Delusions of reference, excessive top-down processing, and default mode network in first-episode schizophrenia

Abstract

BACKGROUND: Delusions of reference (DOR) refer to the detection of spurious self-information in otherwise neutral or ambiguous environmental stimuli. Empirical studies of DOR using an information processing framework are lacking. We hypothesize, at the neurocognitive level, that DOR may be related to an excessive use of an internally generated, top-down processing strategy; whereas at the neurophysiological level, this may be related to the hyperactivity and hyperconnectivity in the default mode network (DMN) of the brain. The DMN has been implicated in self-focused attention and ‘stimulus-independent thoughts’, as well as baseline monitoring and automatic attention to salient environmental stimuli, and a link to psychotic symptoms has been observed. The first part of this study explore whether a relationship exists between DOR and excessive top-down processing; the second part of this study test the hypothesis that patients with DOR as chief compliant specifically present with aberrant DMN function and increased top-down processing. METHODS: In Study 1, a total of 30 schizophrenic patients are assessed for DOR using the Ideas of Reference Interview Schedule (IRIS), and are tested using a visual processing (“contour integration”) and a verbal processing (“babbling”) task. Excessive top-down processing is measured by the score of spurious information perceived in the two tasks. In Study 2, to test the hypothesis that DOR is specifically related to DMN and increased top-down processing, 45 first-episode schizophrenic patients are recruited into one of three groups according to their symptomatology: (A) patient with I/DOR as chief presentation (n = 15); (B) patients with positive symptoms other than I/DOR as chief presentation (n = 15); and (C) patients without clinically significant positive symptoms (n = 15). A group of normal controls (n = 15) is also included. Participants are matched by age, sex and education level. Functional MRI scanning is performed under a resting condition and a block-design 0- and 2-back working memory task condition. ANOVA F test is used for the analysis of between group differences in DMN activity. For functional connectivity analysis, Pearson's correlation is performed in seed regions of interest according to previously defined components of the DMN. RESULTS: In the exploratory study, interim data analysis (n = 9; 5 men, mean age 23.8 years) showed a positive correlation between severity of DOR and spurious information detected in the contour integration test (Spearman's rho = 0.45) and the babble task (Spearman's rho = 0.42), although the results did not reach statistical significance because of the sample size. Spurious information processing in the auditory and visual tasks also showed strong correlation (Spearman's rho = 0.65, p = 0.056). Data collection for both parts of the study is expected to be completed by March 2010. DISCUSSION: This study tests the hypothesis that excessive top-down processing and aberrant DMN function seen in schizophrenia is specifically related to DOR, a group of important symptom central to psychotic disorders. DOR are found in up to 67% of schizophrenic patients, and their roles as prodromal and relapse signal and schizotypal trait highlight their potential as a state and trait marker for schizophrenia. Identification of the neurocognitive and neurophysiological mechanisms of DOR will provide important insight into understanding psychosis. Copyright © 2010 Published by Elsevier B.V.