Apathy But Not Diminished Expression in Schizophrenia Is Associated With Discounting of Monetary Rewards by Physical Effort

Negative symptoms in schizophrenia have been grouped into the 2 factors of apathy and diminished expression, which might be caused by separable pathophysiological mechanisms. Recently, it has been proposed that apathy could be due to dysfunctional integration of reward and effort during decision making. We asked whether apathy in particular is associated with stronger devaluation ("discounting”) of monetary rewards that require physical effort. Thirty-one patients with schizophrenia and 20 healthy control participants performed a computerized effort discounting task in which they could choose to exert physical effort on a handgrip to obtain monetary rewards. This procedure yields an individual measure for the strength of effort discounting. The degree of effort discounting was strongly correlated with apathy, but not with diminished expression. Importantly, the association between apathy and effort discounting was not driven by cognitive ability, antipsychotic medication, or other clinical and demographic variables. This study provides the first evidence for a highly specific association of apathy with effort-based decision making in patients with schizophrenia. Within a translational framework, the present effort discounting task could provide a bridge between apathy as a psychopathological phenomenon and established behavioral tasks to address similar states in animal

Disambiguating ventral striatum fMRI-related bold signal during reward prediction in schizophrenia

Reward detection, surprise detection and prediction-error signaling have all been proposed as roles for the ventral striatum (vStr). Previous neuroimaging studies of striatal function in schizophrenia have found attenuated neural responses to reward-related prediction errors; however, as prediction errors represent a discrepancy in mesolimbic neural activity between expected and actual events, it is critical to examine responses to both expected and unexpected rewards (URs) in conjunction with expected and UR omissions in order to clarify the nature of ventral striatal dysfunction in schizophrenia. In the present study, healthy adults and people with schizophrenia were tested with a reward-related prediction-error task during functional magnetic resonance imaging to determine whether schizophrenia is associated with altered neural responses in the vStr to rewards, surprise prediction errors or all three factors. In healthy adults, we found neural responses in the vStr were correlated more specifically with prediction errors than to surprising events or reward stimuli alone. People with schizophrenia did not display the normal differential activation between expected and URs, which was partially due to exaggerated ventral striatal responses to expected rewards (right vStr) but also included blunted responses to unexpected outcomes (left vStr). This finding shows that neural responses, which typically are elicited by surprise, can also occur to well-predicted events in schizophrenia and identifies aberrant activity in the vStr as a key node of dysfunction in the neural circuitry used to differentiate expected and unexpected feedback in schizophrenia

Effective Connectivity Between the Orbitofrontal Cortex and the Precuneus Differentiates Major Psychiatric Disorders: Results from a Transdiagnostic Spectral DCM Study

Under embargo until: 2022-11-24Background & Objective: We have previously identified aberrant connectivity of the left precuneus, ventrolateral prefrontal cortex, anterior cingulate cortex, and anterior insula in patients with either a paranoid (schizophrenia), or a depressive syndrome (both unipolar and bipolar). In the current study, we attempted to replicate and expand these findings by including a healthy control sample and separating the patients in a depressive episode into two groups: unipolar and bipolar depression. We hypothesized that the connections between those major nodes of the resting state networks would demonstrate different patterns in the three patient groups compared to the healthy subjects. Methods: Resting-state functional MRI was performed on a sample of 101 participants, of which 26 patients with schizophrenia (current psychotic episodes), 24 subjects with Bipolar Disorder (BD), 33 with Major Depressive Disorder (MDD) (both BD and MDD patients were in a current depressive episode), and 21 healthy controls. Spectral Dynamic Causal Modeling was used to calculate the coupling values between eight regions of interest, including the anterior precuneus (PRC), anterior hippocampus, anterior insula, angular gyrus, lateral Orbitofrontal Cortex (OFC), middle frontal gyrus, planum temporale, and anterior thalamus. Results & Conclusion: We identified disturbed effective connectivity from the left lateral orbitofrontal cortex to the left anterior precuneus that differed significantly between unipolar depression, where the influence was inhibitory, and bipolar depression, where the effect was excitatory. A logistic regression analysis correctly classified 75% of patients with unipolar and bipolar depression based solely on the coupling values of this connection. In addition, patients with schizophrenia demonstrated negative effective connectivity from the anterior PRC to the lateral OFC, which distinguished them from healthy controls and patients with major depression. Future studies with unmedicated patients will be needed to establish the replicability of our findings.acceptedVersio

Rostral medial prefrontal dysfunctions and consummatory pleasure in schizophrenia: A meta-analysis of functional imaging studies

A large number of imaging studies have examined the neural correlates of consummatory pleasure and anticipatory pleasure in schizophrenia, but the brain regions where schizophrenia patients consistently demonstrate dysfunctions remain unclear. We performed a series of meta-analyses on imaging studies to delineate the regions associated with consummatory and anticipatory pleasure dysfunctions in schizophrenia. Nineteen functional magnetic resonance imaging or positron emission tomography studies using whole brain analysis were identified through a literature search (PubMed and EBSCO; januaiy 1990-February 2014). Activation likelihood estimation was performed using the GingerALE software. The clusters identified were obtained after controlling for the false discovery rate at p<0.05 and applying a minimum cluster size of 200 mm(3). It was found that schizophrenia patients exhibited decreased activation mainly in the rostral medial prefrontal cortex (rmPFC), the right parahippocampus/ amygala, and other limbic regions (e.g., the subgenual anterior cingulate cortex, the putamen, and the medial globus pallidus) when consummating pleasure. Task instructions (feeling vs stimuli) were differentially related to medial prefrontal dysfunction in schizophrenia. When patients anticipated pleasure, reduced activation in the left putamen was observed, despite the limited number of studies. Our findings suggest that the medial prefrontal cortex and limbic regions may play an important role in neural dysfunction underlying deficits in consummatory pleasure in schizophrenia. (C) 2015 Elsevier Ireland Ltd. All rights reserved

Apathy and Striatal Gray Matter Patterns in Schizophrenia and Huntington’s Disease

Apathy is a symptom of many neurodegenerative and neuropsychiatric disorders, such as Huntington\u27s disease and schizophrenia. Apathy is often conceptualized as a combination of three domains, cognitive, behavioral, and emotional, characterized by impaired goal-directed behavior. The striatum has been shown to be significantly associated with executive functions and planned motor behavior via projection to the prefrontal cortex (PFC). Due to its connection to the PFC and its involvement in the basal ganglia motor circuit, the striatum is thought to be a significant part of the circuit that controls goal-directed behavior. The purpose of this study was to investigate the relationship between apathy severity and dorsal striatal grey matter concentration across several disorders, specifically Huntington\u27s disease and schizophrenia. With access to the PREDICT-HD and FBIRN datasets, structural MRI images and clinical assessments were collected from 823 and 178 participants, respectively. We employed the use of SBM to isolate relevant basal ganglia components and used the resulting loading coefficients for a multivariate analysis. In parallel, we also conducted a univariate analysis using segmented subcortical volumetric data. We then constructed a mixed linear model to examine the relationship between apathy and any gray matter patterns in the striatum. In Huntington’s disease, our results indicate that apathy is significantly related to the caudate and putamen atrophy with covarying in the medial PFC. In schizophrenia, our results indicate that apathy is significantly related to the putamen with covarying regions in the gyrus rectus and orbital medial PFC. We concluded that Huntington’s disease and schizophrenia manifest apathy in different ways in unique structures

Pavlovian Reward Prediction and Receipt in Schizophrenia: Relationship to Anhedonia

Reward processing abnormalities have been implicated in the pathophysiology of negative symptoms such as anhedonia and avolition in schizophrenia. However, studies examining neural responses to reward anticipation and receipt have largely relied on instrumental tasks, which may confound reward processing abnormalities with deficits in response selection and execution. 25 chronic, medicated outpatients with schizophrenia and 20 healthy controls underwent functional magnetic resonance imaging using a Pavlovian reward prediction paradigm with no response requirements. Subjects passively viewed cues that predicted subsequent receipt of monetary reward or non-reward, and blood-oxygen-level-dependent signal was measured at the time of cue presentation and receipt. At the group level, neural responses to both reward anticipation and receipt were largely similar between groups. At the time of cue presentation, striatal anticipatory responses did not differ between patients and controls. Right anterior insula demonstrated greater activation for nonreward than reward cues in controls, and for reward than nonreward cues in patients. At the time of receipt, robust responses to receipt of reward vs. nonreward were seen in striatum, midbrain, and frontal cortex in both groups. Furthermore, both groups demonstrated responses to unexpected versus expected outcomes in cortical areas including bilateral dorsolateral prefrontal cortex. Individual difference analyses in patients revealed an association between physical anhedonia and activity in ventral striatum and ventromedial prefrontal cortex during anticipation of reward, in which greater anhedonia severity was associated with reduced activation to money versus no-money cues. In ventromedial prefrontal cortex, this relationship held among both controls and patients, suggesting a relationship between anticipatory activity and anhedonia irrespective of diagnosis. These findings suggest that in the absence of response requirements, brain responses to reward receipt are largely intact in medicated individuals with chronic schizophrenia, while reward anticipation responses in left ventral striatum are reduced in those patients with greater anhedonia severity

Antipsychotics-induced improvement of cool executive function in individuals living with schizophrenia

Cool executive dysfunction is a crucial feature in people living with schizophrenia which is related to cognition impairment and the severity of the clinical symptoms. Based on electroencephalogram (EEG), our current study explored the change of brain network under the cool executive tasks in individuals living with schizophrenia before and after atypical antipsychotic treatment (before_TR vs. after_TR). 21 patients with schizophrenia and 24 healthy controls completed the cool executive tasks, involving the Tower of Hanoi Task (THT) and Trail-Marking Test A-B (TMT A-B). The results of this study uncovered that the reaction time of the after_TR group was much shorter than that of the before_TR group in the TMT-A and TMT-B. And the after_TR group showed fewer error numbers in the TMT-B than those of the before_TR group. Concerning the functional network, stronger DMN-like linkages were found in the before_TR group compared to the control group. Finally, we adopted a multiple linear regression model based on the change network properties to predict the patient’s PANSS change ratio. Together, the findings deepened our understanding of cool executive function in individuals living with schizophrenia and might provide physiological information to reliably predict the clinical efficacy of schizophrenia after atypical antipsychotic treatment

Dissociation of Response and Feedback Negativity in Schizophrenia: Electrophysiological and Computational Evidence for a Deficit in the Representation of Value

Contrasting theories of schizophrenia propose that the disorder is characterized by a deficit in phasic changes in dopamine activity in response to ongoing events or, alternatively, by a weakness in the representation of the value of responses. Schizophrenia patients have reliably reduced brain activity following incorrect responses but other research suggests that they may have intact feedback-related potentials, indicating that the impairment may be specifically response-related. We used event-related brain potentials and computational modeling to examine this issue by comparing the neural response to outcomes with the neural response to behaviors that predict outcomes in patients with schizophrenia and psychiatrically healthy comparison subjects. We recorded feedback-related activity in a passive gambling task and a time estimation task and error-related activity in a flanker task. Patients’ brain activity following an erroneous response was reduced compared to comparison subjects but feedback-related activity did not differ between groups. To test hypotheses about the possible causes of this pattern of results, we used computational modeling of the electrophysiological data to simulate the effects of an overall reduction in patients’ sensitivity to feedback, selective insensitivity to positive or negative feedback, reduced learning rate, and a decreased representation of the value of the response given the stimulus on each trial. The results of the computational modeling suggest that schizophrenia patients exhibit weakened representation of response values, possibly due to failure of the basal ganglia to strongly associate stimuli with appropriate response alternatives