Brain activation mediates the association between structural abnormality and symptom severity in schizophrenia.

Thought disorder is a symptom of schizophrenia expressed as disorganized or incoherent speech. Severity of thought disorder correlates with decreased left superior temporal gyrus grey matter volume and cortical activation in posterior temporal regions during the performance of language tasks. The goal of this study was to determine whether language-related activation mediates the association between thought disorder and left superior temporal lobe grey matter volume. 12 patients with schizophrenia were assessed for thought disorder. FMRI images were acquired for each subject while they listened to English speech, along with a high resolution structural image. Thought disorder was used as a covariate in the functional analysis to identify brain regions within which activation correlated with symptom severity. Voxel based morphometry was used to calculate grey matter volume of the planum temporale. A mediation model waste-tested using a four-step multiple regression approach incorporating cortical volume, functional activation and symptom severity. Thought disorder correlated with activation in a single cluster within the left posterior middle temporal gyrus during listening to speech. Grey matter volume within the planum temporale correlated significantly with severity of thought disorder and activation within the functional cluster. Regressing thought disorder on grey matter volume and BOLD response simultaneously led to a significant reduction in the correlation between grey matter volume and thought disorder. These results support the hypothesis that the association between decreased grey matter volume in the left planum temporale and severity of thought disorder is mediated by activation in the posterior temporal lobe during language processing.