טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentZur Gil
SubjectMapping Brain Networks using Structural and Functional MRI:
Methods Development and Feasibility Studies in
Healthy Brain and Tremor Related
Pathologies
DepartmentDepartment of Medicine
Supervisor Professor Itamar Kahn
Full Thesis textFull thesis text - English Version


Abstract

Understanding the pathophysiological changes underlying common human brain disorders fundamentally relies on our ability to characterize the structural and functional changes that take place. Magnetic resonance imaging (MRI) allows to identify mesoscopic changes in humans. While it allows to non-invasively characterize the brain in health and disease, it is still limited in its ability to identify cellular-level pathologies. Therefore, bridging the gap between human imaging and non-human animal models of disease is a fundamental challenge. In this thesis, I present a series of studies that aimed to compare brain organization across species often used to model brain disorders, in comparison to humans. Next, I used MRI to map the structural and functional connectivity changes that occur is tremor disorders in patients undergoing a procedure that aimed to reduce tremors. First, I sought to use functional connectivity MRI to compare brain organization of humans to the macaque monkey and mouse. In this study, I characterized the similarities and differences in mesoscopic brain functional connectivity. Specific analyses detailed the connectivity patterns between the cortex and the hippocampus, striatum and thalamus across these species, revealing the changes that occurred in mammalian evolution in connectivity of the cortex, which underwent massive expansion and elaboration in humans relative to lower mammals. Next, I investiagted the structural and functional changes following thalamotomy in tremor disorders. A connectivity-based approach was used to reveal changes in brain organization before and after treatment in Essential tremor and Parkinson disease. Exploring structural white matter changes, I found that the white matter tract between the motor thalamus and the red nucleus showed permanent long-term damage after the treatment. Furthermore, I found that diffusivity measures of the thalamus predicted tremor improvement following this treatment. Functional connectivity analysis of brain changes revealed a possible compensatory mechanism involving the dentate nucleus, striatal motor regions and supplementary motor cortex. Collectivity, the methods developed, their application, and the use of these methods to characterize the pathophysiology in tremor disorders add to our understanding of principles of mesoscopic brain organization mammals in the intact brain and suggest putative regions underlying tremor pathophysiology.