Information exchange in the human brain is crucial for vital tasks and to drive diseases. Neuroimaging techniques allow for the indirect measurement of information flows among brain areas and, consequently, for reconstructing connectomes analyzed through the lens of network science. However, standard analyses usually focus on a small set of network indicators and their joint probability distribution. Here, we propose an information-theoretic approach for the analysis of synthetic brain networks (based on generative models) and empirical brain networks, and to assess connectome’s information capacity at different stages of dementia. Remarkably, our framework accounts for the whole network state, overcoming limitations due to limited sets of descriptors, and is used to probe human connectomes at different scales. We find that the spectral entropy of empirical data lies between two generative models, indicating an interpolation between modular and geometry-driven structural features. In fact, we show that the mesoscale is suitable for characterizing the differences between brain networks and their generative models. Finally, from the analysis of connectomes obtained from healthy and unhealthy subjects, we demonstrate that significant differences between healthy individuals and the ones affected by Alzheimer’s disease arise at the microscale (max. posterior probability smaller than 1%) and at the mesoscale (max. posterior probability smaller than 10%).


Capitalizing on network information theory we propose a new framework for the analysis and comparison of empirical and synthetic human connectomes, in health and disease. We quantitatively assess the ability of our approach in identifying differences and similarities in the structural connectivity of the human brain, ranging between microscopic and macroscopic scales. Relying on two different diffusion processes, namely classic and max-entropy random walks, we show that the mesoscale is suitable for capturing differences between empirical connectomes and their synthetic models, while differences between healthy subjects and patients affected by Alzheimer’s disease are mostly significant at the microscopic scale.

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Competing Interests: The authors have declared that no competing interests exist.

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