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.

The Cognitive Estimation Test (CET) is a widely used test to investigate estimation abilities requiring complex processes such as reasoning, the development and application of appropriate strategies, response plausibility checking as well as general knowledge and numeracy (e.g., Shallice and Evans, 1978; MacPherson et al., 2014). Thus far, it remains unknown whether the CET is both sensitive and specific to frontal lobe dysfunction. Neuroimaging techniques may not represent a useful methodology for answering this question since the complex processes involved are likely to be associated with a large network of brain regions, some of which are not functionally necessary to successfully carry out the CET. Instead, neuropsychological studies may represent a more promising investigation tool for identifying the brain areas necessary for CET performance. We recently developed two new versions of the CET (CET-A and CET-B; MacPherson et al., 2014). We investigated the overall performance and conducted an error analysis on CET-A in patients with focal, unilateral, frontal (n = 38) or posterior (n = 22) lesions and healthy controls (n = 39). We found that frontal patients’ performance was impaired compared to healthy controls on CET. We also found that frontal patients generated significantly poorer estimates than posterior patients on CET-A. This could not be explained by impairments in fluid intelligence. The error analyses suggested that for CET-A, extreme and very extreme responses are impaired following frontal lobe damage. However, only very extreme responses are significantly more impaired following frontal lobe than posterior damage and so represent a measure restricted to frontal “executive” impairment, in addition to overall CET performance.

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Background: Behavioural and language difficulties co-occur in multiple neurodevelopmental conditions. Our understanding of these problems has arguably been slowed by an overreliance on study designs that compare diagnostic groups and fail to capture the overlap across different neurodevelopmental disorders and the heterogeneity within them. Methods: We recruited a large transdiagnostic cohort of children with complex needs (N = 805) to identify distinct subgroups of children with common profiles of behavioural and language strengths and difficulties. We then investigated whether and how these data-driven groupings could be distinguished from a comparison sample (N = 158) on measures of academic and socioemotional functioning and patterns of global and local white matter connectome organisation. Academic skills were assessed via standardised measures of reading and maths. Socioemotional functioning was captured by the parent-rated version of the Strengths and Difficulties Questionnaire. Results: We identified three distinct subgroups of children, each with different levels of difficulties in structural language, pragmatic communication, and hot and cool executive functions. All three subgroups struggled with academic and socioemotional skills relative to the comparison sample, potentially representing three alternative but related developmental pathways to difficulties in these areas. The children with the weakest language skills had the most widespread difficulties with learning, whereas those with more pronounced difficulties with hot executive skills experienced the most severe difficulties in the socioemotional domain. Each data-driven subgroup could be distinguished from the comparison sample based on both shared and subgroup-unique patterns of neural white matter organisation. Children with the most pronounced deficits in language, cool executive, or hot executive function were differentiated from the comparison sample by altered connectivity in predominantly thalamocortical, temporal-parietal-occipital, and frontostriatal circuits, respectively. Conclusions: These findings advance our understanding of commonly co-morbid behavioural and language problems and their relationship to behavioural outcomes and neurobiological substrates.

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