The proposal investigates the differences in physiology, anatomy and organization of the cortex in mouse, non-human primate (NHP) and human. This work requires tight collaborations between physiologists, anatomists and theoreticians. Our capacity to successfully integrate across these approaches is strongly supported by the numerous joint publications linking these disciplines in leading international journals by the PI’s of the consortium. Anatomy: Tract-tracing will be used to build macaque and mouse inter-areal cortical connectomes. This work will generate large data bases on inter-areal connection weights and quantitative measures of laminar distributions as well as atlases of mouse and macaque. The structural basis of hierarchy and local-global integration will be investigated with viral tracers that will be used to map the long distance and local input to the parent neurons of feedforward and feedback connections in visual cortex of mouse and macaque. Physiology: Hierarchical processing in the human, NHP and mouse brains will be compared using electrophysiological and imaging approaches and together with tract tracing, will inform embedded large-scale dynamic models of inter-areal processing in the cortex. Differences in the inter-areal matrix density lead to widely different core structures across the three species, which will be explored by weighted network structural analysis, thereby revealing the core-periphery organization, which we hypothesize could be relevant to the Global Neuronal Workspace theory of consciousness (Figure 4). We will manipulate consciousness with anesthetics and stimulation techniques in macaque and mouse thereby by exploring Global Neuronal Workspace function via auditory signatures of consciousness in a predictive coding paradigm. Modeling: Conditional Granger causality analysis on multi-variate time series recordings will help identify functional subnetwork motifs, in order to explore the links between structural and dynamical features in the networks across the three species. Whole-brain computational modeling will address the functional role of the underlying anatomy by studying in silico theoretical measures of integration and segregation allowing topological hierarchical analyses of effective connectivity as opposed to anatomical or functional connectivity. Altogether, the project aims to provide quantitative metrics of differences in brain organization related to changes in brain size and order, and will demonstrably underpin the relevance of investigations in the mouse and macaque for understanding the human brain.