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Towards a biologically annotated brain connectome

Nature Reviews Neuroscience volume 24, pages 747–760 (2023)Cite this article

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Abstract

The brain is a network of interleaved neural circuits. In modern connectomics, brain connectivity is typically encoded as a network of nodes and edges, abstracting away the rich biological detail of local neuronal populations. Yet biological annotations for network nodes — such as gene expression, cytoarchitecture, neurotransmitter receptors or intrinsic dynamics — can be readily measured and overlaid on network models. Here we review how connectomes can be represented and analysed as annotated networks. Annotated connectomes allow us to reconceptualize architectural features of networks and to relate the connection patterns of brain regions to their underlying biology. Emerging work demonstrates that annotated connectomes help to make more veridical models of brain network formation, neural dynamics and disease propagation. Finally, annotations can be used to infer entirely new inter-regional relationships and to construct new types of network that complement existing connectome representations. In summary, biologically annotated connectomes offer a compelling way to study neural wiring in concert with local biological features.

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Fig. 1: Constructing an annotated connectome.
Fig. 2: Architectural features of annotated connectomes.
Fig. 3: Annotation-enhanced models of the brain.
Fig. 4: Annotation similarity networks.

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Data availability

Data used to generate Fig. 1 are available in the neuromaps toolbox (https://netneurolab.github.io/neuromaps/ (ref. 35)) and the Allen Human Brain Atlas35,44. Synthetic data were used to generate Fig. 2. Figure 3 is a conceptual illustration and is not based on real data. Data used to generate Fig. 4 can be found at https://github.com/netneurolab/hansen_many_networks and the Human Connectome Project204,211.

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Acknowledgements

We thank E. Suarez, A. Luppi, F. Milisav, Z.Q. Liu, E. Ceballos, A. Farahani and M. Pourmajidian for their comments and suggestions. This work was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Institutes of Health Research (CIHR), the Canada Research Chair (CRC) Program, Fonds de Recherche du Quebec–Nature et Technologie (FRQNT), Helmholtz International BigBrain Analytics and Learning Laboratory (HIBALL) and the Brain Canada Foundation.

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  1. Montréal Neurological Institute, McGill University, Montréal, Quebec, Canada

    Vincent Bazinet, Justine Y. Hansen & Bratislav Misic

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Contributions

V.B. and J.Y.H. researched data for the article. All authors made substantial contributions to the discussion of content and wrote, reviewed and edited the manuscript before submission.

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Correspondence to Bratislav Misic.

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Glossary

Annotations

Any measurements or features that can be attached to the nodes of a network, either as a unidimensional scalar or multidimensional vector.

Arealization

The developmental process by which cortical cell types and circuits come to support unique specialized functions.

Cliques and cavities

Cliques are groups of all-to-all connected nodes, and cavities are groups of mutually unconnected nodes that participate in cliques.

Community

A group of nodes densely connected with each other but sparsely connected with the rest of the network.

Connection profiles

Vectors describing the connectivity of a brain region, detailing all of its pairwise connections with other brain regions.

Hub

A region that has many connections.

Multilayer community detection

Techniques for identifying communities that simultaneously take into account multiple types of connectivity or other interactions between nodes, such as annotation similarity.

Stochastic block models

Statistical models of network organization that formally take into account both connection patterns and local node annotations.

Transmodal networks

Networks that respond to multiple sensory modalities and specialize for higher-order cognitive function, such as the salience and default networks.

Unimodal networks

Networks that specialize for one primary sensory or motor function, such as the visual and somatomotor networks.

Vertex or voxel values

The main units of brain images, representing a spatial location in the brain, defined either for a brain volume (voxel) or on the surface (vertex).

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Bazinet, V., Hansen, J.Y. & Misic, B. Towards a biologically annotated brain connectome. Nat. Rev. Neurosci. 24, 747–760 (2023). https://doi.org/10.1038/s41583-023-00752-3

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