General Psychopathology, Cognition, and the Cerebral Cortex in 10-Year-Old Children: Insights From the Adolescent Brain Cognitive Development Study

General psychopathology and cognition are likely to have a bidirectional influence on each other. Yet, the relationship between brain structure, psychopathology, and cognition remains unclear. This brief report investigates the association between structural properties of the cerebral cortex [surface area, cortical thickness, intracortical myelination indexed by the T1w/T2w ratio, and neurite density assessed by restriction spectrum imaging (RSI)] with general psychopathology and cognition in a sample of children from the Adolescent Brain Cognitive Development (ABCD) study. Higher levels of psychopathology and lower levels of cognitive ability were associated with a smaller cortical surface area. Inter-regionally—across the cerebral cortex—the strength of association between an area and psychopathology is strongly correlated with the strength of association between an area and cognition. Taken together, structural deviations particularly observed in the cortical surface area influence both psychopathology and cognition.

Surface area in the insula was associated with 28-month functional outcome in first-episode psychosis

Many studies have tested the relationship between demographic, clinical, and psychobiological measurements and clinical outcomes in ultra-high risk for psychosis (UHR) and first-episode psychosis (FEP). However, no study has investigated the relationship between multi-modal measurements and long-term outcomes for >2 years. Thirty-eight individuals with UHR and 29 patients with FEP were measured using one or more modalities (cognitive battery, electrophysiological response, structural magnetic resonance imaging, and functional near-infrared spectroscopy). We explored the characteristics associated with 13- and 28-month clinical outcomes. In UHR, the cortical surface area in the left orbital part of the inferior frontal gyrus was negatively associated with 13-month disorganized symptoms. In FEP, the cortical surface area in the left insula was positively associated with 28-month global social function. The left inferior frontal gyrus and insula are well-known structural brain characteristics in schizophrenia, and future studies on the pathological mechanism of structural alteration would provide a clearer understanding of the disease.

Correlations between sleep disturbance and brain cortical morphometry in healthy children

Background While the importance of adequate sleep duration to normal brain development is well known, more studies are needed to characterize how undiagnosed sleep disturbance other than suboptimal sleep duration may impact brain development. In this study we aim to understand the relationships between sleep disturbance measures and cortical morphometry in typically-developing children without previous diagnoses of sleep pathology. Methods Healthy 8-year-old children (30 boys, 37 girls) without clinical diagnosis of sleep disorders were prospectively recruited for brain MRI and their parents completed the Children’s Sleep Habits Questionnaire (CSHQ). Total sleep disturbance score, as well as 8 subscales including bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night waking, parasomnias, sleep disordered breathing, and daytime sleepiness were calculated, and their relationships with cortical morphometry features including cortical gray matter volume, cortical thickness, and surface area were investigated, controlled for total cortical volume and sex. Results The CSHQ total sleep disturbance score significantly correlated with cortical surface area in a cluster in the left middle temporal gyrus (P < 0.001, R = -0.54). In addition, the bedtime resistance subscale negatively correlated with cortical surface area in a cluster in the right fusiform gyrus (P < 0.001, R = -0.50). No other clusters showed significant relationships between CSHQ total score or subscales and cortical features for this cohort. Conclusion Significant relationships between sleep disturbance scores in typically-developing children without clinical diagnosis of sleep pathology and their brain cortical surface area in two temporal lobe regions were identified, suggesting that undiagnosed sleep disturbance may potentially impact brain development even in healthy children.

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.

Parental Educational Attainment, the Superior Temporal Cortical Surface Area and Reading Ability among American Children: A Test of Marginalization-Related Diminished Returns

Background: Recent studies have shown that parental educational attainment is associated with a larger superior temporal cortical surface area associated with higher reading ability in children. Simultaneously, the marginalization-related diminished returns (MDRs) framework suggests that, due to structural racism and social stratification, returns of parental education are smaller for black and other racial/ethnic minority children compared to their white counterparts. Purpose: This study used a large national sample of 9–10-year-old American children to investigate associations between parental educational attainment, the right and left superior temporal cortical surface area, and reading ability across diverse racial/ethnic groups. Methods: This was a cross-sectional analysis that included 10,817 9–10-year-old children from the Adolescent Brain Cognitive Development (ABCD) study. Parental educational attainment was treated as a five-level categorical variable. Children’s right and left superior temporal cortical surface area and reading ability were continuous variables. Race/ethnicity was the moderator. To adjust for the nested nature of the ABCD data, mixed-effects regression models were used to test the associations between parental education, superior temporal cortical surface area, and reading ability overall and by race/ethnicity. Results: Overall, high parental educational attainment was associated with greater superior temporal cortical surface area and reading ability in children. In the pooled sample, we found statistically significant interactions between race/ethnicity and parental educational attainment on children’s right and left superior temporal cortical surface area, suggesting that high parental educational attainment has a smaller boosting effect on children’s superior temporal cortical surface area for black than white children. We also found a significant interaction between race and the left superior temporal surface area on reading ability, indicating weaker associations for Alaskan Natives, Native Hawaiians, and Pacific Islanders (AIAN/NHPI) than white children. We also found interactions between race and parental educational attainment on reading ability, indicating more potent effects for black children than white children. Conclusion: While parental educational attainment may improve children’s superior temporal cortical surface area, promoting reading ability, this effect may be unequal across racial/ethnic groups. To minimize the racial/ethnic gap in children’s brain development and school achievement, we need to address societal barriers that diminish parental educational attainment’s marginal returns for middle-class minority families. Social and public policies need to go beyond equal access and address structural and societal barriers that hinder middle-class families of color and their children. Future research should test how racism, social stratification, segregation, and discrimination, which shape the daily lives of non-white individuals, take a toll on children’s brains and academic development.

Variations in structural MRI quality significantly impact commonly used measures of brain anatomy

Subject motion can introduce noise into neuroimaging data and result in biased estimations of brain structure. In-scanner motion can compromise data quality in a number of ways and varies widely across developmental and clinical populations. However, quantification of structural image quality is often limited to proxy or indirect measures gathered from functional scans; this may be missing true differences related to these potential artifacts. In this study, we take advantage of novel informatic tools, the CAT12 toolbox, to more directly measure image quality from T1-weighted images to understand if these measures of image quality: (1) relate to rigorous quality-control checks visually completed by human raters; (2) are associated with sociodemographic variables of interest; (3) influence regional estimates of cortical surface area, cortical thickness, and subcortical volumes from the commonly used Freesurfer tool suite. We leverage public-access data that includes a community-based sample of children and adolescents, spanning a large age-range (N = 388; ages 5–21). Interestingly, even after visually inspecting our data, we find image quality significantly impacts derived cortical surface area, cortical thickness, and subcortical volumes from multiple regions across the brain (~ 23.4% of all areas investigated). We believe these results are important for research groups completing structural MRI studies using Freesurfer or other morphometric tools. As such, future studies should consider using measures of image quality to minimize the influence of this potential confound in group comparisons or studies focused on individual differences.

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers—the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown.We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48 % male) derived from 15 distinct MRI scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers – the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Parental Education, Household Income, and Cortical Surface Area among 9–10 Years Old Children: Minorities’ Diminished Returns

Introduction: Although the effects of parental education and household income on children’s brain development are well established, less is known about possible variation in these effects across diverse racial and ethnic groups. According to the Minorities’ Diminished Returns (MDRs) phenomenon, due to structural racism, social stratification, and residential segregation, parental educational attainment and household income show weaker effects for non-White than White children. Purpose: Built on the MDRs framework and conceptualizing race as a social rather than a biological factor, this study explored racial and ethnic variation in the magnitude of the effects of parental education and household income on children’s whole-brain cortical surface area. Methods: For this cross-sectional study, we used baseline socioeconomic and structural magnetic resonance imaging (sMRI) data of the Adolescent Brain Cognitive Development (ABCD) study. Our analytical sample was 10,262 American children between ages 9 and 10. The independent variables were parental education and household income. The primary outcome was the children’s whole-brain cortical surface area. Age, sex, and family marital status were covariates. Race and ethnicity were the moderators. We used mixed-effects regression models for data analysis as participants were nested within families and study sites. Results: High parental education and household income were associated with larger children’s whole-brain cortical surface area. The effects of high parental education and high household income on children’s whole-brain cortical surface area were modified by race. Compared to White children, Black children showed a diminished return of high parental education on the whole-brain cortical surface area when compared to White children. Asian American children showed weaker effects of household income on the whole-brain cortical surface area when compared to White children. We could not find differential associations between parental education and household income with the whole-brain cortical surface area, when compared to White children, for non-Hispanic and Hispanic children. Conclusions: The effects of parental educational attainment and household income on children’s whole-brain cortical surface area are weaker in non-White than White families. Although parental education and income contribute to children’s brain development, these effects are unequal across racial groups.