First-episode psychosis is characterized by failure of deactivation but not by hypo- or hyperfrontality.
ABSTRACT It is not known whether first-episode psychosis is characterized by the same prefrontal cortex functional imaging abnormalities as chronic schizophrenia.
Thirty patients with a first episode of non-affective functional psychosis and 28 healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back working memory task. Voxel-based analyses of brain activations and deactivations were carried out and compared between groups. The connectivity of regions of significant difference between the patients and controls was also examined.
The first-episode patients did not show significant prefrontal hypo- or hyperactivation compared to controls. However, they showed failure of deactivation in the medial frontal cortex. This area showed high levels of connectivity with the posterior cingulate gyrus/precuneus and parts of the parietal cortex bilaterally. Failure of deactivation was significantly greater in first-episode patients who had or went on to acquire a DSM-IV diagnosis of schizophrenia than in those who did not, and in those who met RDC criteria for schizophrenia compared to those who did not.
First-episode psychosis is not characterized by hypo- or hyperfrontality but instead by a failure of deactivation in the medial frontal cortex. The location and connectivity of this area suggest that it is part of the default mode network. The failure of deactivation seems to be particularly marked in first-episode patients who have, or progress to, schizophrenia.
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ABSTRACT: Numerous neuroimaging studies have examined the function of the dorsolateral prefrontal cortex in schizophrenia; although abnormalities usually are identified, it is unclear why some studies find too little activation and others too much. The authors' goal was to explore this phenomenon. They used the N-back working memory task and functional magnetic resonance imaging at 3 T to examine a group of 14 patients with schizophrenia and a matched comparison group of 14 healthy subjects. Patients' performance was significantly worse on the two-back working memory task than that of healthy subjects. However, there were areas within the dorsolateral prefrontal cortex of the patients that were more active and areas that were less active than those of the healthy subjects. When the groups were subdivided on the basis of performance on the working memory task into healthy subjects and patients with high or low performance, locales of greater prefrontal activation and locales of less activation were found in the high-performing patients but only locales of underactivation were found in the low-performing patients. These findings suggest that patients with schizophrenia whose performance on the N-back working memory task is similar to that of healthy comparison subjects use greater prefrontal resources but achieve lower accuracy (i.e., inefficiency) and that other patients with schizophrenia fail to sustain the prefrontal network that processes the information, achieving even lower accuracy as a result. These findings add to other evidence that abnormalities of prefrontal cortical function in schizophrenia are not reducible to simply too much or too little activity but, rather, reflect a compromised neural strategy for handling information mediated by the dorsolateral prefrontal cortex.American Journal of Psychiatry 01/2004; 160(12):2209-15. · 14.72 Impact Factor
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ABSTRACT: Although there is considerable evidence that patients with schizophrenia fail to activate the dorsolateral prefrontal cortex (DLPFC) to the degree seen in normal comparison subjects when performing working memory or executive tasks, hypofrontality may be coupled with relatively increased activity in other brain regions. However, most imaging studies of working memory in schizophrenia have focused on DLPFC activity. The goal of this work is to review functional neuroimaging studies that contrasted patients with schizophrenia and healthy comparison subjects during a prototypical working memory task, the n-back paradigm, to highlight areas of hyper- and hypoactivation in schizophrenia. We utilize a quantitative meta-analysis method to review 12 imaging studies where patients with schizophrenia were contrasted with healthy comparison subjects while performing the n-back paradigm. Although we find clear support for hypofrontality, we also document consistently increased activation in anterior cingulate and left frontal pole regions in patients with schizophrenia compared to that in controls. These data suggest that whereas reduced DLPFC activation is reported consistently in patients with schizophrenia relative to healthy subjects, abnormal activation patterns are not restricted to this region, raising questions as to whether the pathophysiological dysfunction in schizophrenia is specific to the DLPFC and about the relationship between impaired performance and aberrant activation patterns. The complex pattern of hyper- and hypoactivation consistently found across studies implies that rather than focusing on DLPFC dysregulation, researchers should consider the entire network of regions involved in a given task when making inferences about the biological mechanisms of schizophrenia.Human Brain Mapping 06/2005; 25(1):60-9. · 6.88 Impact Factor
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ABSTRACT: Functional disintegration has been observed in schizophrenia during task performance. We sought to investigate functional disintegration during rest because an intrinsic functional brain organization, including both "task-negative" (i.e., "default mode") and "task-positive" networks, has been suggested to play an important role in integrating ongoing information processing. Additionally, the brain regions that are involved in the intrinsic organization are believed to be abnormal in schizophrenia. Patients with paranoid schizophrenia (N=18) and healthy volunteers (N=18) underwent a resting-state fMRI scan. Functional connectivity analysis was used to identify the connectivity between each pair of brain regions within this intrinsic organization, and differences were examined in patients versus healthy volunteers. Compared to healthy volunteers, patients showed significant differences in connectivity within networks and between networks, most notably in the connectivities associated with the bilateral dorsal medial prefrontal cortex, the lateral parietal region, the inferior temporal gyrus of the "task-negative" network and with the right dorsolateral prefrontal cortex and the right dorsal premotor cortex of the "task-positive" network. These results suggested that the interregional functional connectivities in the intrinsic organization are altered in patients with paranoid schizophrenia. These abnormalities could be the source of abnormalities in the coordination of and competition between information processing activities in the resting brain of paranoid patients.Schizophrenia Research 01/2008; 97(1-3):194-205. · 4.59 Impact Factor