Functional imaging studies of executive-attention in humans: comparing healthy subjects and patients with neuropsychiatric disorders

One of the major goals of cognitive neuroscience is to better understand the psychological and neural bases of human executive-attention. Executive or supervisory attention refers to a collection of higher-order cognitive functions whose primary contribution to behavior is to support controlled information processing and action. The capacity to control attention is essential for our adaptive interaction with the environment because it allows flexibility in our responses to ever changing situational contexts and demands. Executive-attention processes therefore play a unique role in shaping the human experience. Use of three-dimensional functional neuroimaging has fast become the empirical standard for investigating how executive-attention is implemented in the human brain. Most recently, emphasis has been placed on the use of these techniques to parse discrete components of a putative neural network relating to action-monitoring and cognitive control processes of the medial and lateral prefrontal cortex. This work has relied heavily on the use of popular experimental paradigms such as the Stroop task and their unique capacity to challenge such processes in humans. These tasks have also been especially useful for conceptualizing the nature of higher-cognitive dysfunction in complex brain disorders such as schizophrenia. The focus of this thesis concerns a novel application of the Stroop paradigm and functional imaging approach to examine executive-attention performance in healthy subjects and patients with schizophrenia and obsessive-compulsive disorder. On one hand, this work aimed to address current ideas on the nature of executive-control mechanisms and how they may be compromised in these two common psychiatric disorders. On the other hand, this work aimed to examine important conceptual and methodological issues associated with functional imaging approaches to the study of higher-cognition and cognitive psychopathology in humans. In line with connectionist models of executive-attention phenomena, the first study in this thesis investigated the effects of task practice on a larger-scale neurocognitive network associated with performance of the Stroop task in healthy subjects. This study involved the use of a novel methodological approach to model physiological covariances or 'functional connectivity' in PET data, which generated previously unseen and interesting insights into the neural basis of Stroop phenomena, whilst complimenting existing ideas on the role of the anterior cingulate and lateral prefrontal cortex in mediating executive-control functions. These findings were then extended to a comparative study of patients with schizophrenia and obsessive-compulsive disorder. This study largely corroborated previous reports of prefrontal executive dysfunction in schizophrenia, although patients also showed evidence for a compensatory strengthening of connectivity in a fronto-parietal network that accompanied task practice. This finding has important implications for existing models of higher-cognitive dysfunction and abnormal brain integration in schizophrenia. For patients with OCD compared to healthy subjects, performance of the Stroop task evoked a pattern of abnormal connectivity among predominantly corticostriatal regions, including a previously reported hyperfunction of the dorsal anterior cingulate cortex. While this latter result has been linked to a specific disturbance of action-monitoring in patients with OCD, the current study suggests that this may map onto a more extensive corticostriatal network abnormality in line with current theoretical models of this illness. One caveat raised in the first study of patients with schizophrenia concerned the effects of illnesschronicity and medication on functional imaging studies of higher-cognition and prefrontal function in schizophrenia. To address this, a second clinical study was undertaken in patients with a first-episode of schizophrenia (diagnosis confirmed at follow-up) who were examined before and after commencing antipsychotic treatment. Overall, the findings from this study support the idea of trait-like disturbances of prefrontal executive function in schizophrenia; however, they also suggested that aspects of this disturbance may be specific to the critical, early stage of illness - implicating progressive changes with illness chronicity and/or treatment intervention. These findings are discussed in relation to the developmental context of cognitive psychopathology in schizophrenia.