Biology subjects

the CALM Team,

Publications and source records attributed to the CALM Team,.

4 recordsLinked to original sources

bioRxiv2026

Integrating Functional Transdiagnostic Dimensions of Psychopathology with Cortical Organization

Childhood and adolescence represent a critical period in which neurodevelopmental psychiatric conditions emerge; traditional case-control approaches often underestimate the complexity and co-occurrence of psychiatric conditions, calling for a transdiagnostic approach as a complementary measure. Open-access data sharing initiatives provide an opportunity to decipher structural- and functional-based organisational constraints on the relationship between brain connectivity and psychopathology. Using a highly heterogenous and comorbid neurodevelopmental sample of children and adolescents aged between 6 and 17 years old at-risk of neurodevelopmental conditions (N = 174, 114 males, mean age 10.72 {+/-} 2.21 years), and age-matched neurotypical controls (N = 27, 12 males, mean age 10.65 {+/-} 2.07 years), we identified a multivariate association, or latent variable, between resting-state functional connectivity and psychopathology. We extensively benchmarked this latent construct to develop a more parsimonious account of childhood psychopathology though an analytical framework spanning biological maps, brain connectivity, and behaviour. Participant-level expression of this latent brain-behaviour association differed by diagnostic burden and symptomatology, and pre-empted longitudinal psychopathology. Whilst diagnostic status was useful for interpretation, the latent construct transcended traditional diagnostic borders, revealing a neurotypical-neurodivergent continuum. The relationship between functional connectivity and neurodevelopmental psychopathology was circumscribed by functional connectivity networks (visual, fronto-parietal, and dorsal attention) and cytoarchitectonic class (primary/secondary sensory and primary sensory cortices). The latent variable aligned with magnetoencephalography-defined electrophysiological alpha (), high-gamma ({gamma}), and theta ({theta}) frequency bands, and was enriched across cortical distributions of astrocytes and excitatory neurones. The connectivity signature was significantly aligned with the archetypal sensorimotor-to-association axis and validated in an independent sample of pre-adolescents (N = 3504), with the strongest alignment with the principal component of gene expression and myelination and were relatively less enriched in cortical regions related to language, indicating a protective effect, and more positively enriched in regions related to executive functioning, conferring greater risk of psychopathology. Together, our findings suggest that the predictive link between functional connectivity and common symptoms of neurodevelopmental psychopathology are circumscribed by underlying macroscale anatomical, functional, and cognitive-related hierarchies.

neuroscience↗

bioRxiv2024

Canonical neurodevelopmental trajectories of structural and functional manifolds

Organisational gradients refer to a continuous low-dimensional embedding of brain regions and can quantify core organisational principles of complex systems like the human brain. Mapping how these organisational principles are altered or refined across development and phenotypes is essential to understanding the relationship between brain and behaviour. Taking a developmental approach and leveraging longitudinal and cross-sectional data from two multi-modal neuroimaging datasets, spanning the full neurotypical-neurodivergent continuum, we charted the organisational variability of structural (610 participants, N = 390 with one observation, N = 163 with two observations, and N = 57 with three) and functional (512 participants, N = 340 with one observation, N = 128 with two observations, and N = 44 with three). Across datasets, despite differing phenotypes, we observe highly similar structural and functional gradients. These gradients, or organisational principles, are highly stable across development, with the exact same ordering across early childhood into mid-adolescence. However, there is substantial developmental change in the strength of embedding within those gradients: by modelling developmental trajectories as non-linear splines, we show that structural and functional gradients exhibit sensitive periods and are refined across development. Specifically, structural gradients gradually contract in low-dimensional space as networks become more integrated, whilst the functional manifold expands, indexing functional specialisation. The coupling of these structural and functional gradients follows a unimodal-association axis and varies across individuals, with developmental effects concentrated in the more plastic higher-order networks. Importantly, these developmental effects on coupling, in these higher-order networks, are attenuated in the neurodivergent sample. Finally, we mapped structure-function coupling onto dimensions of psychopathology and cognition and demonstrate that dimensions of cognition, such as working memory, are robust predictors of coupling. In summary, across clinical and community samples, we demonstrate consistent principles of structural and functional brain organisation, with progressive structural integration and functional segregation. These gradients are established early in life, refined through development, and their coupling is predicted by working memory.

neuroscience↗

bioRxiv2021

Segregation and integration of the functional connectome in neurodevelopmentally 'at risk' children

Functional connectivity within and between Intrinsic Connectivity Networks (ICNs) transforms over development and supports high order cognitive functions. But how variable is this process, and does it diverge with altered cognitive developmental trajectories? We investigated age-related changes in integration and segregation within and between ICNs in neurodevelopmentally at-risk children, identified by practitioners as experiencing cognitive difficulties in attention, learning, language, or memory. In our analysis we used performance on a battery of 10 cognitive tasks, alongside resting-state functional Magnetic Resonance Imaging in 175 at-risk children and 62 comparison children aged 5-16. We observed significant age-by-group interactions in functional connectivity between two network pairs. Integration between the ventral attention and visual networks and segregation of the limbic and fronto-parietal networks increased with age in our comparison sample, relative to at-risk children. Furthermore, functional connectivity between the ventral attention and visual networks in comparison children significantly mediated age-related improvements in executive function, compared to at-risk children. We conclude that integration between ICNs show divergent neurodevelopmental trends in the broad population of children experiencing cognitive difficulties, and that these differences in functional brain organisation may partly explain the pervasive cognitive difficulties within this group over childhood and adolescence. Research HighlightsO_LIWe investigated functional brain organisation and its development in 175 children who experience neurodevelopmental difficulties in cognition and behaviour, relative to a comparison sample (n=62) C_LIO_LIWe replicated common neurodevelopmental trends across the samples: functional connectivity increased within Intrinsic Connectivity Networks and the default-mode network increasingly segregated with age C_LIO_LINeurodevelopmentally at-risk children also showed different age-related changes in functional connectivity between the ventral attention and visual networks and between the fronto-parietal and limbic networks C_LIO_LIFurthermore, the integration between the ventral attention and visual networks in comparison children mediated age-related changes in cognition, relative to at-risk children C_LI

neuroscience↗

bioRxiv2018

Cognition and behaviour in learning difficulties and ADHD: A dimensional approach

BackgroundAcademic underachievement often accompanies the symptoms of inattention and hyperactivity/ impulsivity associated with ADHD. The aim of the present study is to establish whether learning difficulties have the same cognitive origins in this comorbid condition as in children who do not have ADHD.\n\nMethodsParticipants were 163 school-aged children with learning difficulties. Over a third also had a diagnosis of ADHD. Cognition, behaviour and learning attainments were assessed.\n\nResultsThe sample was distinguished by three cognitive and three behavioural dimensions. Learning was equivalently related to cognitive dimensions for children with and without ADHD. A diagnosis of ADHD was associated only with elevated levels of ADHD symptoms and problems with emotional control.\n\nConclusionsDistinct dimensions underpin academic learning and the control of impulsive and emotional behaviour impaired in ADHD. Phonological deficits are associated with learning problems in literacy and maths, and impairments in nonverbal and executive abilities with mathematical learning difficulties. The comorbid condition of ADHD combined with learning difficulties reflects independent deficits in the cognitive dimensions critical for learning and in the control of impulsive and emotional behaviour.

animal behavior and cognition↗