Neurocognitive capabilities modulate the integration of evidence in schizophrenia

Previous studies have demonstrated a cognitive bias in the integration of disconfirmatory evidence (BADE) in patients with schizophrenia. This bias has been associated with delusions. So far, it is unclear how the integration of evidence is associated with neurocognitive capabilities. In the current study, 31 patients with schizophrenia and 29 healthy controls, matched on age, gender, education and premorbid verbal intelligence, underwent a BADE task. Written scenarios of three consecutive sentences each were presented, which progressively reduced the ambiguity of situations. Participants were asked to rate the plausibility of four possible interpretations and adjust their ratings in response to the provided sentences. Psychometric rating scales and a neuropsychological test battery were applied. Patients displayed a bias in the integration of confirmatory, but not disconfirmatory evidence and a liberal acceptance of belief formation. Correlation analyses revealed no associations of evidence integration with the severity of positive symptoms, but with neurocognitive domains, especially with processing speed, executive functioning, vigilance and working memory. In conclusion, patients with schizophrenia show a bias in evidence integration. Neurocognitive functioning emerged as a modulatory factor that should be considered in further research. Studies investigating BADE in earlier stages of psychosis will be necessary to reveal causal relationship

Overconfidence in incorrect perceptual judgments in patients with schizophrenia

Background: Patients with schizophrenia show overconfidence in memory and social cognition errors. The present investigation examined whether this cognitive distortion also manifests in perceptual tasks. Methods: A total of 55 individuals with schizophrenia, 58 with obsessive–compulsive disorder (OCD) as well as 45 non-clinical controls were presented 24 blurry black and white pictures, half of which contained a hidden object; the other half contained (“snowy”) visual noise. Participants had to judge whether the pictures depicted an object or not and how confident they were in this judgment. Results: Participants with schizophrenia showed overconfidence in errors and an enhanced knowledge corruption index (i.e. rate of high-confident errors on all high-confident responses) relative to both control groups. In contrast, accuracy scores did not differ between clinical groups. Metacognitive parameters were correlated with self-rated levels of current paranoia. Discussion: To the best of our knowledge, this is the first study to demonstrate overconfidence in errors among individuals with psychosis using a visual perception task. Speaking to the specificity of this abnormality for schizophrenia and its pathogenetic relevance, overconfidence in errors and knowledge corruption were elevated in patients with schizophrenia relative to both control groups and were correlated with paranoia

Increased orbitofrontal cortex activation associated with "pro-obsessive" antipsychotic treatment in patients with schizophrenia

Background: Patients with schizophrenia have an approximately 10-fold higher risk for obsessive–compulsive symptoms (OCS) than the general population. A large subgroup seems to experience OCS as a consequence of second-generation antipsychotic agents (SGA), such as clozapine. So far little is known about underlying neural mechanisms.Methods: To investigate the role of SGA treatment on neural processing related to OCS in patients with schizophrenia, we stratified patients according to their monotherapy into 2 groups (group I: clozapine or olanzapine; group II: amisulpride or aripiprazole). We used an fMRI approach, applying a go/no-go task assessing inhibitory control and an n-back task measuring working memory.Results: We enrolled 21 patients in group I and 19 patients in group II. Groups did not differ regarding age, sex, education or severity of psychotic symptoms. Frequency and severity of OCS were significantly higher in group I and were associated with pronounced deficits in specific cognitive abilities. Whereas brain activation patterns did not differ during working memory, group I showed significantly increased activation in the orbitofrontal cortex (OFC) during response inhibition. Alterations in OFC activation were associated with the severity of obsessions and mediated the association between SGA treatment and co-occurring OCS on a trend level.Limitations: The main limitation of this study is its cross-sectional design.Conclusion: To our knowledge, this is the first imaging study conducted to elucidate SGA effects on neural systems related to OCS. We propose that alterations in brain functioning reflect a pathogenic mechanism in the development of SGA-induced OCS in patients with schizophrenia. Longitudinal studies and randomized interventions are needed to prove the suggested causal interrelations.publishe

Aberrant activity and connectivity of the posterior superior temporal sulcus during social cognition in schizophrenia

Schizophrenia is associated with significant impairments in social cognition. These impairments have been shown to go along with altered activation of the posterior superior temporal sulcus (pSTS). However, studies that investigate connectivity of pSTS during social cognition in schizophrenia are sparse. Twenty-two patients with schizophrenia and 22 matched healthy controls completed a social-cognitive task for functional magnetic resonance imaging that allows the investigation of affective Theory of Mind (ToM), emotion recognition and the processing of neutral facial expressions. Moreover, a resting-state measurement was taken. Patients with schizophrenia performed worse in the social-cognitive task (main effect of group). In addition, a group by social-cognitive processing interaction was revealed for activity, as well as for connectivity during the social-cognitive task, i.e., patients with schizophrenia showed hyperactivity of right pSTS during neutral face processing, but hypoactivity during emotion recognition and affective ToM. In addition, hypoconnectivity between right and left pSTS was revealed for affective ToM, but not for neutral face processing or emotion recognition. No group differences in connectivity from right to left pSTS occurred during resting state. This pattern of aberrant activity and connectivity of the right pSTS during social cognition might form the basis of false-positive perceptions of emotions and intentions and could contribute to the emergence and sustainment of delusions.publishe

Metamemory in schizophrenia: retrospective confidence ratings interact with neurocognitive deficits

Prior studies with schizophrenia patients described a reduced ability to discriminate between correct and false memories in terms of confidence compared to control groups. This metamemory bias has been associated with the emergence and maintenance of delusions. The relation to neuropsychological performance and other clinical dimensions is incompletely understood. In a cross-sectional study, metamemory functioning was explored in 32 schizophrenia patients and 25 healthy controls. Metamemory was assessed using a verbal recognition task combined with retrospective confidence level ratings. Associations of metamemory performance with six neuropsychological domains (executive functioning/problem solving, speed of processing, working memory, verbal and visual learning, and attention/vigilance) and psychopathological measures were analyzed. Results revealed a significantly smaller discrepancy between confidence ratings for correct and incorrect recognitions in the patient group. Furthermore, patients showed significantly lower recognition accuracy in the metamemory task and marked deficits in all neuropsychological domains. Across all participants, metamemory performance significantly correlated with executive functioning and working memory. No associations with delusions were found. This data confirms prior findings of metamemory biases in schizophrenia. Selective neuropsychological abilities seem to be modulating factors of metamemory functioning. Longitudinal studies in at risk mental state and first-episode patients are needed to reveal causal interrelation

Reduced activation in ventral striatum and ventral tegmental area during probabilistic decision-making in schizophrenia

Patients with schizophrenia suffer from deficits in monitoring and controlling their own thoughts. Within these so-called metacognitive impairments, alterations in probabilistic reasoning might be one cognitive phenomenon disposing to delusions. However, so far little is known about alterations in associated brain functionality. A previously established task for functional magnetic resonance imaging (fMRI), which requires a probabilistic decision after a variable amount of stimuli, was applied to 23 schizophrenia patients and 28 healthy controls matched for age, gender and educational levels. We compared activation patterns during decision-making under conditions of certainty versus uncertainty and evaluated the process of final decision-making in ventral striatum (VS) and ventral tegmental area (VTA). We replicated a pre-described extended cortical activation pattern during probabilistic reasoning. During final decision-making, activations in several fronto- and parietocortical areas, as well as in VS and VTA became apparent. In both of these regions schizophrenia patients showed a significantly reduced activation. These results further define the network underlying probabilistic decision-making. The observed hypo-activation in regions commonly associated with dopaminergic neurotransmission fits into current concepts of disrupted prediction error signaling in schizophrenia and suggests functional links to reward anticipation. Forthcoming studies with patients at risk for psychosis and drug-naive first episode patients are necessary to elucidate the development of these findings over time and the interplay with associated clinical symptoms.publishe

Early cognitive basic symptoms are accompanied by neurocognitive impairment in patients with an 'at-risk mental state' for psychosis

Aim: Patients with an increased risk for psychosis ('at-risk mental state' (ARMS)) present various neurocognitive deficits. Not least because of differences in identifying the ARMS, results of previous studies are inconsistent. In most studies ARMS-patients are classified by the experience of attenuated psychotic symptoms (APS) and/or brief limited intermittent psychotic symptoms (BLIPS). Few studies additionally assessed cognitive basic symptoms (BS). A comprehensive assessment in the very early stage of the ARMS is missing.Methods: In the present study we characterized ARMS‐patients for cognitive BS (ARMS‐BS), APS and BLIPS (ARMS‐A/B) according to the Early Recognition Inventory based on IRAOS (ERIraos). Furthermore, we assessed neurocognitive deficits using the MATRICS consensus cognitive battery for schizophrenia with a primary hypothesis regarding working memory performance. Groups of 38 ARMS‐patients and 38 healthy controls were matched for age, gender, education and premorbid verbal intelligence.Results: Between‐group comparisons revealed significant poorer working memory performance in addition to lower verbal learning and problem solving, slower processing speed and lower global neurocognitive functioning in ARMS‐patients as compared to controls. ARMS‐BS did not differ from ARMS‐A/B.Conclusions: These results underscore the presence of cognitive limitations in patients only presenting with cognitive BS. Knowledge of these early cognitive deviations supports the inclusion of early ARMS‐stages into a comprehensive concept of the psychosis risk state. Therapeutic interventions already applied at this stage might prevent deterioration of constraints. Longitudinal and interventional studies investigating the interaction of cognitive BS and neurocognitive as well as metacognitive deficits are warranted.publishe

Reduced activation in the ventral striatum during probabilistic decision-making in patients in an at-risk mental state

Background: Patients with schizophrenia display metacognitive impairments, such as hasty decision-making during probabilistic reasoning - the "jumping to conclusion" bias (JTC). Our recent fMRI study revealed reduced activations in the right ventral striatum (VS) and the ventral tegmental area (VTA) to be associated with decision-making in patients with schizophrenia. It is unclear whether these functional alterations occur in the at-risk mental state (ARMS).Methods: We administered the classical beads task and fMRI among ARMS patients and healthy controls matched for age, sex, education and premorbid verbal intelligence. None of the ARMS patients was treated with antipsychotics. Both tasks request probabilistic decisions after a variable amount of stimuli. We evaluated activation during decision-making under certainty versus uncertainty and the process of final decision-making.Results: We included 24 AMRS patients and 24 controls in our study. Compared with controls, ARMS patients tended to draw fewer beads and showed significantly more JTC bias in the classical beads task, mirroring findings in patients with schizophrenia. During fMRI, ARMS patients did not demonstrate JTC bias on the behavioural level, but showed a significant hypoactivation in the right VS during the decision stage.Limitations: Owing to the cross-sectional design of the study, results are constrained to a better insight into the neurobiology of risk constellations, but not prepsychotic stages. Nine of the ARMS patients were treated with antidepressants and/or lorazepam.Conclusion: As in patients with schizophrenia, a striatal hypoactivation was found in ARMS patients. Confounding effects of antipsychotic medication can be excluded. Our findings indicate that error prediction signalling and reward anticipation may be linked to striatal dysfunction during prodromal stages and should be examined for their utility in predicting transition risk.publishe