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.

Symptoms of inattention and hyperactivity frequently co-occur with language difficulties in both clinical and community samples. We explore the specificity and strength of these associations in a heterogeneous sample of 254 children aged 5 to 15 years identified by education and health professionals as having problems with attention, learning and/or memory. Parents/carers rated pragmatic and structural communication skills and behaviour, and children completed standardised assessments of reading, spelling, vocabulary, and phonological awareness. A single dimension of behavioural difficulties including both hyperactivity and inattention captured behaviour problems. This was strongly and negatively associated with pragmatic communication skills. There was less evidence for a relationship between behaviour and language structure: behaviour ratings were more weakly associated with the use of structural language in communication, and there were no links with direct measures of literacy. These behaviour problems and pragmatic communication difficulties co-occur in this sample, but impairments in the more formal use of language that impact on literacy and structural communication skills are tied less strongly to behavioural difficulties. One interpretation is that impairments in executive function give rise to both behavioural and social communication problems, and additional or alternative deficits in other cognitive abilities impact on the development of structural language skills.

Dynamic connectivity in functional brain networks is a fundamental aspect of cognitive development, but we have little understanding of the mechanisms driving variability in these networks. Genes are likely to influence the emergence of fast network connectivity via their regulation of neuronal processes, but novel methods to capture these rapid dynamics have rarely been used in genetic populations. The current study redressed this by investigating brain network dynamics in a neurodevelopmental disorder of known genetic origin, by comparing individuals with a ZDHHC9‐associated intellectual disability to individuals with no known impairment. We characterised transient network dynamics using a Hidden Markov Model (HMM) on magnetoencephalography (MEG) data, at rest and during auditory oddball stimulation. The HMM is a data‐driven method that captures rapid patterns of coordinated brain activity recurring over time. Resting‐state network dynamics distinguished the groups, with ZDHHC9 participants showing longer state activation and, crucially, ZDHHC9 gene expression levels predicted the group differences in dynamic connectivity across networks. In contrast, network dynamics during auditory oddball stimulation did not show this association. We demonstrate a link between regional gene expression and brain network dynamics, and present the new application of a powerful method for understanding the neural mechanisms linking genetic variation to cognitive difficulties.

Learning a new word requires discrimination between a novel sequence of sounds and similar known words. We investigated whether semantic information facilitates the acquisition of new phonological representations in adults and whether this learning enhancement is modulated by overnight consolidation. Participants learned novel spoken words either consistently associated with a visual referent or with no consistent meaning. An auditory oddball task tested discrimination of these newly learned phonological forms from known words. The MMN, an electrophysiological measure of auditory discrimination, was only elicited for words learned with a consistent semantic association. Immediately after training, this semantic benefit on auditory discrimination was linked to explicit learning of the associations, where participants with greater semantic learning exhibited a larger MMN. However, although the semantic-associated words continued to show greater auditory discrimination than nonassociated words after consolidation, the MMN was no longer related to performance in learning the semantic associations. We suggest that the provision of semantic systematicity directly impacts upon the development of new phonological representations and that a period of offline consolidation may promote the abstraction of these representations.