two major steps: first, one performs a univariate statistical test on each individual voxel between each experimental condition. Second, one analyzes the clustering of the voxels that show statistically significant differences, and determines which brain regions exhibit different levels of activation under different experimental conditions. There is great flexibility in the choice of statistical test (and thus the questions that an experiment can be designed to answer), and common choices include the Student's t test or linear regression. An important consideration with SPM, however, is that the large number of comparisons requires one to control the false positive rate with a more stringent significance threshold. This can be done either by modifying the initial statistical test to decrease the α value so as to make it harder for a particular voxel to exhibit a significant difference (e.g., Bonferroni correction), or by modifying the clustering analysis in the second step by only considering a brain region's activation to be significant if it contains a certain number of voxels that exhibit a statistical difference (see random field theory). Voxel-based morphometry Voxel-based morphometry (VBM) is a method that allows one to measure brain tissue composition differences between subjects. To do so, one must first register all images to a standard coordinate system, by mapping them to a reference image. This is done by use of an affine transformation that minimizes the sum-of-squares intensity difference between the experimental image and the reference. Once this is done, the proportion of grey or white matter in a voxel can be determined by intensity. This allows one to compare the tissue composition of corresponding brain regions between different subjects. Applications The ability to visualize whole-brain activity is frequently used in comparing brain function during various sorts of tasks or tests of skill, as well as in comparing brain structure and function between different groups of people. Changes in resting-state brain activation Many previous fMRI studies have seen that spontaneous activation of functionally connected brain regions occurs during the resting state, even in the absence of any sort of stimulation or activity. Human subjects presented with a visual learning task exhibit changes in functional connectivity in the resting state for up to 24 hours and dynamic functional connectivity studies have even shown changes in functional connectivity during a single scan. By taking fMRI scans of subjects before and after the learning task, as well as on the following