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1 Data Processing of Resting-State fMRI (Part 2) YAN Chao-Gan Ph. D. State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, China

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2 Outline Statistical Analysis Results Viewing Multiple Comparisons REST Image Calculator Other Functions

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3 Statistical Analysis One sample T test Two Sample T test Paired T test ANOVA analysis

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4 One sample T test Preparation ALFF: mALFF-1 fALFF: mfALFF-1 ReHo: smReHo-1 FC: zFC

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5 One sample T test

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6 smReHo mALFF g1-1

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7 One sample T test

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8 m*-1 images zFC images Directory for saving SPM.mat Brain Mask

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9 The generated spm.mat One sample T test

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10 The generated spm.mat 1 One sample T test

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11 HeightthresholdT = {p<0.05(FDR)} Extentthresholdk = 10 voxels spmT_0001.img One sample T test

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12 Two sample T test Preparation ALFF mALFF fALFF: mfALFF ReHo: smReHo FC: zFC Mask

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13 Mask Brain Mask Mask=(Patient_1T.img>Thrd)+(CON_1T.img>Thrd) >0 Patient_1T.img CON_1T.img Mask_2T.img (i1>1.96+i2 >1.96)>0 Two sample T test

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14 Two sample T test m* or zFC* images for the two groups Directory for saving SPM.mat Brain Mask or Mask_2T.img

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15 The generated spm.mat Two sample T test

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16 The generated spm.mat 1 -1 Two sample T test

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17 HeightthresholdT = Inf {p<0.05(FDR)} Extentthresholdk = 0 voxels spmT_0001.img Two sample T test

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18 Paired T test

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19 Paired T test m* or zFC* images for each pair Brain Mask

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20 Paired T test

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21 ANOVA Analysis

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22 3 Corresponding level ANOVA Analysis Images for this group

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23 ANOVA Analysis

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24 Statistical Analysis in REST

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25 One-Sample T-Test 0 for m*-1 images 1 for m* images T Statistic Image Brain Mask

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26 Two-Sample T-Test T Statistic Image: positive corresponds to the mean of Group 1 is greater than the mean of Group 2

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27 Two-Sample T-Test Two-Sample T-Test with covariates: e.g. gray matter proportion images (Oakes et al., 2007, Neuroimage) Other covariate can be also specified as text files. (E.g. age, brain size, IQ etc.) Please make sure the correspondence between the group images and the covariate images: order and voxel size

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28 Paired T-Test Situation 1 – Situation 2 Please make sure the correspondence T Statistic Image

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29 ANOVA or ANCOVA ANCOVA: e.g. gray matter proportion images (Oakes et al., 2007, Neuroimage) Other covariate can be also specified as text files. (E.g. age, brain size, IQ etc.) Please make sure the correspondence between the group images and the covariate images: order and voxel size F Statistic Image

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30 Correlation Analysis The imaging measure: ALFF maps Traits: e.g. MMSE.txt …

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31 Outline Statistical Analysis Results Viewing Multiple Comparisons REST Image Calculator Other Functions

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32 Results Viewing SPM5 xjview MRIcroN REST Slice Viewer

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33 Results Viewing - SPM5

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34 Results Viewing - SPM5

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35 Results Viewing - xjview

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36 xjview

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37 Results Viewing - MRIcroN

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38 REST Slice Viewer

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41 For Voxel size = 3*3*3 Voxels are connected if their faces touch rmm=4 Voxels are connected if their faces or edges touch rmm=5; SPM_Criterion Voxels are connected if their faces, edges, or corners touch rmm=6

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47 This report is based on CUI Xu's xjview. (http://www.alivelearn.net/xjview/) Revised by YAN Chao-Gan and ZHU Wei-Xuan : suitable for different Cluster Connectivity Criterion: surface connected, edge connected, corner connected. Number of clusters found: Cluster 1 Number of voxels: 59 Peak MNI coordinate: Peak MNI coordinate region: // Right Cerebrum // Temporal Lobe // Superior Temporal Gyrus // White Matter // undefined // Temporal_Inf_R (aal) Peak intensity: # voxelsstructure 59--TOTAL # VOXELS-- 40Right Cerebrum 33Temporal Lobe 20White Matter 19Temporal_Inf_R (aal) 16Gray Matter 14Superior Temporal Gyrus 13Fusiform_R (aal) 11brodmann area 38 8Inferior Temporal Gyrus 7Middle Temporal Gyrus 7Limbic Lobe 6Uncus 6Temporal_Pole_Mid_R (aal) 5brodmann area 20 3Sub-Gyral Cluster 2 Number of voxels: 98 Peak MNI coordinate:

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50 Create Brodmann Mask Template\brodmann.nii Or Template\Brodmann_61x73x61.nii

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51 Create Brodmann Mask

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52 Data Resample 0 – Nearest Neighbor 1 – Trilinear 2- 2nd degree b-spline

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53 Outline Statistical Analysis Results Viewing Multiple Comparisons REST Image Calculator Other Functions

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54 Multiple Comparisons P=0.05 Probability of not getting a false positive result: = 0.95 P=0.05 Probability of not getting a false positive result: = 0.95 P=0.05 Probability of not getting a false positive result: = 0.95 P=0.05 Probability of not getting a false positive result: = =0.774 P=0.05 Probability of not getting a false positive result: = 0.95

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55 Multiple Comparisons Bonferroni correction: 0.05/5=0.01 Family-Wise Error (FWE) correction False Discovery Rates (FDR) correction Monte Carlo simulations (AlphaSim)

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56 FDR Theory False discovery rate Q e =E(V/(V+S))=E(V/R) Benjamini and Hochberg, 1995, Journal of the Royal Statistical Society

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57 Let H 1, …, H m be the null hypotheses and P 1, …, P m their corresponding p-values. Order these values in increasing order and denote them by P (1), …, P (m). For a given q, find the largest k such that P (k) kq/m. Then reject (i.e. declare positive) all H (i) for i = 1, …, k. FDR Theory

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58 FDR in REST

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59 FDR in REST

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60 FDR in REST

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61 Multiple Comparisons Monte Carlo simulations (AlphaSim) ?

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62 REST AlphaSim

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64 Cl SizeFrequencyCum Propp/VoxelMax FreqAlpha

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65 Outline Statistical Analysis Results Viewing Multiple Comparisons REST Image Calculator Other Functions

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66 REST Image Calculator

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67 REST Image Calculator

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68 REST Image Calculator Example expressions: (a) g1-1 Subtract 1 from each image in group 1 (b) g1-g2 Subtract each image in group 2 from each corresponding image in group1 (c) i1-i2 Subtract image 2 from image 1 (d) i1>100 Make a binary mask image at threshold of 100 (e) g1.*(i1>100) Make a mask and then apply to each image in group 1 (f)mean(g1) Calculate the mean image of group 1 (g)(i1-mean(g1))./std(g1) Calculate the z value of i1 related to group 1 (g) corr(g1,g2,''temporal'') Calculate the temporal correlation between two groups, i.e. one correlation coefficient between two ''time courses'' for each voxel. (h) corr(g1,g2,''spatial'') Calculate the spatial correlation between two groups, i.e. one correlation coefficient between two images for each ''time point''.

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69 Outline Statistical Analysis Results Viewing Multiple Comparisons REST Image Calculator Other Functions

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70 Power Spectrum

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71 Power Spectrum

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72 Power Spectrum

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73 Power Spectrum

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74 Granger Causality Analysis Contributed by Mr. ZANG Zhen-Xiang

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75 Theory of Granger Causality Granger 1969; Ding et al., 2006 Signed path coefficient Chen et al, 2009, ISMRM

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76 Theory of Granger Causality Granger 1969; Ding et al., 2006 Residual based

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78 NIfTI nii to NIfTI pairs

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79 NIfTI.nii to NIfTI pairs

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80 Reading and Writing functions Reading: [Data Vox Head]=rest_readfile('brodmann.nii'); Data – 181*217*181 double Vox – Head - Structure Processing: BA20Data=(Data==20); Writing: rest_WriteNiftiImage(BA20Data,Head,'BA20.img');

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81 Solve Problem "Out Of Memory" 1. Reboot your computer and do not run any other programs. 2. Enlarge your memory. 3. MATLAB Version 7.1 or above is suggested. 4. You can turn on the 3GB switch of Windows XP!!! Please see more details in 5. If this problem remains, please install Linux, especially 64 bit Linux and Matlab.

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82 Solve Problem "Out Of Memory" Enable the 3GB switch on Windows XP * Right-click My Computer -> Properties -> Advanced -> Startup and Recovery -> Settings -> Edit. Modify the following line (maybe not exactly same) in the boot.ini file: multi(0)disk(0)rdisk(0)partition(1)\WINDOWS="WinXP Pro 3GB" /noexecute=optin /fastdetect /3GB * Save and close -> Restart your computer. Enable the 3GB switch on Windows Vista and Windows 7 (32-bit) * Right-click Command Prompt in the Accessories program group of the Start menu. Click Run as Administrator. * At the command prompt, enter "bcdedit /set IncreaseUserVa 3072" * Restart the computer.

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83 Further Help Further questions:

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84 Thanks to DONG Zhang-Ye GUO Xiao-Juan HE Yong LONG Xiang-Yu SONG Xiao-Wei YAO Li ZANG Yu-Feng ZHANG Han ZHU Chao-Zhe ZOU Qi-Hong ZUO Xi-Nian …… All the group members! SPM Team: Wellcome Department of Imaging Neuroscience, UCL MRIcroN Team: Chris RORDEN Xjview Team: CUI Xu ……

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85 Thanks for your attention!

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