Reward Processing In Schizophrenia Research Articles

Pupillary responses as a biomarker of cognitive effort and the impact of task difficulty on reward processing in schizophrenia

Negative symptoms of schizophrenia robustly predict functional outcomes but remain relatively resistant to available treatments. Better measures of negative symptoms, especially motivational deficits, are needed to better understand these symptoms and improve treatment development. Recent research shows promise in linking behavioral effort tasks to motivational negative symptoms, reward processing deficits, and defeatist attitudes, but few studies account for individual or group (patient v. control) differences in cognitive ability to perform the tasks. Individuals with poorer abilities might be less motivated to perform tasks because they find them more difficult to perform. This study used a personalized digit span task to control task difficulty while measuring task effort via pupillary responses (greater dilation indicates greater cognitive effort) at varying monetary rewards ($1 & $2). Participants with schizophrenia (N = 34) and healthy controls (N = 41) performed a digit span task with personalized max span lengths and easy (max− 2 digits) and overload (max+ 2 digits) conditions. Consistent with many studies, pupillary responses (cognitive effort) increased with greater difficulty until exceeding capacity. A similar pattern of reward responsivity was seen in both groups, such that greater reward increased dilation (effort) comparably for both groups when difficulty was within capacity. Neither patients nor controls exerted increased effort for greater reward when difficulty exceeded capacity. In patients, positive relationships were found between pupil dilation and defeatist performance beliefs if task difficulty was within capacity; a relationship that reversed if the task was too difficult. The findings demonstrate the importance of accounting for cognitive capacity and task difficulty when evaluating motivation and reward sensitivity and illustrate the utility of pupillary responses as an objective measure of effort in schizophrenia.

Reduced Reward Processing in Schizophrenia: A Comprehensive EEG Event-Related Oscillation Study.

It is well known that abnormal reward processing is a characteristic feature of various psychopathologies including schizophrenia (SZ). Reduced reward anticipation has been suggested as a core symptom of SZ. The present study aims to evaluate the event-related oscillations (EROs) delta, theta, alpha, beta, and gamma in patients with SZ during the Monetary Incentive Delay (MID) task, which elicits the neural activity of reward processing. Twenty-one patients with SZ and twenty-two demographically matched healthy controls were included in the study. EROs were compared between groups and correlation analyses were conducted to determine a possible relationship between clinical scores and ERO values. Compared with healthy controls, the SZ group had reduced (1) delta and theta amplitudes in the reward condition (2) total beta and non-incentive cue-related beta amplitudes, and (3) incentive cue-related frontal gamma amplitudes. These reductions can be interpreted as impaired dopaminergic neurotransmission and disrupted cognitive functioning in the reward processing of SZ. In contrast, SZ patients showed higher incentive cue-related theta and occipital gamma amplitudes compared to controls. These increments may reflect negative symptoms in SZ. Moreover, theta amplitudes showed a negative correlation with Calgary Depression Scale for Schizophrenia scores and a positive correlation with attentional impulsivity. This is the first study showing the impairments of SZ patients in EROs from delta to gamma frequency bands compared with healthy controls during reward anticipation. Being the first comprehensive study, our results can be interpreted as providing evidence for disrupted brain dynamics in the reward processing of SZ studied by EROs. It may become possible to help patients' wellness by improving our understanding of reward processing in schizophrenia and developing innovative rehabilitation treatments based on these findings.

Alpha Event-Related Desynchronization During Reward Processing in Schizophrenia

BackgroundAlterations in the brain’s reward system may underlie motivation and pleasure deficits in schizophrenia (SZ). Neuro-oscillatory desynchronization in the alpha band is thought to direct resource allocation away from the internal state, to prioritize processing salient environmental events, including reward feedback. We hypothesized reduced reward-related alpha event-related desynchronization (ERD) in SZ, consistent with less externally focused processing during reward feedback. MethodsElectroencephalography was recorded while participants with SZ (n = 54) and healthy control participants (n = 54) played a simple slot machine task. Total alpha band power (8–14 Hz), a measure of neural oscillation magnitude, was extracted via principal component analysis and compared between groups and reward outcomes. The clinical relevance of hypothesized alpha power alterations was examined by testing associations with negative symptoms within the SZ group and with trait rumination, dimensionally, across groups. ResultsA group × reward outcome interaction (p = .018) was explained by healthy control participants showing significant posterior-occipital alpha power suppression to wins versus losses (p < .001), in contrast to participants with SZ (p > .1). Among participants with SZ, this alpha ERD was unrelated to negative symptoms (p > .1). Across all participants, less alpha ERD to reward outcomes covaried with greater trait rumination for both win (p = .005) and loss (p = .002) outcomes, with no group differences in slope. ConclusionsThese findings demonstrate alpha ERD alterations in SZ during reward outcome processing. Additionally, higher trait rumination was associated with less alpha ERD during reward feedback, suggesting that individual differences in rumination covary with external attention to reward processing, regardless of reward outcome valence or group membership.

Reward processing in schizophrenia and its relation to Mu opioid receptor availability and negative symptoms: A [11C]-carfentanil PET and fMRI study

BackgroundReward processing deficits are a core feature of schizophrenia and are thought to underlie negative symptoms. Pre-clinical evidence suggests that opioid neurotransmission is linked to reward processing. However, the contribution of Mu Opioid Receptor (MOR) signalling to the reward processing abnormalities in schizophrenia is unknown. Here, we examined the association between MOR availability and the neural processes underlying reward anticipation in patients with schizophrenia using multimodal neuroimaging. Method37 subjects (18 with Schizophrenia with moderate severity negative symptoms and 19 age and sex-matched healthy controls) underwent a functional MRI scan while performing the Monetary Incentive Delay (MID) task to measure the neural response to reward anticipation. Participants also had a [11C]-carfentanil PET scan to measure MOR availability. ResultsReward anticipation was associated with increased neural activation in a widespread network of brain regions including the striatum. Patients with schizophrenia had both significantly lower MOR availability in the striatum as well as striatal hypoactivation during reward anticipation. However, there was no association between MOR availability and striatal neural activity during reward anticipation in either patient or controls (Pearson's Correlation, controls df = 17, r = 0.321, p = 0.18, patients df = 16, r = 0.295, p = 0.24). There was no association between anticipation-related neural activation and negative symptoms (r = –0.120, p = 0.14) or anhedonia severity (social r = –0.365, p = 0.14 physical r = –0.120, p = 0.63). ConclusionsOur data suggest reduced MOR availability in schizophrenia might not underlie striatal hypoactivation during reward anticipation in patients with established illness. Therefore, other mechanisms, such as dopamine dysfunction, warrant further investigation as treatment targets for this aspect of the disorder.

Aberrant reward processing to positive versus negative outcomes across psychotic disorders

Several studies of reward processing in schizophrenia have shown reduced sensitivity to positive, but not negative, outcomes although inconsistencies have been reported. In addition, few studies have investigated whether patients show a relative deficit to social versus nonsocial rewards, whether deficits occur across the spectrum of psychosis, or whether deficits relate to negative symptoms and functioning. This study examined probabilistic implicit learning via two visually distinctive slot machines for social and nonsocial rewards in 101 outpatients with diverse psychotic disorders and 48 community controls. The task consisted of two trial types: positive (optimal to choose a positive vs. neutral machine) and negative (optimal to choose a neutral vs. negative machine), with two reward conditions: social (faces) and nonsocial (money) reward conditions. A significant group X trial type interaction indicated that controls performed better on positive than negative trials, whereas patients showed the opposite pattern of better performance on negative than positive trials. In addition, both groups performed better for social than nonsocial stimuli, despite lower overall task performance in patients. Within patients, worse performance on negative trials showed significant, small-to-moderate correlations with motivation and pleasure-related negative symptoms and social functioning. The current findings suggest reward processing disturbances, particularly decreased sensitivity to positive outcomes, extend beyond schizophrenia to a broader spectrum of psychotic disorders and relate to important clinical outcomes.

Psychological Dimensions Relevant to Motivation and Pleasure in Schizophrenia.

Motivation and pleasure deficits are common in schizophrenia, strongly linked with poorer functioning, and may reflect underlying alterations in brain functions governing reward processing and goal pursuit. While there is extensive research examining cognitive and reward mechanisms related to these deficits in schizophrenia, less attention has been paid to psychological characteristics that contribute to resilience against, or risk for, motivation and pleasure impairment. For example, psychological tendencies involving positive future expectancies (e.g., optimism) and effective affect management (e.g., reappraisal, mindfulness) are associated with aspects of reward anticipation and evaluation that optimally guide goal-directed behavior. Conversely, maladaptive thinking patterns (e.g., defeatist performance beliefs, asocial beliefs) and tendencies that amplify negative cognitions (e.g., rumination), may divert cognitive resources away from goal pursuit or reduce willingness to exert effort. Additionally, aspects of sociality, including the propensity to experience social connection as positive reinforcement may be particularly relevant for pursuing social goals. In the current review, we discuss the roles of several psychological characteristics with respect to motivation and pleasure in schizophrenia. We argue that individual variation in these psychological dimensions is relevant to the study of motivation and reward processing in schizophrenia, including interactions between these psychological dimensions and more well-characterized cognitive and reward processing contributors to motivation. We close by emphasizing the value of considering a broad set of modulating factors when studying motivation and pleasure functions in schizophrenia.

Alterations of oscillatory neuronal activity during reward processing in schizophrenia

ObjectivesReward system dysfunctions are considered to be a pathophysiological mechanism in schizophrenia. Electrophysiological studies of reward system functions have identified frequency-specific brain networks for the processing of positive (high-beta frequency) and negative (theta frequency) events. Remarkably, midbrain dopaminergic signalling also includes theta and high-beta frequency modes, which have been assumed to reflect tonic and phasic dopamine responses, respectively. The aim of the present study was to identify alterations of oscillatory responses to reward feedback in patients with schizophrenia. MethodsSeventeen patients with schizophrenia and 18 healthy controls performed a gambling task during recording of 64-channel electroencephalography. The theta and high-beta band total power were investigated in response to feedback events depending on feedback valence (loss or gain) and magnitude (5 vs. 25 points). ResultsBoth the increase of theta oscillatory activity in response to loss feedback (compared to gain feedback) and the increase of high-beta oscillatory activity in response to gain feedback (compared to loss feedback) were reduced in patients. The difference in high-beta responses to gain versus loss feedback in patients was associated with the severity of negative symptoms. ConclusionsOur findings are consistent with current models of reward system dysfunction in schizophrenia, and indicate deficits in both cortical tonic and subcortical phasic dopamine activity, consistent with the complex dopaminergic abnormalities in schizophrenia.

Retinal functioning and reward processing in schizophrenia

Retinal responses to light, as measured by electroretinography (ERG), have been shown to be reduced in schizophrenia. Data from a prior ERG study in healthy humans indicated that activity of a retinal cell type affected in schizophrenia can be modified by the presence of a food reward. Therefore, we aimed to determine whether ERG amplitudes would be sensitive to the well-documented reward processing impairment in schizophrenia. Flash ERG data from 15 clinically stable people with schizophrenia or schizoaffective disorder and 15 healthy controls were collected under three conditions: baseline, anticipation of a food reward, and immediately after consuming the food reward. At the group level, data indicated that controls' ERG responses varied as a function of salience of the food reward (baseline vs. anticipation vs. consumption) whereas patients' ERG responses did not vary significantly across conditions. Correlations between ERG amplitudes and scores on measures of hedonic capacity (including motivation and pleasure negative symptom ratings for patients) indicated consistent relationships. These data suggest that flash ERG amplitudes may be a sensitive indicator of the integrity of reward processing mechanisms. However, several differences in the direction of findings between this and a prior study in controls point to the need for further investigation of the contributions of a number of key variables to the observed effects.

147. Social Cognitive Training Improves Measures of Reward Processing in Schizophrenia

Social cognition, reward processing, and motivation are associated in ways which are not yet fully understood. For example, social and monetary reward learning share overlapping neural substrates in humans, and both forms of learning are impaired in schizophrenia. We hypothesized that social cognition impairments in schizophrenia impede ecologically meaningful reward processing and contribute to decreased motivation and reduced functioning.

145. Social Cognitive Training Enhances Neural Activation Patterns Associated With Reward Processing in Schizophrenia

Amotivation in schizophrenia is a central predictor of poor functioning and is thought to occur due to deficits in anticipating future rewards, suggesting that impairments in anticipating pleasure can contribute to functional disability in schizophrenia. In healthy controls (HC), reward motivation is associated with anticipatory activity in frontal-striatal networks. By contrast, schizophrenia participants (SZ) show hypoactivation within these frontal-striatal networks during this motivated anticipatory brain state. Here, we investigated whether intensive computerized social cognitive training in schizophrenia could increase activity within frontal-striatal circuits to improve motivation during the anticipatory phase of stimuli that predicted upcoming reward.

Mechanistic Science: A New Approach to Comprehensive Psychopathology Research That Relates Psychological and Biological Phenomena

Efforts to understand the causes of psychopathology have remained stifled in part because current practices do not clearly describe how psychological constructs differ from biological phenomena and how to integrate them in unified explanations. The present article extends recent work in philosophy of science by proposing a framework called mechanistic science as a promising way forward. This approach maintains that integrating psychological and biological phenomena involves demonstrating how psychological functions are implemented in biological structures. Successful early attempts to advance mechanistic explanations of psychological phenomena are reviewed, and lessons are derived to show how the framework can be applied to a range of clinical psychological phenomena, including gene by environment findings, computational models of reward processing in schizophrenia, and self-related processes in personality pathology. Pursuing a mechanistic approach can ultimately facilitate more productive and successful collaborations across a range of disciplines.

T217. Measures of Neural Oscillation Synchrony During Reward Processing in Schizophrenia

Relatively little is known about the extent to which reward processing deficits persist in schizophrenia in the absence of response planning and execution demands. We therefore used a passive reward paradigm to assess neural oscillation synchrony during anticipation and receipt of monetary rewards in patients with schizophrenia (n=45) in comparison to demographically-matched healthy controls (n=42).

M71. Altered Multi-Voxel Prefrontal and Mesolimbic Patterns Associated With Reward Processing in Schizophrenia: Evidence From Representational Similarity Analysis

M71. Altered Multi-Voxel Prefrontal and Mesolimbic Patterns Associated With Reward Processing in Schizophrenia: Evidence From Representational Similarity Analysis

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.

Abnormal context-reward associations in an immune-mediated neurodevelopmental mouse model with relevance to schizophrenia.

Impairments in central reward processing constitute an important aspect of the negative symptoms of schizophrenia. Despite its clinical relevance, the etiology of deficient reward processing in schizophrenia remains largely unknown. Here, we used an epidemiologically informed mouse model of schizophrenia to explore the effects of prenatal immune activation on reward-related functions. The model is based on maternal administration of the viral mimic PolyI:C and has been developed in relation to the epidemiological evidence demonstrating enhanced risk of schizophrenia and related disorders following prenatal maternal infection. We show that prenatal immune activation induces selective deficits in the expression (but not acquisition) of conditioned place preference for a natural reward (sucrose) without changing hedonic or neophobic responses to the reward. On the other hand, prenatal immune activation led to enhanced place preference for the psychostimulant drug cocaine, while it attenuated the locomotor reaction to the drug. The prenatal exposure did not alter negative reinforcement learning as assessed using a contextual fear conditioning paradigm. Our findings suggest that the nature of reward-related abnormalities following prenatal immune challenge depends on the specificity of the reward (natural reward vs drug of abuse) as well as on the valence domain (positive vs negative reinforcement learning). Moreover, our data indicate that reward abnormalities emerging in prenatally immune-challenged offspring may, at least in part, stem from an inability to retrieve previously established context–reward associations and to integrate such information for appropriate goal-directed behavior.

Translational Rodent Paradigms to Investigate Neuromechanisms Underlying Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia.

Amotivation and reward-processing deficits have long been described in patients with schizophrenia and considered large contributors to patients' inability to integrate well in society. No effective treatments exist for these symptoms, partly because the neuromechanisms mediating such symptoms are poorly understood. Here, we propose a translational neuroscientific approach that can be used to assess reward/motivational deficits related to the negative symptoms of schizophrenia using behavioral paradigms that can also be conducted in experimental animals. By designing and using objective laboratory behavioral tools that are parallel in their parameters in rodents and humans, the neuromechanisms underlying behaviors with relevance to these symptoms of schizophrenia can be investigated. We describe tasks that measure the motivation of rodents to expend physical and cognitive effort to gain rewards, as well as probabilistic learning tasks that assess both reward learning and feedback-based decision making. The latter tasks are relevant because of demonstrated links of performance deficits correlating with negative symptoms in patients with schizophrenia. These tasks utilize operant techniques in order to investigate neural circuits targeting a specific domain across species. These tasks therefore enable the development of insights into altered mechanisms leading to negative symptom-relevant behaviors in patients with schizophrenia. Such findings will then enable the development of targeted treatments for these altered neuromechanisms and behaviors seen in schizophrenia.

A Review of Reward Processing and Motivational Impairment in Schizophrenia

This article reviews and synthesizes research on reward processing in schizophrenia, which has begun to provide important insights into the cognitive and neural mechanisms associated with motivational impairments. Aberrant cortical-striatal interactions may be involved with multiple reward processing abnormalities, including: (1) dopamine-mediated basal ganglia systems that support reinforcement learning and the ability to predict cues that lead to rewarding outcomes; (2) orbitofrontal cortex-driven deficits in generating, updating, and maintaining value representations; (3) aberrant effort-value computations, which may be mediated by disrupted anterior cingulate cortex and midbrain dopamine functioning; and (4) altered activation of the prefrontal cortex, which is important for generating exploratory behaviors in environments where reward outcomes are uncertain. It will be important for psychosocial interventions targeting negative symptoms to account for abnormalities in each of these reward processes, which may also have important interactions; suggestions for novel behavioral intervention strategies that make use of external cues, reinforcers, and mobile technology are discussed.

Salience network-midbrain dysconnectivity and blunted reward signals in schizophrenia

Theories of schizophrenia propose that abnormal functioning of the neural reward system is linked to negative and psychotic symptoms, by disruption of reward processing and promotion of context-independent false associations. Recently, it has been argued that an insula–anterior cingulate cortex (ACC) salience network system enables switching of brain states from the default mode to a task-related activity mode. Abnormal interaction between the insula–ACC system and reward processing regions may help explain abnormal reinforcer processing and symptoms. Here we use functional magnetic resonance imaging to assess the neural correlates of reward processing in schizophrenia. Furthermore, we investigated functional connectivity between the dopaminergic midbrain, a key region for the processing of reinforcers, and other brain regions. In response to rewards, controls activated task related regions (striatum, amygdala/hippocampus and midbrain) and the insula–ACC salience network. Patients similarly activated the insula–ACC salience network system but failed to activate task related regions. Reduced functional connectivity between the midbrain and the insula was found in schizophrenia, with the extent of this abnormality correlating with increased psychotic symptoms. The findings support the notion that reward processing is abnormal in schizophrenia and highlight the potential role of abnormal interactions between the insula–ACC salience network and reward regions.

Influence of apathy and depressive symptoms on reward processing in schizophrenia

The 15th Biennial Winter Workshop in Psychoses, 15–18 November 2009, Barcelona, Spain: IMAGING AND NEUROPATHOLOGY

The relevance of reward pathways for schizophrenia

There has been a resurgence of interest in the field of reward processing in schizophrenia in recent years, aided by insights from functional neuroimaging. We examine how disturbances in reward-related processes relate to the pathophysiology and symptomatology of this disorder. Behavioural and functional neuroimaging studies in psychosis demonstrate impairments in the representation of reward value and in reward-related learning and a failure to motivate behaviour for incentives. These impairments are linked to abnormal mesocorticolimbic and mesostriatal function. Abnormalities in reward processing offer insights into the symptomatology of schizophrenia and its underlying neurobiology. Further investigation is required into the specificity of these deficits to particular symptom expression and to what extent they are improved by antipsychotic treatment.