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The neurocognitive correlates of formal thought disorder in schizophrenia Weinstein, Sara


Formal thought disorder is among the pathognomonic symptoms of schizophrenia, presenting as irregularities in the structure of speech that result in disorganized or incoherent discourse. Evidence from neuroimaging and behavioural research indicates abnormalities in semantic, linguistic and executive processing all contribute to the expression of this symptom. Additionally, changes in grey matter volume in regions of cortex supporting these functions, particularly the left posterior superior temporal lobe, correlate with the severity of thought disorder. The program of study this thesis represents was broadly focused, with the goal of increasing our understanding of the neurocognitive basis of this symptom. Thought disorder has the curious quality of displaying severe dysfunction in one language modality, expression, while function in another, reception, is intact. The first study used functional magnetic resonance imaging to investigate the source of this disparity, by assessing brain activation during listening to speech. The second study expanded on the first, incorporating structural magnetic resonance imaging data into a mediation analysis with the functional and symptom data, to test whether increased activation mediates the association between reduced cortical grey matter volume and severity of thought disorder. As evidence increasingly indicates impaired context processing in thought disorder, the third study investigated the impact of symptom severity on the context-dependant automatic and controlled processes contributing to word recognition. Finally, the fourth study assessed sub clinical thought disorder in a high schizotypy sample, to determine if speech disorder is among the cognitive variables in this population that exhibit continuity with schizophrenia. The results indicate that increased cortical activation in the left posterior temporal lobe may underlie preserved receptive language function in thought disorder. A proof-of-principle mediation analysis demonstrated that functional and structural brain abnormalities are interdependent and should be considered as such when investigating the neurophysiology of symptom expression. Deficient processing of linguistic context results in failures in both controlled and automatic processes contributing to word recognition. Finally, the speech abnormalities characterizing thought disorder are not associated with normal variation in schizotypy, indicating they may be predictive of transition to psychotic illness in high risk individuals.

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