Martha E. Shenton

We examined the status of the neural network mediating the default mode of brain function, which typically exhibits greater activation during rest than during task, in patients in the early phase of schizophrenia and in young first-degree relatives of persons with schizophrenia. During functional MRI, patients, relatives, and controls alternated between rest and performance of working memory (WM) tasks. As expected, controls exhibited task-related suppression of activation in the default network, including medial prefrontal cortex (MPFC) and posterior cingulate cortex/precuneus. Patients and relatives exhibited significantly reduced task-related suppression in MPFC, and these reductions remained after controlling for performance. Increased task-related MPFC suppression correlated with better WM performance in patients and relatives and with less psychopathology in all 3 groups. For WM task performance, patients and relatives had greater activation in right dorsolateral prefrontal cortex (DLPFC) than controls. During rest and task, patients and relatives exhibited abnormally high functional connectivity within the default network. The magnitudes of default network connectivity during rest and task correlated with psychopathology in the patients. Further, during both rest and task, patients exhibited reduced anticorrelations between MPFC and DLPFC, a region that was hyperactivated by patients and relatives during WM performance. Among patients, the magnitude of MPFC task suppression negatively correlated with default connectivity, suggesting an association between the hyperactivation and hyperconnectivity in schizophrenia. Hyperactivation (reduced task-related suppression) of default regions and hyperconnectivity of the default network may contribute to disturbances of thought in schizophrenia and risk for the illness.

BACKGROUND: Data from postmortem, CT, and magnetic resonance imaging (MRI) studies indicate that patients with schizophrenia may have anatomical abnormalities of the left temporal lobe, but it is unclear whether these abnormalities are related to the thought disorder characteristic of schizophrenia. METHODS: We used new MRI neuroimaging techniques to derive (without knowledge of the diagnosis) volume measurements and three-dimensional reconstructions of temporal-lobe structures in vivo in 15 right-handed men with chronic schizophrenia and 15 matched controls. RESULTS: As compared with the controls, the patients had significant reductions in the volume of gray matter in the left anterior hippocampus-amygdala (by 19 percent [95 percent confidence interval, 3 to 36 percent]), the left parahippocampal gyrus (by 13 percent [95 percent confidence interval, 3 to 23 percent], vs. 8 percent on the right), and the left superior temporal gyrus (by 15 percent [95 percent confidence interval, 5 to 25 percent]). The volume of the left posterior superior temporal gyrus correlated with the score on the thought-disorder index in the 13 patients evaluated (r = -0.81, P = 0.001). None of these regional volume decreases was accompanied by a decrease in the volume of the overall brain or temporal lobe. The volume of gray matter in a control region (the superior frontal gyrus) was essentially the same in the patients and controls. CONCLUSIONS: Schizophrenia involves localized reductions in the gray matter of the left temporal lobe. The degree of thought disorder is related to the size of the reduction in volume of the left posterior superior temporal gyrus.