The inevitable inequality of cortical columns.

The idea of columns as an organizing cortical unit emerged from physiologic studies in the sensory systems. Connectional studies and molecular markers pointed to widespread presence of modular label that necessitated revision of the classical concept of columns. The general principle of cortical systematic variation in laminar structure is at the core of cortical organization. Systematic variation can be traced to the phylogenetically ancient limbic cortices, which have the simplest laminar structure, and continues through eulaminate cortices that show sequential elaboration of their six layers. Connections are governed by relational rules, whereby columns or modules with a vertical organization represent the feedforward mode of communication from earlier- to later processing cortices. Conversely, feedback connections are laminar-based and connect later- with earlier processing areas; both patterns are established in development. Based on studies in primates, the columnar/modular pattern of communication appears to be newer in evolution, while the broadly based laminar pattern represents an older system. The graded variation of cortices entails a rich variety of patterns of connections into modules, layers, and mixed arrangements as the laminar and modular patterns of communication intersect in the cortex. This framework suggests an ordered architecture poised to facilitate seamless recruitment of areas in behavior, in patterns that are affected in diseases of developmental origin.