Anatomical Connectivity Profile Development Constrains Medial-lateral Topography in the dlPFC

2209 

Abstract Submission 

Wen Li^1,2, Lingzhong Fan³, Tianzi Jiang¹

¹Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, Beijing, ²Research Center for Augmented Intelligence, Zhejiang Lab, Hangzhou, China, ³Brainnetome Center, Institute of Automation, Chinese Academy of Science, Beijing, China

Wen Li  
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences|Research Center for Augmented Intelligence, Zhejiang Lab
Beijing, Beijing|Hangzhou, China

Lingzhong Fan  
Brainnetome Center, Institute of Automation, Chinese Academy of Science
Beijing, China

Tianzi Jiang  
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences
Beijing, Beijing

The prefrontal cortex (PFC) is a highly variable, evolutionarily expanded brain region that is engaged in multiple cognitive processes [1,2]. The subregions of the PFC mature relatively late compared with other brain regions [3], and the maturation times vary between these subregions. Among these, the dorsomedial and dorsolateral prefrontal cortex (dmPFC and dlPFC) share a parallel topographic pattern of functional connectivity while participating in different types of complex behaviors [4]. However, the developmental trajectories of the two areas remain obscure. In this study, we uncovered differences in the developmental trends of the dmPFC and dlPFC. These differences were mainly caused by structural and functional changes in the medial area of the superior frontal gyrus (SFG). The developmentally different arealization patterns were verified using multiple parcellation approaches with multimodal data and a publicly available transcriptomic dataset. Human brain gene expression data was also used to perform downstream analyses, which could inform us about the potential biological mechanisms underlying the developmentally different arealizations. Furthermore, behavioral analyses hinted at the effects of regionalization on ontogeny. In brief, this study revealed a tendency toward a medial-lateral prefrontal division and can provide a fuller understanding of the potential underlying genetic underpinnings as well as of the potential effects on developmental behavior.

The data used in this article were from HCP-D [5] and IMAGEN [6]. After preprocessing, the dMRI data were used for the parcellation, and multimodal data were used to verify the appropriate patterns (Fig. 1A). Differential gene analysis and gene enrichment analysis were performed to further explore whether subregion division is associated with genetic mechanism and to discover its biological fundamentals (Fig. 1B). The relationship between gene expression and connections was explored using PLS regression (Fig. 1C). Finally, how the functional connections affect behavior was also investigated (Fig. 1D). The detailed description is as follows.

Childhood and adolescence are two periods with extensive cortical maturation in the PFC, causing cortical patterning to be substantially dynamic across the developmental stages and shaped by the interplay of intrinsic and extrinsic mechanisms. In the present study, we delineated the human cortical parcellation trajectory of the SFG based on anatomical connectivity profiles. Specifically, we found that the A9 region separated into medial and lateral subregions with the advent of adulthood (Fig. 2A), as validated by several cohorts with multi-modal data that included cortical thickness, functional connectivity patterns, cytoarchitectonic maps, and transcriptional profiles. This separation revealed by connectivity contrasts may occur gradually with age, reaching a specific boundary at the transition from adolescence to young adulthood (Fig. 2B). Accordingly, we found that the differential gene expression patterns between the areas that showed a tendency to segregate originated in toddlers and widened increasingly distinctly during adolescence (Fig. 2C). These changes may be involved in the process of medial-lateral differentiation in the dorsal PFC (Fig. 2D). In addition, the transformation of connectivity patterns appears to influence development and behavior that is mostly concerned with a young person's persistence and the degree to which they show non-impulsiveness (Fig. 2E).

In this study, we provided a detailed version of a developmental atlas that depicts the changes in the arealization pattern of the frontal lobe and focused on the different developmental trajectories for the dorsomedial and dorsolateral prefrontal cortices, which are mediated by genetically constrained structural and functional connectivity patterns and should have an impact on changes in children's behavior.

Transcriptomics

Normal Brain Development: Fetus to Adolescence ²

Connectivity (eg. functional, effective, structural)

Cortical Anatomy and Brain Mapping

Brain Atlases ¹

Atlasing

Computational Neuroscience

Cortex

Development

MRI