Microstructural development of the brain: Towards understanding the origins of higher-order cognition

• Applicant: Casey Paquola, Ph.D.
• Subject Area: Human Cognitive and Systems Neuroscience
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 524408221

Cognitive neuroscience has extensively focused on outlining where in the brain activity is associated with specific cognitive states. However, this work leaves open important questions concerning how brain regions contribute to cognition. In this project, I aim to characterise how microstructure and connectivity of functional brain networks support higher-order cognition, thereby contributing to mechanistic explanations of human intelligence. Neuroanatomical properties can be correlated with cognitive processes by observing healthy adult brains, but it remains difficult to ascertain the underlying causal relationships. To address this challenge, we will use childhood development to probe the temporal relations between neuroanatomy and cognition. Notably, throughout childhood, profound changes in brain structure and function accompany the acquisition or improvement of cognitive skills (e.g. multi-tasking or theory of mind). Thus, this project aims to determine which neuroanatomical properties are essential to the emergence of specific cognitive faculties. My team and I will advance three interdependent lines of research: First, we aim to fill a gap in the literature concerning neurodevelopment of cortical microstructures. Studies typically depend on histology to measure cortical microstructure, however sample sizes available for human post-mortem analysis, especially of youth, are limited. Building on recent advances in magnetic resonance imaging (MRI), we will develop image processing pipelines that quantify microstructural differences, based on learning the correlation between MRI and histology. Achieving this goal will enable us to capitalise on large open datasets of MRI to track microstructural development across infants and children. Second, we will investigate individual variation in microstructural neurodevelopment, enabling specific links to be drawn between person-specific neuroanatomy and cognition. In particular, we will examine first episode psychosis; depicting how abnormalities in microstructural neurodevelopment can predate the emergence of a cognitive disorder. In doing so, we aim to highlight potential dependencies between developmental neuroanatomy and healthy higher-order cognition. Finally, we will model neural mechanisms that support cognition by characterising the orchestrated activity of microstructurally-distinct brain areas. Specifically, we aim to leverage developmental cohorts to show how neuroanatomical properties can account for the maturation of specific cognitive skills during youth. Altogether, this work will help to establish the anatomical building blocks of higher-order cognitive processes, relevant to further understanding the implementation of human intelligence as well as its disturbance in disease states.

• DFG Programme: Independent Junior Research Groups
• International Connection: Canada
• Cooperation Partner: Professor Boris Bernhardt, Ph.D.