Biology subjects

Ronan, L.

Publications and source records attributed to Ronan, L..

4 recordsLinked to original sources

bioRxiv2022

The genetics of cortical organisation and development: a study of 2,347 neuroimaging phenotypes

Our understanding of the genetic architecture of the human cerebral cortex is limited both in terms of the diversity of brain structural phenotypes and the anatomical granularity of their associations with genetic variants. Here, we conducted genome-wide association meta-analysis of 13 structural and diffusion magnetic resonance imaging derived cortical phenotypes, measured globally and at 180 bilaterally averaged regions in 36,843 individuals from the UK Biobank and the ABCD cohorts. These phenotypes include cortical thickness, surface area, grey matter volume, and measures of folding, neurite density, and water diffusion. We identified 4,349 experiment-wide significant loci associated with global and regional phenotypes. Multiple lines of analyses identified four genetic latent structures and causal relationships between surface area and some measures of cortical folding. These latent structures partly relate to different underlying gene expression trajectories during development and are enriched for different cell types. We also identified differential enrichment for neurodevelopmental and constrained genes and demonstrate that common genetic variants associated with surface area and volume specifically are associated with cephalic disorders. Finally, we identified complex inter-phenotype and inter-regional genetic relationships among the 13 phenotypes which reflect developmental differences among them. These analyses help refine the role of common genetic variants in human cortical development and organisation. One sentence summaryGWAS of 2,347 neuroimaging phenotypes shed light on the global and regional genetic organisation of the cortex, underlying cellular and developmental processes, and links to neurodevelopmental and cephalic disorders.

neuroscience↗

bioRxiv2020

Dispersion of functional gradients across the lifespan

Ageing is commonly associated with changes to segregation and integration of functional brain networks, but, in isolation, current network-based approaches struggle to elucidate changes across the many axes of functional organisation. However, the advent of gradient mapping techniques to neuroimaging provides a new means of studying functional organisation in a multi-dimensional connectivity space. Here, we studied ageing and behaviourally-relevant differences in a three-dimensional connectivity space using the Cambridge Centre for Ageing Neuroscience cohort (n=643). Building on gradient mapping techniques, we developed a set of measures to quantify the dispersion within and between functional communities. We detected a strong shift of the visual network across the lifespan from an extreme to a more central position in the 3D gradient space. In contrast, the dispersion distance of transmodal communities (dorsal attention, ventral attention, frontoparietal and default mode) did not change. However, these communities were increasingly dispersed with increasing age, reflecting more dissimilar functional connectivity profiles within each community. Increasing dispersion of frontoparietal and ventral attention networks, in particular, was associated negatively with cognition, measured by fluid intelligence. By using a technique that explicitly captures the ordering of functional systems in a multi-dimensional hierarchical framework, we identified behaviorally-relevant age-related differences of within and between network organisation. We propose that the study of functional gradients across the lifespan could provide insights that may facilitate the development of new strategies to maintain cognitive ability across the lifespan in health and disease.

neuroscience↗

bioRxiv2018

Neural correlates of reward anticipation in 2000 children aged 9-10 years: relation to psychotic-like experiences and depressive symptoms

BackgroundSchizophrenia spectrum disorders and depression have been associated with reductions in brain activation during reward anticipation. It is not known whether brain signals associated with reward anticipation relate to psychopathology dimensions of depression or schizophrenia in childhood prior to adolescence.\n\nMethodWe examined whether fMRI brain correlates of reward anticipation related to psychotic-like experiences and symptoms of depression, in 2129 children from the ABCD study aged 9-10 years.Psychotic-like experiences and depression were assessed using the Prodromal Questionnaire Brief Child version and the K-SADS. We fused regional MRI summary statistics for reward anticipation activation in the ABCD study data release 1.0 (contrast of expected large reward versus neutral expectation). Relations between brain activation and psychopathology were assessed using linear regressions in R for 82 brain regions, corrected for multiple comparisons for the number of regions using false discovery rate.\n\nResultsFrom several regressions, there was an isolated unilateral association between right parsorbitalis activation and psychotic-like experiences, but no other significant associations between brain activation and psychopathology.\n\nConclusionsIn 9-10 year old children, reward anticipation is not strongly related to psychotic-like experiences or depression. As previous evidence links depression and schizophrenia to reduced reward anticipation in adults and older adolescents, it appears likely that such associations develop over the adolescent period: this can be tested in follow-up studies of the ABCD cohort.

neuroscience↗

bioRxiv2018

Pleiotropic effects drive correlation between body mass index and cortical myelination

BackgroundEpidemiological studies have reported significant associations between obesity and neurocognitive decline. Understanding these associations will require deeper analyses of how body mass index (BMI) and brain structure are related. Here we explore the extent to which shared genetic factors (pleiotropy) govern the association between BMI and cortical myelination.\n\nMethodsStatistical models of bivariate heritability were applied to structural MR image data from a cohort of monozyogotic and dizygotic twins. Estimates of phenotypic and genetic correlation between BMI and cortical myelination were derived. A co-twin control design based on monozygotic twins was used to test the hypothesis of a causal relationship between BMI and myelination. The variation in the genetic correlation across the cortex was compared with the average statistical enrichment of genes associated with obesity derived from data from the Allen brain atlas.\n\nResultsStatistically significant phenotypic and genetic correlation between BMI and cortical myelination was observed across the cortex. Taking the heritability of each trait into account, approximately 80% of the phenotypic correlation between the traits was accounted for by shared genetic factors.\n\nIntra-pair differences between traits in monozygotic twins failed to support a causal relationship. Moreover, variation in genetic correlation across the cortex was significantly associated with the statistical enrichment of genes related to obesity.\n\nConclusionsThese results support the hypothesis that pleiotropic effects drive the association between BMI and cortical myelination. This observation may help to explain the co-occurrence of obesity in neurocognitive decline and mental health disorders characterized by changes in myelination and oligodendrocyte function.

neuroscience↗