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ToolsCALM Team (2021) A generative network model of neurodevelopmental diversity in structural brain organization. Nature Communications, 12 (1). ISSN 2041-1723
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Abstract
The formation of large-scale brain networks, and their continual refinement, represent crucial developmental processes that can drive individual differences in cognition and which are associated with multiple neurodevelopmental conditions. But how does this organization arise, and what mechanisms drive diversity in organization? We use generative network modeling to provide a computational framework for understanding neurodevelopmental diversity. Within this framework macroscopic brain organization, complete with spatial embedding of its organization, is an emergent property of a generative wiring equation that optimizes its connectivity by renegotiating its biological costs and topological values continuously over time. The rules that govern these iterative wiring properties are controlled by a set of tightly framed parameters, with subtle differences in these parameters steering network growth towards different neurodiverse outcomes. Regional expression of genes associated with the simulations converge on biological processes and cellular components predominantly involved in synaptic signaling, neuronal projection, catabolic intracellular processes and protein transport. Together, this provides a unifying computational framework for conceptualizing the mechanisms and diversity in neurodevelopment, capable of integrating different levels of analysis—from genes to cognition.
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| Additional Information: | Funding Information: We thank the whole CALM team for their hard work and significant contribution. We also would like to thank the many professionals working in children’s services in the South-East and East of England for their support, and to the children and their families for giving up their time to visit the clinic. We are particularly grateful for J.B. for his help in guiding us through the construction of the streamline connectomes. We would also like to thank the radiographers who support the excellent pediatric scanning at the MRC Cognition and Brain Sciences Unit. D.A. is supported by the Medical Research Council Doctoral Training Programme and Cambridge Trust Vice Chancellor’s Award Scholarship. D.E.A. is supported by Medical Research Council Program Grant MC-A0606-5PQ41, respectively. Both D.E.A. and D.A. are supported by The James S. McDonnell Foundation Opportunity Award. P.E.V. is a fellow of MQ: Transforming Mental Health (MQF17_24) and of the Alan Turing Institute funded by EPSRC grant EP/N510129/1. E. T.B. is an NIHR Senior Investigator, supported by the NIHR Cambridge Biomedical Research Centre. The views expressed are those of the authors, and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. All opinions expressed in this publication are those of the authors and do not necessarily reflect the views of the funding agencies. Publisher Copyright: © 2021, Crown. |
| Uncontrolled Keywords: | chemistry(all),biochemistry, genetics and molecular biology(all),physics and astronomy(all) ,/dk/atira/pure/subjectarea/asjc/1600 |
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| Depositing User: | LivePure Connector |
| Date Deposited: | 27 Oct 2021 02:24 |
| Last Modified: | 03 Nov 2022 16:34 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/81892 |
| DOI: | 10.1038/s41467-021-24430-z |
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