Most genes with high variation across brain regions are not selective for a single major brain region; rather, they are expressed in multiple regions and non-uniformly within these regions (Supplementary Fig. 5). This suggests that many genes may be quite pleiotropic with respect to brain function, and that local gene regulation in specific cytoarchitectural nuclei is the most important level of resolution. To summarize the complexity of structural variation and examine the extent to which major brain regions display local enrichment in specific fine cytoarchitectural divisions, we created a specificity index for each major region that measures enrichment in subdivisions of that region. This index, defined as the ratio of expression in one subdivision relative to the remaining subdivisions in that region (Supplementary Methods 3 and Supplementary Table 7), measures transcriptional diversity within regions. The results in Fig. 4b bear strong similarity to the plot in Fig. 4a, again with the neocortex and cerebellum displaying the least internal heterogeneity. In contrast, subcortical regions with many well-defined nuclei show the greatest local heterogeneity, including the myelencephalon, mesencephalon, pons, hippocampus and hypothalamus.
