Schizophrenia is a serious mental illness with heterogeneous symptoms. Recent neuroimaging studies have suggested that schizophrenic symptoms arise from functional dysintegration in brain network, not from local brain deficits. This study investigates the functional dysintegration in schizophrenia patients using multimodal neuroimaging techniques, integrating functional magnetic resonance imagining (fMRI) and magnetoencephalography (MEG) data collected during spatial working memory task performance. It has been known that schizophrenia patients have deficits in spatial working memory where prefrontal and posterior sensory processing areas should be functionally coordinated. Twelve schizophrenia patients and eleven normal control subjects participated in this study. This study consists of the following four sub-studies; 1) fMRI regional activation study to identify the brain regions involved in spatial working memory and the regions where schizophrenia patients have deficient task-related activations, 2) cortical source MEG study of local gamma energy to identify brain regions where schizophrenia patients have deficient gamma activity, which is an index of functional integration within local brain area, 3) large scale functional connectivity study using temporal correlation analysis of fMRI time-series between regions of interests (ROIs) in the spatial working memory network and interregional gamma phase synchrony analysis of the cortical source MEG signals of the ROIs to identify brain networks showing abnormal functional connectivity during spatial working memory in schizophrenia patients, and 4) association study to investigate the relationships between the fMRI and the cortical source MEG functional connectivity indices and clinical symptoms of schizophrenia. These studies revealed that schizophrenia patients had dysfunctions in prefrontal and posterior association cortices as well as cortico-thlamo-cerebellar system. In addition, they were also found to have local and large-scale functional connectivity deficits in the spatial working memory network. These functional connectivity indices had associations with the spatial working memory task performace. Specific abnormalities in the interregional functional connectivity also showed differential associations with the schizophrenic symptoms, such as positive, negative, and disorganization symptoms. The neurobiological bases of the functional dysintegration syndrome of schizophrenia and the implications of the syndrome in characterizing schizophrenia were discussed.
University of Minnesota Ph.D. dissertation. January 2009. Major: Psychology. Advisors: Angus W. MacDonald III and Scott R. Sponheim. 1 computer file (PDF); ix, 228 pages.
Kang, Seung Suk.
Functional dysintegration syndrome of schizophrenia: a multimodal neuroimaging study..
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