Architecture of the cerebral cortical association connectome underlying cognition

Abstract

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.T he cerebral cortex is the core of the brain's cognitive system (1, 2). Emerging evidence suggests that misdirected and/or dysfunctional cortical connections established during neurodevelopment, or degenerative events later in life, are fundamental to cognitive alterations associated with brain disorders like Alzheimer's disease, autism spectrum disorder, and schizophrenia (3). Presumably, an understanding of biological mechanisms underlying cognition and the control of voluntary behavior rests at least partly on the structure-function wiring diagram of the cortex. Design principles of this neural circuitry are based on a network of interactions between distributed nervous system regions, and on the underlying function of their constituent neuron populations, and individual neurons.Unfortunately, a global structure-function wiring diagram of the cortex has not yet been elaborated (4). A necessary, but not sufficient, prerequisite for establishing this basic plan is a comprehensive structural model of cortical connectivity (5-7). Such a "roadmap" could then be used as a database scaffolding for molecular, cellular, physiological, behavioral, and cognitive data and for modeling (8)-analogous to a Google Maps for the brain. The research strategy described here provides the starting point for such a model, as well as a framework, benchmark, and infrastructure for developing a global account of nervous system structural network organization as a whole.The conceptual framework underlying our strategy to analyze global nervous system connection architecture is twofold. First, because of considerable complexity-for example, human isocortex on one side has 6-9 billion neurons (9-11) interconnected by orders-of-magnitude-more synapses-three hierarchical (nested) levels analysis are considered (12, 13). A macroconnection be...

Network architecture of the cerebral nuclei (basal ganglia) association and commissural connectome

“…And fourth, the network as a whole does not show small-world organization. There are obvious similarities and differences between the rat cerebral nuclei association network described here and the rat cerebral cortical association network recently analyzed with similar methodology (10). Both networks are quite dense (in the sense that around 40% of all possible connections exist), both display four modules that are asymmetrically interconnected and topographically distinct, and both have a topographically segregated band of rich club and hub regions.…”

“…Instead, the intracerebral nuclei network has several connectional characteristics that set it apart from previous cortico-cortical datasets, including the rat cerebral cortical association macroconnection network (10). For example, the network displays a lesser extent of reciprocity (that is, a greater tendency toward unidirectional or asymmetrically weighted connections), at the level of both individual nodes and network modules.…”

“…From a neuroinformatics perspective, this is simply version 1.0 of the rat intracerebral macroconnectome, and future versions can be easily computed from updated data in Dataset S3. Presumably results will vary in proportion to the magnitude of differences between versioned datasets, but it has been shown that, at least qualitatively, the results of modularity analysis become stable with adjacency matrix fill ratios greater than 60-70% (10).…”

Connectome Networks: From Cells to Systems

“…Mesoscale mouse connectome projects (as well as parallel efforts in the rat cerebral cortex; Bota et al 2015) have produced similar insights. Wang et al (2012) performed a detailed quantitative analysis of the anatomical connections of ten areas of mouse visual cortex, including both their mutual connectivity and their external projection targets.…”

Characteristics of structural and functional organization of the brain

“…В последнее время при изучении психоневрологиче-ской сферы особое внимание уделяется связям как между отдельными нейронами, так и между различными отдела-ми головного мозга [1][2][3][4][5][6][7]. В частности, взаимодействие между нейронами рассматриваются в рамках микромас-шабных связей, между различными областями и путями головного мозга -в рамках макромасшабных связей, а на глобальном уровне между популяциями нейронов и суще-ствующими связями, -в рамках мезомасштабных связей [7].…”