Integrated phylogeny of the primate brain, with special reference to humans and their diseases

Fossil, comparative anatomic and ontogenic data suggest that several systems of functionally and anatomically related brain regions underwent selective expansion or differentiation during primate evolution, according to the principle of 'integrated phylogeny'. This process was closely tied to expansion of the neocortex, particularly of its association areas. System I regions include the association neocortices as well as the nucleus basalis of Meynert, the entorhinal cortex, and subdivisions of the septum, hippocampal formation and amygdaloid complex. This system undergoes degeneration in Alzheimer's and Pick's diseases and Down syndrome. System II includes segregated circuits involving parts of the frontal cortex, basal ganglia, thalamus, and substantia nigra, and can become defective in obsessive-compulsive disorder, Huntington's and Parkinson's diseases. Certain nuclei in the mesencephalon and brainstem, which co-evolved with System I and II regions, also demonstrate pathology in diseases affecting these systems. Integrated phylogeny of each of these systems during primate evolution likely was promoted by regulatory mutations, gene duplications or chromosomal rearrangements. Thus, understanding the genetic basis of integrated phylogeny of systems of brain regions during primate evolution may elucidate the pathogenesis of the human diseases which affect these regions.