Brain Mapping Unit The General Linear Model A Basic Introduction Roger Tait (rt337@cam.ac.uk) Brain Mapping Unit Overview What is imaging data How is data pre-processed Hypothesis testing GLM: simple linear regression Analysis software How to process results Brain Mapping Unit What is imaging data? Brain Mapping Unit Data A stack of numbers Structural fMRI Functional Brain Mapping Unit Multiple Data subjID voxel1 voxel2 voxel 3 voxel 4 …….. voxel n 1 1227.308541 1472.770249 1417.745632 1701.294758 1288.742729 2 1612.461523 1934.953827 1677.661927 2013.194312 1465.051592 3 1466.264739 1759.517687 1559.769586 1871.723503 1827.678127 4 1499.70072 1799.640864 1842.474418 2210.969302 1316.392368 5 1598.121692 1917.746031 1510.850757 1813.020909 1740.286976 6 1408.066243 1689.679492 1399.393815 1679.272578 1534.459154 7 1555.951487 1867.141784 1588.529211 1588.529211 1516.464089 8 1397.721831 1677.266197 1523.825912 1523.825912 1340.814881 9 1333.659118 1600.390941 1384.217926 1384.217926 1461.281399 10 1453.14966 1743.779592 1558.603977 1558.603977 1406.575083 Brain Mapping Unit Reorientation Native Reoriented MNI152 Brain Mapping Unit Basic pre-processing (fmri) omprage.nii obrain.nii omrest.nii nomrest.nii worest.nii wnomrest.nii Brain Mapping Unit Basic pre-processing (structural) omprage.nii gmomprage.nii wgmomprage.nii Brain Mapping Unit How does standard space data help? Brain Mapping Unit Hypothesis testing Statistical inference is commonly done with a test statistic (t, F, c2…) which has a distribution under H0 mathematically derived. For example ^b1 ^b0 t= t ^1 ^b0) SE(b 5% Parametric Null Distribution NB: this assumes that the errors are independent and normally distributed. Brain Mapping Unit Introducing The GLM Y = Xb + e DATA = MODEL + ERROR DATA = KNOWN * UNKNOWN + ERROR Encapsulates: t-test (paired, un-paired), F-test, ANOVA (one-way, two-way, main effects, factorial) MANOVA, ANCOVA, MANCOVA, simple regression, linear regression, multiple regression, multivariate regression…… Brain Mapping Unit GLM definition Y = Xb + e Where Y is a matrix with a series of observed measurements Where X is a matrix that might be a design matrix Where b is a matrix containing parameters to be estimated And e is a matrix containing error or noise Brain Mapping Unit GLM: Simple Linear Regression Y = b0 + X1b1 + e b0: is the Y axis intercept Y b1: is the gradient of slope Y: the black circles e: diff between X predicted Y and observed Y Brain Mapping Unit GLM: Simple Linear Regression Y = b0 + X1b1 + e ^ ^ This is done by choosing b0 and b1 so that the sum of the squares of the estimated errors S ei2 is as small as possible. This is called the Method of Least Squares. S ei2 is called the Residual Sum of Squares (RSS) Brain Mapping Unit GLM example DATA = KNOWN * UNKNOWN + ERROR = mean reaction time + GENDER + AGE Y = b0 + X1b1 + X2b2+ X3b3+ X4b4+ e Brain Mapping Unit Dummy Variables Continuous variables measurements on a continuous scale (age, mRT) (-4.01, -0.47, 6.35, -7.06, -7.69, -14.24) Dummy Variables Code for group membership (disease, gender) controls = 0, patients = 1 females = 1, males = -1 Brain Mapping Unit Usage Hypothesis tests with GLM can be multivariate or several independent univariate tests In multivariate tests the columns of Y are tested together In univariate tests the columns of Y are tested independently (multiple univariate tests with the same design matrix) Brain Mapping Unit fMRI model specification silent naming task The model BOLD signal Brain Mapping Unit Actual retrieved data 30 20 10 Model 0 +ve activation 0 -10 -20 -30 50 100 150 200 250 300 350 400 450 500 -ve activation Brain Mapping Unit fmri analysis with FSL Brain Mapping Unit Structural analysis with CamBA sex group weight Brain Mapping Unit Structural analysis output Brain Mapping Unit Where are my clusters? here is a big cluster here is a big cluster Brain Mapping Unit Where is the cluster I am interested in? position mouse cursor here cluster location information shown here Brain Mapping Unit How do my clusters help me? Brain Mapping Unit Statistical Testing Convert cluster into a binary mask Overlay mask on subject data Extract voxel intensities Do some statistical analysis to get more information from your data Brain Mapping Unit Correlation with behaviour for cluster Pos_002 p>0.05 close but cluster Pos_001 does not significantly correlate with behaviour HIT1 Brain Mapping Unit Other Analyses different from 0 one-sample t-test Difference between means two-sample t-test Linear relationship between 2 variables simple regression Brain Mapping Unit What else can I do to find out more about my data? Brain Mapping Unit Other types of analyses Factorial designs Permits analysis of multiple time data Shows Main effects of Factor 1 (time) Main effects of Factor 2 (group) Interaction between Factor 1 and Factor 2 Brain Mapping Unit Useful software package CamBA – Cambridge http://www-bmu.psychiatry.cam.ac.uk/software/ FSL Randomise – Oxford http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/Randomise SPM8 – UCL http://www.fil.ion.ucl.ac.uk/spm/software/spm8/ Brain Mapping Unit In summary The GLM allows us to summarize a wide variety of research outcomes by specifying the exact equation that best summarizes the data for a study. If the model is wrongly specified, the estimates of the coefficients (the beta values) are likely to be biased (i.e. wrong) and the resulting equation will not describe the data accurately. In complex situations (e.g. cognitive fMRI paradigms), this model specification problem can be a serious and difficult one Brain Mapping Unit Any questions?