Deficits in context-dependent adaptive coding of reward in schizophrenia.
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ABSTRACT:
SUBMITTER: Kirschner M
PROVIDER: S-EPMC4945098 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPeople with schizophrenia (PSZ) have profound deficits in context processing, an executive process that guides adaptive behaviors according to goals and stored contextual information. Although various neural processes are involved in context processing and are affected in PSZ, the core underlying neural dysfunction is unclear.MethodsTo determine the relative importance of neural dysfunctions within prefrontal cognitive control, sensory activity, and motor activity to context processing deficits in PSZ, we examined event-related potentials (ERPs) in 60 PSZ and 51 healthy control subjects during an optimal context processing task. We also analyzed the Ex-Gaussian reaction time distribution to examine abnormalities in motor control variability in PSZ.ResultsCompared with healthy control subjects, PSZ had lower response accuracy and greater variability in their normal reaction times during high context processing demands. Latencies of normal and slow responses were generally increased in PSZ. High context processing-related reductions in frontal ERPs were indicative of specific deficits in proactive and reactive cognitive controls in PSZ, while ERPs associated with visual and motor processes were reduced regardless of context processing demands, indicating generalized visuomotor deficits. In contrast to previous studies, we found that diminished frontal responses reflective of proactive control of the contextual cue, rather than visual responses of cue encoding, predicted response accuracy deficits in PSZ. In addition, probe-related ERP components of motor preparation, prefrontal reactive control, and frontomotor interaction predicted Ex-Gaussian indices of reaction time instability in PSZ.ConclusionsPrefrontal proactive and reactive control deficits associated with failures in using mental representation likely underlie context processing deficits in PSZ.
| S-EPMC6612435 | biostudies-literature
Project description:Schizophrenia has been associated with differences in how the visual system processes sensory input. A fundamental mechanism that regulates sensory processing in the brain is gain control, whereby the responses of sensory neurons to a given stimulus are modulated in accordance with the spatial and temporal context. Some studies indicate an impairment of certain cortical gain control mechanisms in schizophrenia in low-level vision, reflected, for instance, in how the visual appearance of a stimulus is affected by the presence of other stimuli around it. In the present study, we investigated higher-level, social vision in schizophrenia, namely the perception of other people's direction of gaze (i.e. a type of face processing). Recent computational modelling work indicates that perceptual aftereffects-changes in perception that occur following repeated exposure to faces that display a specific direction of gaze-are indicative of two distinct forms of gain control involved in the coding of gaze direction across sensory neurons. We find that individuals with schizophrenia display strong perceptual aftereffects following repeated exposure to faces with averted gaze, and a modelling analysis indicates similarly robust gain control in the form of (i) short-term adjustment of channel sensitivities in response to the recent sensory history and (ii) divisive normalization of the encoded gaze direction. Together, this speaks to the typical coding of other people's direction of gaze in the visual system in schizophrenia, including flexible gain control, despite the social-cognitive impairments that can occur in this condition.
| S-EPMC6304156 | biostudies-literature
Project description:To efficiently represent all of the possible rewards in the world, dopaminergic midbrain neurons dynamically adapt their coding range to the momentarily available rewards. Specifically, these neurons increase their activity for an outcome that is better than expected and decrease it for an outcome worse than expected, independent of the absolute reward magnitude. Although this adaptive coding is well documented, it remains unknown how this rescaling is implemented. To investigate the adaptive coding of prediction errors and its underlying rescaling process, we used human functional magnetic resonance imaging (fMRI) in combination with a reward prediction task that involved different reward magnitudes. We demonstrate that reward prediction errors in the human striatum are expressed according to an adaptive coding scheme. Strikingly, we show that adaptive coding is gated by changes in effective connectivity between the striatum and other reward-sensitive regions, namely the midbrain and the medial prefrontal cortex. Our results provide evidence that striatal prediction errors are normalized by a magnitude-dependent alteration in the interregional connectivity within the brain's reward system.
| S-EPMC3306682 | biostudies-literature
Project description:Negative symptoms of schizophrenia are debilitating and chronic in nature, are difficult to treat, and contribute to poor functional outcomes. Motivational deficits are a core negative symptom and may involve alterations in reward processing, which involve subcortical regions such as the basal ganglia. More specifically, dopamine-rich regions like the ventral striatum, have been implicated in these reward-processing deficits. Inflammation is one mechanism that may underlie negative symptoms, and specifically motivational deficits, via the effects of inflammatory cytokines on the basal ganglia. Previous work has demonstrated that inflammatory stimuli decrease neural activity in the ventral striatum and decrease connectivity in reward-relevant neural circuitry. The immune system has been shown to be involved in the pathophysiology of schizophrenia, and inflammatory cytokines have been shown to be altered in patients with the disorder. This paper reviews the literature on associations between inflammatory markers and negative symptoms of schizophrenia as well as the role of anti-inflammatory drugs to target negative symptoms. We also review the literature on the role of inflammation and reward processing deficits in both healthy controls and individuals with depression. We use the literature on inflammation and depression as a basis for a model that explores potential mechanisms responsible for inflammation modulating certain aspects of negative symptoms in patients with schizophrenia. This approach may offer novel targets to treat these symptoms of the disorder that are significant barriers to functional recovery and do not respond well to available antipsychotic medications.
| S-EPMC7044128 | biostudies-literature
Project description:Context-processing deficits have been shown in schizophrenia during first-episode, medication-naïve status, that persist after short-term antipsychotic treatment and also in first-degree relatives of individuals with schizophrenia. To confirm longer term persistence of deficits, we examined schizophrenia patients (n=63) during first-episode, medication-naïve status through to one-year follow-up, compared to healthy control (n=83) and non-schizophrenia psychosis comparison (n=47) groups, as well as unaffected first-degree relatives of individuals with schizophrenia (n=31). Context-processing ability was assessed by performance on the AX-CPT (Continuous Performance Test) at baseline, 8 weeks, 6 months, and 1 year (relatives only at baseline). Reaction time, error rates and signal detection indices (d'-context) of context processing were analyzed. Linear discriminant analyses (LDA) on early timepoints (baseline, 8 weeks) were conducted to predict confirmatory diagnosis (schizophrenia vs. psychosis control) at 6 months. Schizophrenia patients showed evidence of impaired context-processing relative to both the healthy and psychosis comparator groups at baseline and continued through to 1 year. While context-processing impairments persisted in schizophrenia patients through one year, the impairments in psychosis controls, which were more modest at baseline, remitted at follow-up. First-degree relatives showed deficits that were intermediate between the schizophrenia and healthy control groups. LDA showed 67% classification rates for distinguishing schizophrenia from non-schizophrenia psychosis. The persistence, diagnostic specificity and association with genetic liability give support for context processing impairments serving as a cognitive endophenotype for schizophrenia and evaluation of context processing could contribute to diagnostic assessments.
| S-EPMC3650125 | biostudies-literature
Project description: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.
| S-EPMC5068811 | biostudies-other
Project description:BackgroundReinforcement learning has been proposed to contribute to the development of amotivation in individuals with schizophrenia (SZ). Accumulating evidence suggests dysfunctional learning in individuals with SZ in Go/NoGo learning and expected value representation. However, previous findings might have been confounded by the effects of antipsychotic exposure. Moreover, reinforcement learning also rely on the learning context. Few studies have examined the learning performance in reward and loss-avoidance context separately in medication-naïve individuals with first-episode SZ. This study aimed to explore the behaviour profile of reinforcement learning performance in medication-naïve individuals with first-episode SZ, including the contextual performance, the Go/NoGo learning and the expected value representation performance.MethodsTwenty-nine medication-naïve individuals with first-episode SZ and 40 healthy controls (HCs) who have no significant difference in age and gender, completed the Gain and Loss Avoidance Task, a reinforcement learning task involving stimulus pairs presented in both the reward and loss-avoidance context. We assessed the group difference in accuracy in the reward and loss-avoidance context, the Go/NoGo learning and the expected value representation. The correlations between learning performance and the negative symptom severity were examined.ResultsIndividuals with SZ showed significantly lower accuracy when learning under the reward than the loss-avoidance context as compared to HCs. The accuracies under the reward context (90%win- 10%win) in the Acquisition phase was significantly and negatively correlated with the Scale for the Assessment of Negative Symptoms (SANS) avolition scores in individuals with SZ. On the other hand, individuals with SZ showed spared ability of Go/NoGo learning and expected value representation.ConclusionsDespite our small sample size and relatively modest findings, our results suggest possible reduced learning bias towards reward context among medication-naïve individuals with first-episode SZ. The reward learning performance was correlated with amotivation symptoms. This finding may facilitate our understanding of the underlying mechanism of negative symptoms. Reinforcement learning performance under the reward context may be important to better predict and prevent the development of schizophrenia patients' negative symptom, especially amotivation.
| S-EPMC8851841 | biostudies-literature
Project description:Prominent neurobiological theories of addiction posit a central role for aberrant mesolimbic dopamine release but disagree as to whether repeated drug experience blunts or enhances this system. Although drug withdrawal diminishes dopamine release, drug sensitization augments mesolimbic function, and both processes have been linked to drug seeking. One possibility is that the dopamine system can rapidly switch from dampened to enhanced release depending on the specific drug-predictive environment. To test this, we examined dopamine release when cues signaled delayed cocaine delivery versus imminent cocaine self-administration.Fast-scan cyclic voltammetry was used to examine real-time dopamine release while simultaneously monitoring behavioral indexes of aversion as rats experienced a sweet taste cue that predicted delayed cocaine availability and during self-administration. Furthermore, the impact of cues signaling delayed drug availability on intracranial self-stimulation, a broad measure of reward function, was assessed.We observed decreased mesolimbic dopamine concentrations, decreased reward sensitivity, and negative affect in response to the cocaine-predictive taste cue that signaled delayed cocaine availability. Importantly, dopamine concentration rapidly switched to elevated levels to cues signaling imminent cocaine delivery in the subsequent self-administration session.These findings show rapid, bivalent contextual control over brain reward processing, affect, and motivated behavior and have implications for mechanisms mediating substance abuse.
| S-EPMC3090459 | biostudies-literature
Project description:BackgroundRecent theoretical models of schizophrenia posit that dysfunction of the neural mechanisms subserving predictive coding contributes to symptoms and cognitive deficits, and this dysfunction is further posited to result from N-methyl-D-aspartate glutamate receptor (NMDAR) hypofunction. Previously, by examining auditory cortical responses to self-generated speech sounds, we demonstrated that predictive coding during vocalization is disrupted in schizophrenia. To test the hypothesized contribution of NMDAR hypofunction to this disruption, we examined the effects of the NMDAR antagonist, ketamine, on predictive coding during vocalization in healthy volunteers and compared them with the effects of schizophrenia.MethodsIn two separate studies, the N1 component of the event-related potential elicited by speech sounds during vocalization (talk) and passive playback (listen) were compared to assess the degree of N1 suppression during vocalization, a putative measure of auditory predictive coding. In the crossover study, 31 healthy volunteers completed two randomly ordered test days, a saline day and a ketamine day. Event-related potentials during the talk/listen task were obtained before infusion and during infusion on both days, and N1 amplitudes were compared across days. In the case-control study, N1 amplitudes from 34 schizophrenia patients and 33 healthy control volunteers were compared.ResultsN1 suppression to self-produced vocalizations was significantly and similarly diminished by ketamine (Cohen's d = 1.14) and schizophrenia (Cohen's d = .85).ConclusionsDisruption of NMDARs causes dysfunction in predictive coding during vocalization in a manner similar to the dysfunction observed in schizophrenia patients, consistent with the theorized contribution of NMDAR hypofunction to predictive coding deficits in schizophrenia.
| S-EPMC5203970 | biostudies-literature
Project description:Poor context integration, the process of incorporating both previous and current information in decision making, is a cognitive symptom of schizophrenia. The maintenance of the contextual information has been shown to be sensitive to changes in excitation-inhibition (EI) balance. Many regions of the brain are sensitive to EI imbalances, however, so it is unknown how systemic manipulations affect the specific regions that are important to context integration. We constructed a multi-structure, biophysically-realistic agent that could perform context-integration as is assessed by the dot pattern expectancy task. The agent included a perceptual network, a memory network, and a decision making system and was capable of successfully performing the dot pattern expectancy task. Systemic manipulation of the agent's EI balance produced localized dysfunction of the memory structure, which resulted in schizophrenia-like deficits at context integration. When the agent's pyramidal cells were less excitatory, the agent fixated upon the cue and initiated responding later than the default agent, which were like the deficits one would predict that individuals on the autistic spectrum would make. This modelling suggests that it may be possible to parse between different types of context integration deficits by adding distractors to context integration tasks and by closely examining a participant's reaction times.
| S-EPMC8184155 | biostudies-literature