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McAlonan, G. M.

Publications and source records attributed to McAlonan, G. M..

3 recordsLinked to original sources

Early development of cerebellar functional connectivity

The cerebellum makes a critical contribution to cognitive and behavioural function, extending well beyond motor control, and is recognised as an important determinant of neurodevelopmental outcome. Despite this, little is known about the foundations of cerebellar functional organisation in early life. Addressing this gap is essential for establishing typical developmental trajectories against which atypical development can be assessed. Here, we analysed fMRI data from term-born neonates (n=155) scanned between 37 and 44 weeks postmenstrual age and mapped intra-cerebellar and cerebro-cerebellar functional connectivity across multiple levels of organisation. We identified 13 intrinsic connectivity networks (ICNs) within the neonatal cerebellum that recapitulated adult subdivisions, with two ICNs showing age-related increases in coverage and strength. Analysis of cerebro-cerebellar connectivity identified 15 sensory, motor and association cerebral clusters, seven increasing connectivity with age. Functional gradient analysis identified a continuous axis from somatomotor to association regions within intra-cerebellar and cerebro-cerebellar organisation, which became more pronounced with age. Together, these findings suggest that the foundations of adult cerebellar functional organisation are present at birth but undergo rapid and regionally heterogeneous maturation over the first weeks of postnatal life. This developmental framework provides a normative reference for understanding cerebellar development and its implications for later neurodevelopmental variation.

neuroscience↗

Motifs of brain cortical folding from birth to adulthood: structural asymmetry and folding-functional links

Cortical folding of brain is widely regarded as an interplay between genetic programming and biomechanical forces, closely linked to cytoarchitectonic regionalisation. Abnormal folding patterns are frequently observed in neurodevelopmental conditions and psychiatric disorders. However, significant inter-individual variability of secondary and tertiary folds obscures detection of shape biomarkers and confounds investigation of folding-functional relationships. Here we investigate cortical folding heterogeneity at fine scale, using novel hierarchical surface registration (MSM-HT) to parse cortical folding patterns into a representative family of distinct anatomical templates. By applying this technique both to young adults from the Human Connectome Project (HCP) and neonates in the Developing HCP and Brain Imaging in Babies (BIBS) cohorts, we identify and characterize common lobe-wise folding patterns: observing consistency across both age groups, with neonatal samples showing less variation. Crucially, we highlight significant hemispheric asymmetry within the temporal lobe for both adults and neonates, and show that improved correspondence of shape does not translate to improved areal correspondence, affirming previous studies that have pointed to dissociation of folding and functional organisation. This study provides a critical step towards understanding brain asymmetry and complex relationships between folding and function, offering a robust framework to generalise the uncovered cortical folding motifs across datasets and developmental stages.

neuroscience↗

Differences in social brain function in autism spectrum disorder are linked to the serotonin transporter

Alterations in the serotonergic control of brain pathways responsible for facial-emotion processing in people with autism spectrum disorder (ASD) may be a target for intervention. However, the molecular underpinnings of autistic-neurotypical serotonergic differences are challenging to access in vivo. Receptor-Enriched Analysis of functional Connectivity by Targets (REACT) has helped define molecular-enriched fMRI brain networks based on a priori information about the spatial distribution of neurochemical systems from available PET templates. Here, we used REACT to estimate the dominant fMRI signal related to the serotonin transporter (5-HTT) distribution during processing of aversive facial expressions of emotion processing in adults with and without ASD. We first predicted a group difference in baseline (placebo) functioning of this system. We next used a single 20 mg oral dose of citalopram, i.e. a serotonin reuptake inhibitor, to test the hypothesis that network activity in people with and without ASD would respond differently to inhibition of 5-HTT. To confirm the specificity of our findings, we also repeated the analysis with 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 receptor maps. We found a baseline group difference in the 5-HTT-enriched response to faces in the ventromedial prefrontal cortex. A single oral dose of citalopram shifted the response in the ASD group towards the neurotypical baseline but did not alter response in the control group. Our findings suggest that the 5HTT-enriched functional network is dynamically different in ASD during processing of socially relevant stimuli. Whether this acute neurobiological response to citalopram in ASD translates to a clinical target will be an important next step.

neuroscience↗