Neuroanatomical scaling, neurotopography of gene expression, and sex chromosome aneuploidy

The publication of topographically-defined, whole-transcriptome quantifications in the human brain has created the opportunity to mine the association of imaging findings with genetic data. An increasingly popular analysis is to connect groupwise anatomical differences in imaging space with differential expression of genes as defined by their topographical expression across the cortical mantle. This thesis uses this approach to address two problems in neuroimaging: 1) total brain size normalization and 2) association of anatomical changes with gene expression in health. The thesis begins by examining surface area scaling in the cortex and subcortex. It describes the regions of non-linear surface area scaling in both compartments --- and claims those foci of non-linear scaling may pose challenges for the analysis of disease. Next, the thesis considers the biological meaning of surface area scaling in the cortex by comparing regions of non-linear scaling to known maps of developmental and evolutionary expansion --- among others. A spatially sensitive bootstrapping procedure is introduced to quantify similarity or disimilarity amongst cortical maps. Lastly, this thesis applies a scaling-sensitive normalization framework for total brain size differences in the analysis of a neurogenetic disease cohort. In particular, scaling-sensitive analysis of the striatum, thalamus, and globus pallidus in Sex Chromosome Aneuploidy results in increased specificity for disease specific anatomical changes in both nucleus volume and shape.