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: Impaired working memory is a core feature of schizophrenia and is linked with altered engagement the lateral prefrontal cortex. Although altered PFC activation has been reported in people with increased risk of psychosis, at present it is not clear if this neurofunctional alteration differs between familial and clinical risk states and/or increases in line with the level of psychosis risk. We addressed this issue by using functional MRI and a working memory paradigm to study familial and clinical high-risk groups. We recruited 17 subjects at ultra-high-risk (UHR) for psychosis, 10 non-affected siblings of patients with schizophrenia (familial high risk [FHR]) and 15 healthy controls. Subjects were scanned while performing the N-back working memory task. There was a relationship between the level of task-related deactivation in the medial PFC and precuneus and the level of psychosis risk, with deactivation weakest in the UHR group, greatest in healthy controls, and at an intermediate level in the FHR group. In the high-risk groups, activation in the precuneus was associated with the level of negative symptoms. These data suggest that increased vulnerability to psychosis is associated with a failure to deactivate in the medial PFC and precuneus during a working memory task, and appears to be most evident in subjects at clinical, as opposed to familial high risk. Copyright © 2015. Published by Elsevier Masson SAS.European Psychiatry 04/2015; DOI:10.1016/j.eurpsy.2015.03.003 · 3.21 Impact Factor
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ABSTRACT: Social interaction requires mirroring to other people's mental state. Psychotic disorders have been connected to social interaction and emotion recognition impairment. We compared the brain activity between young adults with familial risk for psychosis (FR) and matched controls during visual exposure to emotional facial expression. We also investigated the role of the amygdala, the key region for social interaction and emotion recognition. 51 FR and 52 control subjects were drawn from the Northern Finland 1986 Birth Cohort (Oulu Brain and Mind Study). None of the included participants had developed psychosis. The FR group was defined as having a parent with psychotic disorder according to the Finnish Hospital Discharge Register. Participants underwent functional MRI (fMRI) using visual presentation of dynamic happy and fearful facial expressions. FMRI data were processed to produce maps of activation for happy and fearful facial expression, which were then compared between groups. Two spherical regions of interest (ROIs) in the amygdala were set to extract BOLD responses during happy and fearful facial expression. BOLD responses were then compared with subjects' emotion recognition, which was assessed after fMRI. Psychophysiological interaction (PPI) for the left and right amygdala during happy and fearful facial expression was conducted using the amygdala as seed regions. FR subjects had increased activity in the left premotor cortex and reduced deactivation of medial prefrontal cortex structures during happy facial expression. There were no between-group differences during fearful facial expression. The FR group also showed a statistically significant linear correlation between mean amygdala BOLD response and facial expression recognition. PPI showed that there was a significant negative interaction between the amygdala and the dorsolateral prefrontal cortex (dlPFC) and superior temporal gyrus in FR subjects. Increased activations by positive valence in FR were in brain regions crucial to emotion recognition and social interaction. Increased activation of the premotor cortex may serve as a compensatory mechanism as FR subjects may have to exert more effort on processing the stimuli, as has been found earlier in schizophrenia. Failure to deactivate PFC structures may imply error in the default mode network. Abnormal PFC function in FR was also suggested by PPI, as the dlPFC showed decreased functional connectivity with the amygdala in the FR group. This may indicate that in FR subjects the amygdala have to take a greater role in emotion recognition and social functioning. This inference was supported by our discovery of statistically significant correlations between the amygdala BOLD response and emotion recognition in the FR group but not in controls. Copyright © 2015 Elsevier B.V. All rights reserved.Schizophrenia Research 02/2015; 164(1-3). DOI:10.1016/j.schres.2015.01.039 · 4.43 Impact Factor
American Academy of Child and Adolescent Psychiatry/Canadian Academy of Child and Adolescent Psychiatry Joint Annual Meeting; 10/2011