Unveiling Co-Development of Cortical Surface Area and Thickness Asymmetry in Young Brain

1282 

Abstract Submission 

Xinran Wu¹, Xiangzhen Kong², Lena Palaniyappan³, Gunter Schumann⁴, Jianfeng Feng⁵, Jie Zhang⁶

¹Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, Shanghai, ²Department of Psychology and Behavioral Sciences, Zhejiang University, Zhejiang, China, Hangzhou, Zhejiang, ³Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia, Parkville, Victoria, ⁴Centre for Population Neuroscience and Stratified Medicine (PONS), Fudan University and Charite, Shanghai, Shanghai, ⁵Institute of Science and Technology for Brain inspired Intelligence, Shanghai, Shanghai, ⁶Institute of Science and Technology for Brain-inspired Intelligence (ISTBI), Shanghai, Shanghai

Xinran Wu  
Institute of Science and Technology for Brain-inspired Intelligence, Fudan University
Shanghai, Shanghai

Xiangzhen Kong  
Department of Psychology and Behavioral Sciences, Zhejiang University, Zhejiang, China
Hangzhou, Zhejiang

Lena Palaniyappan  
Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia
Parkville, Victoria

Gunter Schumann  
Centre for Population Neuroscience and Stratified Medicine (PONS), Fudan University and Charite
Shanghai, Shanghai

Jianfeng Feng  
Institute of Science and Technology for Brain inspired Intelligence
Shanghai, Shanghai

Jie Zhang  
Institute of Science and Technology for Brain-inspired Intelligence (ISTBI)
Shanghai, Shanghai

Hemispheric asymmetry is a fundamental aspect of human brain organization (Duboc et al., 2015), yet its developmental processes remain poorly understood. Unique asymmetrical patterns have been identified in cortical surface area (CSA) and cortical thickness (CT) (Kong et al., 2018), and undergoing various developmental changes with age (Roe et al., 2023). Abnormal alterations in asymmetry have been linked to certain neurodevelopmental disorders in adolescents, such as autism (Postema et al., 2019), underscoring the significance of comprehending the asymmetric development of the brain for overall brain health. However, the current study exclusively delineated the trajectories of asymmetry development for different features, and the correlation between the asymmetry development of distinct modalities remains incompletely understood.

This study investigates brain structural asymmetry development, genetic factors, and cognitive/psychiatric associations in youths. We used MRI data from two longitudinal datasets: Adolescent Brain Cognitive Development (ABCD) study (N>11,000, 2 time points: 10 and 12 years) and IMAGEN study (N>2,000, 3 time points: 14, 19, 22 years). Asymmetry indices (AI) from CT, CSA, and subcortical volume were assessed with linear mixed models (LMM) for age-related effects. Cognitive processes associated with CSA and CT asymmetry developmental pattern were determined through a Neurosynth-based meta-analysis. Besides, the associations between AI and cognitive / psychiatric phenotype were investigated using LMM. Finally, genetic association analysis (GWAS), gene enrichment analysis, and temporal expression analysis using BrainSpan dataset were performed on ABCD genetic sequencing data to investigate genetic factors influencing CSA and CT asymmetry and its changing rates (ΔAI) from ages 10 to 12.

Despite baseline CT and CSA AI pattern differences with each other (Fig 1A), CT and CSA asymmetry showed similar developmental trajectories: Frontal and temporal regions exhibited increasing left-lateralization with age (Fig 1B, C), which associated with language and emotion functions (by Neurosynth, Fig 1D, E). Age-related changes in CSA and CT within these regions indicated that asymmetry development was driven by more rapid CSA and CT reduction in the right frontotemporal regions during adolescence than their left homotopic regions. Phenotype association analysis suggested prolonged CT asymmetry development in the superior frontal cortex (less leftward than peers) related to better cognitive function (Fig 2A). Genetic analysis revealed more genes linked to ΔAI than AI, and enrichment analysis revealed the genes influencing both CSA and CT ΔAI primarily associated with neural and synapse development (Fig 2B, C, D); besides, these genes had increased expression upon adolescence (especially in frontal lobe) (Fig2 E).

In summary, this study showed that despite CSA and CT were influenced by distinct developmental and genetic mechanism, a similar co-developmental trajectory still exists between asymmetry of the two different morphological features, primarily in frontotemporal regions. This shared trajectory may result from common biological pathways in adolescent brain like synaptic pruning and dendritic changes affecting both CSA and CT. Leftward development in these regions may underlie advanced cognitive abilities, including language. Prolonged cortical thickness asymmetry growth in superior frontal gyrus correlated with higher cognitive abilities, which might suggest more neural plastic and less inflammation (Tooley, Bassett, & Mackey, 2021) that can preserve neurons and synapses, and finally enhanced brain function. These findings hold important implications for understanding normal and abnormal brain development.

Early life, Adolescence, Aging

Normal Brain Development: Fetus to Adolescence ¹

Cortical Anatomy and Brain Mapping ²

Normal Development

Cortex

Development

Hemispheric Specialization

Morphometrics

MRI

NORMAL HUMAN

PEDIATRIC

Phenotype-Genotype

STRUCTURAL MRI