In fMRI experiments, small but meaningful changes in brain activity lie buried within highly variable measurements. To understand how small fMRI signal changes are, even in the very best cases, consider the two brain images shown in Figure 8.1A and B. Both are T2 *-weighted images taken from the same subject while the subject performed a hand-squeezing task, which is one of the most reliable and robust ways of evoking large BOLD signal changes. One image (Figure 8.1A) was taken while the subject was resting, while the other (Figure 8.1B) was acquired at the maximum of the BOLD hemodynamic response. These images appear nearly identical to the naked eye, despite an intensity change of about 5% in voxels within the primary motor cortex (Figure 8.1C and D). Figure 8.1E shows a plot of these signal changes over time. This discrepancy illustrates the first fundamental problem of fMRI data analysis: the measured BOLD signal change is very small compared with the total intensity of the MR signal.