Deciphering reward-based decision-making in schizophrenia: a meta-analysis and behavioral modeling of the Iowa Gambling Task

Background: Patients with schizophrenia (SZP) have been reported to exhibit impairments in reward-based decision-making, but results are heterogeneous with multiple potential confounds such as age, intelligence level, clinical symptoms or medication, making it difficult to evaluate the robustness of these impairments. Methods: We conducted a meta-analysis of studies comparing the performance of SZP and healthy controls (HC) in the Iowa Gambling Task (IGT) as well as comprehensive analyses based on subject-level data (n = 303 SZP, n = 188 HC) to investigate reward-based decision-making in SZP. To quantify differences in the influence of individual deck features (immediate gain, gain frequency, net loss) between SZP and HC, we additionally employed a least-squares model. Results: SZP showed statistically significant suboptimal decisions as indicated by disadvantageous deck choices (d from 0.51 to −0.62) and lower net scores (d from −0.35 to −1.03) in a meta-analysis of k = 29 samples (n = 1127 SZP, n = 1149 HC) and these results were confirmed in a complementary subject-level analysis. Moreover, decision-making in SZP was characterized by a relative overweighting of immediate gain and net losses and an underweighting of gain frequency. Moderator analyses revealed that in part, decision-making in the IGT was moderated by intelligence level, medication and general symptom scores. Conclusion: Our results indicate robust impairments in reward-based decision-making in SZP and suggest that decreased cognitive resources, such as working memory, may contribute to these alterations

Orbitofrontal cortex, emotional decision-making and response to cognitive behavioural therapy for psychosis

Grey matter volume (GMV) in the orbitofrontal cortex (OFC) may relate to better response to cognitive behavioural therapy for psychosis (CBTp) because of the region's role in emotional decision-making and cognitive flexibility. This study aimed to determine the relation between pre-therapy OFC GMV or asymmetry and CBTp responsiveness and emotional decision-making as measured by the Iowa Gambling Task (IGT). Thirty patients received CBTp + standard care (CBTp+SC; 25 completers) for 6-8 months. All patients (before receiving CBTp) and 25 healthy participants underwent structural magnetic resonance imaging and performed the IGT. Patients' symptoms were assessed before and after therapy. Pre-therapy OFC GMV, measured using a region-of-interest approach, and IGT performance, measured as overall learning, attention to reward, memory for past outcomes and choice consistency, were comparable between patient and healthy groups. In the CBTp+SC group, greater OFC GMV was correlated with positive symptom improvement, specifically hallucinations and persecution. Greater rightward OFC asymmetry correlated with improvement in several negative and general psychopathology symptoms. Greater left OFC GMV was associated with lower IGT attention to reward. The findings suggest that greater OFC volume and rightward asymmetry, which maintain the OFC's function in emotional decision-making and cognitive flexibility, are beneficial for CBTp responsiveness

Association between a longer duration of illness, age and lower frontal lobe grey matter volume in schizophrenia

The frontal lobe has an extended maturation period and may be vulnerable to the long-term effects of schizophrenia. We tested this hypothesis by studying the relationship between duration of illness (DoI), grey matter (GM) and cerebro-spinal fluid (CSF) volume across the whole brain. Sixty-four patients with schizophrenia and 25 healthy controls underwent structural MRI scanning and neuropsychological assessment. We performed regression analyses in patients to examine the relationship between DoI and GM and CSF volumes across the whole brain, and correlations in controls between age and GM or CSF volume of the regions where GM or CSF volumes were associated with DoI in patients. Correlations were also performed between GM volume in the regions associated with DoI and neuropsychological performance. A longer DoI was associated with lower GM volume in the left dorsomedial prefrontal cortex (PFC), right middle frontal cortex, left fusiform gyrus (FG) and left cerebellum (lobule III). Additionally, age was inversely associated with GM volume in the left dorsomedial PFC in patients, and in the left FG and CSF excess near the left cerebellum in healthy controls. Greater GM volume in the left dorsomedial PFC was associated with better working memory, attention and psychomotor speed in patients. Our findings suggest that the right middle frontal cortex is particularly vulnerable to the long-term effect of schizophrenia illness whereas the dorsomedial PFC, FG and cerebellum are affected by both a long DoI and aging. The effect of illness chronicity on GM volume in the left dorsomedial PFC may be extended to brain structure–neuropsychological function relationships

Neural changes following cognitive behaviour therapy for psychosis: a longitudinal study

A growing body of evidence demonstrates that persistent positive symptoms, particularly delusions, can be improved by cognitive behaviour therapy for psychosis. Heightened perception and processing of threat are believed to constitute the genesis of delusions. The present study aimed to examine functional brain changes following cognitive behaviour therapy for psychosis. The study involved 56 outpatients with one or more persistent positive distressing symptoms of schizophrenia. Twenty-eight patients receiving cognitive behaviour therapy for psychosis for 6–8 months in addition to their usual treatment were matched with 28 patients receiving treatment as usual. Patients’ symptoms were assessed by a rater blind to treatment group, and they underwent functional magnetic resonance imaging during an affect processing task at baseline and end of treatment follow-up. The two groups were comparable at baseline in terms of clinical and demographic parameters and neural and behavioural responses to facial and control stimuli. The cognitive behaviour therapy for psychosis with treatment-as-usual group (22 subjects) showed significant clinical improvement compared with the treatment-as-usual group (16 subjects), which showed no change at follow-up. The cognitive behaviour therapy for psychosis with treatment-as-usual group, but not the treatment-as-usual group, showed decreased activation of the inferior frontal, insula, thalamus, putamen and occipital areas to fearful and angry expressions at treatment follow-up compared with baseline. Reduction of functional magnetic resonance imaging response during angry expressions correlated directly with symptom improvement. This study provides the first evidence that cognitive behaviour therapy for psychosis attenuates brain responses to threatening stimuli and suggests that cognitive behaviour therapy for psychosis may mediate symptom reduction by promoting processing of threats in a less distressing way

Beyond Dopamine: Functional MRI Predictors of Responsiveness to Cognitive Behaviour Therapy for Psychosis

Despite the favourable effects of antipsychotics on positive symptoms of schizophrenia, many patients continue to suffer from distressing symptoms. Additional benefits of cognitive behaviour therapy for psychosis (CBTp) have been reported for approximately 50% of such patients. Given the role of left hemisphere-based language processes in responsiveness to CBT for depression, and language pathway abnormalities in psychosis, this study examined whether pre-therapy brain activity during a verbal monitoring task predicts CBTp responsiveness in schizophrenia. Fifty-two outpatients, stable on antipsychotics with at least one persistent distressing positive symptom and wishing to receive CBTp adjunctive to their treatment-as-usual, and 20 healthy participants underwent fMRI during monitoring of self- and externally-generated (normal and distorted) speech. Subsequently, 26 patients received CBTp for 6–8 months adjunctive to their treatment-as-usual (CBTp + TAU, 20 completers), and 26 continued with their treatment-as-usual (TAU-alone, 18 completers). Symptoms were assessed (blindly) at entry and follow-up. The CBTp + TAU and TAU-alone groups had comparable demographic characteristics, performance and baseline symptoms. Only the CBTp + TAU group showed improved symptoms at follow-up. CBTp responsiveness was associated with (i) greater left inferior frontal gyrus (IFG) activity during accurate monitoring, especially of own voice, (ii) less inferior parietal deactivation with own, relative to others’, voice, and (iii) less medial prefrontal deactivation and greater thalamic and precuneus activation during monitoring of distorted, relative to undistorted, voices. CBTp + TAU patients, on average, displayed left IFG and thalamic hypo-activation (<healthy participants). The findings implicate language processing (IFG), attention (thalamus), insight and self-awareness (medial prefrontal and parietal cortices) in CBTp responsiveness in schizophrenia

Neural processing of criticism and positive comments from relatives in individuals with schizotypal personality traits

Objectives. High negative expressed emotion by family members towards schizophrenia patients increases the risk of subsequent relapse. The study aimed to determine whether individuals with high schizotypy (HS) and low schizotypy (LS) would differ in activation of brain areas involved in cognitive control when listening to relative criticism

Neural responses to criticism and praise vary with schizotypy and perceived emotional support

Higher Education Funding Council for England quality-related research (QR

The relation between schizotypy and early attention to rejecting interactions: The influence of neuroticism

© 2015 The Author(s). Published by Taylor & Francis. Objectives: Schizotypy relates to rejection sensitivity (anxiety reflecting an expectancy of social exclusion) and neuroticism (excessive evaluation of negative emotions). Positive schizotypy (e.g., perceptual aberrations and odd beliefs) and negative schizotypy (e.g., social and physical anhedonia) could relate to altered attention to rejection because of neuroticism. Methods: Forty-one healthy individuals were assessed on positive and negative schizotypy and neuroticism, and event-related potentials during rejecting, accepting and neutral scenes. Participants were categorised into high, moderate and low neuroticism groups. Using temporo-spatial principal components analyses, P200 (peak latency =290 ms) and P300 amplitudes (peak latency = 390 ms) were measured, reflecting mobilisation of attention and early attention, respectively. Results: Scalp-level and cortical source analysis revealed elevated fronto-parietal N300/P300 amplitude and P200-related dorsal anterior cingulate current density during rejection than acceptance/neutral scenes. Positive schizotypy related inversely to parietal P200 amplitude during rejection. Negative schizotypy related positively to P200 middle occipital current density. Negative schizotypy related positively to parietal P300, where the association was stronger in high and moderate, than low, neuroticism groups. Conclusions: Positive and negative schizotypy relate divergently to attention to rejection. Positive schizotypy attenuates, but negative schizotypy increases rejection-related mobilisation of attention. Negative schizotypy increases early attention to rejection partly due to elevated neuroticism