Structural and functional magnetic resonance imaging of the cerebellum in schizophrenia and bipolar disorder

Functional imaging research in the past two decades has provided evidence that the cerebellum is involved in functions apart from pure motor processing. Studies of such cognitive tasks as language generation, shifting attention, and non-motor learning, all produce increased metabolic activity in portions of the cerebellum. This information has lead investigators to reconsider the meaning behind earlier reports of structural abnormalities of the cerebellum in patients with psychiatric diagnoses. New research into this area has produced varied findings at the structural level, while only limited functional imaging research has focused on the cerebellum and its role in psychiatric illness. The main goal of this dissertation is to apply multiple neuroimaging techniques to examine the role of the cerebellum in relation to symptoms of psychosis. Magnetic Resonance Imaging (MRI) technology, was used to identify changes in the cerebellum of patients with schizophrenia and bipolar disorder. High-resolution structural T1*-weighted images coupled with segmentation and 3-D reconstruction software provided a measure of tissue change in individual compartments of the cerebellum. This analysis showed that patients (1) had less cerebellar hemisphere volume asymmetry than comparison subjects, and (2) reduced volume of the neovermis. In addition, Blood-Oxygen-Level Dependent functional MRI (BOLD fMRI) techniques in combination with cognitive challenge paradigms elicited information about the metabolic state and functional capacity of cerebellar tissue. These studies addressed the specific function of the cerebellum in human behavior. To test the hypothesis that the primary function of the cerebellum is to search for appropriate responses to stimuli, paradigms that involve searching for an appropriate response within the language and visuo-spatial domain were used. During performance of these tasks, the patients produced (1) less cerebellar activation than comparison subjects. Patients (2) did not produce right lateralized activation of the superior cerebellum as observed in the comparison subjects during a stem-completion task, (3) nor did they have the opposite lateralization of activation of the inferior hemisphere seen in comparison subjects during a picture-completion task. Patients also (4) failed to activate the cerebellum during a sentence completion task, while comparison subjects produced bilateral activation. Eye-tracking was performed throughout both tasks providing a complete record of subjects' fixation locations.