The subcortical morphology correlates of autistic traits in school-age children: a population-based neuroimaging study

Background There is emerging evidence that the neuroanatomy of autism forms a spectrum which extends into the general population. However, whilst several studies have identified cortical morphology correlates of autistic traits, it is not established whether morphological differences are present in the subcortical structures of the brain. Additionally, it is not clear to what extent previously reported structural associations may be confounded by co-occurring psychopathology. To address these questions, we utilised neuroimaging data from the Adolescent Brain Cognitive Development Study to assess whether a measure of autistic traits was associated with differences in child subcortical morphology, and if any observed differences persisted after adjustment for child internalising and externalising symptoms. Methods Our analyses included data from 7,005 children aged 9-10 years (female: 47.19%) participating in the Adolescent Brain Cognitive Development Study. Autistic traits were assessed using scores from the Social Responsiveness Scale. Volumes of subcortical regions-of-interest were derived from structural magnetic resonance imaging data. Results Overall, we did not find strong evidence for an association of autistic traits with differences in subcortical morphology in this sample of school-aged children. Whilst lower absolute volumes of the nucleus accumbens and putamen were associated with higher scores of autistic traits, these differences did not persist once a global measure of brain size was accounted for. Conclusions These findings from our well-powered study suggest that other metrics of brain morphology, such as cortical morphology or shape-based phenotypes, may be stronger candidates to prioritise when attempting to identify robust neuromarkers of autistic traits.

Multilevel neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology

It is increasingly recognized that multiple psychiatric conditions are underpinned by shared neural pathways, affecting similar brain systems. Here, we assessed i) shared dimensions of alterations in cortical morphology across six major psychiatric conditions (autism spectrum disorder, attention deficit/hyperactivity disorder, major depression, obsessive-compulsive disorder, bipolar disorder, schizophrenia) and ii) carried out a multiscale neural contextualization, by cross-referencing shared anomalies against cortical myeloarchitecture and cytoarchitecture, as well as connectome and neurotransmitter organization. Pooling disease-related effects on MRI-based cortical thickness measures across six ENIGMA working groups, including a total of 28,546 participants (12,876 patients and 15,670 controls), we computed a shared disease dimension on cortical morphology using principal component analysis that described a sensory-fugal pattern with paralimbic regions showing the most consistent abnormalities across conditions. The shared disease dimension was closely related to cortical gradients of microstructure and intrinsic connectivity, as well as neurotransmitter systems, specifically serotonin and dopamine. Our findings embed the shared effects of major psychiatric conditions on brain structure in multiple scales of brain organization and may provide novel insights into neural mechanisms into transdiagnostic vulnerability.

Cortical Morphology in Cannabis Use Disorder: Implications for Transcranial Direct Current Stimulation Treatment

Introduction: Transcranial direct current stimulation (tDCS) has been studied as an adjunctive treatment option for substance use disorders (SUDs). Alterations in brain structure following SUD may change tDCS-induced electric field (EF) and subsequent responses. However, group-level differences between healthy controls (HC) and participants with SUDs in terms of EF and its association with cortical architecture have not yet been modeled quantitatively. Objective: We provided a methodology for group-level analysis of computational head models (CHMs) to investigate the influence of cortical morphology metrics on EFs. Method: Whole-brain surface-based morphology was conducted and cortical thickness, volume, and surface area were compared between participants with CUD (n=20) and age-matched HC (n=22). We also simulated EFs for bilateral tDCS over DLPFC. Effects of structural alterations on EF distribution were investigated based on individualized CHMs. Results: In terms of EF, no significant difference was found within the prefrontal cortex. However, EFs were significantly different in left-postcentral and right-superior temporal gyrus (P < 0.05) with higher level of variance in CUD compared to HC (F39,43=5.31,P<0.0001,C =0.95). We found significant differences in cortical area (caudal anterior cingulate and rostral middle frontal), thickness (lateral orbitofrontal), and volume (paracentral and fusiform) between two groups. Conclusion: Brain morphology and tDCS-induced EFs may be changed following CUD. However, differences between CUD and HCs in EFs do not always overlap with brain areas that showed structural alterations. To sufficiently modulate stimulation targets, it should be checked if individuals with CUD need to be given different stimulation dose based on tDCS target location.

Structural Differences Across Multiple Visual Cortical Regions in the Absence of Cone Function in Congenital Achromatopsia

Most individuals with congenital achromatopsia (ACHM) carry mutations that affect the retinal phototransduction pathway of cone photoreceptors, fundamental to both high acuity vision and colour perception. As the central fovea is occupied solely by cones, achromats have an absence of retinal input to the visual cortex and a small central area of blindness. Additionally, those with complete ACHM have no colour perception, and colour processing regions of the ventral cortex also lack typical chromatic signals from the cones. This study examined the cortical morphology (grey matter volume, cortical thickness, and cortical surface area) of multiple visual cortical regions in ACHM (n = 15) compared to normally sighted controls (n = 42) to determine the cortical changes that are associated with the retinal characteristics of ACHM. Surface-based morphometry was applied to T1-weighted MRI in atlas-defined early, ventral and dorsal visual regions of interest. Reduced grey matter volume in V1, V2, V3, and V4 was found in ACHM compared to controls, driven by a reduction in cortical surface area as there was no significant reduction in cortical thickness. Cortical surface area (but not thickness) was reduced in a wide range of areas (V1, V2, V3, TO1, V4, and LO1). Reduction in early visual areas with large foveal representations (V1, V2, and V3) suggests that the lack of foveal input to the visual cortex was a major driving factor in morphological changes in ACHM. However, the significant reduction in ventral area V4 coupled with the lack of difference in dorsal areas V3a and V3b suggest that deprivation of chromatic signals to visual cortex in ACHM may also contribute to changes in cortical morphology. This research shows that the congenital lack of cone input to the visual cortex can lead to widespread structural changes across multiple visual areas.

Cortical morphology and illness insight in patients with schizophrenia

Insight into illness in schizophrenia (SZ) patients has a major impact on treatment adherence and outcome. Previous studies have linked distinct deviations of brain structure to illness insight, specifically in frontoparietal and subcortical regions. Some of these abnormalities are thought to reflect aberrant cortical development. In this study, we used cross-sectional data to examine associations between illness insight and two cortical surface markers that are known to follow distinct neurodevelopmental trajectories, i.e. cortical gyrification (CG) and thickness (CT). CG and CT was investigated in SZ patients (n = 82) and healthy controls (HC, n = 48) using 3 T structural magnetic resonance imaging. Illness insight in SZ patients was measured using the OSSTI scale, an instrument that provides information on two distinct dimensions of illness insight, i.e. treatment adherence (OSSTI-A) and identification of disease-related symptoms (OSSTI-I). CT and CG were computed using the Computational Anatomy Toolbox (CAT12). Whole-brain and regions-of-interest (ROI)-based analyses were performed. SZ patients showed higher CG in anterior cingulate, superior frontal and temporal gyrus and reduced CG in insular and superior frontal cortex when compared to HC. SZ patients showed decreased CT in pre- and paracentral, occipital, cingulate, frontoparietal and temporal regions. Illness insight in SZ patients was significantly associated with both CG and CT in the left inferior parietal lobule (OSSTI-A) and the right precentral gyrus (CG/OSSTI-A, CT/OSSTI-I). The data support a multi-parametric neuronal model with both pre- and postnatal brain developmental factors having an impact on illness insight in patients with SZ.

Evidence from imaging resilience genetics for a protective mechanism against schizophrenia in the ventral visual pathway

Recently, the first genetic variants conferring resilience to schizophrenia have been identified. However, the neurobiological mechanisms underlying their protective effect remain unknown. Current models implicate adaptive neuroplastic changes in the visual system and their pro-cognitive effects in schizophrenia resilience. Here, we test the hypothesis that comparable changes can emerge from schizophrenia resilience genes. To this end, we used structural magnetic resonance imaging to investigate the effects of a schizophrenia polygenic resilience score (PRSResilience) on cortical morphology (discovery sample: n=101; UK Biobank replication sample: n=33,224). We observed positive correlations between PRSResilience and cortical volume in the fusiform gyrus, a central hub within the ventral visual pathway. Our findings indicate that resilience to schizophrenia arises partly from genetically mediated enhancements of visual processing capacities for social and non-social object information. This implies an important role of visual information processing for mitigating schizophrenia risk, which might also be exploitable for early intervention studies.

Cortical Morphometric Abnormality and Its Association with Working Memory in Children with Attention-Deficit/Hyperactivity Disorder

Objective Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents. The present study investigated the cortical morphology features and their relationship with working memory (WM).Methods In the present study, a total of 36 medication naïve children with ADHD (aged from 8 to 15 years) and 36 age- and gendermatched healthy control (HC) children were included. The digit span test was used to evaluate WM. The magnetic resonance imaging (MRI) was used to examine the characteristics of cortical morphology. Firstly, we compared the cortical morphology features between two groups to identify the potential structural alterations of cortical volume, surface, thickness, and curvature in children with ADHD. Then, the correlation between the brain structural abnormalities and WM was further explored in children with ADHD.Results Compared with the HC children, the children with ADHD showed reduced cortical volumes in the left lateral superior temporal gyrus (STG) (p=6.67×10-6) and left anterior cingulate cortex (ACC) (p=3.88×10-4). In addition, the cortical volume of left lateral STG was positively correlated with WM (r=0.36, p=0.029).Conclusion Though preliminary, these findings suggest that the reduced cortical volumes of left lateral STG may contribute to the pathogenesis of ADHD and correlate with WM in children with ADHD.