Abnormal prediction error processing in schizophrenia and depression.
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ABSTRACT:
SUBMITTER: Yaple ZA
PROVIDER: S-EPMC8249895 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression.
| S-EPMC4526479 | biostudies-literature
Project description:Current theories of cognitive dysfunction in schizophrenia emphasize an impairment in the ability of individuals suffering from this disorder to monitor their own performance, and adjust their behavior to changing demands. Detecting an error in performance is a critical component of evaluative functions that allow the flexible adjustment of behavior to optimize outcomes. The dorsal anterior cingulate cortex (dACC) has been repeatedly implicated in error-detection and implementation of error-based behavioral adjustments. However, accurate error-detection and subsequent behavioral adjustments are unlikely to rely on a single brain region. Recent research demonstrates that regions in the anterior insula, inferior parietal lobule, anterior prefrontal cortex, thalamus, and cerebellum also show robust error-related activity, and integrate into a functional network. Despite the relevance of examining brain activity related to the processing of error information and supporting behavioral adjustments in terms of a distributed network, the contribution of regions outside the dACC to error processing remains poorly understood. To address this question, we used functional magnetic resonance imaging to examine error-related responses in 37 individuals with schizophrenia and 32 healthy controls in regions identified in the basic science literature as being involved in error processing, and determined whether their activity was related to behavioral adjustments. Our imaging results support previous findings showing that regions outside the dACC are sensitive to error commission, and demonstrated that abnormalities in brain responses to errors among individuals with schizophrenia extend beyond the dACC to almost all of the regions involved in error-related processing in controls. However, error related responses in the dACC were most predictive of behavioral adjustments in both groups. Moreover, the integration of this network of regions differed between groups, with the cerebellar regions and the dACC less connected to the network in individuals with schizophrenia compared to controls. Our findings demonstrate a blunted response to error commission in the dACC that is associated with reduced error-related behavioral adjustments in individuals with schizophrenia. This result supports the hypothesis that a failure to respond appropriately to errors in individuals with schizophrenia is linked to alterations in dACC function leading to a compromise in the implementation of cognitive control. Our findings highlight the importance of examining brain activity related to the processing of error information and supporting error-related behavioral adjustments in terms of a distributed network.
| S-EPMC2997133 | biostudies-literature
Project description:Goal-directed human behavior is enabled by hierarchically-organized neural systems that process executive commands associated with higher brain areas in response to sensory and motor signals from lower brain areas. Psychiatric diseases and psychotic conditions are postulated to involve disturbances in these hierarchical network interactions, but the mechanism for how aberrant disease signals are generated in networks, and a systems-level framework linking disease signals to specific psychiatric symptoms remains undetermined. In this study, we show that neural networks containing schizophrenia-like deficits can spontaneously generate uncompensated error signals with properties that explain psychiatric disease symptoms, including fictive perception, altered sense of self, and unpredictable behavior. To distinguish dysfunction at the behavioral versus network level, we monitored the interactive behavior of a humanoid robot driven by the network. Mild perturbations in network connectivity resulted in the spontaneous appearance of uncompensated prediction errors and altered interactions within the network without external changes in behavior, correlating to the fictive sensations and agency experienced by episodic disease patients. In contrast, more severe deficits resulted in unstable network dynamics resulting in overt changes in behavior similar to those observed in chronic disease patients. These findings demonstrate that prediction error disequilibrium may represent an intrinsic property of schizophrenic brain networks reporting the severity and variability of disease symptoms. Moreover, these results support a systems-level model for psychiatric disease that features the spontaneous generation of maladaptive signals in hierarchical neural networks.
| S-EPMC3364276 | biostudies-literature
Project description:The clinical presentation of major depression (MD) is heterogenous and comprises various affective and cognitive symptoms including an increased sensitivity to errors. Various electrophysiological but only few functional magnetic resonance imaging (fMRI) studies investigated neural error processing in MD with inconsistent findings. Thus, reliable evidence regarding neural signatures of error processing in patients with current MD is limited despite its potential relevance as viable neurobiological marker of psychopathology. We therefore investigated a sample of 16 young adult female patients with current MD and 17 healthy controls (HC). During fMRI, we used an established Erikson-flanker Go/NoGo-paradigm and focused on neural alterations during errors of commission. In the absence of significant differences in rates of errors of commission in MD compared to HC, we observed significantly (p < 0.05, FWE-corrected on cluster level) enhanced neural activations of the dorsal anterior cingulate cortex (dACC) and the pre-supplementary motor area (pre-SMA) in MD relative to HC and thus, in brain regions consistently associated to neural error processing and corresponding behavioral adjustments. Considering comparable task performance, in particular similar commission error rates in MD and HC, our results support the evidence regarding an enhanced responsivity of neural error detection mechanisms in MD as a potential neural signature of increased negative feedback sensitivity as one of the core psychopathological features of this disorder.
| S-EPMC8429380 | biostudies-literature
Project description:BackgroundRecent findings demonstrate that patients with schizophrenia are worse at learning to predict rewards than losses, suggesting that motivational context modulates learning in this disease. However, these findings derive from studies in patients treated with antipsychotic medications, D2 receptor antagonists that may interfere with the neural systems that underlie motivation and learning. Thus, it remains unknown how motivational context affects learning in schizophrenia, separate from the effects of medication.MethodsTo examine the impact of motivational context on learning in schizophrenia, we tested 16 unmedicated patients with schizophrenia and 23 matched controls on a probabilistic learning task while they underwent functional magnetic resonance imaging (fMRI) under 2 conditions: one in which they pursued rewards, and one in which they avoided losses. Computational models were used to derive trial-by-trial prediction error responses to feedback.ResultsPatients performed worse than controls on the learning task overall, but there were no behavioral effects of condition. FMRI revealed an attenuated prediction error response in patients in the medial prefrontal cortex, striatum, and medial temporal lobe when learning to predict rewards, but not when learning to avoid losses.ConclusionsPatients with schizophrenia showed differences in learning-related brain activity when learning to predict rewards, but not when learning to avoid losses. Together with prior work, these results suggest that motivational deficits related to learning in schizophrenia are characteristic of the disease and not solely a result of antipsychotic treatment.
| S-EPMC5049527 | biostudies-literature
Project description:Depression has been associated with poor performance following errors, but the clinical implications, response to treatment and neurobiological mechanisms of this post-error behavioral adjustment abnormality remain unclear. To fill this gap in knowledge, we tested depressed patients in a partial hospital setting before and after treatment (cognitive behavior therapy combined with medication) using a flanker task. To evaluate the translational relevance of this metric in rodents, we performed a secondary analysis on existing data from rats tested in the 5-choice serial reaction time task after treatment with corticotropin-releasing factor (CRF), a stress peptide that produces depressive-like signs in rodent models relevant to depression. In addition, to examine the effect of treatment on post-error behavior in rodents, we examined a second cohort of rodents treated with JDTic, a kappa-opioid receptor antagonist that produces antidepressant-like effects in laboratory animals. In depressed patients, baseline post-error accuracy was lower than post-correct accuracy, and, as expected, post-error accuracy improved with treatment. Moreover, baseline post-error accuracy predicted attentional control and rumination (but not depressive symptoms) after treatment. In rats, CRF significantly degraded post-error accuracy, but not post-correct accuracy, and this effect was attenuated by JDTic. Our findings demonstrate deficits in post-error accuracy in depressed patients, as well as a rodent model relevant to depression. These deficits respond to intervention in both species. Although post-error behavior predicted treatment-related changes in attentional control and rumination, a relationship to depressive symptoms remains to be demonstrated.
| S-EPMC4471285 | biostudies-literature
Project description:Midbrain dopaminergic neurons code a computational quantity, reward prediction error (RPE), which has been causally related to learning. Recently, this insight has been leveraged to link phenomenological and biological levels of understanding in psychiatric disorders, such as schizophrenia. However, results have been mixed, possibly due to small sample sizes. Here we present results from two studies with relatively large Ns to assess VS RPE in schizophrenia.In the current study we analyzed data from two independent studies, involving a total of 87 chronic medicated schizophrenia patients and 61 controls. Subjects completed a probabilistic reinforcement-learning task in conjunction with fMRI scanning. We fit each participant's choice behavior to a Q-learning model and derived trial-wise RPEs. We then modeled BOLD signal data with parametric regressor functions using these values to determine whether patient and control groups differed in prediction-error-related BOLD signal modulations.Both groups demonstrated robust VS RPE BOLD activations. Interestingly, these BOLD activation patterns did not differ between groups in either study. This was true when we included all participants in the analysis, as well as when we excluded participants whose data was not sufficiently fit by the models.These data demonstrate the utility of computational methods in isolating/testing underlying mechanisms of interest in psychiatric disorders. Importantly, similar VS RPE signal encoding across groups suggests that this mechanism does not drive task deficits in these patients. Deficits may instead stem from aberrant prefrontal/parietal circuits associated with maintenance and selection of goal-relevant information.
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Project description:The cognitive impairment in individuals with schizophrenia includes deficits of working memory in dorsolateral prefrontal cortex and deficits of performance monitoring in medial prefrontal cortex (MPFC). Recent work suggests a more general role for MPFC in predicting the outcome of actions and then evaluating those predictions. Here we investigate, in individuals with schizophrenia, two specific effects associated with this role: the error likelihood effect (occurring on trials with correct performance, but features that predict a high probability of errors), and the error unexpectedness effect (occurring on trials with an error, but features that predict errors are of low probability). In a rapid event-related fMRI design with a modified version of the change-signal task, a cue incidentally predicting error likelihood was encoded into working memory by participants in order to perform a secondary delayed match-to-sample task. There were four key findings: (1) individuals with schizophrenia exhibited poorer working memory performance and reduced error signals in MPFC; (2) even in control and schizophrenia subgroups matched on working memory performance, the schizophrenia subgroup showed a deficit in error-likelihood prediction in MPFC at the time of the predictive cue; (3) the schizophrenia subgroup also showed a deficit in evaluative error-unexpectedness activity when errors were committed; and (4) a mediation analysis indicated that error-likelihood predictions successfully explained error-unexpectedness evaluations in both controls and patients. Collectively, these findings suggest that individuals with schizophrenia have a disturbance in the evaluation of outcomes that is the result of a primary deficit in the prediction of error likelihood in MPFC.
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Project description:Increased striatal dopamine synthesis capacity has consistently been reported in patients with schizophrenia. However, the mechanism translating this into behavior and symptoms remains unclear. It has been proposed that heightened striatal dopamine may blunt dopaminergic reward prediction error signaling during reinforcement learning. In this study, we investigated striatal dopamine synthesis capacity, reward prediction errors, and their association in unmedicated schizophrenia patients (n = 19) and healthy controls (n = 23). They took part in FDOPA-PET and underwent functional magnetic resonance imaging (fMRI) scanning, where they performed a reversal-learning paradigm. The groups were compared regarding dopamine synthesis capacity (Kicer), fMRI neural prediction error signals, and the correlation of both. Patients did not differ from controls with respect to striatal Kicer. Taking into account, comorbid alcohol abuse revealed that patients without such abuse showed elevated Kicer in the associative striatum, while those with abuse did not differ from controls. Comparing all patients to controls, patients performed worse during reversal learning and displayed reduced prediction error signaling in the ventral striatum. In controls, Kicer in the limbic striatum correlated with higher reward prediction error signaling, while there was no significant association in patients. Kicer in the associative striatum correlated with higher positive symptoms and blunted reward prediction error signaling was associated with negative symptoms. Our results suggest a dissociation between striatal subregions and symptom domains, with elevated dopamine synthesis capacity in the associative striatum contributing to positive symptoms while blunted prediction error signaling in the ventral striatum related to negative symptoms.
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Project description:The involvement of the gamma-aminobutyric acid (GABA) system in schizophrenia is suggested by postmortem studies and the common use of GABA receptor-potentiating agents in treatment. In a recent study, we used a benzodiazepine challenge to demonstrate abnormal GABAergic function during processing of negative visual stimuli in schizophrenia. This study extended this investigation by mapping GABAergic mechanisms associated with face processing and social appraisal in schizophrenia using a benzodiazepine challenge. Fourteen stable, medicated schizophrenia/schizoaffective patients (SZ) and 13 healthy controls (HC) underwent functional MRI using the blood oxygenation level-dependent (BOLD) technique while they performed the Socio-emotional Preference Task (SePT) on emotional face stimuli ("Do you like this face?"). Participants received single-blinded intravenous saline and lorazepam (LRZ) in two separate sessions separated by 1-3weeks. Both SZ and HC recruited medial prefrontal cortex/anterior cingulate during the SePT, relative to gender identification. A significant drug by group interaction was observed in the medial occipital cortex, such that SZ showed increased BOLD signal to LRZ challenge, while HC showed an expected decrease of signal; the interaction did not vary by task. The altered BOLD response to LRZ challenge in SZ was significantly correlated with increased negative affect across multiple measures. The altered response to LRZ challenge suggests that abnormal face processing and negative affect in SZ are associated with altered GABAergic function in the visual cortex, underscoring the role of impaired visual processing in socio-emotional deficits in schizophrenia.
| S-EPMC4591218 | biostudies-literature