 hour period of immobilization or normal hand use, we collected MEP and TMS-evoked thumb movement recruitment curves, and subjects practiced a ballistic motor skill involving rapid thumb extension. After motor practice, MEP and TMS-evoked thumb movement recruitment curves were re-tested. Retention of the motor skill was tested 30 minutes and 24 hours after motor practice. Reduced effector use did not impact pre-practice corticospinal excitability but did facilitate practice-dependent changes in corticospinal excitability, and this enhancement was specific to the trained muscle. In contrast, reducing effector use did not affect practice-dependent changes in TMS-evoked thumb movements nor did it promote acquisition or retention of the skill. Finally, we detected some associations between pre-practice excitability levels, plasticity effects and learning effects, but these did not reach our adjusted criterion for significance. Experimentally enhancing practice-dependent changes in corticospinal excitability is not sufficient to promote learning or memory of a ballistic motor skill.

Transcranial magnetic stimulation in sleep fragmentation: a model to better understand sleep disorders

ObjectiveTo investigate practice-dependent plasticity and cortical inhibition/excitability in good sleepers after a night of sleep fragmentation (SF), by means of transcranial magnetic stimulation (TMS). MethodsIn basal condition (BC), after a full night of spontaneous sleep, and in fragmented condition (FC), after a fragmented night of sleep, motor evoked potential (MEP) amplitude, motor threshold (MT), silent period (SP), and intracortical inhibition were assessed. In both conditions subjects performed, also, a bimanual motor task: MEPs were recorded before and after exercise, and after rest. We evaluated the presence of post-exercise facilitation and delayed facilitation. Subjects reported their alertness level (Stanford Sleepiness Scale–SSS). ResultsMT and SSS were significantly increased in SF. Instead, no significant differences for MEP amplitude or SP or intracortical inhibition were found. In both conditions post-exercise facilitation and delayed facilitation were present. ConclusionSF produces disruption of nocturnal sleep and increases daytime sleepiness. Confirmatory features of this clinical behaviour could be that in FC we observed a significant increase in SSS and in MT. SF was unable to modify cortical inhibition\\excitability and\\or to influence plasticity-related parameters. These results seem inconsistent with some of TMS alterations observed in sleep deprivation (SD) and restless legs syndrome (RLS). We suggest that SD and SF represent different phenomena that can depend on various networks acting on motor cortex. We speculate that alterations in cortical excitability found in RLS are intrinsically related to the underlying disease itself and are not instead directly associated with the SF present in RLS.

Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using 18F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging

γ-aminobutyric acid (GABA)-A receptor-mediated neural transmission is important to promote practice-dependent plasticity after brain injury. This study investigated alterations in GABA-A receptor binding and functional and anatomic connectivity within the motor cortex in children with cerebral palsy (CP). We conducted (18)F-fluoroflumazenil PET on children with hemiplegic CP to investigate whether in vivo GABA-A receptor binding is altered in the ipsilateral or contralateral hemisphere of the lesion site. To evaluate changes in the GABA-A receptor subunit after prenatal brain injury, we performed GABA-A receptor immunohistochemistry using rat pups with a diffuse hypoxic ischemic insult. We also performed diffusion tensor MR imaging and resting-state functional MR imaging on the same children with hemiplegic CP to investigate alterations in anatomic and functional connectivity at the motor cortex with increased GABA-A receptor binding. In children with hemiplegic CP, the (18)F-fluoroflumazenil binding potential was increased within the ipsilateral motor cortex. GABA-A receptors with the α1 subunit were highly expressed exclusively within cortical layers III, IV, and VI of the motor cortex in rat pups. The motor cortex with increased GABA-A receptor binding in children with hemiplegic CP had reduced thalamocortical and corticocortical connectivity, which might be linked to increased GABA-A receptor distribution in cortical layers in rats. Increased expression of the GABA-A receptor α1 subunit within the ipsilateral motor cortex may be an important adaptive mechanism after prenatal brain injury in children with CP but may be associated with improper functional connectivity after birth and have adverse effects on the development of motor plasticity.

Altered Resting Brain Function and Structure in Professional Badminton Players

Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills.

Age-related modulation in post-movement alpha power increase following motor sequence learning

Age-related modulation in post-movement alpha power increase following motor sequence learning

Deficient Homeostatic Regulation of Practice-Dependent Plasticity in Writer’s Cramp

Homeostatic metaplasticity is important to maintain overall synaptic weight in neuronal networks. Previous work suggested that homeostatic metaplasticity in motor cortex is impaired in writer's cramp, the most common form of task-specific focal dystonia, when explored by the interactions between 2 successive plasticity inducing transcranial brain stimulation protocols (Quartarone Rizzo V, Bagnato S, Morgante F, Sant'angelo A, Romano M, Crupi D, Girlanda P, Rothwell JC, Siebner HR. 2005. Homeostatic-like plasticity of the primary motor hand area is impaired in focal hand dystonia. Brain. 128:1943-1950.). To which extent deficient homeostatic metaplasticity applies also to the behavioral level of practice-dependent plasticity is unknown. Here, we examined the interactions of 3 paired associative transcranial magnetic stimulation protocols (motor cortical excitability-enhancing paired associative stimulation (PAS)(25ms), excitability-depressing PAS(10ms), and control PAS(100ms)) with subsequent practice-dependent plasticity. Ten patients with writer's cramp and 10 healthy controls practiced rapid thumb abductions for 30 min. Practice-dependent plasticity was quantified by the increase in peak acceleration of the trained movement. The healthy controls but not the writer's cramp patients showed homeostatic suppression of practice-dependent plasticity after PAS(25ms) when compared with practice-dependent plasticity after PAS(10ms) and PAS(100ms). The lack of the PAS(25ms)-induced suppression of practice-dependent plasticity in writer's cramp correlated with clinical severity of the focal hand dystonia. Findings support the notion that deficient homeostatic metaplasticity of practice-dependent plasticity plays a significant role in the pathophysiology of writer's cramp.

Reduced motor cortex plasticity following inhibitory rTMS in older adults

Ageing is accompanied by diminished practice-dependent plasticity. We investigated the effect of age on another plasticity inducing paradigm, repetitive transcranial magnetic stimulation (rTMS). Healthy young (n=15; 25+/-4 years) and old (n=15; 67+/-5 years) adults participated in two experiments. Motor evoked potentials (MEPs) were measured in the target muscle (first dorsal interosseus, FDI) and a remote muscle (abductor digiti minimi) during a set of single stimuli. Subjects then received real or sham inhibitory rTMS (intermittent subthreshold trains of 6Hz stimulation for 10min). MEPs were measured for 30min after rTMS. In young adults, MEPs in the target FDI muscle were approximately 15% smaller in the real rTMS experiment than in the sham rTMS experiment (P<0.026). In old adults, FDI MEP size did not differ between experiments. Advancing age is associated with reduced efficacy of inhibitory rTMS. This work has important implications for the potential therapeutic use of rTMS in stroke and neurological disease.

Intracortical Excitability After Repetitive Hand Movements is Differentially Affected in Cortical Versus Subcortical Strokes

Repetitive training of isolated movements induces reorganization of motor cortical representations. To elucidate the mechanisms of practice-dependent cortical plasticity within the lesioned central motor system at the time of the application of a therapeutic intervention, we examined the effect of repetitive movements on intracortical facilitation (ICF) and inhibition of agonist (extensor carpi radialis [ECR]) and antagonist (flexor carpi ulnaris) muscles of the hand shortly after the movements, by the paired-pulse technique in patients with cortical (n = 9) and subcortical strokes (n = 11). Short intracortical inhibition and ICF were studied by using interstimulus intervals of 2 and 8 milliseconds, respectively, and their interaction with active or passive movement. The active movement produced significantly larger motor-evoked potentials in the ECR muscle in both patient groups. Short intracortical inhibition was particularly decreased after cortical stroke, whereas it was still significant after subcortical stroke. ICF increased significantly after movements compared with rest in the ECR for subcortical stroke patients only. We conclude that repetitive active movements increase the excitability of the motor cortex representing the agonist muscle and interact with intracortical facilitatory circuits in the subcortical stroke group but not in the cortical stroke group. This interaction of circuitry has been reported previously in control subjects and seems to still operate after subcortical stroke during active movement. Alternative networks may be recruited for active movement after cortical stroke. This finding proposes lesion-specific mechanisms of reorganization during the same rehabilitative intervention. Distinct rehabilitative strategies may be required to optimize the activation of the physiologic motor network for different lesions.

Changes of cortical excitability after dopaminergic treatment in restless legs syndrome

Objective Dopaminergic pathways are most likely involved in the pathophysiology of restless legs syndrome (RLS). In previous investigations, an alteration of cortical excitability was suggested to be related to a dopaminergic dysfunction in RLS. The purpose of our study was to compare practice-dependent plasticity in RLS patients before and after a month of dopaminergic treatment. Methods Single-pulse transcranial magnetic stimulation (TMS) was used to define motor evoked potential (MEP) amplitude, motor threshold, and silent period (SP) as well. Subjects performed three exercise blocks (bimanual motor task). MEP amplitude, registered immediately after each exercise block and after a rest period, was compared to baseline. The time course of intra-cortical inhibition was tested using paired-pulse TMS at short inter-stimulus intervals. For the single-pulse TMS procedures, we enrolled 12 patients affected by primary RLS and 12 normal subjects. For the paired-pulse TMS procedures, only six patients underwent the examination. RLS patients underwent the examination in both pre- and post-dopaminergic treatment conditions. Results In RLS patients MEP amplitude increased after the rest period only in the post-treatment condition, showing a delayed facilitation. After exercise, MEP amplitude increased, but not enough to be significant, showing a positive trend but not a clear-cut post-exercise facilitation. In the pre-treatment condition instead, MEP amplitude did not change either after rest period or after exercise. RLS patients showed a marked increase of the central motor inhibition, assessed by using paired-pulse TMS at short inter-stimulus intervals after pramipexole treatment. On the contrary, the duration of the SP did not change compared to the pre-treatment condition. Conclusions In RLS patients after dopaminergic treatment, the main finding was the changing of MEP amplitude after rest following a motor task. Since dopaminergic treatment can reverse delayed facilitation in RLS, we hypothesized that cortical plasticity related to dopaminergic systems may play a crucial role in RLS pathophysiology.

Differing effects of intracortical circuits on plasticity

Practice of a motor task leads to an increase in amplitude of motor-evoked potentials (MEP) in the exercised muscle. This is termed practice-dependent plasticity, and is abolished by the NMDA antagonist dextromethorphan and the GABA(A) agonist lorazepam. Here, we sought to determine whether specific subtypes of GABA(A) circuits are responsible for this effect by comparing the action of the non-selective agonist, lorazepam with that of the selective GABA(A)-alpha(1) receptor agonist, zolpidem. In seven healthy subjects, transcranial magnetic stimulation (TMS) was used to quantify changes in amplitude of MEP after practice of a ballistic motor task. In addition we measured how the same drugs affected MEP amplitudes and the excitability of a number of cortical inhibitory circuits [short-interval intracortical inhibition (SICI), short-interval afferent inhibition (SAI) and long-interval intracortical inhibition]. This allowed us to explore correlations between drugs effects in measures of cortical excitability and practice-dependent plasticity of MEP amplitudes. As previously reported, lorazepam increased SICI and decreased SAI, while zolpidem only decreased SAI. The new findings were that practice-dependent plasticity of MEPs was impaired by lorazepam but not zolpidem, and that this was negatively correlated with lorazepam-induced changes in SICI but not SAI. This suggests that the intracortical circuits involved in SICI (and not neurons expressing GABA(A)-alpha(1) receptor subunits that are implicated in SAI) may be involved in controlling the amount of practice-dependent MEP plasticity.

Differences in intracortical circuits that inhibit practice-dependent plasticity

Practice of a motor task leads to an increase in amplitude of motor-evoked potentials (MEP) in the exercised muscle. This is termed practice-dependent plasticity, and is abolished by the NMDA antagonist dextromethorphan or the GABAA agonist lorazepam.

Pharmacological enhancement of motor recovery in subacute and chronic stroke

Pharmacological agents, known to modulate practice-dependent plasticity in animal models of brain damage, have recently received increased interest for treatment of motor recovery after stroke. The present paper gives an overview of agents that are currently available. Amphetamines have been repeatedly shown to promote recovery of function in animals, but clinical data remain inconclusive. Other pharmacological agents evaluated for motor recovery include selective norepinephrine re-uptake inhibitors, dopamine, dopamine agonists, cholinergic substances, serotonin re-uptake inhibitors, and granulocyte-colony stimulating factor. Although preliminary data from animal and human experimental studies on these agents are promising, larger clinical trials are needed before any of the available agents may be recommended for routine use.

Deafferentation of neighbouring motor cortex areas does not further enhance saturated practice-dependent plasticity in healthy adults

Objective To assess effects of deafferentation of the arm representation of primary motor cortex (M1) on practice-dependent plasticity in healthy adults. Methods Twelve healthy, right-handed adults (18–48 years, median 20.2 years) performed two consecutive experiments (exp. 1 and exp. 2). Exp. 1 consisted of a motor practice (MP) of repeated ballistic flexion movements of the left thumb. This was followed by exp. 2 consisting of selective anaesthesia of the upper brachial plexus (SPA) to disinhibit the training M1 and a second period of the same MP. Peak acceleration of the trained thumb movement and the motor evoked potential (MEP) amplitude in the flexor pollicis brevis muscle elicited by single-pulse transcranial magnetic stimulation of the training M1 were studied before and after exp. 1 and after exp. 2. Results After exp. 1 all subjects demonstrated an increase of peak acceleration (baseline: 19.23 ± 3.81 m s −2; after exp. 1: 43.28 ± 17.63 m s −2, p = 0.008) and MEP amplitude (from 0.46 ± 0.23 mV to 1.26 ± 0.77 mV, p = 0.03). There was no additional increase of these measures after exp. 2 (44.37 ± 19.56 m s −2, p = 0.78, 1.69 ± 1.21 mV ( p = 0.07)). Conclusions Training of ballistic thumb movements leads to behavioural improvement as well as to an increased excitability of the corresponding M1 representation. These effects do not increase further during deafferentation of the training M1. In contrast to stroke patients [Muellbacher W, Richards C, Ziemann U, Wittenberg G, Weltz D, Boroojerdi B, et al. Improving hand function in chronic stroke. Arch Neurol 2002;59:1278–82], practice-dependent plasticity in healthy subjects cannot be enhanced by deafferentation of neighbouring motor cortex areas. Significance Healthy subjects, in contrast to patients with central motor lesions, are capable of saturating practice-dependent plasticity to a level that cannot be further enhanced by experimental manipulation.

Contrasting Interpretations of the Nonuniform Distribution of Preferred Directions Within Primary Motor Cortex

to the editor: A recent paper by Georgopoulos and colleagues ([Naselaris et al. 2006][1]) revisits the influential and controversial issue of population coding within primary motor cortex (M1). Although researchers uniformly recognize that neural activity in M1 often covaries with the direction of

PR_280: Reorganization of Motor Cortical Activity Induced by High-Frequency Repetitive Transcranial Magnetic Stimulation in Chronic Stroke Patients

Objective: To investigate high-frequency repetitive transcranial magnetic stimulation (rTMS)−induced cortical plasticity associated with motor skill acquisition in chronic stroke patients. Design: Before-after study. Setting: University hospital. Participants: 6 patients with chronic hemiparetic stroke (3 men, 3 women; mean age, 54.5±8.62y). Interventions: We applied rTMS over their contralateral primary motor cortex for 10 days. We applied 50 pulses at 10Hz of rTMS for a period of 5 seconds with a resting motor threshold of 80%. As soon as the rTMS was finished, the patients practiced a complex sequential finger motor task (training block) using their paretic fingers for 50 seconds. The rTMS and motor training block was repeated 10 times for each training session. Main Outcome Measures: Movement accuracy and time before and after the rTMS training, and also at 1 week and 1 month after cessation of the training for the measurement of motor performance, and functional magnetic resonance imaging (fMRI) before and after the intervention for the determination of neuroplastic changes. Results: High-frequency rTMS accompanied by motor training showed improved motor performances in both movement accuracy and movement time (P<.05). The behavioral effects were retained until 1 month after cessation of the training. fMRI data showed decreased activities of the ipsilateral primary motor cortex and increased activity of the contralateral motor cortex and the ipsilateral cerebellum after receiving rTMS and motor training. Conclusions: High-frequency rTMS can facilitate practice-dependent plasticity in chronic stroke patients.