Using a generative model of affect to characterize affective variability and its response to treatment in bipolar disorder.

The affective variability of bipolar disorder (BD) is thought to qualitatively differ from that of borderline personality disorder (BPD), with changes in affect persisting longer in BD. However, quantitative studies have not been able to confirm this distinction. It has therefore not been possible to accurately quantify how treatments like lithium influence affective variability in BD. We assessed the affective variability associated with BD and BPD as well as the effect of lithium using a computational model that defines two subtypes of variability: affective changes that persist (volatility) and changes that do not (noise). We hypothesized that affective volatility would be raised in the BD group, noise would be raised in the BPD group, and that lithium would impact affective volatility. Daily affect ratings were prospectively collected for up to 3 y from patients with BD or BPD and nonclinical controls. In a separate experimental medicine study, patients with BD were randomized to receive lithium or placebo, with affect ratings collected from week -2 to +4. We found a diagnostically specific pattern of affective variability. Affective volatility was raised in patients with BD, whereas affective noise was raised in patients with BPD. Rather than suppressing affective variability, lithium increased the volatility of positive affect in both studies. These results provide a quantitative measure of the affective variability associated with BD and BPD. They suggest a mechanism of action for lithium, whereby periods of persistently low or high affect are avoided by increasing the volatility of affective responses.

Depression is associated with reduced outcome sensitivity in a dual valence, magnitude learning task.

BACKGROUND: Learning from rewarded and punished choices is perturbed in depressed patients, suggesting that abnormal reinforcement learning may be a cognitive mechanism of the illness. However, previous studies have disagreed about whether this behavior is produced by alterations in the rate of learning or sensitivity to experienced outcomes. This previous work has generally assessed learning in response to binary outcomes of one valence, rather than to both rewarding and punishing continuous outcomes. METHODS: A novel drifting reward and punishment magnitude reinforcement-learning task was administered to patients with current (n = 40) and remitted depression (n = 39), and healthy volunteers (n = 40) to capture potential differences in learning behavior. Standard questionnaires were administered to measure self-reported depressive symptom severity, trait and state anxiety and level of anhedonic symptoms. RESULTS: Our findings demonstrate that patients with current depression adjust their learning behaviors to a lesser degree in response to trial-by-trial variations in reward and loss magnitudes than the other groups. Computational modeling revealed that this behavioral signature of current depressive state is better accounted for by reduced reward and punishment sensitivity (all p < 0.031), rather than a change in learning rate (p = 0.708). However, between-group differences were not related to self-reported symptom severity or comorbid anxiety disorders in the current depression group. CONCLUSION: These findings suggest that current depression is associated with reduced outcome sensitivity rather than altered learning rate. Previous findings reported in this domain mainly from binary learning tasks seem to generalize to learning from continuous outcomes.

A translational perspective on the anti-anhedonic effect of ketamine and its neural underpinnings.

Anhedonia, a pronounced reduction in interest or pleasure in any of life's daily activities, is a cardinal symptom of major depression. In this Perspective article, we synthesise the recent evidence from rodent, monkey and human neuroimaging literature to highlight how the habenula, a small evolutionarily conserved subcortical structure located in the midbrain, may orchestrate the behavioural expression of anhedonia across fronto-mesolimbic networks. We then review how this circuitry can be modulated by ketamine, an NMDA receptor antagonist with rapid antidepressant properties. We propose that experimental paradigms founded in reinforcement learning and value-based decision-making can usefully probe this network and thereby help elucidate the mechanisms underlying ketamine's rapid antidepressant action.

Individualistic attitudes in Iterated Prisoner's Dilemma undermine evolutionary fitness and may drive cooperative human players to extinction.

Inarguably, humans perform the richest plethora of prosocial behaviours in the animal kingdom, and these are important for understanding how humans navigate their social environment. The success and failure of strategies human players devise also have implications for determining long-term socio-economic/evolutionary fitness. Following the footsteps of Press and Dyson (2012), I implemented their evolutionary game-theoretic modelling from Iterated Prisoner's Dilemma (a behavioural economic probe of interpersonal cooperation) and re-analysed already published data on human proposer behaviour in the Ultimatum Game (a behavioural economic probe of altruistic punishment) involving 50 human participants versus stochastic computerized opponents with prosocial and individualistic social value orientations. Although the results indicate that it is more likely to break cycles of mutual defection in ecosystems in which humans interact with individualistic opponents, analysis of social-economic fitness at the Markov stationary states suggested that this comes at an evolutionary cost. Overall, human players acted in a significantly more cooperative manner than their opponents, but they failed to overcome extortion from individualistic agents, risking 'extinction' in 70% of the cases. These findings demonstrate human players might be short-sighted, and social interactive decision strategies they devise while adjusting to different types of opponents may not be optimal in the long run.

Value-based decision-making between affective and non-affective memories.

Affective biases can change how past events are recalled from memory. To capture mechanisms underlying affective memory formation, recall, and bias, we studied value-based decision-making (VBDM) between reward memories encoded in different mood states. Our findings suggest that following discrete affective events, created by large magnitude wins and losses on a Wheel of Fortune (WoF), healthy volunteers display an overall positive memory bias [favoring higher probability shapes learned after a WoF win compared with those learnt after a WoF loss outcome]. During this VBDM process, participants' pupils constrict before decision-onset for higher-value choices, and remained dilated for a sustained period after choice. Sustained pupil dilation was particularly sensitive to the reward values of abstract memories encoded in a positive mood. Taken together, we demonstrate that experimentally induced affective memories are recalled with a positive bias, and pupil-linked central arousal systems are actively engaged during VBDM between affective and non-affective memories.

Adaptive learning from outcome contingencies in eating-disorder risk groups.

Eating disorders are characterised by altered eating patterns alongside overvaluation of body weight or shape, and have relatively low rates of successful treatment and recovery. Notably, cognitive inflexibility has been implicated in both the development and maintenance of eating disorders, and understanding the reasons for this inflexibility might indicate avenues for treatment development. We therefore investigate one potential cause of this inflexibility: an inability to adjust learning when outcome contingencies change. We recruited (n = 82) three groups of participants: those who had recovered from anorexia nervosa (RA), those who had high levels of eating disorder symptoms but no formal diagnosis (EA), and control participants (HC). They performed a reinforcement learning task (alongside eye-tracking) in which the volatility of wins and losses was independently manipulated. We predicted that both the RA and EA groups would adjust their learning rates less than the control participants. Unexpectedly, the RA group showed elevated adjustment of learning rates for both win and loss outcomes compared to control participants. The RA group also showed increased pupil dilation to stable wins and reduced pupil dilation to stable losses. Their learning rate adjustment was associated with the difference between their pupil dilation to volatile vs. stable wins. In conclusion, we find evidence that learning rate adjustment is unexpectedly higher in those who have recovered from anorexia nervosa, indicating that the relationship between eating disorders and cognitive inflexibility may be complex. Given our findings, investigation of noradrenergic agents may be valuable in the field of eating disorders.

Dynamic modulation of inequality aversion in human interpersonal negotiations.

Negotiating with others about how finite resources should be distributed is an important aspect of human social life. However, little is known about mechanisms underlying human social-interactive decision-making in gradually evolving environments. Here, we report results from an iterative Ultimatum Game (UG), in which the proposer's facial emotions and offer amounts were sampled probabilistically based on the participant's decisions. Our model-free results confirm the prediction that both the proposer's facial emotions and the offer amount should influence acceptance rates. Model-based analyses extend these findings, indicating that participants' decisions in the UG are guided by aversion to inequality. We highlight that the proposer's facial affective reactions to participant decisions dynamically modulate how human decision-makers perceive self-other inequality, relaxing its otherwise negative influence on decision values. This cognitive model underlies how offers initially rejected can gradually become more acceptable under increasing affective load (predictive accuracy ~86%). Furthermore, modelling human choice behaviour isolated the role of the central arousal systems, assessed by measuring pupil size. We demonstrate that pupil-linked central arousal systems selectively encode a key component of subjective decision values: the magnitude of self-other inequality. Taken together, our results demonstrate that, under affective influence, aversion to inequality is a malleable cognitive process.

Population Modelling in Affective Disorders.

PURPOSE OF REVIEW: The prevalence of affective disorders is on the rise. This upward trajectory leads to a substantial personal and societal cost. There is growing body of literature demonstrating decision-making impairments associated with affective disorders, and more studies are using computational modelling methods to infer underlying mechanisms of these impairments from participant choice behaviour. However, lack of population modelling suggests that data resources may still be underutilised. RECENT FINDINGS: A number of recent studies associated major depression with abnormal risky decision-making as well as impairments in temporal discounting and social decision-making. These domains capture relevant aspects of real-life decision-making. Consequently, data from these studies can be used to define behavioural phenotypes for major depression. SUMMARY: The manuscript describes a detailed proposal for population modelling to capture changes in the prevalence rate of major depression. The population modelling approach can also identify which decision-making domains can account for a larger part of impairments in psychosocial functioning and how behavioural interventions built on computational principles can target these to improve real-life psychosocial functioning in patient groups.

How representative are neuroimaging samples? Large-scale evidence for trait anxiety differences between fMRI and behaviour-only research participants.

Over the past three decades, functional magnetic resonance imaging (fMRI) has become crucial to study how cognitive processes are implemented in the human brain. However, the question of whether participants recruited into fMRI studies differ from participants recruited into other study contexts has received little to no attention. This is particularly pertinent when effects fail to generalize across study contexts: for example, a behavioural effect discovered in a non-imaging context not replicating in a neuroimaging environment. Here, we tested the hypothesis, motivated by preliminary findings (N = 272), that fMRI participants differ from behaviour-only participants on one fundamental individual difference variable: trait anxiety. Analysing trait anxiety scores and possible confounding variables from healthy volunteers across multiple institutions (N = 3317), we found robust support for lower trait anxiety in fMRI study participants, consistent with a sampling or self-selection bias. The bias was larger in studies that relied on phone screening (compared with full in-person psychiatric screening), recruited at least partly from convenience samples (compared with community samples), and in pharmacology studies. Our findings highlight the need for surveying trait anxiety at recruitment and for appropriate screening procedures or sampling strategies to mitigate this bias.

Value computations underlying human proposer behavior in the ultimatum game.

Interacting with others to decide how finite resources should be allocated between potentially competing parties is an important part of social life. Considering that not all of our proposals to others are always accepted, the outcomes of such social interactions are probabilistic and risky. Here, we highlight cognitive processes related to value computations in human social interactions, based on mathematical modeling of the proposer behavior in the Ultimatum Game. Our results suggest that the perception of risk is an overarching process across nonsocial and social decision-making domains, whereas the nonlinear weighting of others' acceptance probabilities appears to be more closely associated with social interactive decision-making situations in which others' valuation processes needs to be inferred. Despite the complexity of social interactive decision-making, human participants adjust their risk and probability weighting parameters while interacting with opponents with different social value orientations, and these parameters governing participants' decision-making strategies are influenced by the inferences participants make about their opponents (e.g., how prosocial they think their opponent is relative to themselves), as well as their own social value orientation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The Misestimation of Uncertainty in Affective Disorders.

Our knowledge about the state of the world is often incomplete, making it difficult to select the best course of action. One strategy that can be used to improve our ability to make decisions is to identify the causes of our ignorance (i.e., why an unexpected event might have occurred) and use estimates of the uncertainty induced by these causes to guide our learning. Here, we explain the logic behind this process and describe the evidence that human learners use estimates of uncertainty to sculpt their learning. Finally, we describe recent work suggesting that misestimation of uncertainty is involved in the development of anxiety and depression and describe how these ideas may be advanced.

The Effects of the Angiotensin II Receptor Antagonist Losartan on Appetitive Versus Aversive Learning: A Randomized Controlled Trial.

BACKGROUND: Exposure therapy is a first-line treatment for anxiety disorders but remains ineffective in a large proportion of patients. A proposed mechanism of exposure involves inhibitory learning whereby the association between a stimulus and an aversive outcome is suppressed by a new association with an appetitive or neutral outcome. The blood pressure medication losartan augments fear extinction in rodents and may have similar synergistic effects on human exposure therapy, but the exact cognitive mechanisms underlying these effects remain unknown. METHODS: We used a reinforcement learning paradigm with compound rewards and punishments to test the prediction that losartan augments learning from appetitive relative to aversive outcomes. In a double-blind parallel design, healthy volunteers were randomly assigned to single-dose losartan (50 mg) (n = 28) versus placebo (n = 25). Participants then performed a reinforcement learning task, which simultaneously probes appetitive and aversive learning. Participant choice behavior was analyzed using both a standard reinforcement learning model and analysis of choice switching behavior. RESULTS: Losartan significantly reduced learning rates from aversive events (losses) when participants were first exposed to the novel task environment, while preserving learning from positive outcomes. The same effect was seen in choice switching behavior. CONCLUSIONS: This study shows that losartan enhances learning from positive relative to negative events. This effect may represent a computationally defined neurocognitive mechanism by which the drug could enhance the effect of exposure in clinical populations.

Affective bias as a rational response to the statistics of rewards and punishments.

Affective bias, the tendency to differentially prioritise the processing of negative relative to positive events, is commonly observed in clinical and non-clinical populations. However, why such biases develop is not known. Using a computational framework, we investigated whether affective biases may reflect individuals' estimates of the information content of negative relative to positive events. During a reinforcement learning task, the information content of positive and negative outcomes was manipulated independently by varying the volatility of their occurrence. Human participants altered the learning rates used for the outcomes selectively, preferentially learning from the most informative. This behaviour was associated with activity of the central norepinephrine system, estimated using pupilometry, for loss outcomes. Humans maintain independent estimates of the information content of distinct positive and negative outcomes which may bias their processing of affective events. Normalising affective biases using computationally inspired interventions may represent a novel approach to treatment development.

Self-report distortions of puffing topography in daily smokers.

Under-reporting tobacco consumption is common, although there is lack of evidence whether under-reporting is associated with health risk perception. In this study, smoking topography from 110 smokers was recorded over 24 hours, aiming to capture a representative average of smoking behaviour. Participants significantly under-reported the duration of secondary exposure, and there was a significant interaction between self-report distortion type and risk perception. Analysis showed that smokers under-reporting puff number declared perceiving significantly less susceptibility to acquiring airway diseases, which is correlating significantly with the level of under-reporting. The present findings may suggest that under-reporting smoking behaviour has psychological functions beyond achieving social desirability.

Neural origins of psychosocial functioning impairments in major depression.

Major depressive disorder, a complex neuropsychiatric condition, is associated with psychosocial functioning impairments that could become chronic even after symptoms remit. Social functioning impairments in patients could also pose coping difficulties to individuals around them. In this Personal View, we trace the potential neurobiological origins of these impairments down to three candidate domains-namely, social perception and emotion processing, motivation and reward value processing, and social decision making. We argue that the neural basis of abnormalities in these domains could be detectable at different temporal stages during social interactions (eg, before and after decision stages), particularly within frontomesolimbic networks (ie, frontostriatal and amygdala-striatal circuitries). We review some of the experimental designs used to probe these circuits and suggest novel, integrative approaches. We propose that an understanding of the interactions between these domains could provide valuable insights for the clinical stratification of major depressive disorder subtypes and might inform future developments of novel treatment options in return.

An evolutionary perspective on gradual formation of superego in the primal horde.

Freud proposed that the processes which occurred in the primal horde are essential for understanding superego formation and therefore, the successful dissolution of the Oedipus complex. However, Freud theorized superego formation in the primal horde as if it is an instant, all-or-none achievement. The present paper proposes an alternative model aiming to explain gradual development of superego in the primitive man. The proposed model is built on knowledge from evolutionary and neural sciences as well as anthropology, and it particularly focuses on the evolutionary significance of the acquisition of fire by hominids in the Pleistocene period in the light of up-to-date archaeological findings. Acquisition of fire is discussed as a form of sublimation which might have helped Prehistoric man to maximize the utility of limited evolutionary biological resources, potentially contributing to the rate and extent of bodily evolution. The limitations of both Freud's original conceptualization and the present model are discussed accordingly in an interdisciplinary framework.

Increased amygdala response to shame in remitted major depressive disorder.

Proneness to self-blaming moral emotions such as shame and guilt is increased in major depressive disorder (MDD), and may play an important role in vulnerability even after symptoms have subsided. Social psychologists have argued that shame-proneness is relevant for depression vulnerability and is distinct from guilt. Shame depends on the imagined critical perception of others, whereas guilt results from one's own judgement. The neuroanatomy of shame in MDD is unknown. Using fMRI, we compared 21 participants with MDD remitted from symptoms with no current co-morbid axis-I disorders, and 18 control participants with no personal or family history of MDD. The MDD group exhibited higher activation of the right amygdala and posterior insula for shame relative to guilt (SPM8). This neural difference was observed despite equal levels of rated negative emotional valence and frequencies of induced shame and guilt experience across groups. These same results were found in the medication-free MDD subgroup (N = 15). Increased amygdala and posterior insula activations, known to be related to sensory perception of emotional stimuli, distinguish shame from guilt responses in remitted MDD. People with MDD thus exhibit changes in the neural response to shame after symptoms have subsided. This supports the hypothesis that shame and guilt play at least partly distinct roles in vulnerability to MDD. Shame-induction may be a more sensitive probe of residual amygdala hypersensitivity in MDD compared with facial emotion-evoked responses previously found to normalize on remission.

Enhanced subgenual cingulate response to altruistic decisions in remitted major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is associated with functional abnormalities in fronto-meso-limbic networks contributing to decision-making, affective and reward processing impairments. Such functional disturbances may underlie a tendency for enhanced altruism driven by empathy-based guilt observed in some patients. However, despite the relevance of altruistic decisions to understanding vulnerability, as well as everyday psychosocial functioning, in MDD, their functional neuroanatomy is unknown. METHODS: Using a charitable donations experiment with fMRI, we compared 14 medication-free participants with fully remitted MDD and 15 demographically-matched control participants without MDD. RESULTS: Compared with the control group, the remitted MDD group exhibited enhanced BOLD response in a septal/subgenual cingulate cortex (sgACC) region for charitable donation relative to receiving simple rewards and higher striatum activation for both charitable donation and simple reward relative to a low level baseline. The groups did not differ in demographics, frequency of donations or response times, demonstrating only a difference in neural architecture. CONCLUSIONS: We showed that altruistic decisions probe residual sgACC hypersensitivity in MDD even after symptoms are fully remitted. The sgACC has previously been shown to be associated with guilt which promotes altruistic decisions. In contrast, the striatum showed common activation to both simple and altruistic rewards and could be involved in the so-called "warm glow" of donation. Enhanced neural response in the depression group, in areas previously linked to altruistic decisions, supports the hypothesis of a possible association between hyper-altruism and depression vulnerability, as shown by recent epidemiological studies.

The role of self-blaming moral emotions in major depression and their impact on social-economical decision making.

People with major depressive disorder (MDD) are more prone to experiencing moral emotions related to self-blame, such as guilt and shame. DSM-IV-TR recognizes excessive or inappropriate guilt as one of the core symptoms of current MDD, whereas excessive shame is not part of the criteria for MDD. However, previous studies specifically assessing shame suggested its involvement in MDD. In the first part of this review, we will consider literature discussing the role of self-blaming moral emotions in MDD. These self-blaming moral emotions have been purported to influence people when they make social and financial decisions in cognitive studies, particularly those using neuroeconomical paradigms. Such paradigms aim to predict social behavior in activities of daily living, by using important resource tangibles (especially money) in laboratory conditions. Previous literature suggests that guilt promotes altruistic behavior via acting out reparative tendencies, whereas shame reduces altruism by means of increasing social and interpersonal distance. In the second part of this review, we will discuss the potential influence of self-blaming moral emotions on overt behavior in MDD, reviewing clinical and experimental studies in social and financial decision-making, in which guilt, and shame were manipulated. This is not a well-established area in the depression literature, however in this opinion paper we will argue that studies of moral emotions and their impact on behavioral decision-making are of potential importance in the clinical field, by linking specific symptoms of a disorder to a behavioral outcome which may lead to stratification of clinical diagnoses in the future.