The evolutionary and cellular bases of human brain organization: an integrative approach with implications for late life aging
Date of Award
Spring 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Psychology
First Advisor
Holmes, Avram
Abstract
The human brain is organized into large-scale, spatially distributed systems consisting of multiple interacting regions. Changes in the brain likely do not occur in silos but across linked regions embedded within circuitries and through engagement between networks. A comprehensive understanding of complex systems such as the human brain requires characterization of the system's architecture across multiple levels of organization from neurons to local circuits, to brain regions, and ultimately large-scale brain networks. Although direct translation between neuroscientific levels has traditionally been a challenge, modern scientific breakthroughs have enabled novel ways to bridge observations across a spectrum of spatial scales. This dissertation incorporates an integrative, multi-scale framework in contributing towards the understanding of brain changes through the timeline of evolution and in human lifespan aging. This comprises of a theoretical review (Chapter 2) that presents support for an integrative perspective of brain evolution, demonstrating that evolutionary pressures have acted not in isolation but across anatomically and functionally coupled networks, followed by two empirical studies (Chapters 3 and 4) which investigate age-related changes of major structural features that support macroscale properties of brain function in the form of underlying white matter tracts, linking findings from neuroimaging, genetics, and single-cell transcriptomics. Specifically, in Chapter 3, we first characterized age-related differences and genetic architecture of structural wiring properties of in vivo brain white matter in a mid-to-older aged large-scale community cohort. Chapter 4 then builds upon these findings through the interrogation of cell type markers of age-related differences in in vivo microstructural properties of brain white matter tracts. Across these three chapters that examine brain changes through different passages of time, we employ an integrative, multiscale lens that combine micro- and macro-scale data, bridging genetics, cell-type composition, neuroanatomical features, and network properties. Finally in the Discussion, we take a prospective look at how cross-modal neurobiological data can be combined with predictive modeling approaches in generating more sensitive markers of brain aging, and going beyond, how this may potentially fit within a broader landscape that integrates across multiple systems in the body.
Recommended Citation
Chin, Rowena, "The evolutionary and cellular bases of human brain organization: an integrative approach with implications for late life aging" (2024). Yale Graduate School of Arts and Sciences Dissertations. 1501.
https://elischolar.library.yale.edu/gsas_dissertations/1501
