This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liepert, J. Articles by Weiller, C. Search for Related Content PubMed PubMed Citation Articles by Liepert, J. Articles by Weiller, C. Pubmed/NCBI databases Medline Plus Health Information Stroke Related Collections Electrophysiology Exercise/exercise testing/rehabilitation Rehabilitation, Stroke

(Stroke. 2000;31:1210.)
© 2000 American Heart Association, Inc.

Original Contributions

Treatment-Induced Cortical Reorganization After Stroke in Humans

Joachim Liepert, MD; Heike Bauder, PhD; Wolfgang H. R. Miltner, PhD; Edward Taub, PhD Cornelius Weiller, MD

From the Departments of Neurology (J.L., C.W.) and Biological and Clinical Psychology (H.B., W.H.R.M.), Friedrich-Schiller-University of Jena, Jena, Germany; and Department of Psychology (E.T.), University of Alabama at Birmingham and Physical Medicine Service, Birmingham VA Medical Center.

Correspondence to Priv-Doz Dr J. Liepert, Neurologische Klinik der Friedrich Schiller Universität, Philosophenweg 3, D-07743 Jena, Germany. E-mail liepert{at}neuro.uni-jena.de

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose—Injury-induced cortical reorganization is a widely recognized phenomenon. In contrast, there is almost no information on treatment-induced plastic changes in the human brain. The aim of the present study was to evaluate reorganization in the motor cortex of stroke patients that was induced with an efficacious rehabilitation treatment.

Methods—We used focal transcranial magnetic stimulation to map the cortical motor output area of a hand muscle on both sides in 13 stroke patients in the chronic stage of their illness before and after a 12-day-period of constraint-induced movement therapy.

Results—Before treatment, the cortical representation area of the affected hand muscle was significantly smaller than the contralateral side. After treatment, the muscle output area size in the affected hemisphere was significantly enlarged, corresponding to a greatly improved motor performance of the paretic limb. Shifts of the center of the output map in the affected hemisphere suggested the recruitment of adjacent brain areas. In follow-up examinations up to 6 months after treatment, motor performance remained at a high level, whereas the cortical area sizes in the 2 hemispheres became almost identical, representing a return of the balance of excitability between the 2 hemispheres toward a normal condition.

Conclusions—This is the first demonstration in humans of a long-term alteration in brain function associated with a therapy-induced improvement in the rehabilitation of movement after neurological injury.

Key Words: plasticity, neuronal • transcranial magnetic stimulation • reorganization • physical therapy • stroke

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Research with animals has led to the discovery that cortical reorganization occurs after injury to the nervous system.^{1 2 3} Spontaneously occurring cortical reorganization phenomena that result from nervous system damage or conditions that involve abnormal sensory input have been shown to be associated with pathological states in humans; these include phantom limb pain,⁴ tinnitus,⁵ and focal hand dystonia.⁶ After motor stroke, a complex pattern of reorganization has been described.^{7 8 9 10 11 12 13 14 15 16 17 18 19 20} In the subacute stage after a stroke, a reduction in motor cortex excitability and a decrease in the cortical representation area of paretic muscles have been found to occur.^{17 19} This may represent a disadvantageous reorganization associated with an impaired motor function and could be due to the damage of neuronal structures or could reflect the disuse of the affected limb.^{21 22} In addition to injury-related cortical reorganization, there is a second kind of process, use-dependent cortical reorganization, that results from the increased use of body parts in behaviorally relevant tasks and leads to an enhancement of the representation of those body parts in the cerebral cortex.^{21 23 24 25 26} It is possible that this process could be used to remediate pathological symptoms through the reversal or elimination of disadvantageous cortical reorganization produced with nervous system damage.

Constraint-induced movement therapy (CI therapy) has been shown in controlled studies to be efficacious in chronic stroke patients.²⁷ At this stage of their illness, these patients are presumed to have a stable motor deficit.^{28 29 30} Moreover, the short duration of CI therapy (12 days) further minimizes the possibility that spontaneous recovery of function could give the appearance of a treatment effect. CI therapy stems jointly from basic research in neuroscience with monkeys with somatosensory deafferentation of a single forelimb and from behavioral psychology.^{31 32} The effective therapeutic factor in this treatment^{33 34} appears to be the massing or concentration of practice in use of the extremity affected by a stroke for many hours a day during a period of consecutive weeks. This therapy has been found to produce a substantial long-term improvement in the amount of use of an affected upper extremity that transfers into the real world environment.^{34 35 36 37 38} It is possible that CI therapy might produce its therapeutic effect through the induction of a use-dependent cortical reorganization that counteracts adverse brain function changes and enhances recovery-associated plastic changes that occur in the human brain after stroke.^{7 8 9 17 18 19}

The main goal of the present study was not to evaluate the clinical effects of CI therapy or to compare this treatment with other physiotherapeutic approaches but rather to use CI therapy as a model to assess therapy-induced plasticity in stroke patients. Therefore, we did not introduce a control group. However, we did use a control procedure (ie, 2 complete pretreatment test batteries separated by the same length of time required by the intervention), and placebo controls have been used in other CI therapy research.^{34 38}

We used focal transcranial magnetic stimulation (TMS) to assess plastic alterations that may have been induced by CI therapy. TMS involves the noninvasive mapping of motor regions of the brain to determine the cortical representation areas of muscles with the use of a focused magnetic field to stimulate loci in motor areas from points on the scalp. It has been used to assess the amount of reorganization of motor representations consequent to injury of the peripheral and central nervous systems and after various conditions of use.^{17 18 19 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55} The amplitude-weighted center of the TMS map of a hand muscle corresponds closely to the hand area within the primary motor cortex as determined with anatomic and functional MRI (fMRI) studies.^{56 57 58 59} In contrast to typical fMRI or positron emission tomography (PET) experiments in stroke patients, TMS mapping is performance independent and therefore ideally suited for longitudinal studies as in rehabilitation of stroke, where motor ability may change markedly. Preliminary results from a limited sample of patients had indicated that motor cortex reorganization occurs immediately after CI therapy.⁶⁰ In contrast to this earlier study, we performed TMS mappings and evaluations of motor functions in parallel at several time points before and after CI therapy to investigate the stability of the baseline and to determine short- and long-term effects of the therapy on the functional organization of the primary motor area of the brain in relation to clinical recovery.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Thirteen patients (10 men; mean age 56.7±10.3 years, age range 33 to 73 years; duration of hemiparesis 4.9±4.7 years [mean±SD], range 0.5 to 17 years) with chronic stroke (>6 months) were studied. Eleven of the subjects had a right-sided paresis; 3 had cortical lesions (2 ischemic and 1 hemorrhagic in origin), and 10 had lacunar subcortical lesions that involved the internal capsule. Informed consent for participation in the study was obtained from all patients. The study was approved by the local ethics committee.

Functional inclusion criteria were (1) the ability to extend 20° at the wrist and 10° at the fingers and (2) sufficient stability to walk when the less-affected arm is immobilized. Exclusion criteria were (1) serious uncontrolled medical conditions, (2) global aphasia or cognitive impairments that might interfere with understanding instructions for motor testing, (3) anything in the head that contained metal, (4) pregnancy, (5) epilepsy, and (6) cardiac pacemaker.

Each subject received 12 days of CI therapy preceded and followed by periods in which electrophysiological, neurological, and behavioral testing was conducted. For CI therapy, subjects agreed to wear a resting hand splint secured in a sling that prevented use of the nonparetic upper extremity for a target of 90% of waking hours. This arrangement induced greatly increased use of the paretic arm. In addition, on the 8 weekdays during the treatment period, the subjects came into the laboratory and received 6 hours per day of training in use of the affected arm in a variety of tasks according to a behavioral technique termed "shaping."⁶¹ The shaping was designed to produce intensive use of the more-affected extremity while at the same time improving the quality of movement. Treatment efficacy was evaluated with the motor activity log (MAL),³⁴ which tracked arm use in 20 common and important activities of daily living (ADL) performed outside the laboratory (1) for the week before the subject’s visit to the laboratory 2 weeks before the beginning of treatment, (2) for the week before the beginning of treatment, (3) 1 day after treatment, and (4) 4 weeks and (5) 6 months after the end of treatment (follow-up). The MAL has exhibited excellent intertest reliability for chronic stroke patients across a 2-week interval equal in length to the treatment period when no treatment was provided³⁷ and when a placebo treatment was administered.³⁶ Further details of the intervention and testing are available elsewhere.^{34 37} We mapped the cortical output area of the abductor pollicis brevis (APB) muscle of the more-affected and less-affected hands with TMS on the same day as the MAL was administered 1 day before treatment and 1 day and 4 weeks after treatment. (Two subjects died before the 4-week posttreatment testing could be carried out, and 1 subject had to be excluded at this time because of the intervening occurrence of an epileptic seizure.) As a control procedure, to confirm the stability of the electrophysiological and behavioral measures, 10 subjects were tested 2 weeks before the beginning of treatment. This is the same temporal interval that separates the second pretreatment and posttreatment tests and therefore controls for such nonspecific effects as expectancy of improved extremity function, initial contact with experimenters, and increased attention to use of the affected upper extremity. During the period between the testing 2 weeks and 1 day before treatment, there was no contact between patients and the project. Eight subjects have been tested 6 months after treatment to date.

For magnetic stimulation, we used a figure-8 coil (The Magstim Company) kept in an anteroposterior position with the grip pointing backward. The coil was moved systematically over the skull in steps of 1 cm to identify all scalp positions whose stimulation produced an EMG response in APB muscle. "Motor threshold" was defined as the minimal intensity of stimulation capable of inducing motor evoked potentials (MEPs) of >0.05 mV in at least 5 of 10 trials. Five transcranial magnetic pulses with an intensity 10% above the individual motor threshold were applied over each position to be tested. Both hemispheres were studied consecutively in a pseudorandom order. MEPs were recorded with surface electrodes from the contralateral and the ipsilateral APB muscle, respectively (Viking IV; Nicolet).

The subjects were seated comfortably in a chair with hands resting in their laps and wore a tight-fitting cap with a coordinate system (distances of 1 cm) indicated on it. They were provided with information about their muscular tension through auditory signals presented over a speaker that were proportional to the amount of prestimulation EMG activity recorded from APB muscle. The instruction was to relax the target muscle completely during the TMS mapping. Three parameters were used for analysis of the neurophysiological data: (1) size of the cortical motor output map, defined as the number of positions whose stimulation evoked MEPs of >0.05 mV, (2) motor thresholds, expressed as a percentage of the maximal stimulator output intensity, and (3) location of the amplitude-weighted center of gravity (CoG) of the motor output map. A detailed description of the calculation of the CoG is given elsewhere.⁶² Changes in all parameters were calculated for the more-affected and less-affected hemispheres. The investigator who performed the TMS mapping (J.L.) was blinded for the motor treatment outcome data. The experimenter who evaluated the motor function (H.B.) was blinded for the TMS mapping data. The behavioral and electrophysiological data were analyzed with repeated measures ANOVAs, followed by Tukey’s tests. Bonferroni-corrected paired t tests were used to compare the motor output area size of the affected and the unaffected hemisphere at each measurement day. P<0.05 was used as the criterion for statistical significance.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The MAL data are presented in Figure 1. CI therapy produced a significant and large improvement in motor functions from 1 day before treatment to 1 day after treatment (t₁₂=-12.781, P<0.0001). The MAL scores at 2 weeks and 1 day before treatment were not significantly different from each other. The treatment gain persisted undiminished in follow-up. Four weeks after treatment, the MAL scores were not significantly different from the scores at 1 day after treatment (t₉=-1.026, NS). A separate analysis for just the 8 subjects for whom there were 6-month follow-up data indicated that, again, the change from day 1 before treatment to the first day after treatment was significant (F_4,20=31.4, P<0.001, =0.336) and that the change remained undiminished 4 weeks and 6 months after treatment. The subjects scored a mean of 2.2 on the MAL 1 day before treatment and a mean of 3.7 at 1 day after treatment. To provide an idea of the nature of the treatment change, a score of 2 indicates slight use; 3, half as much use as before stroke, and 4, three fourths as much use as before stroke. The effect size was 1.5; in the meta-analysis literature, effect sizes of >0.8 are considered large.⁶³ Clinical and electrophysiological results were very similar in patients with cortical and subcortical strokes (P>0.1), so the data from both groups were combined.

View larger version (17K): [in this window] [in a new window]   Figure 1. MAL scores 2 weeks and 1 day before treatment and 1 day, 4 weeks, and 6 months after treatment for each patient.

The TMS mapping data 1 day after treatment paralleled the behavioral results. Figure 2 indicates that the area of the cortex that yielded a response of the paretic hand muscle to stimulation of the contralateral hemisphere showed a massive increase from 1 day before treatment to 1 day after treatment. One day before treatment, there were 40% fewer active positions in the infarcted hemisphere than in the noninfarcted hemisphere (P<0.001). By the first day after treatment, this relationship had reversed, with 37.5% more active positions in the infarcted hemisphere than in the noninfarcted hemisphere. The number of active positions in the infarcted hemisphere had nearly doubled from before to after treatment (12 to 22 active positions; P=0.002). At the same time, the number of active positions in the noninfarcted hemisphere was nonsignificantly reduced. Four weeks after treatment, the motor output map of the affected side was still significantly larger than before therapy (P=0.036). There was a small, nonsignificant decrease in the number of infarcted hemisphere active positions and a similarly small increase in noninfarcted hemisphere active positions. The result of these 2 opposite changes was to normalize hemispheric responsivity, making the number of active positions on the 2 sides of the brain nearly equal (ie, approaching the condition in normal subjects). Six months after treatment, the trend toward normalization observed 4 weeks after therapy was even more evident. The TMS data obtained 2 weeks before treatment and, after a 2-week nontreatment interval, at 1 day before treatment (Figure 2) showed a close correspondence.

View larger version (28K): [in this window] [in a new window]   Figure 2. Number of active TMS positions in the infarcted (black bars) and noninfarcted (gray bars) hemisphere 2 weeks and 1 day pretreatment and 1 day, 4 weeks, and 6 months after treatment. , Corresponding MAL data for the paretic limb. *P<0.05

The amplitude-weighted center of activation sites or CoG showed almost identical results in both hemispheres on comparison of the 2 baseline measurements (Figure 3) (mean displacement 2 mm). These small shifts could be due to technical limitations of the method^{62 64} or could indicate spontaneous fluctuations of the location of the center of the representation map. The CoG showed a significantly larger shift in the mediolateral dimension in the infarcted hemisphere than in the noninfarcted from 1 day before to 1 day after treatment (Figure 3, P<0.01). Nine of the shifts were in the lateral direction, whereas 4 of the shifts were medial. No significant changes were observed in the anteroposterior direction. Between 1 day after treatment and 4 weeks after treatment, further displacements of the CoG in the infarcted hemisphere were observed that showed a trend toward statistical significance: in 7 patients, the CoG moved medially; in 2, it remained in the same position; and in 1, a lateral shift occurred.

View larger version (14K): [in this window] [in a new window]   Figure 3. Differences in the location of the center of the cortical motor output map (CoG) in comparisons of the 2 pretreatment baseline conditions with each other, pretreatment with posttreatment, and posttreatment with 4-weeks posttreatment. Shifts of CoG location in the infarcted (black bars) and noninfarcted (gray bars) hemisphere were tabulated independent of lateromedial direction. , Corresponding MAL data for the paretic limb at the second baseline, posttreatment, and 4-week posttreatment time points. *P<0.05

The motor threshold was elevated over the affected hemisphere and remained very similar at the different times throughout the experiment (infarcted hemisphere: before treatment -55.3±13.7, after treatment -54.7±13.5, 4 weeks after treatment -53.7±12.8; noninfarcted hemisphere: before treatment -45.7±10.3, after treatment -44.9±10.1, 4 weeks after treatment -44.8±10.3 [values indicate a percentage of the maximal stimulator output intensity]). We did not observe any MEPs when stimulating the ipsilateral cortex on either the more- or the less-affected side.

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The most salient result of the present study is the almost doubling of the excitable cortex, yielding responses of a muscle in the more-affected hand of patients with chronic stroke after CI therapy. This result is paralleled by the large improvement produced by this intervention in the same subjects in the amount of use of the more-affected extremity in the real world setting. The behavioral and electrophysiological changes were consistent across individuals, with both being observed in each patient.

The comparison of the results of the 2 baseline measurements before therapy yielded a good reproduction of the MAL and TMS mapping data, with both indicating stability of motor performance in the patients and a good reproducibility of the TMS mapping and providing a control for certain nonspecific effects. The stability of both parameters is of importance for the interpretation of the posttreatment results in that it indicates the clinical and electrophysiological changes observed after CI therapy cannot be attributed to spontaneous recovery.

The decreased cortical representation area of the paretic muscle of the more-affected hand before therapy reflects a reduced excitability of the motor cortex in the more-affected hemisphere. This is probably due, at least in part, to a reduced use of the paretic hand before therapy or may be the result of the infarct itself.⁷ The complete reversal of this abnormally small excitable cortical area for the APB muscle in subjects whose stroke had occurred a mean of 4.9 years earlier took place during the very short period of 12 days. The mechanism of this massive cortical reorganization probably reflects either an increase in the excitability of neurons already involved in the innervation of more-affected hand movements or an increase in excitable neuronal tissue in the infarcted hemisphere, or both. The short time course of 12 days makes the formation of new anatomic connections by means of sprouting as a major mechanism unlikely because clear evidence of axonal growth has not been found until months after a lesion occurred.⁶⁵ A more likely mechanism is a reduction in activity of local inhibitory interneurons, thus unmasking preexisting excitatory connections.⁶⁶ An alternate and possibly complementary mechanism would be the enhancement of the synaptic strength of existing synaptic connections.⁶⁷ Regardless of the mechanism, rehabilitation appears to lead to a recruitment of a large number of neurons in the innervation of movements of the stroke-affected extremity adjacent to those involved before therapy. This hypothesis is further supported by larger shifts of the CoGs in the infarcted hemisphere. These CoG dislocations suggest that in addition to the enlargement of excitable cortical areas, a new maximum had developed adjacent to the former one. A similar finding was reported in adult monkeys that had received a unilateral lesion of the motor cortex during infancy: a relatively complete hand representation was found to occupy a new territory, medial to the old lesion.⁶⁸ In another intracortical microstimulation study, Nudo et al⁶⁹ demonstrated in adult squirrel monkeys that received a surgically induced ischemic infarct in a cortical area that controlled the movements of a hand that training of the more-affected limb and partial restraint of the less-affected extremity resulted in both improved motor functioning and cortical reorganization. The intervention was similar to the CI therapy approach that had been used previously.^{31 32 34} The present study demonstrates that CI therapy has a parallel effect in humans after stroke. Similarly, in recovered stroke patients, a large lateral extension of the brain area that is active during finger movements was found.⁷ Our results suggest that a reorganization occurred on a cortical level. However, the results do not permit exclusion of the possibility that additional plastic changes occurred on a subcortical or spinal level.

Some PET and fMRI studies in recovered stroke patients have suggested that plastic changes take place in the ipsilateral, noninfarcted hemisphere that might contribute to the restitution of motor function.^{7 8 9 10 12 70} In our study, MEPs could not be evoked with ipsilateral brain stimulation; therefore, no evidence for an involvement of the motor cortex ipsilateral to the paretic arm was found in this subgroup of patients. This does not exclude the possibility of an additional ipsilateral cortical reorganization because different factors (eg, submaximal intensity of the magnetic stimulator output, recordings from relaxed muscles, selection of patients, passive response to stimulation rather than active movement) could be responsible for our result.

It is interesting that at 4 weeks and 6 months after treatment, the number of active positions in the 2 hemispheres were almost identical. This represents a return of the balance of area of excitability in the innervation of muscular activity between the 2 hemispheres toward what is, in effect, a normal condition after a temporary, therapy-induced hyperexcitability. Because the MAL data remained unchanged, the TMS data could indicate that with continued increased use of the more-affected upper extremity for 6 months after treatment, there was an improvement in effective connectivity of the neuronal networks involved in the motor performance. Such a plastic change, presumably involving an increase in synaptic efficiency, would permit the reduction in the excitability of the neuronal connections without a deterioration of function.²⁰ A similar reduction in excitability along with an increased effective connectivity associated with repeated exposure to identical stimuli in associative learning was reported by Büchel et al.⁷¹ Pascual-Leone et al⁴⁰ demonstrated that gaining explicit knowledge of a task also reduced motor cortex excitability. An analogous process might have occurred here as the patients became adjusted with time to the newly acquired increased use of the more-affected extremity. Another explanation of our results could be that brain areas that are not accessible by focal TMS took over the execution of motor functions, thus allowing a reduction in the excitability of the primary motor cortex. This possibility could be addressed experimentally with fMRI techniques. Before treatment, the representation area of the nonparetic muscle in the unaffected hemisphere was significantly larger than the motor representation of the paretic muscle in the infarcted hemisphere. This area in the unaffected hemisphere decreased nonsignificantly after therapy. Several factors might have contributed to these changes. Before treatment, an increase in unaffected hand use, which was required to compensate for the greatly decreased use of the paretic hand in everyday life, could have resulted in relative large cortical representations. During and after therapy, the nonparetic hand was used less frequently than before therapy. Similar to results obtained in an immobilization study,⁴⁴ this reduced use might have produced a shrinkage of the representation area. An alternate explanation could be a transhemispheric cross-talk between the 2 primary motor cortices (M1), mediated through transcallosal fibers. In normal subjects, TMS over 1 M1 was found to reduce the excitability of the contralateral M1.⁷² This interhemispheric inhibition may still be operative in stroke patients with intact transcallosal connections.⁷³ Thus, a therapy-associated enhanced activation of M1 in the affected hemisphere could induce an increased inhibition of the contralateral M1.

CI therapy is predicated on the demonstration in deafferented monkeys^{31 32} after neurological injury that the nonuse of an affected extremity can be due to a learning phenomenon that involves a conditioned suppression of movement. CI therapy is considered to be effective because it increases the motivation to use the extremity and thereby overcomes the "learned nonuse." (This formulation has been described in detail elsewhere.^{31 32 36} ) The current results indicate that the intervention, which involves massed and sustained practice of functional arm movements, also produces a massive use-dependent cortical reorganization that may provide the basis for the long-term persistence of the treatment effect for the 6 months studied in this experiment and for the 2 years reported in other research.²⁵ Other examples of use-dependent cortical plasticity, resulting from the increased use of body parts in behaviorally relevant tasks, have been described in animals^{21 23 24} and humans.^{7 25 26 39 40 41 42}

One of the aims of neuroscience has been to generate effective new rehabilitation strategies that would give pragmatic importance to this area of basic research. Moreover, if a central nervous system correlate of such a therapy could be found, a new vista would be opened in which further improvements in rehabilitation might be produced through manipulation of that correlate. The present study addresses both of these objectives.

	Acknowledgments

 
This work was supported by a grant from the Kuratorium ZNS (Bonn) (Dr Miltner), by a grant from the BMBF Mednet (Drs Weiller and Liepert), by the DFG and the EU (Dr Weiller), and by grant B95-975R from the Rehabilitation Research and Development Service, US Department of Veterans Affairs (Dr Taub). We thank Monika Sommer for her help in providing treatment and Dr C. Dettmers for his assistance in the neurological examinations.

Received December 21, 1999; revision received March 9, 2000; accepted March 9, 2000.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 
1. Merzenich MM, Nelson RJ, Stryker MP, Cynader MS, Shoppmann A, Zook JM. Somatosensory cortical map changes following digit amputation in adult monkeys. J Comp Neurol. 1984;224:591–605.[Medline] [Order article via Infotrieve]

2. Kaas J, Florence SL, Jain N. Reorganization of sensory systems of primates after injury. Neuroscientist. 1997;3:123–130.[Abstract/Free Full Text]

3. Pons TP, Garraghty PE, Ommaya AK, Kaas JH, Taub E, Mishkin M. Massive cortical reorganization after sensory deafferentation in adult macaques. Science. 1991;252:1857–1860.[Abstract/Free Full Text]

4. Flor H, Elbert T, Knecht S, Wienbruch C, Pantev C, Birbaumer N, Larbig W, Taub E. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature. 1995;375:482–484.[Medline] [Order article via Infotrieve]

5. Mühlnickel W, Elbert T, Taub E, Flor H. Reorganization of auditory cortex in tinnitus. Proc Natl Acad Sci U S A. 1998;95:10340–10343.[Abstract/Free Full Text]

6. Elbert T, Candia V, Altenmüller E, Rau H, Sterr A, Rockstroh B, Pantev C, Taub E. Alteration of digital representations in somatosensory cortex in focal hand dystonia. Neuroreport. 1998;9:3571–3575.[Medline] [Order article via Infotrieve]

7. Weiller C, Chollet F, Friston KJ, Wise RJS, Frackowiak RSJ. Functional reorganization of the brain in recovery from striatocapsular infarction in man. Ann Neurol. 1992;31:463–472.[Medline] [Order article via Infotrieve]

8. Weiller C, Ramsay SC, Wise RJS, Friston KJ, Frackowiak RSJ. Individual patterns of functional reorganization in the human cerebral cortex after capsular infarction. Ann Neurol. 1993;33:181–189.[Medline] [Order article via Infotrieve]

9. Dettmers C, Stephan KM, Lemon RN, Frackowiak RSJ. Reorganization of the executive motor system after stroke. Cerebrovasc Dis. 1997;7:187–200.

10. Cramer SC, Nelles G, Benson RR, Kaplan JD, Parker RA, Kwong KK, Kennedy DN, Finklestein SP, Rosen BR. A functional MRI study of subjects recovered from hemiparetic stroke. Stroke. 1997;28:2518–2527.[Abstract/Free Full Text]

11. Cao Y, D’Olhaberriague L, Vikingstad EM, Levine SR, Welch KM. Pilot study of functional MRI to assess cerebral activation of motor function after poststroke hemiparesis. Stroke. 1998;29:112–122.[Abstract/Free Full Text]

12. Seitz RJ, Hoflich P, Binkowski F, Tellmann L, Herzog H, Freund HJ. Role of the premotor cortex in recovery from middle cerebral artery infarction. Arch Neurol. 1998;55:1081–1088.[Abstract/Free Full Text]

13. Binkowski F, Seitz RJ, Arnold S, Classen J, Bnecke R, Freund HJ. Thalamic metabolism and corticospinal tract integrity determine motor recovery in stroke. Ann Neurol. 1996;39:460–470.[Medline] [Order article via Infotrieve]

14. Seitz RJ, Azari NP, Knorr U, Binkofski F, Herzog H, Freund HJ. The role of diaschisis in stroke recovery. Stroke. 1999;30:1844–1850.[Abstract/Free Full Text]

15. Infeld B, Davis SM, Lichtenstein M, Mitchell PJ, Hopper JL. Crossed cerebellar diaschisis and brain recovery after stroke. Stroke. 1995;26:90–95.[Abstract/Free Full Text]

16. Palmer E, Ashby P, Hajek VE. Ipsilateral fast corticospinal pathways do not account for recovery in stroke. Ann Neurol. 1992;32:519–525.[Medline] [Order article via Infotrieve]

17. Cicinelli P, Traversa R, Rossini PM. Post-stroke reorganization of brain motor output to the hand: a 2–4 month follow-up with focal magnetic transcranial stimulation. Electroencephalogr Clin Neurophysiol. 1997;105:438–450.

18. Rossini PM, Caltagirone C, Castriota-Scanderbeg A, Cicinelli P, Del Gratta C, Demartin M, Pizzella V, Traversa R, Romani GL. Hand motor cortical area reorganization in stroke: a study with fMRI, MEG and TCS maps. Neuroreport. 1998;9:2141–2146.[Medline] [Order article via Infotrieve]

19. Traversa R, Cicinelli P, Bassi A, Rossini PM, Bernardi G. Mapping of motor cortical reorganization after stroke. Stroke. 1997;28:110–117.[Abstract/Free Full Text]

20. Weiller C, Rijntjes M. Learning, plasticity, and recovery in the central nervous system. Exp Brain Res. 1999;128:134–138.[Medline] [Order article via Infotrieve]

21. Nudo RJ, Milliken GW, Jenkins WM, Merzenich MM. Use-dependent alterations of movement representations in primary motor cortex of adult squirrel monkeys. J Neurosci. 1996;16:785–807.[Abstract/Free Full Text]

22. Nudo RJ, Milliken GW. Reorganization of movement representations in primary motor cortex following focal ischemic infarcts in adult squirrel monkeys. J Neurophysiol. 1996;75:2144–2149.[Abstract/Free Full Text]

23. Jenkins WM, Merzenich MM, Ochs MT, Allard T, Guic-Robles E. Functional reorganization of primary somatosensory cortex in adult owl monkeys after behaviorally controlled tactile stimulation. J Neurophysiol. 1990;3:82–104.

24. Recanzone GH, Merzenich MM, Jenkins WM. Frequency discrimination training engaging a restricted skin surface results in an emergence of a cutaneous response zone in cortical area 3a. J Neurophysiol. 1992;65:1057–1070.

25. Elbert T, Pantev C, Wienbruch C, Rockstroh B, Taub E. Increased cortical representation of the fingers of the left hand in string players. Science. 1995;270:305–307.[Abstract/Free Full Text]

26. Sterr A, Müller MM, Elbert T, Rockstroh B, Pantev C, Taub E. Changed perceptions in Braille readers. Nature. 1998;391:134–135.[Medline] [Order article via Infotrieve]

27. Duncan PW. Synthesis of intervention trials to improve motor recovery following stroke. Top Stroke Rehabil. 1997;3:1–20.

28. Twitchell TE. The restoration of motor function following hemiplegia in man. Brain. 1951;74:443–480.[Free Full Text]

29. Bard G, Hirschberg GG. Recovery of voluntary movement in upper extremity following hemiplegia. Arch Phys Med Rehab. 1965;46:567–572.[Medline] [Order article via Infotrieve]

30. Parker VM, Wade DT, Langton HR. Loss of arm function after stroke: measurement, frequency, and recovery. Int Rehab Med. 1986;8:69–73.

31. Taub E. Somatosensory deafferentation research with monkeys: implications for rehabilitation medicine. In: Ince LP, ed. Behavioral Psychology in Rehabilitation Medicine: Clinical Applications. New York, NY: Williams & Wilkins; 1980:371–401.

32. Taub E. Movement in nonhuman primates deprived of somatosensory feedback. Exerc Sports Sci Rev. 1977;4:335–374.

33. Wolf SL, Lecraw DE, Barton LA, Jann BB. Forced use of hemiplegic upper extremities to reverse the effect of learned nonuse among chronic stroke and head-injured patients. Exp Neurol. 1989;104:125–132.[Medline] [Order article via Infotrieve]

34. Taub E, Miller NE, Novack TA, Cook EW III, Fleming WC, Nepomuceno CS, Connell JS, Crago JE. Technique to improve chronic motor deficit after stroke. Arch Phys Med Rehab. 1993;74:347–354.[Medline] [Order article via Infotrieve]

35. Taub E, Pidikiti RD, DeLuca SC, Crago JE. Effects of motor restriction on an unimpaired upper extremity and training on improving functional tasks and altering brain behaviors. In: Toole JF, Good DC, eds,. Imaging in Neurologic Rehabilitation. New York, NY: Demos Vermande; 1996:133–154.

36. Taub E, Crago JE, Uswatte G. Constraint-induced movement therapy. a new approach to treatment in physical rehabilitation. Rehab Psychol. 1998;43:152–170.

37. Miltner WHR, Bauder H, Sommer M, Dettmers C, Taub E. Effects of constraint-induced movement therapy on patients with chronic motor deficits after stroke: a replication. Stroke. 1999;30:586–592.[Abstract/Free Full Text]

38. Taub E, Uswatte G, Pidikiti RD. Constraint-induced movement therapy. a new family of techniques with broad application to physical rehabilitation-a clinical review. J Rehab Res Dev. 1999;36:237–251.[Medline] [Order article via Infotrieve]

39. Pascual-Leone A, Dang N, Cohen LG, Brasil-Neto JP, Cammarota A, Hallett M. Modulation of muscle responses evoked by transcranial magnetic stimulation during the acquisition of new fine motor skills. J Neurophysiol. 1995;74:1037–1045.[Abstract/Free Full Text]

40. Pascual-Leone A, Grafman J, Hallett M. Modulation of cortical motor output maps during development of implicit and explicit knowledge. Science. 1994;263:1287–1289.[Abstract/Free Full Text]

41. Pascual-Leone A, Cammarota A, Wassermann E. M, Brasil-Neto JP, Cohen LG, Hallett M. Modulation of motor cortical outputs to the reading hand of Braille readers. Ann Neurol. 1993;34:33–37.[Medline] [Order article via Infotrieve]

42. Pascual-Leone A, Wassermann EM, Sadato N, Hallett M. The role of reading activity on the modulation of motor cortical outputs to the reading hand in Braille readers. Ann Neurol. 1995;38:910–915.[Medline] [Order article via Infotrieve]

43. Pascual-Leone A, Peris M, Tormos JM, Pascual-Leone Pascual A, Catala MD. Reorganization of human cortical motor output maps following traumatic forearm amputation. Neuroreport. 1996;7:2068–2070.[Medline] [Order article via Infotrieve]

44. Liepert J, Tegenthoff M, Malin J-P. Changes of cortical motor area size during immobilization. Electroencephalogr Clin Neurophysiol. 1995;97:382–386.

45. Cohen LG, Bandinelli S, Findley TW, Hallett M. Motor reorganization after upper limb amputation in man. Brain. 1991;114:615–627.[Abstract/Free Full Text]

46. Ridding MC, Rothwell JC. Reorganisation in human motor cortex. Can J Physiol Pharmacol. 1995;73:218–222.[Medline] [Order article via Infotrieve]

47. Rijntjes M, Tegenthoff M, Liepert J, Leonhardt G, Kotterba S, Müller S, Kiebel S, Malin J-P, Diener H-C, Weiller C. Cortical reorganization in patients with facial palsy. Ann Neurol. 1997;41:621–630.[Medline] [Order article via Infotrieve]

48. Mano Y, Nakamuro T, Tamura R, Takayanagi T, Kawanishi K, Tamai S, Mayer RF. Central motor reorganization after anastomosis of the musculocutaneous and intercostal nerves following cervical root avulsion. Ann Neurol. 1995;38:15–20.[Medline] [Order article via Infotrieve]

49. Rossini PM, Rossi S, Tecchio F, Pasqualetti P, Finazzi-Agro A, Sabato A. Focal brain stimulation in healthy humans: motor maps changes following partial hand sensory deprivation. Neurosci Lett. 1996;214:191–195.[Medline] [Order article via Infotrieve]

50. Topka H, Cohen LG, Cole RA, Hallett M. Reorganization of corticospinal pathways following spinal cord injury. Neurology. 1991;41:1276–1283.[Abstract/Free Full Text]

51. Brasil-Neto JP, Cohen LG, Pascual-Leone A, Jabir FK, Wall RT, Hallett M. Rapid reversible modulation of human cortical motor outputs after transient deafferentation of the forearm: a study with transcranial magnetic stimulation. Neurology. 1992;42:1302–1306.[Abstract/Free Full Text]

52. Brasil-Neto JP, Valls-Solé J, Pascual-Leone A, Cammarota A, Amassian VE, Cracco R, Maccabee P, Cracco J, Hallett M, Cohen LG. Rapid modulation of human cortical motor outputs following ischaemic nerve block. Brain. 1993;116:511–525.[Abstract/Free Full Text]

53. Fuhr P, Cohen LG, Dang N, Findley TW, Haghighi S, Oro J, Hallett M. Physiological analysis of motor reorganization following lower limb amputation. Electroencephalogr Clin Neurophysiol. 1992;85:53–60.

54. Levy WJ Jr, Amassian VE, Traad M, Cadwell J. Focal magnetic coil stimulation reveals motor cortical system reorganized in humans after traumatic quadriplegia. Brain Res. 1990;510:130–134.[Medline] [Order article via Infotrieve]

55. Byrnes ML, Thickbroom GW, Phillips BA, Wilson SA, Mastaglia FL. Physiological studies of the corticomotor projection to the hand after subcortical stroke. Clin Neurophysiol. 1999;110:487–498.[Medline] [Order article via Infotrieve]

56. Boroojerdi B, Foltys H, Krings T, Spetzger U, Thron A, Töpper R. Localization of the motor hand area using transcranial magnetic stimulation and functional magnetic resonance imaging. Clin Neurophysiol. 1999;110:699–704.[Medline] [Order article via Infotrieve]

57. Krings T, Buchbinder BR, Bulter WE, Chiappa KH, Jiang HJ, Cosgrove GR, Rosen BR. Functional magnetic resonance imaging and transcranial magnetic stimulation: complementary approaches in the evaluation of cortical motor function. Neurology. 1997;48:1406–1416.[Abstract/Free Full Text]

58. Bastings EP, Gage HD, Greenberg JP, Hammond G, Hernandez L, Santago P, Hamilton CA, Moody DM, Singh KD, Ricci PE, Pons TP, Good DC. Co-registration of cortical magnetic stimulation and functional magnetic resonance imaging. Neuroreport. 1998;9:1941–1946.[Medline] [Order article via Infotrieve]

59. Singh KD, Hamdy S, Aziz Q, Thompson DG. Topographic mapping of trans-cranial magnetic stimulation data on surface rendered MR images of the brain. Electroencephalogr Clin Neurophysiol. 1997;105:345–351.

60. Liepert J, Miltner WHR, Bauder H, Sommer M, Dettmers C, Taub E, Weiller C. Motor cortex plasticity during constraint-induced movement therapy in stroke patients. Neurosci Lett. 1998;250:5–8.[Medline] [Order article via Infotrieve]

61. Taub E, Crago JE, Burgio LD, Groomes TE, Cook EW III, DeLuca SC, Miller NE. An operant approach to rehabilitation medicine: overcoming learned nonuse by shaping. J Exp Anal Behav. 1994;61:281–293.[Medline] [Order article via Infotrieve]

62. Liepert J, Terborg C, Weiller C. Motor plasticity induced by synchronized thumb and foot movements. Exp Brain Res. 1999;125:435–439.[Medline] [Order article via Infotrieve]

63. Cohen J. Statistical Power Analysis in the Behavioral Sciences. New York, NY: Academic Press; 1997.

64. Miranda PC, de Carvalho M, Conceicao I, Luis MLS, Ducla-Soares E. A new method for reproducible coil positioning in transcranial magnetic stimulation mapping. Electroencephalogr Clin Neurophysiol. 1997;105:116–123.

65. Darian-Smith C, Gilbert CD. Topographic reorganization in the striate cortex of the adult cat and monkey is cortically mediated. J Neurosci. 1995;15:1631–1647.[Abstract]

66. Jacobs KM, Donoghue JP. Reshaping the cortical motor map by unmasking latent intracortical connections. Science. 1991;251:944–947.[Abstract/Free Full Text]

67. Hebb DO. Organization of Behaviour. New York, NY: Wiley; 1949.

68. Rouiller EM, Yu XH, Moret V, Tempini A, Wiesendanger M, Liang F. Dexterity in adult monkeys following early lesion of the motor cortical hand area: the role of cortex adjacent to the lesion. Eur J Neurosci. 1998;10:729–740.[Medline] [Order article via Infotrieve]

69. Nudo RJ, Wise BM, SiFuentes F, Milliken GW. Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Science. 1996;272:1791–1794.[Abstract]

70. Chollet F, DiPiero V, Wise RJ, Brooks DJ, Dolan RJ, Frackowiak RS. The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography. Ann Neurol. 1991;29:63–71.[Medline] [Order article via Infotrieve]

71. Büchel C, Coull JT, Friston KJ. The predictive value of changes in effective connectivity for human learning. Science. 1999;283:1538–1541.[Abstract/Free Full Text]

72. Ferbert A, Priori A, Rothwell JC, Day BL, Colebatch JG, Marsden CD. Interhemispheric inhibition of the human motor cortex. J Physiol. 1992;453:525–546.[Abstract/Free Full Text]

73. Boroojerdi B, Diefenbach K, Ferbert A. Transcallosal inhibition in cortical and subcortical cerebral vascular lesions. J Neurol Sci. 1996;144:160–170.[Medline] [Order article via Infotrieve]

This article has been cited by other articles:

				J. Charles and S. L. Wolf Invited Commentary Physical Therapy, November 1, 2009; 89(11): 1142 - 1143. [Full Text] [PDF]

				M. D. Ellis, T. Sukal-Moulton, and J. P. A. Dewald Progressive Shoulder Abduction Loading is a Crucial Element of Arm Rehabilitation in Chronic Stroke Neurorehabil Neural Repair, October 1, 2009; 23(8): 862 - 869. [Abstract] [PDF]

				A. Cacchio, E. De Blasis, V. De Blasis, V. Santilli, and G. Spacca Mirror Therapy in Complex Regional Pain Syndrome Type 1 of the Upper Limb in Stroke Patients Neurorehabil Neural Repair, October 1, 2009; 23(8): 792 - 799. [Abstract] [PDF]

				I. R. Winship and T. H. Murphy Remapping the Somatosensory Cortex after Stroke: Insight from Imaging the Synapse to Network Neuroscientist, October 1, 2009; 15(5): 507 - 524. [Abstract] [PDF]

				Transformational Technologies in Single-Event Neurological Conditions: Applying Lessons Learned in Stroke to Cerebral Palsy (August 14-15, 2008) Neurorehabil Neural Repair, September 1, 2009; 23(7): 747 - 765. [PDF]

				T. Endo, T. Tominaga, and L. Olson Cortical Changes Following Spinal Cord Injury with Emphasis on the Nogo Signaling System Neuroscientist, June 1, 2009; 15(3): 291 - 299. [Abstract] [PDF]

				M. F. Levin, J. A. Kleim, and S. L. Wolf What Do Motor "Recovery" and "Compensation" Mean in Patients Following Stroke? Neurorehabil Neural Repair, May 1, 2009; 23(4): 313 - 319. [Abstract] [PDF]

				S. J. Page, J. P. Szaflarski, J. C. Eliassen, H. Pan, and S. C. Cramer Cortical Plasticity Following Motor Skill Learning During Mental Practice in Stroke Neurorehabil Neural Repair, May 1, 2009; 23(4): 382 - 388. [Abstract] [PDF]

				E. B. Plow, J. R. Carey, R. J. Nudo, and A. Pascual-Leone Invasive Cortical Stimulation to Promote Recovery of Function After Stroke: A Critical Appraisal Stroke, May 1, 2009; 40(5): 1926 - 1931. [Abstract] [Full Text] [PDF]

				C. F Siengsukon and L. A Boyd Does Sleep Promote Motor Learning? Implications for Physical Rehabilitation Physical Therapy, April 1, 2009; 89(4): 370 - 383. [Abstract] [Full Text] [PDF]

				M. Rijntjes, K. Haevernick, A. Barzel, H. van den Bussche, G. Ketels, and C. Weiller Repeat Therapy for Chronic Motor Stroke: A Pilot Study for Feasibility and Efficacy Neurorehabil Neural Repair, March 1, 2009; 23(3): 275 - 280. [Abstract] [PDF]

				D. S. Marigold and J. E. Misiaszek Whole-Body Responses: Neural Control and Implications for Rehabilitation and Fall Prevention Neuroscientist, February 1, 2009; 15(1): 36 - 46. [Abstract] [PDF]

				P. Kluding and B. Gajewski Lower-Extremity Strength Differences Predict Activity Limitations in People With Chronic Stroke Physical Therapy, January 1, 2009; 89(1): 73 - 81. [Abstract] [Full Text] [PDF]

				A. Mirelman, P. Bonato, and J. E. Deutsch Effects of Training With a Robot-Virtual Reality System Compared With a Robot Alone on the Gait of Individuals After Stroke Stroke, January 1, 2009; 40(1): 169 - 174. [Abstract] [Full Text] [PDF]

				M. Rabadi, M. Galgano, D. Lynch, M Akerman, M. Lesser, and B. Volpe A pilot study of activity-based therapy in the arm motor recovery post stroke: a randomized controlled trial Clinical Rehabilitation, December 1, 2008; 22(12): 1071 - 1082. [Abstract] [PDF]

				N. N. Byl, E. A. Pitsch, and G. M. Abrams Functional Outcomes Can Vary by Dose: Learning-Based Sensorimotor Training for Patients Stable Poststroke Neurorehabil Neural Repair, September 1, 2008; 22(5): 494 - 504. [Abstract] [PDF]

				J. Langan and P. van Donkelaar The Influence of Hand Dominance on the Response to a Constraint-Induced Therapy Program Following Stroke Neurorehabil Neural Repair, June 1, 2008; 22(3): 298 - 304. [Abstract] [PDF]

				M. Richter, W. H. R. Miltner, and T. Straube Association between therapy outcome and right-hemispheric activation in chronic aphasia Brain, May 1, 2008; 131(5): 1391 - 1401. [Abstract] [Full Text] [PDF]

				L. V. Gauthier, E. Taub, C. Perkins, M. Ortmann, V. W. Mark, and G. Uswatte Remodeling the Brain: Plastic Structural Brain Changes Produced by Different Motor Therapies After Stroke * Supplemental Material Stroke, May 1, 2008; 39(5): 1520 - 1525. [Abstract] [Full Text] [PDF]

				J. M. W. W. Myint, G. F. C. Yuen, T. K. K. Yu, C. P. L. Kng, A. M. Y. Wong, K. K. C. Chow, H. C. K. Li, and Chun Por Wong A study of constraint-induced movement therapy in subacute stroke patients in Hong Kong Clinical Rehabilitation, February 1, 2008; 22(2): 112 - 124. [Abstract] [PDF]

				J. A. Kleim and T. A. Jones Principles of Experience-Dependent Neural Plasticity: Implications for Rehabilitation After Brain Damage J Speech Lang Hear Res, February 1, 2008; 51(1): S225 - S239. [Abstract] [Full Text] [PDF]

				A. M. Raymer, P. Beeson, A. Holland, D. Kendall, L. M. Maher, N. Martin, L. Murray, M. Rose, C. K. Thompson, L. Turkstra, et al. Translational Research in Aphasia: From Neuroscience to Neurorehabilitation J Speech Lang Hear Res, February 1, 2008; 51(1): S259 - S275. [Abstract] [Full Text] [PDF]

				C.-L. Yen, R.-Y. Wang, K.-K. Liao, C.-C. Huang, and Y.-R. Yang Gait Training Induced Change in Corticomotor Excitability in Patients With Chronic Stroke Neurorehabil Neural Repair, February 1, 2008; 22(1): 22 - 30. [Abstract] [PDF]

				I. Loubinoux, S. Dechaumont-Palacin, E. Castel-Lacanal, X. De Boissezon, P. Marque, J. Pariente, J.-F. Albucher, I. Berry, and F. Chollet Prognostic Value of fMRI in Recovery of Hand Function in Subcortical Stroke Patients Cereb Cortex, December 1, 2007; 17(12): 2980 - 2987. [Abstract] [Full Text] [PDF]

				T. L. Sutcliffe, W. C. Gaetz, W. J. Logan, D. O. Cheyne, and D. L. Fehlings Cortical Reorganization After Modified Constraint-Induced Movement Therapy in Pediatric Hemiplegic Cerebral Palsy J Child Neurol, November 1, 2007; 22(11): 1281 - 1287. [Abstract] [PDF]

				S. S.M. Ng and C. W.Y. Hui-Chan Transcutaneous Electrical Nerve Stimulation Combined With Task-Related Training Improves Lower Limb Functions in Subjects With Chronic Stroke Stroke, November 1, 2007; 38(11): 2953 - 2959. [Abstract] [Full Text] [PDF]

				S. L. Wolf, C. J. Winstein, J. P. Miller, S. Blanton, P. C. Clark, and D. Nichols-Larsen Looking in the Rear View Mirror When Conversing With Back Seat Drivers: The EXCITE Trial Revisited Neurorehabil Neural Repair, October 1, 2007; 21(5): 379 - 387. [Abstract] [PDF]

				S. L Wolf Revisiting Constraint-Induced Movement Therapy: Are We Too Smitten With the Mitten? Is All Nonuse "Learned"? and Other Quandaries Physical Therapy, September 1, 2007; 87(9): 1212 - 1223. [Abstract] [Full Text] [PDF]

				P. G. Lindberg, C. Schmitz, M. Engardt, H. Forssberg, and J. Borg Use-Dependent Up- and Down-Regulation of Sensorimotor Brain Circuits in Stroke Patients Neurorehabil Neural Repair, July 1, 2007; 21(4): 315 - 326. [Abstract] [PDF]

				S. C. Cramer, T. B. Parrish, R. M. Levy, G. T. Stebbins, S. D. Ruland, D. W. Lowry, T. P. Trouard, S. W. Squire, M. E. Weinand, C. R. Savage, et al. Predicting Functional Gains in a Stroke Trial Stroke, July 1, 2007; 38(7): 2108 - 2114. [Abstract] [Full Text] [PDF]

				A. J Butler and S. L Wolf Putting the Brain on the Map: Use of Transcranial Magnetic Stimulation to Assess and Induce Cortical Plasticity of Upper-Extremity Movement Physical Therapy, June 1, 2007; 87(6): 719 - 736. [Abstract] [Full Text] [PDF]

				M. Desmurget, F. Bonnetblanc, and H. Duffau Contrasting acute and slow-growing lesions: a new door to brain plasticity Brain, April 1, 2007; 130(4): 898 - 914. [Abstract] [Full Text] [PDF]

				M Davare, J Duque, Y Vandermeeren, J-L Thonnard, and E Olivier Role of the Ipsilateral Primary Motor Cortex in Controlling the Timing of Hand Muscle Recruitment Cereb Cortex, February 1, 2007; 17(2): 353 - 362. [Abstract] [Full Text] [PDF]

				S. L Fritz, S. Z George, S. L Wolf, and K. E Light Participant Perception of Recovery as Criterion to Establish Importance of Improvement for Constraint-Induced Movement Therapy Outcome Measures: A Preliminary Study Physical Therapy, February 1, 2007; 87(2): 170 - 178. [Abstract] [Full Text] [PDF]

				B. H. Dobkin Confounders in Rehabilitation Trials of Task-Oriented Training: Lessons From the Designs of the EXCITE and SCILT Multicenter Trials Neurorehabil Neural Repair, January 1, 2007; 21(1): 3 - 13. [Abstract] [PDF]

				L Henriksson, A Raninen, R Nasanen, L Hyvarinen, and S Vanni Training-induced cortical representation of a hemianopic hemifield J. Neurol. Neurosurg. Psychiatry, January 1, 2007; 78(1): 74 - 81. [Abstract] [Full Text] [PDF]

				J. E Harris and J. J Eng Paretic Upper-Limb Strength Best Explains Arm Activity in People With Stroke Physical Therapy, January 1, 2007; 87(1): 88 - 97. [Abstract] [Full Text] [PDF]

				N. Dancause Vicarious Function of Remote Cortex following Stroke: Recent Evidence from Human and Animal Studies Neuroscientist, December 1, 2006; 12(6): 489 - 499. [Abstract] [PDF]

				L. Richards, L. J Gonzalez Rothi, S. Davis, S. S Wu, and S. E Nadeau Limited dose response to Constraint-Induced Movement Therapy in patients with chronic stroke Clinical Rehabilitation, December 1, 2006; 20(12): 1066 - 1074. [Abstract] [PDF]

				M. Schenkman, J. E Deutsch, and K. M Gill-Body An Integrated Framework for Decision Making in Neurologic Physical Therapist Practice Physical Therapy, December 1, 2006; 86(12): 1681 - 1702. [Abstract] [Full Text] [PDF]

				S. C. Deluca, K. Echols, C. R. Law, and S. L. Ramey Intensive Pediatric Constraint-Induced Therapy for Children With Cerebral Palsy: Randomized, Controlled, Crossover Trial J Child Neurol, November 1, 2006; 21(11): 931 - 938. [Abstract] [PDF]

				S. L. Wolf, C. J. Winstein, J. P. Miller, E. Taub, G. Uswatte, D. Morris, C. Giuliani, K. E. Light, D. Nichols-Larsen, and for the EXCITE Investigators Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial. JAMA, November 1, 2006; 296(17): 2095 - 2104. [Abstract] [Full Text] [PDF]

				A. R. Luft and D. F. Hanley Stroke recovery--moving in an EXCITE-ing direction. JAMA, November 1, 2006; 296(17): 2141 - 2143. [Full Text] [PDF]

				S.-F. Sun, C.-W. Hsu, C.-W. Hwang, P.-T. Hsu, J.-L. Wang, and C.-L. Yang Application of Combined Botulinum Toxin Type A and Modified Constraint-Induced Movement Therapy for an Individual With Chronic Upper-Extremity Spasticity After Stroke Physical Therapy, October 1, 2006; 86(10): 1387 - 1397. [Abstract] [Full Text] [PDF]

				J. R. Carey, K. R. Greer, T. K. Grunewald, J. L. Steele, J. W. Wiemiller, E. Bhatt, A. Nagpal, O. Lungu, and E. J. Auerbach Primary Motor Area Activation during Precision-Demanding versus Simple Finger Movement Neurorehabil Neural Repair, September 1, 2006; 20(3): 361 - 370. [Abstract] [PDF]

				J. E. Harris and J. J. Eng Individuals with the Dominant Hand Affected following Stroke Demonstrate Less Impairment Than Those with the Nondominant Hand Affected Neurorehabil Neural Repair, September 1, 2006; 20(3): 380 - 389. [Abstract] [PDF]

				J. Underwood, P. C Clark, S. Blanton, D. M Aycock, and S. L Wolf Pain, Fatigue, and Intensity of Practice in People With Stroke Who Are Receiving Constraint-Induced Movement Therapy Physical Therapy, September 1, 2006; 86(9): 1241 - 1250. [Abstract] [Full Text] [PDF]

				F. Fregni, P. S. Boggio, A. C. Valle, R. R. Rocha, J. Duarte, M. J.L. Ferreira, T. Wagner, S. Fecteau, S. P. Rigonatti, M. Riberto, et al. A Sham-Controlled Trial of a 5-Day Course of Repetitive Transcranial Magnetic Stimulation of the Unaffected Hemisphere in Stroke Patients Stroke, August 1, 2006; 37(8): 2115 - 2122. [Abstract] [Full Text] [PDF]

				N. Sharma, V. M. Pomeroy, and J.-C. Baron Motor Imagery: A Backdoor to the Motor System After Stroke? Stroke, July 1, 2006; 37(7): 1941 - 1952. [Abstract] [Full Text] [PDF]

				J. Higgins, N. M Salbach, S. Wood-Dauphinee, C. L Richards, R. Cote, and N. E Mayo The effect of a task-oriented intervention on arm function in people with stroke: a randomized controlled trial Clinical Rehabilitation, April 1, 2006; 20(4): 296 - 310. [Abstract] [PDF]

				B. H. Dobkin Rehabilitation and Functional Neuroimaging Dose-Response Trajectories for Clinical Trials Neurorehabil Neural Repair, December 1, 2005; 19(4): 276 - 282. [Abstract] [PDF]

				V. M. Pomeroy, E. Cooke, S. Hamilton, A. Whittet, and R. C. Tallis Development of a Schedule of Current Physiotherapy Treatment Used to Improve Movement Control and Functional Use of the Lower Limb after Stroke: A Precursor to a Clinical Trial Neurorehabil Neural Repair, December 1, 2005; 19(4): 350 - 359. [Abstract] [PDF]

				S. L. Thomas and M. A. Gorassini Increases in Corticospinal Tract Function by Treadmill Training After Incomplete Spinal Cord Injury J Neurophysiol, October 1, 2005; 94(4): 2844 - 2855. [Abstract] [Full Text] [PDF]

				M. Rijntjes, V. Hobbeling, F. Hamzei, S. Dohse, G. Ketels, J. Liepert, and C. Weiller Individual Factors in Constraint-Induced Movement Therapy after Stroke Neurorehabil Neural Repair, September 1, 2005; 19(3): 238 - 249. [Abstract] [PDF]

				U. Gabr, P. Levine, and S. J Page Home-based electromyography-triggered stimulation in chronic stroke Clinical Rehabilitation, July 1, 2005; 19(7): 737 - 745. [Abstract] [PDF]

				M. Meinzer, D. Djundja, G. Barthel, T. Elbert, and B. Rockstroh Long-Term Stability of Improved Language Functions in Chronic Aphasia After Constraint-Induced Aphasia Therapy Stroke, July 1, 2005; 36(7): 1462 - 1466. [Abstract] [Full Text] [PDF]

				S. H. You, S. H. Jang, Y.-H. Kim, M. Hallett, S. H. Ahn, Y.-H. Kwon, J. H. Kim, and M. Y. Lee Virtual Reality-Induced Cortical Reorganization and Associated Locomotor Recovery in Chronic Stroke: An Experimenter-Blind Randomized Study Stroke, June 1, 2005; 36(6): 1166 - 1171. [Abstract] [Full Text] [PDF]

				S. L Fritz, Y.-P. Chiu, M. P Malcolm, T. S Patterson, and K. E Light Feasibility of Electromyography-Triggered Neuromuscular Stimulation as an Adjunct to Constraint-Induced Movement Therapy Physical Therapy, May 1, 2005; 85(5): 428 - 442. [Abstract] [Full Text] [PDF]

				V. M. Pomeroy, C. A. Clark, J. S. G. Miller, J.-C. Baron, H. S. Markus, and R. C. Tallis The Potential for Utilizing the "Mirror Neurone System" to Enhance Recovery of the Severely Affected Upper Limb Early after Stroke: A Review and Hypothesis Neurorehabil Neural Repair, March 1, 2005; 19(1): 4 - 13. [Abstract] [PDF]

				S. J. Page, P. Levine, and A. C. Leonard Modified Constraint-Induced Therapy in Acute Stroke: A Randomized Controlled Pilot Study Neurorehabil Neural Repair, March 1, 2005; 19(1): 27 - 32. [Abstract] [PDF]

				K. S. Beekhuizen and E. C. Field-Fote Massed Practice versus Massed Practice with Stimulation: Effects on Upper Extremity Function and Cortical Plasticity in Individuals with Incomplete Cervical Spinal Cord Injury Neurorehabil Neural Repair, March 1, 2005; 19(1): 33 - 45. [Abstract] [PDF]

				K Rasova, J Krasensky, E Havrdova, J Obenberger, Z Seidel, O Dolezal, P Rexova, and M Zalisova Is it possible to actively and purposely make use of plasticity and adaptability in the neurorehabilitation treatment of multiple sclerosis patients? A pilot project Clinical Rehabilitation, February 1, 2005; 19(2): 170 - 181. [Abstract] [PDF]

				M. C. Stoeckel, B. Pollok, O. W. Witte, R. J. Seitz, and A. Schnitzler Shrinkage of Somatosensory Hand Area in Subjects With Upper Extremity Dysmelia Revealed by Magnetoencephalography J Neurophysiol, February 1, 2005; 93(2): 813 - 818. [Abstract] [Full Text] [PDF]

				L. Koski, T. J. Mernar, and B. H. Dobkin Immediate and Long-Term Changes in Corticomotor Output in Response to Rehabilitation: Correlation with Functional Improvements in Chronic Stroke Neurorehabil Neural Repair, December 1, 2004; 18(4): 230 - 249. [Abstract] [PDF]

				J. E Sullivan and L. D Hedman A Home Program of Sensory and Neuromuscular Electrical Stimulation With Upper-Limb Task Practice in a Patient 5 Years After a Stroke Physical Therapy, November 1, 2004; 84(11): 1045 - 1054. [Abstract] [Full Text] [PDF]

				J. C. Grotta, E. A. Noser, T. Ro, C. Boake, H. Levin, J. Aronowski, and T. Schallert Constraint-Induced Movement Therapy Stroke, November 1, 2004; 35(11_suppl_1): 2699 - 2701. [Abstract] [Full Text] [PDF]

				A. R. Luft, S. McCombe-Waller, J. Whitall, L. W. Forrester, R. Macko, J. D. Sorkin, J. B. Schulz, A. P. Goldberg, and D. F. Hanley Repetitive Bilateral Arm Training and Motor Cortex Activation in Chronic Stroke: A Randomized Controlled Trial JAMA, October 20, 2004; 292(15): 1853 - 1861. [Abstract] [Full Text] [PDF]

				A. J Turton and S. R Butler A multiple case design experiment to investigate the performance and neural effects of a programme for training hand function after stroke Clinical Rehabilitation, July 1, 2004; 18(7): 754 - 763. [Abstract] [PDF]

				S.-W. Park, A. J. Butler, V. Cavalheiro, J. L. Alberts, and S. L. Wolf Changes in Serial Optical Topography and TMS during Task Performance after Constraint-Induced Movement Therapy in Stroke: A Case Study Neurorehabil Neural Repair, June 1, 2004; 18(2): 95 - 105. [Abstract] [PDF]

				D. A. Drubach, M. Makley, and M. L. Dodd Manipulation of Central Nervous System Plasticity: A New Dimension in the Care of Neurologically Impaired Patients Mayo Clin. Proc., June 1, 2004; 79(6): 796 - 800. [Abstract] [PDF]

				J.H. van der Lee, H. Beckerman, D.L. Knol, H.C.W. de Vet, and L.M. Bouter Clinimetric Properties of the Motor Activity Log for the Assessment of Arm Use in Hemiparetic Patients Stroke, June 1, 2004; 35(6): 1410 - 1414. [Abstract] [Full Text] [PDF]

				C. M. Butefisch, V. Khurana, L. Kopylev, and L. G. Cohen Enhancing Encoding of a Motor Memory in the Primary Motor Cortex By Cortical Stimulation J Neurophysiol, May 1, 2004; 91(5): 2110 - 2116. [Abstract] [Full Text] [PDF]

				T. Elbert and B. Rockstroh Reorganization of Human Cerebral Cortex: The Range of Changes Following Use and Injury Neuroscientist, April 1, 2004; 10(2): 129 - 141. [Abstract] [PDF]

				M. Weinrich, D. C. Good, M. Reding, E. J. Roth, D. X. Cifu, K. H. Silver, R. L. Craik, J. Magaziner, M. Terrin, M. Schwartz, et al. Timing, Intensity, and Duration of Rehabilitation for Hip Fracture and Stroke: Report of a Workshop at the National Center for Medical Rehabilitation Research Neurorehabil Neural Repair, March 1, 2004; 18(1): 12 - 28. [Abstract] [PDF]

				E. Taub, S. L. Ramey, S. DeLuca, and K. Echols Efficacy of Constraint-Induced Movement Therapy for Children With Cerebral Palsy With Asymmetric Motor Impairment Pediatrics, February 1, 2004; 113(2): 305 - 312. [Abstract] [Full Text] [PDF]

				M. Kobayashi, S. Hutchinson, H. Theoret, G. Schlaug, and A. Pascual-Leone Repetitive TMS of the motor cortex improves ipsilateral sequential simple finger movements Neurology, January 13, 2004; 62(1): 91 - 98. [Abstract] [Full Text] [PDF]

				G. N Lewisand and W. D Byblow Neurophysiological and behavioural adaptations to a bilateral training intervention in individuals following stroke Clinical Rehabilitation, January 1, 2004; 18(1): 48 - 59. [Abstract] [PDF]

				J. V Bastille and K. M Gill-Body A Yoga-Based Exercise Program for People With Chronic Poststroke Hemiparesis Physical Therapy, January 1, 2004; 84(1): 33 - 48. [Abstract] [Full Text] [PDF]

				S. R. Pierce, K. G. Gallagher, S. W. Schaumburg, A. M. Gershkoff, J. P. Gaughan, and L. Shutter Home Forced Use in an Outpatient Rehabilitation Program for Adults with Hemiplegia: A Pilot Study Neurorehabil Neural Repair, December 1, 2003; 17(4): 214 - 219. [Abstract] [PDF]

				S. C DeLuca, K. Echols, S. L. Ramey, and E. Taub Pediatric Constraint-Induced Movement Therapy for a Young Child With Cerebral Palsy: Two Episodes of Care Physical Therapy, November 1, 2003; 83(11): 1003 - 1013. [Abstract] [Full Text] [PDF]

				A. Sterr and S. Freivogel Motor-improvement following intensive training in low-functioning chronic hemiparesis Neurology, September 23, 2003; 61(6): 842 - 844. [Abstract] [Full Text] [PDF]

				N. Byl, J. Roderick, O. Mohamed, M. Hanny, J. Kotler, A. Smith, M. Tang, and G. Abrams Effectiveness of Sensory and Motor Rehabilitation of the Upper Limb Following the Principles of Neuroplasticity: Patients Stable Poststroke Neurorehabil Neural Repair, September 1, 2003; 17(3): 176 - 191. [Abstract] [PDF]

				P. Duncan, S. Studenski, L. Richards, S. Gollub, S. M. Lai, D. Reker, S. Perera, J. Yates, V. Koch, S. Rigler, et al. Randomized Clinical Trial of Therapeutic Exercise in Subacute Stroke Stroke, September 1, 2003; 34(9): 2173 - 2180. [Abstract] [Full Text] [PDF]

				L. Lee, H. R. Siebner, J. B. Rowe, V. Rizzo, J. C. Rothwell, R. S. J. Frackowiak, and K. J. Friston Acute Remapping within the Motor System Induced by Low-Frequency Repetitive Transcranial Magnetic Stimulation J. Neurosci., June 15, 2003; 23(12): 5308 - 5318. [Abstract] [Full Text] [PDF]

				S. B. Frost, S. Barbay, K. M. Friel, E. J. Plautz, and R. J. Nudo Reorganization of Remote Cortical Regions After Ischemic Brain Injury: A Potential Substrate for Stroke Recovery J Neurophysiol, June 1, 2003; 89(6): 3205 - 3214. [Abstract] [Full Text] [PDF]

				J. Chae and R. Hart Intramuscular Hand Neuroprosthesis for Chronic Stroke Survivors Neurorehabil Neural Repair, June 1, 2003; 17(2): 109 - 117. [Abstract] [PDF]

				C. Calautti and J.-C. Baron Functional Neuroimaging Studies of Motor Recovery After Stroke in Adults: A Review Stroke, June 1, 2003; 34(6): 1553 - 1566. [Abstract] [Full Text] [PDF]

				N. Bonifer and K. M Anderson Application of Constraint-Induced Movement Therapy for an Individual With Severe Chronic Upper-Extremity Hemiplegia Physical Therapy, April 1, 2003; 83(4): 384 - 398. [Abstract] [Full Text] [PDF]

				G. F. Wittenberg, R. Chen, K. Ishii, K. O. Bushara, E. Taub, L. H. Gerber, M. Hallett, and L. G. Cohen Constraint-Induced Therapy in Stroke: Magnetic-Stimulation Motor Maps and Cerebral Activation Neurorehabil Neural Repair, March 1, 2003; 17(1): 48 - 57. [Abstract] [PDF]

				R. M. Dijkhuizen, A. B. Singhal, J. B. Mandeville, O. Wu, E. F. Halpern, S. P. Finklestein, B. R. Rosen, and E. H. Lo Correlation between Brain Reorganization, Ischemic Damage, and Neurologic Status after Transient Focal Cerebral Ischemia in Rats: A Functional Magnetic Resonance Imaging Study J. Neurosci., January 15, 2003; 23(2): 510 - 517. [Abstract] [Full Text] [PDF]

				J. L. Tillerson and G. W. Miller Book Review: Forced Limb-Use and Recovery following Brain Injury Neuroscientist, December 1, 2002; 8(6): 574 - 585. [Abstract] [PDF]

				J. D. Schaechter, E. Kraft, T. S. Hilliard, R. M. Dijkhuizen, T. Benner, S. P. Finklestein, B. R. Rosen, and S. C. Cramer Motor Recovery and Cortical Reorganization after Constraint-Induced Movement Therapy in Stroke Patients: A Preliminary Study Neurorehabil Neural Repair, December 1, 2002; 16(4): 326 - 338. [Abstract] [PDF]

				H. Reddy, S. Narayanan, M. Woolrich, T. Mitsumori, Y. Lapierre, D. L. Arnold, and P. M. Matthews Functional brain reorganization for hand movement in patients with multiple sclerosis: defining distinct effects of injury and disability Brain, December 1, 2002; 125(12): 2646 - 2657. [Abstract] [Full Text] [PDF]

				H. Johansen-Berg, H. Dawes, C. Guy, S. M. Smith, D. T. Wade, and P. M. Matthews Correlation between motor improvements and altered fMRI activity after rehabilitative therapy Brain, December 1, 2002; 125(12): 2731 - 2742. [Abstract] [Full Text] [PDF]

				J. Chae, G. Yang, B. K. Park, and I. Labatia Muscle Weakness and Cocontraction in Upper Limb Hemiparesis: Relationship to Motor Impairment and Physical Disability Neurorehabil Neural Repair, September 1, 2002; 16(3): 241 - 248. [Abstract] [PDF]

				A. S Merians, D. Jack, R. Boian, M. Tremaine, G. C Burdea, S. V Adamovich, M. Recce, and H. Poizner Virtual Reality-Augmented Rehabilitation for Patients Following Stroke Physical Therapy, September 1, 2002; 82(9): 898 - 915. [Abstract] [Full Text] [PDF]

				T. Shimizu, A. Hosaki, T. Hino, M. Sato, T. Komori, S. Hirai, and P. M. Rossini Motor cortical disinhibition in the unaffected hemisphere after unilateral cortical stroke Brain, August 1, 2002; 125(8): 1896 - 1907. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liepert, J. Articles by Weiller, C. Search for Related Content PubMed PubMed Citation Articles by Liepert, J. Articles by Weiller, C. Pubmed/NCBI databases Medline Plus Health Information Stroke Related Collections Electrophysiology Exercise/exercise testing/rehabilitation Rehabilitation, Stroke