A generative network model of neurodevelopmental diversity in structural brain organization

Author:

Akarca DanyalORCID,Vértes Petra E.,Bullmore Edward T.ORCID,Baker Kate,Gathercole Susan E.,Holmes Joni,Kievit Rogier A.,Manly Tom,Bathelt Joe,Bennett Marc,Bignardi Giacomo,Bishop Sarah,Bottacin Erica,Bridge Lara,Brkic Diandra,Bryant Annie,Butterfield Sally,Byrne Elizabeth M.,Crickmore Gemma,Dalmaijer Edwin S.,Daly Fánchea,Emery Tina,Forde Laura,Franckel Grace,Fuhrmann Delia,Gadie Andrew,Gharooni Sara,Guy Jacalyn,Hawkins Erin,Jaroslawska Agnieszka,Joeghan Sara,Johnson Amy,Jones Jonathan,Mareva Silvana,Ng-Cordell Elise,O’Brien Sinead,O’Leary Cliodhna,Rennie Joseph P.,Simpson-Kent Ivan,Siugzdaite Roma,Smith Tess A.,Uh Stephani,Vedechkina Maria,Woolgar Francesca,Zdorovtsova Natalia,Zhang Mengya,Astle Duncan E.,

Abstract

AbstractThe 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.

Funder

RCUK | Medical Research Council

James S. McDonnell Foundation

Cambridge Commonwealth, European and International Trust

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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