General cortical and special prefrontal connections: principles from structure to function.

How is the vast brain communication system organized? A structural model relates connections to laminar differences between linked areas. The model is based on the principle of systematic structural variation in the cortex, extending from the simplest limbic cortices to eulaminate areas with elaborate lamination. The model accounts for laminar patterns and for the strength and topography of connections between nearby or distant cortices and subcortical structures, exemplified quantitatively for the principal and special prefrontal connections. Widespread connections of limbic areas and focal connections of eulaminate areas yield a broad range of circuit patterns for diverse functions. These diverse pathways innervate excitatory and functionally distinct inhibitory neurons, providing the basis for differential recruitment of areas for flexible behavior. Systematic structural variation likely emerges by timing differences in the development of distinct areas and has important implications for altered connections in diseases of developmental origin.