The Formation of Abnormal Associations in Schizophrenia: Neural and Behavioral Evidence

Abstract

It is hypothesized that due to an abnormal functioning of the reward system patients with schizophrenia form context-inappropriate associations. It has been shown that the dopamine target regions, especially the ventral striatum, are critical in the formation of reward associations. We wanted to examine how the ventral striatum responds as patients learn reward-related associations and how this neural response is linked to objective and subjective behavioral measures. Functional magnetic resonance imaging (fMRI) Blood oxygen level dependent (BOLD) responses were examined using aversive Pavlovian learning in 13 medicated patients with schizophrenia and 13 matched healthy controls. Colored circles served as conditioned stimulus (CS + ) while a loud, individually adjusted, noise served as the unconditioned stimulus. Circles of another color served as neutral comparators (CSÀ). Subjective indices were assessed by a post-scan self-report, and galvanic skin responses (GSR) were used as objective measures of associative learning. fMRI data were analyzed using a random effects model in SPM2. Patients showed inappropriately strong activations in the ventral striatum in response to the neutral stimulus (CSÀ) as compared to the healthy controls. Consistent with this neural evidence of aberrant learning, patients also showed evidence of abnormal learning by self-report and as indexed by GSR. The main finding here is that patients with schizophrenia, when exposed to neutral stimuli in a threatening situation, show an abnormal pattern of learning. The aberrant activations and response are consistent with the idea that patients aberrantly assign motivational salience to neutral stimuli, and this process may be one of the aberrations that predisposes them to psychosis.

Ventral Striatal Dysfunction and Symptom Expression in Individuals With Schizotypal Personality Traits and Early Psychosis

“…Importantly, increased striatal activity during reward anticipation was mostly driven by positive symptoms, which is consistent with our previous study in unmedicated individuals atrisk for psychosis. 19 These findings are in line with studies showing a relation between positive symptoms and increased hemodynamic responses to reward-predicting cues 55 or neutral stimuli in the mesolimbic reward system 21,32,56,57 in individuals at-risk for psychosis and patients with psychotic disorders. In contrast, a recent study in unmedicated patients with schizophrenia has reported a negative association between VS activity during anticipation of wins and losses, ie, salience, with positive symptoms.…”

The emerging biology of delusions

“…Abnormalities in reward processing in schizophrenia can be exacerbated by medication (Schlagenhauf et al 2008), but deficits are also present in patients who are not taking dopamine receptor antagonists (Murray et al 2008b). Furthermore, in schizophrenia, learning about important events is linked with dysfunction in dopaminergic regions such as the striatum and midbrain (Jensen et al 2008 ;Murray et al 2008c). Frontal, temporal and parietal cortical abnormalities are also seen in such processes (Murray et al 2008c, and recent evidence suggests that the degree of abnormality of cortical response is linked to the severity of delusional ideation (Corlett et al 2007 ;Schlagenhauf et al 2009).…”

Altered Transfer of Momentary Mental States (Atoms) as the Basic Unit of Psychosis Liability in Interaction With Environment and Emotions

“…from subclinical to clinical psychotic expression) [13], linking expression of psychosis at 'brain-level' with 'mind-level' 9 . The hypothesized role of aberrant salience as the driving force behind psychotic symptoms has been supported by empirical studies showing that psychotic symptoms were associated with aberrant salience in both patients with schizophrenia and controls with increased liability for psychosis [14] and by imaging studies showing that patients with schizophrenia show abnormal neural patterns in response to neutral stimuli [15,16]. Furthermore, support comes from work in psychopharmacology, suggesting that antipsychotic medication attenuates both the level of psychotic symptoms and the level of aberrant salience [12,14].…”