Microstructural Characterization of White Matter in Schizophrenia

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DESCRIPTION (provided by applicant): Schizophrenia is a chronic, severe, and disabling disorder that is characterized by hallucinations, delusions, and motor deficits. In addition, cognitive deficits including problems with attention, language, memory, and the executive functions are also associated with the disorder and greatly affect normal day by day functioning of the schizophrenic patients. Pathological, functional, and morphometric studies have implied that the brain abnormalities that are observed in schizophrenia are associated with macro and microstructural alterations of the white matter pathways connecting different brain regions. Models of fronto-temporal disconnectivity have been proposed to explain some of the deficits observed in schizophrenia. Microstructural integrity of white matter has been extensively investigated using diffusion tensor imaging (DTI) techniques and either voxel based morphometry techniques or region of interest approaches. However, findings are rather inconsistent across different studies. Few studies have explored the behavioral correlations of the white matter abnormalities depicted by DTI. The goal of this project is to investigate the microstructure integrity of white matter mater in schizophrenia using both typical DTI measures of microstructural integrity - the mean diffusivity and fractional anisotropy and a new metric - the mean kurtosis, which has shown promise to better discriminate microstructural alterations of white matter. The mean kurtosis will be derived using the Diffusion Kurtosis Imaging technique, a generalization of the DTI formalism. We will also explore the relation between the white matter microstructure and a set of measures describing cognitive function. Two approaches will be undertaken: 1) Voxel based morphometry techniques will be used to explore differences in white microstructure between a group of patients with schizophrenia and a control group of healthy subjects. 2) White matter tractography techniques will be used to segment out the trajectory and extent of the superior longitudinal fasciculus, a white matter tract that connects the prefrontal, temporal, and parietal lobes. Both global and local tract microstructural diffusion measures will be investigated in patients versus the control group. The results of this study may reveal connectivity alterations in specific pathways or brain regions and thereby contribute to the understanding of the mechanisms underlying brain dysfunction in schizophrenia. The study of the white matter pathways connecting the frontal and temporal lobe will also contribute to the understanding of the abnormal fronto-temporal functional connectivity that is generally observed in schizophrenia. PUBLIC HEALTH RELEVANCE: Schizophrenia is a severe mental disorder associated with significant lifelong impairment and high prevalence, affecting more than two millions of people in the United States. This study will investigate the integrity of the white matter pathways that connect functional brain regions responsible for cognitive control. Knowledge of the impaired brain connectivity will provide new insights into the mechanisms that underlie brain dysfunction in schizophrenia and has the potential to improve our ability to better diagnose and assess treatment of this disorder.