The role of prefrontal sulcal morphology and brain network architecture in cognitive development

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PROJECT SUMMARY A distinctive feature of the human brain is the many folds (sulci) in the cortex. Estimates are that 60-70% of the cortex is hidden in sulcal depths. Sulci appear at different time periods in the womb: those that appear early (primary) are hypothesized to be under tighter genetic control, and therefore more similar in location and shape across people, than those that develop later (tertiary). Although modern cognitive neuroscience has largely overlooked these later-developing sulci, for historical and methodological reasons, patterns of tertiary sulci are theorized to have functional significance (Sanides, 1964). Elaborating on this idea, we theorize that sulcal deepening during development pulls cortical regions closer together, which minimizes wiring length and increases the efficiency of local neural signals, which in turn could contribute to improved cognitive functioning. The central hypothesis of this R21 proposal is that the development of tertiary sulci in association cortices has consequences for the development of functional brain architecture and high-level cognition. We propose to test this hypothesis for the first time, focusing on the long overlooked tertiary sulci in lateral prefrontal cortex (latPFC), a brain region implicated in higher-level cognitive capacities such as reasoning. To explore the functional significance of these latPFC sulci, we propose to characterize the relationships between sulcal anatomy, reasoning ability, and functional brain architecture in individual participants. To this end, we will leverage an existing multimodal, longitudinal dataset of 148 participants ages 6-20 that includes anatomical and functional MRI and behavioral measures. In Aim 1a, all latPFC tertiary sulci in both hemispheres of the brain in each individual will be manually defined, as modern automated methods to identify sulci do not include tertiary sulci. Aim 1b is to develop an automated approach to identify all latPFC tertiary sulci that we will share freely with the field. Once the lengthy process of sulcal definition is complete, we will examine whether features of latPFC tertiary sulci develop with age (Aim 2a). We will then test whether individual differences in these features helps to explain and/or predict differences in reasoning ability, measured as a latent factor based on three standardized assessments (Aim 2b). Finally, to relate brain anatomy with brain function, we will test whether individual latPFC tertiary sulci serve as landmarks identifying functional regions during a reasoning task, and whether sulcal- functional relationships are stable or change over development (Aim 3). Theoretically, our proposal advances theories linking the development of neuroanatomical and functional features of latPFC to cognitive development and tests a classic hypothesis. Methodologically, it should yield automated tools to define latPFC tertiary sulci, which could also be applied to other cortical locations in the future. Translationally, as previous studies reported latPFC sulcal anomalies in ADHD, schizophrenia, and bipolar disorder, but did not consider tertiary sulci or examine developmental trajectories, the proposed research will serve as a foundation for future studies of the role of sulcal anatomy in neurodevelopmental disorders.