|Ph.D Student||Bergmann Eyal|
|Subject||From Connectivity to Function: Comparative Analasis of|
Mesoscopic Organization of Mouse and Human
|Department||Department of Medicine||Supervisor||Professor Itamar Kahn|
A fundamental challenge in neuroscience is translating findings from advanced microscopic techniques used in animal models to the non-invasive macroscopic data available in humans. A compelling approach that can bridge the gap between human and non-human brain research is cross-species parallelism, which promotes collection of identical types of data in humans and animal models. A useful method that supports such parallel experiments is functional MRI, and specifically resting-state functional connectivity MRI (fcMRI), which estimates organization of brain networks based on coherent spontaneous fluctuations in the fMRI signal. In this thesis I present a set of experiments that compare the mesoscopic organization of mouse and human brain networks using fcMRI, demonstrating its applications to understanding brain organization as it evolved in mammals, pathology in disease models and the contribution of individual variability to connectivity. Chapter 1 reviews the literature of resting-state functional connectivity, highlighting the advantages and limitations of this technique and setting the stage to the comparative approach developed in this thesis. Chapter 2 describes a cross-species comparison of organization of cortico-hippocampal networks in mice and humans, revealing differential representation of sensory and association networks across species, suggesting a rerouting of sensory information flow to the hippocampus that occurred in the evolution of the brain from rodents to humans. Chapter 3 extends the cross-species comparison to characterize pathological brain development, showing similar mesoscopic alterations in children with the neurodevelopmental disorder neurofibromatosis type 1 and mice with a heterozygous mutation in the Nf1 gene. A posterior-anterior functional connectivity disruption is demonstrated along the cingulate cortex and alterations in corticostriatal connectivity are observed. Homologue disruptions are observed in both species, bridging the gap between known microscopic findings in this mouse model and clinical symptoms in the human patients. Chapter 4 presents a modeling experiment that utilizes the rich structural connectivity data available in mice to characterize the relations between structural and functional connectivity. Then, this gold standard structural connectivity dataset is compared to individual diffusion MRI-based structural and resting-state functional MRI connectivity to examine the role of individuality in structure-function relations and to characterize the advantages and limitations of diffusion-MRI which is commonly used in human brain research. Collectivity, the methods developed, and results presented in this thesis lay the foundation for understanding the principles of mesoscopic brain organization across mice and humans in health and disease. Further, the translation of multiscale findings of brain organization in health and disease across species provides initial understanding on the potential impact of individual variability on brain organization.