Inhibitory dysfunction and social processing difficulties in autism: A comprehensive narrative review.

The primary inhibitory neurotransmitter γ-aminobutyric acid (GABA) has a prominent role in regulating neural development and function, with disruption to GABAergic signalling linked to behavioural phenotypes associated with neurodevelopmental disorders, particularly autism. Such neurochemical disruption, likely resulting from diverse genetic and molecular mechanisms, particularly during early development, can subsequently affect the cellular balance of excitation and inhibition in neuronal circuits, which may account for the social processing difficulties observed in autism and related conditions. This comprehensive narrative review integrates diverse streams of research from several disciplines, including molecular neurobiology, genetics, epigenetics, and systems neuroscience. In so doing it aims to elucidate the relevance of inhibitory dysfunction to autism, with specific focus on social processing difficulties that represent a core feature of this disorder. Many of the social processing difficulties experienced in autism have been linked to higher levels of the excitatory neurotransmitter glutamate and/or lower levels of inhibitory GABA. While current therapeutic options for social difficulties in autism are largely limited to behavioural interventions, this review highlights the psychopharmacological studies that explore the utility of GABA modulation in alleviating such difficulties.

Childhood development of brain white matter myelin: a longitudinal T1w/T2w-ratio study.

Myelination of human brain white matter (WM) continues into adulthood following birth, facilitating connection within and between brain networks. In vivo MRI studies using diffusion weighted imaging (DWI) suggest microstructural properties of brain WM increase over childhood and adolescence. Although DWI metrics, such as fractional anisotropy (FA), could reflect axonal myelination, they are not specific to myelin and could also represent other elements of WM microstructure, for example, fibre architecture, axon diameter and cell swelling. Little work exists specifically examining myelin development. The T1w/T2w ratio approach offers an alternative non-invasive method of estimating brain myelin. The approach uses MRI scans that are routinely part of clinical imaging and only require short acquisition times. Using T1w/T2w ratio maps from three waves of the Neuroimaging of the Children's Attention Project (NICAP) [N = 95 (208 scans); 44% female; ages 9.5-14.20 years] we aimed to investigate the developmental trajectories of brain white matter myelin in children as they enter adolescence. We also aimed to investigate whether longitudinal changes in myelination of brain WM differs between biological sex. Longitudinal regression modelling suggested non-linear increases in WM myelin brain wide. A positive parabolic, or U-shaped developmental trajectory was seen across 69 of 71 WM tracts modelled. At a corrected level, no significant effect for sex was found. These findings build on previous brain development research by suggesting that increases in brain WM microstructure from childhood to adolescence could be attributed to increases in myelin.

Fronto-parietal white matter microstructure associated with working memory performance in children with ADHD.

INTRODUCTION: Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with many functional impairments thought to be underpinned by difficulties in executive function domains such as working memory. The superior longitudinal fasciculus (SLF) plays an integral role in the development of working memory in neurotypical children. Neuroimaging research suggests reduced white matter organization of the SLF may contribute to working memory difficulties commonly seen in ADHD. This study aimed to examine the relationship between white matter organization of the SLF and working memory in children with ADHD. METHODS: We examined the association of tract volume and apparent fibre density (AFD) of the SLF with working memory in children with ADHD (n = 64) and controls (n = 58) aged 9-11years. Children completed a computerized spatial n-back task and underwent diffusion magnetic resonance imaging (dMRI). Constrained spherical deconvolution-based tractography was used to construct the three branches of the SLF bilaterally and examine volume and AFD of the SLF. RESULTS: Regression analyses revealed children with ADHD exhibited poorer working memory, and lower volume and AFD of the left SLF-II compared to healthy controls. There was also an association between reaction time and variability (RT and RT-V) and the left SLF-II. Further analyses revealed volume of the left SLF-II mediated the relationship between ADHD and working memory performance (RT and RT-V). DISCUSSION: These findings add to the current body of ADHD literature, revealing the potential role of frontoparietal white matter in working memory difficulties in ADHD.