Deficits in context-dependent adaptive coding of reward in schizophrenia

Theoretical principles of information processing and empirical findings suggest that to efficiently represent all possible rewards in the natural environment, reward-sensitive neurons have to adapt their coding range dynamically to the current reward context. Adaptation ensures that the reward system is most sensitive for the most likely rewards, enabling the system to efficiently represent a potentially infinite range of reward information. A deficit in neural adaptation would prevent precise representation of rewards and could have detrimental effects for an organism’s ability to optimally engage with its environment. In schizophrenia, reward processing is known to be impaired and has been linked to different symptom dimensions. However, despite the fundamental significance of coding reward adaptively, no study has elucidated whether adaptive reward processing is impaired in schizophrenia. We therefore studied patients with schizophrenia (n=27) and healthy controls (n=25), using functional magnetic resonance imaging in combination with a variant of the monetary incentive delay task. Compared with healthy controls, patients with schizophrenia showed less efficient neural adaptation to the current reward context, which leads to imprecise neural representation of reward. Importantly, the deficit correlated with total symptom severity. Our results suggest that some of the deficits in reward processing in schizophrenia might be due to inefficient neural adaptation to the current reward context. Furthermore, because adaptive coding is a ubiquitous feature of the brain, we believe that our findings provide an avenue in defining a general impairment in neural information processing underlying this debilitating disorder

Apathy in schizophrenia as a deficit in the generation of options for action

Negative symptoms are a core feature of schizophrenia and have been grouped into 2 factors: a motivational factor, which we refer to as apathy, and a diminished expression factor. Recent studies have shown that apathy is closely linked to functional outcome. However, knowledge about its mechanisms and its relation to decision-making is limited. In the current study, we examined whether apathy in schizophrenia is associated with predecisional deficits, that is, deficits in the generation of options for action. We applied verbal protocol analysis to investigate the quantity of options generated in ill-structured real world scenarios in 30 patients with schizophrenia or schizoaffective disorder and 21 healthy control participants. Patients generated significantly fewer options than control participants and clinical apathy ratings correlated negatively with the quantity of generated options. We show that the association between measures of psychopathology and option generation is most pronounced in regard to apathy symptoms and that it is only partially mediated by deficits in verbal fluency. This study provides empirical support for dysfunctional option generation as a possible mechanism for apathy in schizophrenia. Our data emphasize the potential importance of predecisional stages in the development and persistence of apathy symptoms in neuropsychiatric disorders and might also inform the development of novel treatment options in the realm of cognitive remediation

Combining actigraphy, ecological momentary assessment and neuroimaging to study apathy in patients with schizophrenia

Apathy can be defined as a reduction of goal-directed behavior and is a strong predictor for poor functional outcome in schizophrenia. However, no objective measure of apathy has been identified and assessment is limited to retrospective interview-based ratings. Here we aimed to identify more precise objective readouts of apathy for translational research and clinical practice

The association of neurocognitive impairment with diminished expression and apathy in schizophrenia

Negative symptoms can be grouped into the two dimensions of diminished expression and apathy, which have been shown to be dissociable regarding external validators, such as functional outcome. Here, we investigated whether these two dimensions differentially relate to neurocognitive impairment in schizophrenia. 47 patients with schizophrenia or schizoaffective disorder and 33 healthy control participants were subjected to a neurocognitive test battery assessing multiple cognitive domains (processing speed, working memory, verbal fluency, verbal learning and memory, mental planning), which are integrated into a composite cognition score. Negative symptoms in patients were assessed using the Brief Negative Symptom Scale. We found that diminished expression significantly related to neurocognitive impairment, while severity of apathy symptoms was not directly associated with neurocognition. Other assessed clinical variables include chlorpromazine equivalents, positive symptoms, and depressive symptoms and did not influence the results. Our results are in line with a cognitive resource limitation model of diminished expression in schizophrenia and indicate that cognitive remediation therapy might be helpful to ameliorate expressive deficits

The brief negative symptom scale: validation of the German translation and convergent validity with self-rated anhedonia and observer-rated apathy

Negative symptoms are considered core symptoms of schizophrenia. The Brief Negative Symptom Scale (BNSS) was developed to measure this symptomatic dimension according to a current consensus definition. The present study examined the psychometric properties of the German version of the BNSS. To expand former findings on convergent validity, we employed the Temporal Experience Pleasure Scale (TEPS), a hedonic self-report that distinguishes between consummatory and anticipatory pleasure. Additionally, we addressed convergent validity with observer-rated assessment of apathy with the Apathy Evaluation Scale (AES), which was completed by the patient's primary nurse

Ventral striatal hypoactivation is associated with apathy but not diminished expression in patients with schizophrenia

BACKGROUND: Negative symptoms of schizophrenia can be grouped in 2 dimensions: apathy and diminished expression. Increasing evidence suggests that negative symptoms are associated with altered neural activity of subcortical and cortical regions in the brain reward system. However, the neurobiological basis of the distinct symptom dimensions within negative symptoms is still poorly understood. The primary aim of our study was to examine the neural correlates of the negative symptom dimensions apathy and diminished expression during a reward processing task. METHODS: Patients with schizophrenia and healthy controls underwent event-related fMRI while performing a variant of the Monetary Incentive Delay Task. We assessed negative symptom dimensions using the Brief Negative Symptom Scale. RESULTS: We included 27 patients and 25 controls in our study. Both groups showed neural activation indicated by blood oxygen-level dependent signal in the ventral striatum during reward anticipation. Ventral striatal activation during reward anticipation showed a strong negative correlation with apathy. Importantly, this effect was not driven by cognitive ability, medication, depressive or positive symptoms. In contrast, no significant correlation with the diminished expression dimension was observed. LIMITATIONS: Although the results remain significant when controlling for chlorpromazine equivalents, we cannot fully exclude potential confounding effects of medication with atypical antipsychotics. CONCLUSION: The specific correlation of ventral striatal hypoactivation during reward anticipation with apathy demonstrates a differentiation of apathy and diminished expression on a neurobiological level and provides strong evidence for different pathophysiological mechanisms underlying these 2 negative symptom dimensions. Our findings contribute to a multilevel framework in which apathy and motivational impairment in patients with schizophrenia can be described on psychopathological, behavioural and neural levels

Apathy in schizophrenia as a deficit in the generation of options for action

Negative symptoms are a core feature of schizophrenia and have been grouped into 2 factors: a motivational factor, which we refer to as apathy, and a diminished expression factor. Recent studies have shown that apathy is closely linked to functional outcome. However, knowledge about its mechanisms and its relation to decision-making is limited. In the current study, we examined whether apathy in schizophrenia is associated with predecisional deficits, that is, deficits in the generation of options for action. We applied verbal protocol analysis to investigate the quantity of options generated in illstructured real world scenarios in 30 patients with schizophrenia or schizoaffective disorder and 21 healthy control participants. Patients generated significantly fewer options than control participants and clinical apathy ratings correlated negatively with the quantity of generated options. We show that the association between measures of psychopathology and option generation is most pronounced in regard to apathy symptoms and that it is only partially mediated by deficits in verbal fluency. This study provides empirical support for dysfunctional option generation as a possible mechanism for apathy in schizophrenia. Our data emphasize the potential importance of predecisional stages in the development and persistence of apathy symptoms in neuropsychiatric disorders and might also inform the development of novel treatment options in the realm of cognitive remediation

Reward-dependent modulation of working memory is associated with negative symptoms in schizophrenia

The negative symptoms of schizophrenia have been associated with altered neural activity during both reward processing and cognitive processing. Even though increasing evidence suggests a strong interaction between these two domains, it has not been studied in relation to negative symptoms. To elucidate neural mechanisms of the reward-cognition interaction, we applied a letter variant of the n-back working memory task and varied the financial incentives for performance. In the interaction contrast, we found a significantly activated cluster in the rostral anterior cingulate cortex (ACC), the middle frontal gyrus, and the bilateral superior frontal gyrus. The interaction did not differ significantly between the patient group and a healthy control group, suggesting that patients with schizophrenia are on average able to integrate reward information and utilize this information to maximize cognitive performance. However within the patient group, we found a significant inverse correlation of ACC activity with the factor diminished expression. This finding is consistent with the model that a lack of available cognitive resources leads to diminished expression. We therefore argue that patients with diminished expression have difficulties in recruiting additional cognitive resources (as implemented in the ACC) in response to an anticipated reward. Due to this lack of cognitive resources, less processing capacity is available for effective expression, resulting in diminished expressive behavior