edicine and Rehabilitation

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Archives of Physical Medicine and Rehabilitation 2015;96:69-75

ORIGINAL ARTICLE

Corticospinal Integrity and Motor Impairment PredictOutcomes After Excitatory Repetitive TranscranialMagnetic Stimulation: A Preliminary Study

Chih-Jou Lai, MD, MS,a,b Chih-Pin Wang, MD,c Po-Yi Tsai, MD,a,b Rai-Chi Chan, MD,a,b

Shan-Hui Lin, MD,a Fu-Gong Lin, PhD,d Chin-Yi Hsieh, MDc

From the aDepartment of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei; bNational Yang-Ming University,School of Medicine, Taipei; cDepartment of Emergency, Mackay Memorial Hospital, Taipei; and dSchool of Public Health, National DefenseMedical Center, Taipei, Taiwan.

Abstract

Objective: To identify the effective predictors for therapeutic outcomes based on intermittent theta-burst stimulation (iTBS).

Design: A sham-controlled, double-blind parallel study design.

Setting: A tertiary hospital.

Participants: People with stroke (NZ72) who presented with unilateral hemiplegia.

Interventions: Ten consecutive sessions of real or sham iTBS were implemented with the aim of enhancing hand function. Patients were

categorized into 4 groups according to the presence (MEPþ) or absence (MEP�) of motor-evoked potentials (MEPs) and grip strength according

to the Medical Research Council (MRC) scale.

Main Outcome Measures: Cortical excitability, Wolf Motor Function Test (WMFT), finger-tapping task (FT), and simple reaction time were

performed before and after the sessions.

Results: MEPs and the MRC scale were predictive of iTBS therapeutic outcomes. Group A (MEPþ, MRC>1) exhibited the greatest WMFT

change (7.6�2.3, P<.001), followed by group B (MEP�, MRC>1; 5.2�2.2 score change) and group C (MEP�, MRCZ0; 2.3�1.5 score change).

These improvements were correlated significantly with baseline motor function and ipsilesional maximum MEP amplitude.

Conclusions: The effectiveness of iTBS modulation for poststroke motor enhancement depends on baseline hand grip strength and the presence

of MEPs. Our findings indicate that establishing neurostimulation strategies based on the proposed electrophysiological and clinical criteria can

allow iTBS to be executed with substantial precision. Effective neuromodulatory strategies can be formulated by using electrophysiological

features and clinical presentation information as guidelines.

Archives of Physical Medicine and Rehabilitation 2015;96:69-75

ª 2015 by the American Congress of Rehabilitation Medicine

Stroke is a major medical problem and the leading cause ofdisability worldwide.1 Motor recovery after a stroke depends onthe reorganization of the perilesional region, axonal regenerationwithin connected motor networks, and the unmasking of the po-tential secondary motor areas.2,3 The postulated role of synapticplasticity in poststroke motor recovery has awakened great interestin the applicability of noninvasive brain stimulation,4,5 includingrepetitive transcranial magnetic stimulation (rTMS), which has

Supported by the Taipei Veterans General Hospital (grant no. V103C-168).

Clinical Trial Registration No.: NCT02006615.

Disclosures: none.

0003-9993/14/$36 - see front matter ª 2015 by the American Congress of Re

http://dx.doi.org/10.1016/j.apmr.2014.08.014

shown promise in promoting motor relearning and enhancingneurologic recovery.6 This is because rTMS generates long-termpotentiation and long-term depression-like synaptic plasticity,which are associated with augmented neural plasticity.7,8 TheN-methyl-D-aspartate receptoredependent aftereffects of high-frequency rTMS have been shown to upregulate corticalplasticity, leading to the consolidation of adaptive neuro-modulation.9,10 Participant responses to rTMS vary greatly;possible modulatory factors include the participant’s age, theduration of the poststroke period, the lesion location, andthe severity of baseline motor impairment.10-12 Identifying thereceptiveness of patients with various characteristics to rTMS

habilitation Medicine

Table 1 Demographic data and clinical characteristics of all patients

Characteristics Group A (nZ21) Group B (nZ17) Group C (nZ17) Group D (nZ17)

Age (y) 62.6�11.6 60.4�10.4 63.4�12.1 62.1�10.5

M/F 17/4 14/3 13/4 13/4

Ischemic/hemorrhagic 15/6 12/5 13/4 13/4

Cortical�CR/BG 8 6 7 6

CR/BG 13 11 10 11

Right/left brain lesion 11/10 9/8 10/7 8/9

Lesion volume (cm3) 37.0�21.4 39.5�28.4 34.7�23.6 38.2�20.6

NIHSS 11.8�3.8 11.4�4.1 12.1�3.7 11.4�3.5

Months poststroke 10.4�5.8 9.7�5.1 11.4�4.3 10.6�4.6

NOTE. Values are mean � SD or n.

Abbreviations: BG, basal ganglia; CR, corona radiata; F, female; M, male; NIHSS, National Institutes of Health Stroke Scale.

70 C.-J. Lai et al

conditioning may help determine which stroke patients should betargeted for conditioning and help predict therapeutic outcomes.

Elicited motor-evoked potentials (MEPs) recorded in the tar-geted muscles represent the excitability of intracortical connec-tions, indicating the functional integrity of the corticospinal tract(CST).13 The absence of detectable MEPs after ipsilesionalstimulation soon after a stroke is considered a predictor of poorfunctional outcomes.14,15 Applying focal rTMS to the target pri-mary motor cortex activates both neural synaptic transmission toremote motor networks and crucial elements involved in theeffective neural regeneration of new functions.16

The connection between a disrupted CST and the efficacy ofintermittent theta-burst stimulation (iTBS), an excitatory rTMSparadigm for motor enhancement, has not been examined. Wehypothesized that by determining the integrity of the CST and theseverity of baseline motor impairment, the effectiveness of iTBStreatment in motor recovery could be predicted. Thus, wecompared groups of motor-impaired stroke patients with variouslycategorized MEPs; we also sought to identify other possiblecontributing factors underlying the receptiveness of stroke patientsto iTBS treatment.

Methods

Participants

Seventy-two stroke patients (15 women; mean age, 62.5y) whopresented with unilateral hemiplegia secondary to a first-everstroke were recruited from a rehabilitation center at a tertiaryhospital. All fulfilled the following conditions: (1) a diagnosis of

List of abbreviations:

aMT active motor threshold

CST corticospinal tract

FDI first dorsal interosseous

fMRI functional magnetic resonance imaging

FT finger-tapping task

iTBS intermittent theta-burst stimulation

MEP motor-evoked potential

MRC Medical Research Council

MT motor threshold

RT reaction time

rTMS repetitive transcranial magnetic stimulation

WMFT Wolf Motor Function Test

unilateral, ischemic, or hemorrhagic supratentorial stroke at least2 months prior, as confirmed by magnetic resonance imaging; (2)no history of concomitant neurodegenerative diseases or brainsurgery; (3) no aphasia, spatial neglect, visual field deficit,emotional problems, or communication problems; and (4) norTMS contraindications. All patients underwent detailed clinicaland neurologic examinations including the National Institutes ofHealth Stroke Scale, the distal Medical Research Council (MRC)scale of 0 to 5 points,17 the FIM system,18 and electroencepha-lography. All the patients recruited to the study gave their writteninformed consent before participating, in accordance with the2008 Declaration of Helsinki. The study was approved by thelocal institutional review board.

Fifty-three patients were diagnosed with ischemic stroke and27 with cortical involvement (with or without subcorticallesion). All patients were in the chronic stage of stroke, with amean poststroke duration � SD of 10.5�5.0 months. Otherbaseline demographic and clinical features are presentedin table 1.

Electrophysiological measures and motor assessments wereperformed at inception (baseline), midterm in the 10-sessionintervention, and immediately after the 10 sessions of interven-tion. We divided the patients into 4 groups: 3 groups received areal iTBS treatment, and 1 group received a sham iTBS inter-vention. The real iTBS groups included patients (group A, nZ21)who had inducible MEPs (MEPþ) recorded from the paretic firstdorsal interosseous (FDI) and exhibited preserved hand gripstrength (MRC>1) before iTBS intervention; group B (nZ17)included patients who had undetectable MEPs (MEP�) butexhibited preserved hand grip strength (MRC>1); and group C(nZ17) included patients with undetectable MEPs and no evi-dence of hand grip strength (MEP� and MRCZ0). Group D(nZ17), to which the sham treatment was administered, had apatient composition similar to that of group A and included pa-tients who exhibited positive MEPs (MEPþ) and positive gripstrength (MRC>1), but underwent a placebo iTBS treatment.Patients with both MEPþ and MRC>1 were randomly assigned toeither group A or group D. No patient with a totally paretic handgrip presented with elicited MEPs. Figure 1 summarizes thecriteria used for group categorization.

Interventions

Patients in the experimental groups underwent a real iTBSprotocol administered using the Magstim Rapid2,a with a 70-mm

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Fig 1 Criteria for patient allocation, proposed adjustment, and adjuvant therapy to augment the effects of iTBS. Group A showed favorable

outcomes post-iTBS conditioning following the original settings of the iTBS paradigm. Group B, whose motor control may emerge from the more

distant secondary motor area, showed a pronounced response to adopting a high-intensity paradigm (such as 5-Hz rTMS), or determined the

stimulation loci according to the functional neuroimaging assessment. Group C, without any motor control from either cortex, was supposed

to show a high likelihood of benefiting from adjuvant physiotherapy and advanced protocols. Abbreviations: AH, affected hemisphere;

rTMSexc, excitatory rTMS; rTMSinh, inhibitory rTMS; UH, unaffected hemisphere.

Outcome predictors of repetitive transcranial magnetic stimulation 71

figure-8 coil. We adopted the iTBS as our intervention paradigmbecause it induces long-lasting changes in excitability in stim-ulated areas.19 Bursts of 3 pulses at 50Hz were administered tothe FDI hot spot at 80% of the active motor threshold (aMT) at200-millisecond intervals for 2 seconds. A 2-second train ofiTBS was repeated every 10 seconds for a total of 190 secondsand 600 pulses. All patients underwent 10 intervention sessionsthat were conducted 5 days per week for 2 weeks. A placebocoila was used for the sham stimulation, which produced a scalpsensation and an audible click on discharge but did not allow theelectrical current to penetrate into the brain tissue. For patientsin groups B and C, for whom MEPs could not be elicited byusing the maximal stimulator output on their affected hemi-spheres, the target area was homologous to the FDI hot spot inan unaffected hemisphere.20,21 In these cases, we determined thestimulus intensity as 49% stimulator output based on the meanintensity averaged from the patients with positive MEPs elicitedfrom the affected cortex. This dosage was identical to themean conditioned intensity used in group A. All the patientscontinued the same amount of daily physical rehabilitationprograms. The conventional physiotherapy program includedstrength training for the shoulder, wrist, finger flexors, andextensors, combined with repetitive and augmentative train-ing and active participation. These sessions were conducted for1 hour daily, 5 times per week, immediately after theintervention.

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Assessments

Cortical excitabilityTo evaluate cortical excitability, we measured the MEP parametersand motor map area at the baseline, midterm in the 10-sessionintervention, and immediately after the 10 sessions of interventionusing themonophasicMagstim 2002,a and standard procedures.22,23

Patients were instructed to sit in an armchair and to keep theireyes open. An elastic cap was attached to the head of each patientand placed based on the nasion-inion line and the interaural line.A grid (9�9cm) was drawn over the frontal area along theinteraural and nasion-inion lines and labeled with numbers onboth sides. MEPs were recorded from FDI muscles using bilateralsurface Ag/AgCl electrodes. A Dantec Keypoint electro-myographb connected to the stimulator was used to record theMEP signals. The raw signals were amplified (50mV to 1mV perdivision), bandpass filtered (1e2000Hz), and digitized at a 2-kHzsampling rate. The resting motor threshold (MT) and aMT for FDIwere determined based on the lowest intensity required to elicitMEPs of >100mV in 5 of 10 consecutive trials, respectively, at restor during weak voluntary hand contraction (5%e15% of maximalforce). The maximum MEP amplitude for each patient was ob-tained using 100% of maximal stimulator output. If we were notable to obtain the maximum MEP using this method, the patientwas instructed to contract the affected FDI at maximal forceduring stimulation. If MEPs were still absent after stimulation, the

Table 2 Results of hierarchical multiple linear regression ana-

lyses on improvement of WMFT in iTBS groups

WMFT (Postbaseline) b Coefficients SE P

Constant 2.69 1.40 .068

Pathology (ischemic,

hemorrhagic)

�2.71 2.0 .197

Cortical involvement 2.18 1.87 .248

Time poststroke �0.067 0.064 .301

WMFT (baseline) 0.14 0.04 .001*

Group

B vs C 7.59 2.38 .003*

A vs C 13.17 2.93 <.001*

* The variables of group and baseline WMFT predict the motor

improvement at significant levels (P<.05).

72 C.-J. Lai et al

patient was categorized as “absent MEP” (MEP�). Otherwise, thepatient was categorized as “elicited MEP” (MEPþ). Test sites ofeach mapping position were recorded as “excitable” when at least2 reproducible MEPs were induced by 3 stimuli in the applicationof rTMS at 110% of the resting MT intensity. The motor map areawas the sum of the excitable sites.23

Motor function assessmentsThe outcome measures included the Wolf Motor Function Test(WFMT), Functional Ability Scale,24 simple reaction time (RT)task, and an index fingeretapping task (FT) performed shortlybefore the first intervention, after the fifth session, and aftercompletion of 10 sessions. The procedures for these motor as-sessments were described in a previous study.25

Statistics

The mean values of the motor assessments and clinical charac-teristics were compared between the groups at the baseline usingthe 1-way analysis of variance for independent samples forcontinuous data and the chi-square test for categorical data. Hi-erarchical multiple regression analyses were conducted usingSPSS software (version 18c), to determine the variables that pre-dict the change in WMFT score after intervention. First, weincorporated the potential variables of cortical involvement, pa-thology (ischemic or hemorrhagic stroke), and lesion volume intothe model, then added the variables of time poststroke, groupallocation, and the baseline values of WMFT into the model todetermine whether the added variables could facilitate statisticallysignificant incremental improvement in the analyses. We per-formed analysis of covariance to investigate intergroup compari-sons of motor improvement. In cases in which significantdifferences were observed, the Bonferroni procedure was used toconduct post hoc pairwise comparison. P<.05 was consid-ered significant.

Correlation analyses for changes to motor function, baselinemotor impairment, and cortex excitability were performed usingthe Spearman test. A P value <.05 was considered significant.

Results

We observed no significant differences in age, sex, lesion pa-thology, cortical involvement, lesion volume, time poststroke, orNational Institutes of Health Stroke Scale score at baseline be-tween the groups (see table 1). After intervention, the measures,

including WMFT, FT, RT, and motor map area, were found to besignificantly altered relative to baseline levels for all patients ingroups A, B, and C (P<.001).

Prediction of response to iTBS modulation

Table 2 depicts the results of linear regression analysis. Amongthe variables we considered in this study, group assignment wasrevealed as a strong predictor of improved WMFT (R2Z.28,F3,51Z6.74, PZ.001), as were baseline WMFT values (R2Z.28,F3,51Z6.74, PZ.001). Group A yielded a higher coefficient(13.17) and lower P value (P<.001) than did group B (coef-ficientZ7.59, PZ.003), when group C was treated as the refer-ence. Lesion pathology, presence of cortical involvement, lesionvolume, and time poststroke were not significantly predictive oftreatment outcomes (PZ.197e.301).

Differential responses for intergroup comparison

Among the patients able to perform the hand grip test, we notedmore favorable responses to the iTBS treatment in group A than ingroup B, as reflected in the increase in FT values (F3,68Z16.6,P<.001, h2Z.43) and WMFT (F3,68Z8.6, P<.001, h2Z.29),accompanied by electrophysiological changes in the contralesionalmotor map area (F3,67Z4.96, PZ.004, h2Z.19) (table 3, fig 2).Group A exhibited a greater WMFT change (7.6�2.3) than didgroup B (5.2�2.2), followed by group C (2.3�1.5). Comparedwith group C, group A had a greater increase in FT values(P<.001) and a greater decrease in the contralesional motor maparea (PZ.002). Moreover, when compared with sham group D,group A showed greater improvement in FT (P<.001) andWMFT (P<.001).

Correlation analyses

Table 4 illustrates the results of the correlation analyses betweenchanges in motor performance, motor map area, and their initialvalues before intervention. The change in FT was correlatedpositively with the baseline level of FT (P<.001, rZ.703) andnegatively with the baseline level of RT (P<.001, rZ�.730). Thechange in FT and RTwas correlated significantly with the baselineWMFT (PZ.001 and PZ.04, respectively). Overall, favorableinitial hand function led to a greater responsiveness to iTBSintervention.

The electrophysiological evidence demonstrated the close re-lationships among the cortical map area, MEP amplitude, and thebehavior gain. Table 4 depicts the significant correlation betweenipsilesional MEP amplitude and the change in WMFT (PZ.048,rZ.308), FT (P<.001, rZ.539), and RT (PZ.047, rZ�.313).The higher amplitude of the evoked potential in the affected cortexand greater rTMS-induced aftereffects were noted in WMFT, FT,and RT. Similarly, the status of initial motor impairment inbaseline WMFT and RT was highly correlated with reductions incontralesional motor map area (PZ.046, rZ�.306 and PZ.024,rZ.348, respectively). The interactions between the MEP ampli-tude and decrease in map area (P<.001, rZ�.857) indicated thathigher MEPs evoked from the affected side led to a higher ten-dency toward iTBS-induced contralesional suppression.

Discussion

Our study indicated that the presence of MEPs and grip strength inthe paretic hand is a determining predictor of positive motor re-sponses to iTBS conditioning. Therapeutic gain, as assessed by

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Table

3Comparisonsofchanges

inmotortasksandcontralesional

motormap

area

betweengroups

Param

eter

GroupA(nZ21)

MEPþ,

MRC>

1

GroupB(nZ

17)

MEP�,

MRC>

1

GroupC(nZ17)

MEP�,

MRCZ

0

GroupD(nZ

17)

MEPþ,

MRC>

1,Sham

iTBS

Baseline

Post

Change

Baseline

Post

Change

Baseline

Post

Change

Baseline

Post

Change

WMFT

46.3�1

0.4

54.1�1

3.4

7.6�2

.3*

31.7�1

1.7

37.0�1

1.3

5.2�2

.22.2�1

.44.6�2

.22.3�1

.544.8�1

2.4

45.9�1

1.6

1.3�0

.6z

FT(%

ofsoundside)

49.0�2

7.1

62.2�2

2.7

12.3�5

.9*

42.1�9

.647.6�1

1.3

5.2�2

.50

1.4�1

.31.4�1

.3y

43.7�2

1.1

48.6�2

1.6

4.2�2

.8z

RT(%

ofsoundside)

181.8�6

9.1

121�3

0.5

�60.8�2

3.8

176.9�5

5.4

122.3�3

8.9

�54.5�3

4.7

0231�1

06.2

NA

192.1�7

1.2

180.4�6

8.1

�11.5�8

.1

Motormap

area

(cm2)

13.0�5

.48.1�3

.2�4

.8�2

.1*

13.7�4

.810.1�3

.3�3

.4�1

.512.3�4

.712.1�4

.6�1

.1�0

.3y

12.8�4

.513.7�4

.90.8�0

.5

NOTE.Values

aremean�

SD.ChangeZ

post

(immediately

afterthe10sessionsofintervention)minus

baseline.

Abbreviation:ANCO

VA,analysisofcovariance;NA,notapplicable

(dueto

novalueobtained

atbaseline).

*Changes

inWMFT,FT,andmotormap

area

showed

difference

betweengroups

AandB.Significance

levelat

P<.05in

ANCO

VAandpost

hocanalyses

withBonferronicorrection.

yGroupAmanifestedsuperioroutcomein

FTandmotormap

area

overgroupC.

Sign

ificance

levelat

P<.05in

ANCO

VAandpost

hocanalyses

withBonferronicorrection.

zChanges

inWMFT

andFT

showed

difference

betweengroups

AandD.Sign

ificance

levelat

P<.05in

ANCO

VAandpost

hocanalyses

withBonferronicorrection.

Outcome predictors of repetitive transcranial magnetic stimulation 73

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improvements in hand dexterity and movement velocity, correlatespositively with preserved hand function and ipsilesional MEPamplitude. The electrophysiological and clinical criteria proposedin this study could assist in determining which individualizedneurostimulation strategies should be harnessed for rehabilitationapproaches.

Group A had both positive MEPs and grip strength andexperienced a greater conditioning effect in terms of therapeuticoutcomes, followed by groups B and C. The group effect wasindependent of ischemic or hemorrhagic pathology, corticalinvolvement, lesion size, and time poststroke. Our results areconsistent with the research of Khedr et al,20 who investigated theaftereffects of rTMS on motor function by using various excitatoryparadigms (3- and 10-Hz rTMS), and found that patients withsevere motor impairment failed to exhibit any therapeutic benefits.Based on studies that have addressed whether motor map reor-ganization could shift neighborly, caudally to the sensorimotorcortex, ventrally to invade the face area,2 or cephalically to invadethe premotor area,26 we know that ipsilesional MEPs can be ob-tained around the perilesional area. In such cases, patients havemanifested satisfactory outcomes after iTBS modulation, whichour study demonstrated as closely paralleling ipsilesionalMEP amplitude.

Group A comprised patients who exhibited brain lesionswithout destruction of the primary CST or who had recovered andexhibited successful reorganization. However, group B, whichconsisted of patients who had regained partial hand function buthad demonstrated no electrophysiological evidence of MEPs afteripsilesional cortical stimulation, was of particular interest. Afterinjury to the primary motor cortex and its pathway, the reroutingof corticospinal control may emerge from the more distant, sec-ondary motor area at the corticosubcortical level or the cortico-cortical level,27 as appears to have occurred with group B.Therefore, even with maximal stimulation intensity, MEPs maynot be provoked under these conditions. The contralesional motorcortex, such as the premotor cortex, could be crucial forsubstituting severely damaged motor areas, possibly mediatedthrough the transcallosal pathway.26 Our findings indicate thatpatients in group B experienced only a marginal therapeuticbenefit from iTBS because conditioning was applied over theipsilesional motor area, the counterpart of the opposite hot spot.26

We suggest that greater effects could be achieved by applyingexcitatory rTMS over motor-facilitating sites, as was demon-strated in a functional magnetic resonance imaging (fMRI) studyin which the new reorganization areas could generate beneficialcompensatory movement in certain cases.

By considering stimulation intensity, the therapeutic efficacycould be further improved. The iTBS stimulation paradigm usedin this rTMS study used the relatively low intensity of 80% of theaMT. To stimulate as much of the remaining neural transmissionand as deep subcortical reorganization as possible, a higher con-ditioning intensity could be necessary. In the study by Khedr,20 a130% resting MTwas used for 3-Hz rTMS conditioning and 100%resting MT for 10-Hz rTMS to improve motor recovery in patientswith acute stroke. Therefore, the ipsilesional facilitatory strategyused for group B could include an emphasis on augmentingstimulation intensity, adjusted with a lower conditioning fre-quency (3e10Hz).

Group C, which showed neither MEPs nor volitional move-ment in the paretic hand, responded to the iTBS protocol at aminor magnitude. The failure of group C patients to regain handgrip strength may have resulted from the lesion interruption of the

Fig 2 Changes in mean group values of the FT task during iTBS intervention. Group A patients manifested increased responses in finger-tapping

rate after intervention, followed by groups B, D, and C. *Intergroup comparison was significant at P<.05 with Bonferroni correction.

74 C.-J. Lai et al

key motor pathway. Ultimate motor recovery is inevitably limitedby the level of impaired functional integrity, even after compen-satory brain reorganization.28 Regaining hand motor function islimited by the tremendous impedance of contralesional inhibition.Patients with stroke demonstrating neither MEPs nor hand motionare more prone to engaging in contralesional recruitment forparetic hand-related movement. fMRI techniques, combined withneuronavigation, could help to identify both the target area forstimulation at the center of neural reorganization and the locationwhere excitatory rTMS should be applied. These techniques couldalso establish whether deleterious hyperexcitability has developedin the contralesional cortex and, consequently, where inhibitoryrTMS could appropriately be administered.

We found that a more serious hand deficit yielded a poorerresponse to the protocol. In such cases, the model of training-dependent neuroplasticity to help lateralize brain activation backtoward the affected hemisphere, complementary physiotherapy suchas robot-based training, peripheral nerve stimulation, and behaviorintervention could further maximize the effects of rTMS.29,30

Study limitations

Our ability to adequately address the neural projections from thecontralesional motor cortex to the paretic FDI muscles was hin-dered by the lack of neuroimaging evidence. Both diffusion tensorimaging and fMRI are useful tools for registering active, beneficial

Table 4 Correlation between the changes of motor assessments, contra

groups

Baseline Values

Change of WMFT

P (r)

Change o

P (r)

WMFT .045 (.33) .001 (.49

FT (% of sound side) .010 (.459) <.001 (.

RT (% of sound side) .003 (�.523) <.001 (�Ipsilesional MEP amplitude .048 (.308) <.001 (.

NOTE. ChangeZpost (immediately after the 10 sessions of intervention) min

modulating areas31,32 and should be used in future studies.Moreover, introducing greater stratification in participant recruit-ment could provide more explicit information regarding individ-ualized responses to specific interventions.

Conclusions

Using basic electrophysiological assessment and neurologic ex-amination, we revealed useful predictors for identifying patientswith hand motor deficits as potential candidates for iTBS inter-vention. We also identified associations for the degree of residualmotor function and the amplitude of initial MEPs with the degreeof the effect of neuromodulation intervention. These findingsprovided a sound basis for us to propose possible approaches toimprove therapeutic outcomes. Future research should seek toclarify the evolved circuit reorganization of patients who respondpoorly to intervention, and the effect of plasticity-promotingintervention.

Suppliers

a. The Magstim Company Ltd, Spring Gardens, Whitland, Car-marthenshire, SA34 0HR, United Kingdom.

b. Natus Medical Inc, Corporate Headquarters, 1501 IndustrialRd, San Carlos, CA 94070.

c. SPSS Inc, 233 S Wacker Dr, 11th Fl, Chicago, IL 60606.

lesional motor map area, and the baseline values for patients in iTBS

f FT Change of RT

P (r)

Change of Motor Map Area

P (r)

5) .04 (�.315) .046 (�.306)

703) <.001 (�.528) .080 (�.270)

.730) <.001 (�.886) .024 (.348)

539) .047 (�.313) <.001 (�.857)

us baseline value. Significance levels: P<.05 on the Spearman test.

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Outcome predictors of repetitive transcranial magnetic stimulation 75

Keywords

Motor cortex; Prognosis; Rehabilitation; Stroke; Transcranialmagnetic stimulation

Corresponding author

Po-Yi Tsai, MD, Department of Physical Medicine and Rehabil-itation, Taipei Veterans General Hospital, Taipei, Taiwan. NationalYang-Ming University, School of Medicine, Taipei, Taiwan. No.201, Shih- Pai Rd, Sec. 2, Taipei, 11217 Taiwan. E-mail address:pytsai@vghtpe.gov.tw.

Acknowledgments

We thank Hsin-Yi Huang, MS, (Biostatistics Task Force, TaipeiVeterans General Hospital) for statistical assistance and EricChuang for editing assistance.

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