Functional anatomy of the human forebrain assessed by fluorodeoxyglucose-18 positron emission tomography and coregistered standardized magnetic resonance imaging in normal subjects and patients with schizophrenia

This dissertation develops and validates novel morphometric methodology and uses it to examine structural and functional changes in the elements of the prefronto-striato-pallido-thalamo-cortical pathways in schizophrenia. There is evidence to suggest that schizophrenia may result from disturbances in these pathways.; The study has generated a new method for the neuroanatomical standardization of the basal forebrain suited for functional image coregistration and morphometric analysis. This has been tested for reliability and applied to a cohort of normal subjects and unmedicated, carefully diagnosed age-matched schizophrenic subjects to assess basal forebrain morphology and metabolism.; Evaluation of cortical/subcortical metabolic relationships has revealed that the normal dorsoventral topography of fronto-striatal connectivity is missing in schizophrenics. There are also structural differences in the anterior segments of the major striatal structures that parallel the metabolic differences, which also correlate with cognitive task performance. Lastly, observed metabolic decreases in ventral frontostriatal structures are consistent with this theory.; Together, these differences provide strong evidence for fronto-striatal involvement in schizophrenic symptomatology. The evidence generated from this study is discussed in the light of evidence derived from previous developmental, neuropharmacological, neuroanatomical and functional imaging studies in schizophrenia.