Structural Development of Early Emerging Sulcal Folds During the First Year of Human Life

1290 

Abstract Submission 

Sarah Tung¹, Xiaoqian Yan², Bella Fascendini³, Christina Tyagi¹, Charleny Martinez Reyes¹, Keithan Ducre¹, Karla Perez¹, Ahmad Allen¹, Juliet Horenziak¹, Hua Wu⁴, Vaidehi Natu¹, Kalanit Grill-Spector^1,5

¹Psychology Department, Stanford University, Stanford, USA, ²Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China, ³Department of Psychology, Princeton University, Princeton, USA, ⁴Center for Cognitive and Neurobiological Imaging, Stanford, USA, ⁵Wu Tsai Neurosciences Institute, Stanford University, Stanford, USA

Sarah Tung  
Psychology Department, Stanford University
Stanford, USA

Xiaoqian Yan  
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University
Shanghai, China

Bella Fascendini  
Department of Psychology, Princeton University
Princeton, USA

Christina Tyagi  
Psychology Department, Stanford University
Stanford, USA

Charleny Martinez Reyes  
Psychology Department, Stanford University
Stanford, USA

Keithan Ducre  
Psychology Department, Stanford University
Stanford, USA

Karla Perez  
Psychology Department, Stanford University
Stanford, USA

Ahmad Allen  
Psychology Department, Stanford University
Stanford, USA

Juliet Horenziak  
Psychology Department, Stanford University
Stanford, USA

Hua Wu  
Center for Cognitive and Neurobiological Imaging
Stanford, USA

Vaidehi Natu  
Psychology Department, Stanford University
Stanford, USA

Kalanit Grill-Spector  
Psychology Department, Stanford University|Wu Tsai Neurosciences Institute, Stanford University
Stanford, USA|Stanford, USA

Cortical folding varies widely among mammals and is particularly pronounced in human brains [1]. Sulcal deepening begins in utero and continues in the first two years of life [2]. It has been hypothesized that sulci deepen to accommodate for cortical expansion. However, how early emerging sulcal folds deepen during infancy remains largely unknown. Here, we examined how early emerging sulcal folds deepen in the first year of human life and whether sulcal deepening is associated with changes in (1) macrostructural features such as curvature, surface area, and cortical thickness, and (2) microstructural tissue properties in gray and adjacent white matter such as increases in tissue microstructure associated with myelination [3, 4].

We used MRI to measure T1- and T2-weighted anatomicals and quantitative MRI to measure relaxation rate (R₁) in 43 infants over 87 session (27 infants are longitudinal) in newborns (n=27, 10 females, M= 29.1 days, SD=9.9 days), 3-month-olds (n=27, 14 females, M=105.8 days, SD=18.6 days), 6-month-olds (n= 22, 10 females, M=189.3 days, SD=15.8 days), and 1-year-olds (n=11, 4 females, M=385.1 days, SD=16.9 days). Higher R₁ indicates higher tissue density and a more developed cortex. To test sulcal development, we analyzed 12 sulcal folds that emerge in utero between 16 - 31 gestational weeks [5], distributed across the cortical surface (Fig 1A). We used the adult average FreeSurfer brain and cortex-based alignment to identify each sulcal fold in every individual infant's brain and age (Fig 1B). We validated the reliability of automated sulcal fold identification by comparing the accuracy of automated versus hand-drawn sulci using dice coefficients. We found no significant age-related effect of dice coefficient (3-way ANOVA, with factors: age, hemisphere, and sulcus, no main effect of age: F=0.20, p=0.90, sulcus: F=0.73, p=0.70, or hemisphere: F=1.04, p=0.31). Then, in each individual sulcus, we measured the average sulcal depth, surface area, thickness, curvature, and R₁. Using linear mixed models (LMMs), we quantified the development of sulci as a function of age and tested if sulcal deepening is significantly related to macro- and microstructural properties.

Our study revealed five main findings: First, all sulcal folds significantly deepen in the first year of life, except for the calcarine sulcus, which remains unchanged (Fig 1C). Second, early emerging sulci are deeper at birth than later emerging sulci, but deepen more slowly after birth (Fig 1I,O). Third, surface area and cortical thickness increase with age (Fig 1D,E), but all sulci become less concave (Fig 1F). Fourth, R₁ linearly increases in both gray and white matter in all sulci, with R₁ being larger at birth in gray matter than in white matter (Fig 1G,H). However, this pattern reverses after birth, whereby the rate of R₁ development in white matter is higher than that in gray matter (Fig 1M,N). Together, these data suggest heterogenous development of macro- and microstructural properties in these sulci. LMMs relating sulcal depth with macro- and microstructural properties revealed that a linear combination of surface area, curvature, thickness, and R₁ best predict sulcal depth across the first year of life (R²=0.78; AIC= 2150). This combined model demonstrated a significant positive relationship between sulcal depth and R₁ (β=2.08; p=0.0005), thickness (β=0.248, p=0.005), surface area (β=0.0008, p<0.0001), and a negative relationship with curvature (β=-6.09, p=6.46x10-6).

Our results indicate that there are differential developments in macro- and microstructural properties of early emerging sulcal folds of the human brain. Mechanistically, we propose that cortical expansion, characterized by changes in surface area, thickness, and curvature, and microstructural tissue growth contribute to sulcal deepening during the first year of human life.

Normal Brain Development: Fetus to Adolescence ¹

Cortical Anatomy and Brain Mapping ²

Development

MRI

Myelin

STRUCTURAL MRI

Vision

White Matter