Architecture of the cerebral cortical association connectome underlying cognition

Significance Connections between cerebral cortex regions are known as association connections, and neural activity in the network formed by these connections is thought to generate cognition. Network analysis of microscopic association connection data produced over the last 40 years in a small, easily studied mammal suggests a new way to describe the organization of the cortical association network. Basically, it consists of four modules with an anatomical shell–core arrangement and asymmetric connections within and between modules, implying at least partly “hardwired,” genetically determined biases of information flow through the cortical association network. The results advance the goal of achieving a global nervous system wiring diagram of connections and provide another step toward understanding the cellular architecture and mechanisms underpinning cognition. Cognition presumably emerges from neural activity in the network of association connections between cortical regions that is modulated by inputs from sensory and state systems and directs voluntary behavior by outputs to the motor system. To reveal global architectural features of the cortical association connectome, network analysis was performed on >16,000 reports of histologically defined axonal connections between cortical regions in rat. The network analysis reveals an organization into four asymmetrically interconnected modules involving the entire cortex in a topographic and topologic core–shell arrangement. There is also a topographically continuous U-shaped band of cortical areas that are highly connected with each other as well as with the rest of the cortex extending through all four modules, with the temporal pole of this band (entorhinal area) having the most cortical association connections of all. These results provide a starting point for compiling a mammalian nervous system connectome that could ultimately reveal novel correlations between genome-wide association studies and connectome-wide association studies, leading to new insights into the cellular architecture supporting cognition.