Alternatively, they can simply test if the density or thickness of a tissue in a brain region is affected by age, or if it relates to a clinical variable of interest. One such statistical mapping method, VBM, begins by spatially normalizing all MRI scans from a group of subjects into the same space. The scans are then segmented into gray matter, white matter, Inhibitors,research,lifescience,medical and cerebrospinal fluid (CSF), maps of each

tissue are smoothed, and statistical tests are 5-HT receptor agonist and antagonist review performed at each voxel—or 3D location—in the brain, to determine where age related changes occur, and what other factors affect the brain measures. The values in VBM analyses then represent the average proportion of gray matter in a small region around any given Inhibitors,research,lifescience,medical voxel. To be clear, “density” here is not intended to measure axonal or cellular packing density,19 but it offers a gross anatomical measure of regional tissue volumes, offering spatial detail on the pattern of tissue in the brain. TBM is a more computationally intensive method, in which a deformation field is obtained for each subject, warping their Inhibitors,research,lifescience,medical brain to match a common brain template, and encoding the relative positions of various brain landmarks. Tensor fields, or Jacobian matrices, are then calculated from the gradient of the deformation

field, at each point, representing the volume of the unit-cube after the deformation.20 From these, it is possible to determine the degree of regional volume expansion Inhibitors,research,lifescience,medical or shrinkage across scans taken at different times,21 or to determine anatomical differences in a set of

scans. These can then be analyzed statistically, to identify characteristic diagnostic group differences, age effects, or links with clinical or cognitive measures. Cortical thickness assessments use semiautomated methods to reconstruct Inhibitors,research,lifescience,medical 3D representations of the gray matter–white matter boundary and the pial surface, and they calculate the distance between the two for every point across the cortex.22,23 Using cortical thickness maps, timelapse movies have been created to show the shifting pattern of cortical thinning in typically developing children between ages 4 and 21,1 and in disorders such as childhood-onset Calpain schizophrenia,24,25 or before and after the onset of bipolar disorder.26 Between age 5 and adulthood, important changes occur in higher cognitive functions that in part reflect changes in brain structure. Total brain volume increases with age, and many studies have found that the growth rate varies across the brain, and over time. Gray matter volume increases into adolescence, when it plateaus and begins to decline, but white matter volume usually increases into adulthood.13,27 Myelination continues throughout life—even well into old age—and white matter volume reductions only begin to be observed when the balance between myelin production and degeneration tilts in favor of white matter loss.