Value Representations of Spite Sensitivity in Psychosis on the Minnesota Trust Game.

BACKGROUND: Spite sensitivity provides a valuable construct to understand persecutory ideation and its underlying neural mechanisms. We examined the relationship between persecution and spite sensitivity in psychosis to identify their neural substrates. METHODS: In a 3T magnetic resonance imaging scanner, 49 participants with psychosis played the Minnesota Trust Game, in which they decided whether to take a small amount of money or trust a partner to choose between fair and unfair distributions of money. In some conditions, the partner benefited from the unfair option, while in others, the partner lost money. Participants who were untrusting in the second condition (suspiciousness) showed heightened sensitivity to spite. Behavioral measures included mistrust during the 2 conditions of the game, which were compared with Brief Psychiatric Rating Scale persecution and computational modeling. Functional connectivity and blood oxygen level-dependent analyses were also conducted on a priori regions during spite-sensitive decisions. RESULTS: Behavioral results replicated previous findings; participants who experienced more persecutory ideation trusted less, specifically in the suspiciousness condition. Functional connectivity findings showed that decreased connectivity between the orbitofrontal cortex-insula and the left frontoparietal network was associated with increased persecutory ideation and estimated spite-guilt (a marker of spite sensitivity). Additionally, we found differences between conditions in caudate nucleus, medial prefrontal cortex, and lateral orbitofrontal cortex activation. CONCLUSIONS: These findings provide a new perspective on the origin of positive symptoms by identifying primary brain circuits that are related to both spite sensitivity and persecutory ideation.

Lesions to different regions of frontal cortex have dissociable effects on voluntary persistence.

Deciding how long to keep waiting for uncertain future rewards is a complex problem. Previous research has shown that choosing to stop waiting results from an evaluative process that weighs the subjective value of the awaited reward against the opportunity cost of waiting. In functional neuroimaging data, activity in ventromedial prefrontal cortex (vmPFC) tracks the dynamics of this evaluation, while activation in the dorsomedial prefrontal cortex (dmPFC) and anterior insula (AI) ramps up before a decision to quit is made. Here, we provide causal evidence of the necessity of these brain regions for successful performance in a willingness-to-wait task. 28 participants with frontal lobe lesions were tested on their ability to adaptively calibrate how long they waited for monetary rewards. We grouped the participants based on the location of their lesions, which were primarily in ventromedial, dorsomedial, or lateral parts of their prefrontal cortex (vmPFC, dmPFC, and lPFC, respectively), or in the anterior insula. We compared the performance of each subset of lesion participants to behavior in a control group without lesions (n=18). Finally, we fit a newly developed computational model to the data to glean a more mechanistic understanding of how lesions affect the cognitive processes underlying choice. We found that participants with lesions to the vmPFC waited less overall, while participants with lesions to the dmPFC and anterior insula were specifically impaired at calibrating their level of persistence to the environment. These behavioral effects were accounted for by systematic differences in parameter estimates from a computational model of task performance: while the vmPFC group showed reduced initial willingness to wait, lesions to the dmPFC/anterior insula were associated with slower learning from negative feedback. These findings corroborate the notion that failures of persistence can be driven by sophisticated cost-benefit analyses rather than lapses in self-control. They also support the functional specialization of different parts of the prefrontal cortex in service of voluntary persistence.

Sunk cost sensitivity during change-of-mind decisions is informed by both the spent and remaining costs.

Sunk cost sensitivity describes escalating decision commitment with increased spent resources. On neuroeconomic foraging tasks, mice, rats, and humans show similar escalations from sunk costs while quitting an ongoing countdown to reward. In a new analysis taken across computationally parallel foraging tasks across species and laboratories, we find that these behaviors primarily occur on choices that are economically inconsistent with the subject's other choices, and that they reflect not only the time spent, but also the time remaining, suggesting that these are change-of-mind re-evaluation processes. Using a recently proposed change-of-mind drift-diffusion model, we find that the sunk cost sensitivity in this model arises from decision-processes that directly take into account the time spent (costs sunk). Applying these new insights to experimental data, we find that sensitivity to sunk costs during re-evaluation decisions depends on the information provided to the subject about the time spent and the time remaining.

Decision value signals in the ventromedial prefrontal cortex and motivational and hedonic symptoms across mood and psychotic disorders.

Deficits in motivation and pleasure are common across many psychiatric disorders, and manifest as symptoms of amotivation and anhedonia, which are prominent features of both mood and psychotic disorders. Here we provide evidence for an association between neural value signals and symptoms of amotivation and anhedonia across adults with major depression, bipolar disorder, schizophrenia, or no psychiatric diagnosis. We found that value signals in the ventromedial prefrontal cortex (vmPFC) during intertemporal decision-making were dampened in individuals with greater motivational and hedonic deficits, after accounting for primary diagnosis. This relationship remained significant while controlling for diagnosis-specific symptoms of mood and psychosis, such as depression as well as positive and negative symptoms. Our results demonstrate that dysfunction in the vmPFC during value-based decision-making is specifically linked to motivational and hedonic impairments. These findings provide a quantitative neural target for the potential development of novel treatments for amotivation and anhedonia.

A Computational Model of Non-optimal Suspiciousness in the Minnesota Trust Game.

This study modelled spite sensitivity, the worry that others are willing to incur a loss to hurt you, which is thought to undergird suspiciousness and persecutory ideation. Two samples performed a parametric, non-iterative trust game known as the Minnesota Trust Game (MTG). The MTG distinguishes suspicious decision-making from otherwise rational mistrust by incentivizing the player to trust in certain situations but not others. In Sample 1, 243 undergraduates who completed the MTG showed less trust as the amount of money they could lose increased. However, only for choices where partners had a financial disincentive to betray the player was variation in the willingness to trust associated with suspicious beliefs. We modified the Fehr-Schmidt (1999) inequity aversion model, which compares unequal outcomes in social decision-making tasks, to include the possibility for spite sensitivity. An anticipated partner's dislike of advantageous inequity (i.e., guilt) parameter included negative values, with negative guilt indicating spite. We hypothesized that the anticipated guilt parameter would be strongly related to suspicious beliefs. Our modification of the Fehr-Schmidt model improved estimation of MTG behavior. Furthermore, the estimation of partner's spite-guilt was highly correlated with choices associated with beliefs in persecution. We replicated our findings in a second sample. This parameter was weakly correlated with a self-reported measure of persecutory ideation in Sample 2. The "Suspiciousness" condition, unique to the MTG, can be modeled to isolate spite sensitivity, suggesting differentiation from inequity aversion or risk aversion. The MTG offers promise for future studies to quantify persecutory beliefs in clinical populations.

Resting-State Networks Associated with Behavioral and Self-Reported Measures of Persecutory Ideation in Psychosis.

Persecutory ideations are self-referential delusions of being the target of malevolence despite a lack of evidence. Wisner et al. (2021) found that reduced connectivity between the left frontoparietal (lFP) network and parts of the orbitofrontal cortex (OFC) correlated with increased persecutory behaviors among psychotic patients performing in an economic social decision-making task that can measure the anticipation of a partner's spiteful behavior. If this pattern could be observed in the resting state, it would suggest a functional-structural prior predisposing individuals to persecutory ideation. Forty-four patients in the early course of a psychotic disorder provided data for resting-state functional connectivity magnetic resonance imaging across nine brain networks that included the FP network and a similar OFC region. As predicted, we found a significant and negative correlation between the lFP-OFC at rest and the level of suspicious mistrust on the decision-making task using a within-group correlational design. Additionally, self-reported persecutory ideation correlated significantly with the connectivity between the right frontoparietal (rFP) network and the OFC. We extended the previous finding of reduced connectivity between the lFP network and the OFC in psychosis patients to the resting state, and observed a possible hemispheric difference, such that greater rFP-OFC connectivity predicted elevated self-reported persecutory ideation, suggesting potential differences between the lFP and rFP roles in persecutory social interactions.

Sensitivity to Sunk Costs Depends on Attention to the Delay.

In the WebSurf task, humans forage for videos paying costs in terms of wait times on a time-limited task. A variant of the task in which demands during the wait time were manipulated revealed the role of attention in susceptibility to sunk costs. Consistent with parallel tasks in rodents, previous studies have found that humans (undergraduates measured in lab) preferred shorter delays, but waited longer for more preferred videos, suggesting that they were treating the delays economically. In an Amazon Mechanical Turk (mTurk) sample, we replicated these predicted economic behaviors for a majority of participants. In the lab, participants showed susceptibility to sunk costs in this task, basing their decisions in part on time they have already waited, which we also observed in the subset of the mTurk sample that behaved economically. In another version of the task, we added an attention check to the wait phase of the delay. While that attention check further increased the proportion of subjects with predicted economic behaviors, it also removed the susceptibility to sunk costs. These findings have important implications for understanding how cognitive processes, such as the deployment of attention, are key to driving re-evaluation and susceptibility to sunk costs.

Multiple Facets of Value-Based Decision Making in Major Depressive Disorder.

Depression is clinically characterized by obvious changes in decision making that cause distress and impairment. Though several studies suggest impairments in depressed individuals in single tasks, there has been no systematic investigation of decision making in depression across tasks. We compare participants diagnosed with Major Depressive Disorder (MDD) (n = 64) to healthy controls (n = 64) using a comprehensive battery of nine value-based decision-making tasks which yield ten distinct measures. MDD participants performed worse on punishment (d = -0.54) and reward learning tasks (d = 0.38), expressed more pessimistic predictions regarding winning money in the study (d = -0.47) and were less willing to wait in a persistence task (d = -0.39). Performance on learning, expectation, and persistence tasks each loaded on unique dimensions in a factor analysis and punishment learning and future expectations each accounted for unique variance in predicting depressed status. Decision-making performance alone could predict depressed status out-of-sample with 72% accuracy. The findings are limited to MDD patients ranging between moderate to severe depression and the effects of medication could not be accounted for due to the cross sectional nature of the study design. These results confirm hints from single task studies that depression has the strongest effects on reinforcement learning and expectations about the future. Our results highlight the decision processes that are impacted in major depression, and whose further study could lead to a more detailed computational understanding of distinct facets of this heterogeneous disorder.

Taking an engineer's view: Implications of network analysis for computational psychiatry.

An engineer's viewpoint on psychiatry asks: What are the failure modes that underlie psychiatric dysfunction? And: How can we modify the system? Psychiatry has made great strides in understanding and treating disorders using biology; however, failure modes and modification access points can also exist extrinsically in environmental interactions. The network analysis suggested by Borsboom et al. in the target article provides a new viewpoint that should be incorporated into current theoretical constructs, not placed in opposition to them.

Alpha suppression following performance errors is correlated with depression, affect, and coping behaviors.

This study tested the hypothesis that enhanced neural arousal in response to performance errors would predict poor affect and coping behaviors in everyday life. Participants were preselected as either low-depressed (LD) or high-depressed (HD) based on a screening questionnaire, and they then completed a laboratory Stroop task while EEG was recorded, followed by a 2-week period of daily reports of affect and coping behaviors. The EEG measure of arousal response to errors was the degree of error-related alpha suppression (ERAS) in the intertrial interval, that is the reduction in alpha power following errors compared with correct responses. ERAS was relatively heightened at frontal sites for the HD versus the LD group, and frontal ERAS predicted lower positive affect, higher negative affect, and less adaptive coping behaviors in the daily reports. Together, the results imply that heightened arousal following mistakes is associated with suboptimal emotion and coping with stressors.

Stress regulation and cognitive control: evidence relating cortisol reactivity and neural responses to errors.

In this study, we tested the relationship between error-related signals of cognitive control and cortisol reactivity, investigating the hypothesis of common systems for cognitive and emotional self-regulation. Eighty-three participants completed a Stroop task while electroencephalography (EEG) was recorded. Three error-related indices were derived from the EEG: the error-related negativity (ERN), error positivity (Pe), and error-related alpha suppression (ERAS). Pre- and posttask salivary samples were assayed for cortisol, and cortisol change scores were correlated with the EEG variables. Better error-correct differentiation in the ERN predicted less cortisol increase during the task, whereas greater ERAS predicted greater cortisol increase during the task; the Pe was not correlated with cortisol changes. We concluded that an enhanced ERN, part of an adaptive cognitive control system, predicts successful stress regulation. In contrast, an enhanced ERAS response may reflect error-related arousal that is not adaptive. The results support the concept of overlapping systems for cognitive and emotional self-regulation.