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Limbic and paralimbic cortex dysfunction during salient stimulus processing in schizophrenia Laurens, Kristin Robyn

Abstract

Schizophrenia is characterised by difficulties in processing and responding to incoming information. Accumulating evidence suggests that the core problem may represent a difficulty in focusing limited processing resources on salient exogenous stimuli so that an appropriate response to the stimuli can be performed. The present thesis comprises four event-related functional magnetic resonance imaging experiments that are designed to elucidate the neural sites that support the processing of salient exogenous stimuli in healthy individuals, and further, to characterise functional abnormality present during salient stimulus processing by patients with schizophrenia. Experiment One characterises the neural response elicited in healthy participants and patients during the processing of infrequent target stimuli that prescribe a subsequent motor response (Part A) and during the processing of infrequent novel stimuli that automatically reorient processing resources away from the ongoing target detection task (Part B). Experiment Two elucidates the supramodal network of brain areas that supports the processing of frequent target stimuli presented in the auditory and visual modalities in healthy participants. The auditory version of that task is subsequently employed in Experiment Three to compare the healthy participant and patient response during frequent target stimulus processing. Finally, Experiment Four examines the brain response evoked in healthy participants and patients when salient stimuli are processed incorrectly and an error ensues. The results demonstrate that, in healthy participants, a distributed corticolimbic network of brain areas is active during the processing of salient exogenous events. This network incorporates limbic cortex (i.e., amygdala-hippocampus), paralimbic cortex in the cingulate gyrus and frontal operculum, frontoparietal association cortex, and subcortical structures in the basal ganglia, thalamus, midbrain, and cerebellum. The network is particularly engaged during the processing of stimuli that signal the need to perform an overt behavioural response. Despite relatively preserved behavioural performance on all tasks, patients with schizophrenia were characterised by functional abnormality throughout the corticolimbic network during both accurate and inaccurate (i.e., erroneous) salient stimulus processing. Particular abnormality was apparent in limbic and paralimbic cortex. Dysfunction within the corticolimbic network during information processing in schizophrenia suggests that there may be insufficient biasing of limited resources to processing salient features of the environment.

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