Aberrant Salience Is Related to Dysfunctional Self-Referential Processing in Psychosis

Abstract

Background: A dysfunctional differentiation between self-relevant and irrelevant information may affect the perception of environmental stimuli as abnormally salient. The aberrant salience hypothesis assumes that positive symptoms arise from an attribution of salience to irrelevant stimuli accompanied by the feeling of self-relevance. Self-referential processing relies on the activation of cortical midline structures which was demonstrated to be impaired in psychosis. We investigated the neural correlates of self-referential processing, aberrant salience attribution, and the relationship between these 2 measures across the psychosis continuum.

Methods: Twenty-nine schizophrenia patients, 24 healthy individuals with subclinical delusional ideation, and 50 healthy individuals participated in this study. Aberrant salience was assessed behaviorally in terms of reaction times to task irrelevant cues. Participants performed a self-reference task during fMRI in which they had to apply neutral trait words to them or to a public figure. The correlation between self-referential processing and aberrant salience attribution was tested.

Results: Schizophrenia patients displayed increased aberrant salience attribution compared with healthy controls and individuals with subclinical delusional ideation, while the latter exhibited intermediate aberrant salience scores. In the self-reference task, schizophrenia patients showed reduced activation in the ventromedial prefrontal cortex (vmPFC), but individuals with subclinical delusional ideation did not differ from healthy controls. In schizophrenia patients, vmPFC activation correlated negatively with implicit aberrant salience attribution.

Conclusions: Higher aberrant salience attribution in schizophrenia patients is related to reduced vmPFC activation during self-referential judgments suggesting that aberrant relevance coding is reflected in decreased neural self-referential processing as well as in aberrant salience attribution.

Keywords: fMRI; psychosis; psychosis continuum; salience; self-referential processing; vmPFC.

Fig. 1.

Mean square root transformed aberrant salience scores (± SE) for 50 healthy controls (3.08±0.17), 24 delusion-prone subjects (3.40±0.27), and 29 schizophrenia patients (3.89±0.25).

Fig. 2.

(A) All participants taken together (n = 88) for the contrast self > other reported at P < .05 FWE corrected for the whole brain. (B) Group by self > other interaction in the right vmPFC (9/38/1, F[2,170] = 13.73, P _{FWE for self > other} = .008) and left vmPFC (−3/50/−2, F[2,170] = 11.71, P _{FWE for self > other} = .036; displayed at .001 uncorrected k > 50). (C) Parameter estimates in right vmPFC (at 9/38/1) for self, other, and syllables condition. For self, schizophrenia patients (red) showed decreased activation compared with healthy controls (blue; t[62] = 4.701, P < .001) and to individuals with subclinical delusional ideation (purple; t[44] = 3.65, P > .001). For other, schizophrenia patients displayed increased activation compared with healthy controls (t[62] = 3.95, P < .001) and compared with individuals with subclinical delusional ideation (t[44] = 3.26, P = .002). There were no differences between healthy controls and individuals with subclinical delusional ideation for self or other (P > .6) and no group differences for syllables (P > .2). Error bars show the standard error of the mean. Order of bars for each condition in panel C: healthy controls, individuals with subclinical delusional ideation, schizophrenia patients. (Note: For colour interpretation, please see figure online.)

Fig. 3.

The correlation between reduced activation in the vmPFC for the contrast self> other (10-mm sphere around peak of the contrast at −9/44/−2) and the aberrant salience score in schizophrenia patients (n = 20, r[1,18] = −0.470, P = .037, R ² = 0.221).