4.5.2 rfa MEP rcmct

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2 DTI TMS DTI TMS DTI DTI TBSS BRS ROI FA TBSS BRS rfa ROI

3 DTI ROI TMS MEP CMCT MEP CMCT MEP CMCT DTI ROI MEP CMCT ROI rfa MEP rcmct rfa MEP rcmct

4 4.5.2 rfa MEP rcmct

5 1 n= BRS ROI rfa n= n= TBSS n=10 n= rfa ROC n= BRS rfa n= DTT rfa MEP rcmct DTI TMS...38 n= DTI TMS n=

6 ARAT action research arm test BRS Brunnstrom recovery stage CMCT central motor conduction time DTI diffusion tensor imaging DTT diffusion tensor tractography FA fractional anisotropy FMA Fugle-Meyer assessment MEP motor evoked potential MRC scale medical research council scale MRI magnetic resonance imaging rcmct central motor conduction time ratio rfa fractional anisotropy ratio ROI region of interest ROA region of avoidance TBSS tract-based spatial statistics 5

7 [1,2] [3,4] [4] 1.1 [5] [6 10] [11] [7,8,12,13] [9,10] 1.2 diffusion tensor imaging DTI DTI magnetic resonance imaging MRI [14,15] fractional anisotropy FA [16,17] FA FA [18] FA [16] FA region of interest ROI FA ROI ROI 6

8 FA [16,17] diffusion tensor tractography DTT [19,20] ROI DTI ROI FA ROI [16] ROI [17] Oxford FMRIB Software Library Tract-based spatial statistics TBSS [21] DTT FA ROI ROI [20] 1.3 DTI Koyama [22 25] ROI FA FA ratio rfa Brunnstrom recovery stage BRS Medical research council MRC scale ROI ROI [22] [23] [23 25] rfa BRS MRC scale Jang [26] DTT DTT 6 modified brunnstrom classification motricity index DTT DTI DTI 1.4 DTI transcranial magnetic stimulation TMS TMS motor evoked potential MEP central 7

9 motor conduction time CMCT [27] MEP MEP MEP MEP [27] CMCT M F MEP CMCT [27] 1.5 TMS TMS MEP CMCT MEP MEP [28 33] CMCT Heald [32] CMCT CMCT Escudero [33] CMCT Piron [34] MEP Hemiplegic stroke scale MEP Hendricks [35] MEP Fugle-Meyer assessment Hendricks MEP CMCT MEP CMCT CMCT 8

10 1.6 DTI TMS DTI TMS [36 38] Stinear [37] 72 TMS MEP ROI FA asymmetry FA- FA/ FA+ FA 3 Complete Notable Limited None 72 MRC scale Complete 8 MEP MEP Notable MEP FA asymmetry FA asymmmetry 0.15 Limited 0.15 None Stinaer DTI ROI 3 DTI TMS 4 DTI TMS 5 9

11 2.1 diffusion tensor imaging DTI [14,15] DTI [28,39 41] DTI ROI FA [22,25,37,42 47] ROI [25,42 44] [23,37] [22,45] [46,47] ROI ROI [22,25,37] ROI [42 44] ROI FA [22,48,49] FA [50] DTI 2.2 ROI DTI ROI TBSS FA ROI FA 10

12 DTI MRI ± DTI DSI studio DTI b0 Brunnstrom Recovery Stage BRS [51] DTI 1.5T-MRI TOSHIBA EXCELART Vantage, MRT-2003 DTI single shot spin echo EPI TR=10000ms TE=100ms motion-probing gradient orientation=6 b=1000 field of view 260mm 260mm 1 1 1mm mm DTI DTI Oxford FMRIB Software Library [52] Eddy current correction b0 brain extraction tool b0 FMRIB s diffusion toolbox FA 11

13 2.3.5 TBSS TBSS TBSS 2 FA FA FA FA [21] [6 11] BRS BRS Ⅲ BRS Ⅳ ± ± TBSS FA FA FA FMRIB58 FA FA FA [21] FA FA 0.35 FA FA FA n=5000 threshold-free cluster enhancement [53] BRS ROI FA BRS ROI FA FA FA FMRIB58 ROI ROI TBSS [23,25,42 44,54,55] ROI Oxford FMRIB Software Library JHU ICBM-DTI-81 white-matter labels atlas [56] ROI FA FA FA FA ratio; rfa rfa= FA / FA [25,44] rfa ROI FA 12

14 2.3.7 t BRS DTI Mann-Whitney U BRS ROI rfa Spearman BRS receiver operating characteristic ROC area under the curve AUC R

15 BRS 1 p<0.05 BRS p<0.01 BRS p<0.01 BRS p<0.01 p<0.05 BRS BRS BRS Ⅲ BRS Ⅲ p=0.98 p=0.37 p=0.73 DTI p=0.21 p= n=23 DTI diffusion tensor imaging 14

16 2.4.2 TBSS TBSS FA p< ROI R Y = -13 L R Z = 6 L Z = 13 Z = 20 1 TBSS n=10 n=13 TBSS Montreal Neurological Institute 152 T1 FA FA 15

17 2.4.3 BRS TBSS ROI rfa BRS BRS rfa 2 rfa r=0.70 p<0.01 r=0.66 p<0.01 r=0.64 p<0.01 BRS BRS 2 BRS ROI rfa n=23 rfa fractional anisotropy ratio 16

18 2.4.4 rfa BRS rfa ROC 2 rfa AUC=0.846 BRS AUC= AUC= BRS rfa rfa 0.80 BRS rfa ROC n=23 BRS rfa AUC= AUC= AUC= TBSS ROI FA ROI BRS TBSS FA BRS ROI rfa 17

19 BRS rfa FA [22,48,49] Schaechter [50] FA FA [50] Yin [57] 3 Paralyzed Hand Function Assessment TBSS FA FA FA [57] FA [23] FA FA DTI 2 [57] [50] FA [47,55] T2 3 [58] Schaechter[50] ROI TBSS ROI rfa BRS 18

20 rfa BRS ROI FA ROI [22,25,37,42 47] ROI ROI rfa AUC 0.8 rfa [42,54] 0.80 [46] rfa BRS rfa rfa rfa=0.80 a b c rfa r = 0.70 p < 0.01 rfa r = 0.66 p < 0.01 rfa r = 0.64 p < rfa =.80 3 BRS rfa n=23 a BRS b BRS c BRS rfa BRS rfa rfa 0.80 BRS rfa fractional anisotropy ratio 19

21 2.5.3 BRS BRS [59 61] DTI [28,40] rfa BRS BRS BRS ROI rfa ROI rfa BRS 3 FA BRS Fugl-Meyer assessment[62] 20

22 4 3.1 ROI FA FA ratio rfa rfa rfa DTI TMS MEP CMCT [27] MEP [28,32,33] MEP [34,35] MEP [35] MEP CMCT CMCT [32,35] CMCT [33] CMCT 72 CMCT TMS DTI rfa TMS MEP CMCT 3.2 rfa 1 4 TMS MEP CMCT 21

23 BRS action research arm test ARAT BRS [51] ARAT[63] ARAT [64,65] DTI 1.5T-MRI TOSHIBA EXCELART Vantage MRT-2003 DTI single shot spin echo EPI TR=10000ms TE=100ms motion-probing gradient orientation=6 b=1000 field of view 260mm 260mm 1 1 1mm mm ROI ROI Oxford FMRIB Software Library FSL, [52] ROI 1 eddy-current correction brain extraction tool b0 FMRIB s diffusion toolbox FA FA 22

24 FMRIB58 FA region of interest ROI [37] ROI FSL JHU ICBM-DTI-81 white-matter labels atlas [56] ROI FA FA FA FA ratio rfa rfa= FA / FA rfa 1 FA diffusion tensor tractography DTT ROI ROI [19,20] ROI rfa DTT DTT DSI studio DTT multiple ROI approach[20] ROI region of avoidance ROA ROI FSL JHU ICBM-DTI-81 white-matter labels atlas Harvard-Oxford cortical structural atlases [56,66] FA ROA FA threshold > 0.2 maximum angle = TMS MEP CMCT MEP M F MEP 150% MEP 5 MEP M F M M F 16 CMCT MEP M F CMCT=MEP -(F +M -1)/2 [27] CMCT CMCT CMCT ratio rcmct 23

25 rcmct= CMCT/ CMCT rcmct 1 CMCT MEP MEP+ MEP- rcmct MEP rcmct- 3.4 BRS ARAT MEP rcmct DTT 3 3 BRS Brunnstrom recovery stage ARAT action arm research test rfa fractional anisotoropy ratio DTT diffusion tensor tractography MEP motor evoked potential rcmct central motor conduction time ratio DTI diffusion tensor imagein TMS transcranial magnetic stimulation A 30 ROI rfa 0.93 DTT 4A MEP rcmct BRS ARAT 57 /57 B 50 ROI rfa 0.90 DTT 4B MEP rcmct

26 BRS ARAT 54 /57 C 70 ROI rfa 0.89 DTT 4C MEP rcmct 1.35 BRS ARAT 3 /57 D 50 ROI rfa 0.88 DTT 4D MEP rcmct BRS ARAT 10 /57 T 25

27 A B C D b0 DTT 4 DTT b0 DTT DTT diffusion tensor tractography ROI 0.9 rfa 1 rfa DTT 4 MEP MEP C A D A B MEP C A CMCT A MEP C MEP MEP CMCT B ROI 4 B C C DTT MEP rcmct MEP rcmct 26

28 3.5.1 MEP CMCT 4 MEP MEP MEP 6-12 [30 33] MEP MRC scale Nine-hole peg test Frenchay arm test MEP MEP CMCT [31 33] Motricity index MRC scale BRS ARAT CMCT B A Heald [32] Nine-hole peg test CMCT CMCT CMCT MEP CMCT MEP MEP CMCT [34,35] MEP BRS MEP MEP CMCT MEP CMCT 27

29 [67 69] [33] DTI TMS 4 28

30 DTI rfa TMS MEP rcmct TMS MEP rcmct 4.2 DTI rfa TMS MEP rcmct DTI MRI ± / 5 DTI TMS

31 4 DTI diffusion tensor imaging TMS transcranial magnetic stimulation Fugl-Meyer assessment FMA ARAT FMA [62,70,71] ARAT[63] DTI 1.5T-MRI TOSHIBA EXCELART Vantage MRT-2003 DTI single shot spin echo EPI TR=10000ms TE=100ms motion-probing gradient orientation=6 b=1000 field of view 260mm 260mm 1 1 1mm mm 30

32 4.3.4 ROI ROI Oxford FMRIB Software Library FSL, [52] ROI 1 eddy-current correction brain extraction tool b0 FMRIB s diffusion toolbox FA FA FMRIB58 FA region of interest ROI [37] ROI FSL JHU ICBM-DTI-81 white-matter labels atlas [56] ROI FA FA FA FA ratio rfa rfa= FA / FA rfa 1 FA MEP CMCT 2 MEP M F MEP 150% MEP 5 MEP M F M M F 16 CMCT M F MEP CMCT=MEP -(F +M -1)/2 [27] CMCT CMCT CMCT ratio rcmct rcmct= CMCT/ CMCT rcmct 1 CMCT MEP rcmct FMA ARAT FMA rfa Spearman FMA ARAT FMA rcmct Spearman MEP FMA 31

33 ARAT FMA Wilcoxon MEP rfa rcmct t R ROI rfa MEP rcmct FMA ARAT 5 No.5 ARAT ARAT n=17 rfa fractional anisotropy ratio MEP motor evoked potential rcmct central motor conduction time ratio FMA Fugle-Meyer assessment ARAT action research arm test 32

34 4.4.2 ROI rfa rfa FMA r=0.77 p<0.01 ARAT r=0.72 p<0.01 rfa FMA r=0.46 p= rfa 0.85 FMA ARAT rfa p=0.29 a b c FMA r=0.77 p<0.01 ARAT r=0.73 p<0.01 FMA r=0.46 p= rfa rfa rfa 5 rfa a FMA n=17 b ARAT n=16 c FMA n=17 rfa FMA ARAT rfa FMA rfa rfa 0.85 rfa fractional anisotropy ratio FMA Fugle-Meyer assessment 33

35 4.4.3 MEP MEP MEP MEP FMA p<0.01 ARAT p<0.01 MEP 6 FMA p=0.43 MEP p=0.34 FMA ** ** a b c ARAT FMA ** p< MEP MEP MEP 6 MEP MEP FMA n=17 b ARAT n=16 MEP n=6 MEP n=11 b FMA n=17 MEP n=5 MEP n=12 34

36 4.4.4 rcmct rcmct ARAT r=-0.87 p<0.01 rcmct FMA r=-0.57 p=0.07 FMA r=-0.54 p= rcmct 1.5 FMA ARAT rcmct p=0.05 rcmct 1.3 a b c FMA r=-0.57 p=0.07 ARAT r=-0.87 p<0.01 FMA r=-0.54 p= rcmct rcmct rcmct 7 rcmct rcmct a FMA n=11 b ARAT n=10 c FMA n=12 ARAT rcmct 4.5 DTI TMS ROI rfa FMA ARAT FMA rfa rfa 0.85 TMS MEP FMA ARAT MEP FMA rcmct FMA FMA 35

37 ARAT ARAT rfa MEP rcmct 1 BRS rfa FMA ARAT rfa [22 25,37,42 47] rfa 0.85 rfa ROI [42,46,54] MEP FMA ARAT [28 33] MEP rcmct ARAT CMCT CMCT [31 33] ARAT CMCT FMA ARAT rfa MEP rcmct 1 rfa BRS FMA rfa BRS stage 6 FMA MEP FMA rcmct FMA [34,35] TMS MEP CMCT central pattern generator CPG 36

38 CPG [72] Hendricks [35] MEP CMCT Maeshima [73] DTI ROI FA FA FA % ROI rfa rfa 0.85 Maeshima TMS MEP rcmct rcmct

39 1 3 8 ARAT DTI ROI rfa rfa 0.85 rfa 0.85 TMS MEP MEP MEP rcmct rcmct >1.5 CMCT rcmct 1 <1.5 CMCT 9 3 MEP M MEP MEP /M rfa <0.85 >0.85 MEP rcmct >1.5 <1.5 8 DTI TMS ARAT rfa rfa<0.85 rfa>0.85 MEP MEP rcmct rcmct>1.5 rcmct<1.5 38

40 ARAT n=16 ARAT action research arm test 39

41 10 FMA rcmct FMA 2 MEP M MEP MEP /M MEP rfa <0.85 >0.85 MEP rcmct >1.3 < DTI TMS FMA rfa rfa<0.85 rfa>0.85 MEP MEP rcmct rcmct>1.3 rcmct<1.3 40

42 FMA n=17 FMA DTI TMS rfa rcmct 41

43 42

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