An fMRI investigation of trait and state markers in schizophrenia

Several contemporary theories of schizophrenia have implicated different neural networks in the pathophysiology of this disorder, including fronto-temporal circuitry, fronto-thalamo-cerebellar network, as well as cingulate gyrus with interconnected structures. The present thesis was designed to elucidate the precise nature of cerebral dysfunction and determine which parts of the distorted circuitry represent state and which are trait markers of schizophrenia. In order to achieve our goal we performed three experiments using functional magnetic resonance imaging (fMRI) and an "N-back" working memory task. In the Experiment 1 we explored the pattern of cerebral activity in healthy volunteers during performance of the "N-back" task. We observed significant activations and deactivations in a widespread network of areas we were interested in, including prefrontal cortex, thalamus, cerebellum, temporal cortex, as well as anterior and posterior cingulate. These results confirmed that the "N-back" task was well suited to examine cerebral functional anomalies in schizophrenia. In the Experiment 2 we investigated integrity of three circuits implicated in schizophrenia, in clinically stable patience and matched controls. The results revealed that patients exhibited decreased activity in the left dorsolateral prefrontal cortex (DLPFC) and the right cerebellum, increased activity in the left cerebellum, and failure to suppress cingulate gyrus and right superior temporal gyrus, as compared with healthy participants during performance of the "N-back" task. In the Experiment 3 we examined first-episode schizophrenic patients in two different stages of their illness and compared their data with control participants who were also scanned on two occasions, six to eight weeks apart. The results disclosed significant underactivation of the left DLPFC, left thalamus, and right cerebellum in patients relative to controls during both scanning sessions, whereas the function of the right DLPFC, right thalamus, left cerebellum, and posterior cingulate normalized over time with remission of psychotic state. Overall, the present investigation provided evidence that underactivation of the left DLPFC and right cerebellum, represents a stable trait marker of schizophrenia, whereas disturbances of the right DLPFC, left cerebellum, thalamus, and cingulate gyrus are state-related.Medicine, Faculty ofGraduat