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dc.contributor.authorTian, Ye
dc.date.accessioned2020-11-27T07:15:25Z
dc.date.available2020-11-27T07:15:25Z
dc.date.issued2020
dc.identifier.urihttp://hdl.handle.net/11343/252677
dc.description© 2020 Ye Tian
dc.description.abstractThe structure, function and connectivity of the human brain are topographically organized. This topographic organization provides profound insight into cortical information processing, representation of mental states, and accounts for individual variation in behavioral traits and cognition. Whereas classical models of brain topography focus on distinct cortical patches defined by discrete boundaries, contemporary evidence from neuroimaging suggests that topographic variation may be better conceptualized in terms of a set of continuous gradients of gradual change that overlap in space. My work aims to reconcile these two conceptualizations of brain topography, particularly with respect to the insular cortex, a topographically complex and functionally heterogeneous cortical lobe whose organization has remained disputed for centuries. Using modern functional neuroimaging techniques, I showed that the insula’s topography is best conceptualized as a continuum of gradual change oriented along an anterior-posterior axis. I found that individual variation in the insula’s functional topography associates with human cognitive and emotional traits as well as somatosensory functions. Having characterized the functional architecture of the insular cortex in healthy adults, my next aim was to investigate whether neuropsychiatric illness is associated with alterations in the insula’s functional organization. To this end, I compared the insula’s functional connectivity gradients between individuals with schizophrenia and healthy controls. I found evidence suggesting subtle reorganization of the insula’s functional topography in schizophrenia. In particular, the connectivity profile along the anterior-posterior topographic axis of the insular cortex was altered and less differentiated in individuals with schizophrenia. I showed that the extent of reorganization of the insula’s functional topography significantly associates with the severity of clinical symptoms, particularly negative symptoms of psychosis and intellectual impairment. Finally, I applied the new methodology that I developed to map the insula’s topography to study other brain regions, including the entire human subcortex. This unveiled four hierarchical scales of subcortical organization, recapitulating well-known anatomical nuclei at the coarsest scale and delineating 27 new bilateral regions at the finest. Based on this work, I developed a new MRI subcortical atlas to enable holistic connectome mapping and characterization of cortico-subcortical circuits. The new subcortex atlas was personalized to account for connectivity differences across individuals and utilized to uncover a reproducible association between subcortical functional connectivity and tobacco use. Overall, this thesis provides fundamental insight into the functional organization of the human insular cortex and subcortex in health and neuropsychiatric illness, particularly focusing on the distinction between classical models of topographic variation based on discrete regions and contemporary representations involving continuous gradients. The new methodology that I developed is not limited to the insular cortex and the subcortex and can be applied to other cortical and subcortical regions in humans as well as other species.
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dc.subjectBrain parcellation
dc.subjectBrain gradients
dc.subjectSubcortex atlas
dc.subjectFunctional connectivity gradients
dc.subjectGradientography
dc.subjectBrain topography
dc.subjectFunctional connectivity
dc.subjectBrain connectome
dc.subjectResting-state fMRI
dc.subjectTask-evoked fMRI
dc.subjectInsular cortex
dc.subjectSubcortical nuclei
dc.subjectSchizophrenia
dc.subjectTobacco use
dc.subjectHuman brain-behaviour relationship
dc.titleTopographic organization of the human insular cortex and subcortex in health and neuropsychiatric illness
dc.typePhD thesis
melbourne.affiliation.departmentPsychiatry
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.affiliation.facultyMelbourne Medical School
melbourne.thesis.supervisornameAndrew Zalesky
melbourne.contributor.authorTian, Ye
melbourne.thesis.supervisorothernameChad Bousman
melbourne.thesis.supervisorothernameChristos Pantelis
melbourne.tes.fieldofresearch1320221 Psychiatry (incl. psychotherapy)
melbourne.tes.fieldofresearch2320902 Cellular nervous system
melbourne.accessrightsOpen Access


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