Speaker
Description
The human prefrontal cortex (PFC) plays a central role in cognitive control and emotion regulation, supported by a protracted and heterogeneous maturation across its subregions (e.g., dorsolateral vs. ventromedial, medial vs. lateral) [1, 2]. This intra-PFC variability is a hallmark of its functional specialization [3, 4]. Importantly, the developmental trajectory of the PFC is shaped not only by intrinsic cortical mechanisms but also through dynamic interactions with subcortical structures such as amygdala, thalamus, and basal ganglia [5]. Yet, most current models of brain development remain cortico-centric, frequently overlooking how the timing and strength of subcortical inputs influence the specialization of different PFC subregions. To address this gap, we propose a novel framework for quantifying cortico-subcortical co-maturation using the Wasserstein distance, a metric from optimal transport theory [6]. This approach is designed to measure divergence between normative developmental trajectories of cortical and subcortical regions, enabling a more precise mapping of how subcortical inputs scaffold PFC maturation. We will apply this framework to high-resolution morphometric and diffusion MRI data from large-scale open-access datasets, including the Human Connectome Project – Youth and Young Adult cohorts [7, 8]. Analyses will examine whether mismatches in maturation patterns differentiate PFC subregions. Methodologically, our approach will be compared to existing tools such as MIND (Morphometric INverse Divergence) to assess robustness [9]. Crucially, we will validate anatomical plausibility against the histological BigBrain dataset, focusing on laminar thickness, cytoarchitectural boundaries, and regional differentiation within the PFC [10]. By anchoring MRI-based maturation measures to cellular-scale histology, we aim to ensure that our framework captures biologically meaningful patterns of development. Conceptually, this project contributes a methodological foundation for modeling cortico-subcortical co-development at high spatial resolution. Beyond advancing basic neuroscience, it may provide insights into sensitive developmental periods and mechanisms of neuropsychiatric vulnerability.
Reference:
1. Kolk, S. M. & Rakic, P. Development of prefrontal cortex. Neuropsychopharmacology 47, 41–57 (2022)
2. Sydnor, V. J. et al. Heterochronous laminar maturation in the human prefrontal cortex.
Preprint at https://doi.org/10.1101/2025.01.30.635751 (2025).
3. Deco, G. et al. One ring to rule them all: The unifying role of prefrontal cortex in steering
task-related brain dynamics. Prog. Neurobiol. 227, 102468 (2023)
4. Kringelbach, M. L. & Deco, G. Prefrontal cortex drives the flexibility of whole-brain orchestration of cognition. Curr. Opin. Behav. Sci. 57, 101394 (2024)
5. Chin, R., Chang, S. W. C. & Holmes, A. J. Beyond cortex: The evolution of the human brain. Psychol. Rev. 130, 285–307 (2023).
6. Panaretos, V. M. & Zemel, Y. Statistical Aspects of Wasserstein Distances. Annu. Rev. Stat. Its Appl. 6, 405–431 (2019).
7. Van Essen et al. The Human Connectome Project: A data acquisition perspective. NeuroImage 62 4, pp. 2222-2231 (2012).
8. Somerville et al. The Lifespan Human Connectome Project in Development: A large-scale study of brain connectivity development in 5-21 year olds. Neuroimage 183: 456–468. (2018)
9. Sebenius, I. et al. Robust estimation of cortical similarity networks from brain MRI. Nat. Neurosci. 26, 1461-1471 (2023).
10. Amunts, K. et al. BigBrain: An Ultrahigh-Resolution 3D Human Brain Model. Science 340, 1472–1475 (2013).
