Dopamine Increases a Value-Independent Gambling Propensity

Although the impact of dopamine on reward learning is well documented, its influence on other aspects of behavior remains the subject of much ongoing work. Dopaminergic drugs are known to increase risk-taking behavior, but the underlying mechanisms for this effect are not clear. We probed dopamine’s role by examining the effect of its precursor L-DOPA on the choices of healthy human participants in an experimental paradigm that allowed particular components of risk to be distinguished. We show that choice behavior depended on a baseline (ie, value-independent) gambling propensity, a gambling preference scaling with the amount/variance, and a value normalization factor. Boosting dopamine levels specifically increased just the value-independent baseline gambling propensity, leaving the other components unaffected. Our results indicate that the influence of dopamine on choice behavior involves a specific modulation of the attractiveness of risky options—a finding with implications for understanding a range of reward-related psychopathologies including addiction

The Psychological and Neural Basis of Loss Aversion

Loss aversion is a central element of prospect theory, the dominant theory of decision making under uncertainty for the past four decades, and refers to the overweighting of potential losses relative to equivalent gains, a critical determinant of risky decision making. Recent advances in affective and decision neuroscience have shed new light on the psychological and neurobiological mechanisms underlying loss aversion. Here, integrating disparate literatures from the level of neurotransmitters to subjective reports of emotion, we propose a novel neural and computational framework that links norepinephrine to loss aversion and identifies a distinct role for dopamine in risk taking for rewards. We also propose that loss aversion specifically relates to anticipated emotions and aspects of the immediate experience of realized gains and losses but not their long-term emotional consequences, highlighting an underappreciated temporal structure. Finally, we discuss challenges to loss aversion and the relevance of loss aversion to understanding psychiatric disorders. Refining models of loss aversion will have broad consequences for the science of decision making and for how we understand individual variation in economic preferences and psychological well-being across both healthy and psychiatric populations

Bipolar spectrum risk and social network dimensions in emerging adults: Two social sides?

Introduction: Bipolar spectrum disorders (BSDs) encompass severe and chronic mood disorders associated with social functioning difficulties. However, little work has examined more nuanced aspects of social functioning in BSDs. Methods: This investigation recruited 1, 934 emerging adult college students to examine associations of self-reported bipolar spectrum risk (including both BSD risk and current mania and depressive mood symptoms) with social functioning with peers (including social network quantity and quality, social support, and social strain). Results: Self-reported BSD risk was associated with greater social strain, but also greater social network quantity (or size) and social support. Post-hoc results suggest that self-reported mood symptoms were similarly associated with increased social conflict, but also greater social network quantity (or size) and social support. Discussion: Taken together, these findings indicate a complex picture in which BSD risk and mood symptoms are associated with both social struggles as well as strengths. Implications for the involvement of social functioning in mood disturbance are discussed

Neurocomputational mechanisms underpinning aberrant social learning in young adults with low self-esteem

Funder: UCLH NIHR BRCAbstract: Low self-esteem is a risk factor for a range of psychiatric disorders. From a cognitive perspective a negative self-image can be maintained through aberrant learning about self-worth derived from social feedback. We previously showed that neural teaching signals that represent the difference between expected and actual social feedback (i.e., social prediction errors) drive fluctuations in self-worth. Here, we used model-based functional magnetic resonance imaging (fMRI) to characterize learning from social prediction errors in 61 participants drawn from a population-based sample (n = 2402) who were recruited on the basis of being in the bottom or top 10% of self-esteem scores. Participants performed a social evaluation task during fMRI scanning, which entailed predicting whether other people liked them as well as the repeated provision of reported feelings of self-worth. Computational modeling results showed that low self-esteem participants had persistent expectations that others would dislike them, and a reduced propensity to update these expectations in response to social prediction errors. Low self-esteem subjects also displayed an enhanced volatility in reported feelings of self-worth, and this was linked to an increased tendency for social prediction errors to determine momentary self-worth. Canonical correlation analysis revealed that individual differences in self-esteem related to several interconnected psychiatric symptoms organized around a single dimension of interpersonal vulnerability. Such interpersonal vulnerability was associated with an attenuated social value signal in ventromedial prefrontal cortex when making predictions about being liked, and enhanced dorsal prefrontal cortex activity upon receipt of social feedback. We suggest these computational signatures of low self-esteem and their associated neural underpinnings might represent vulnerability for development of psychiatric disorder

Neurocomputational mechanisms underpinning aberrant social learning in young adults with low self-esteem.

Funder: UCLH NIHR BRCLow self-esteem is a risk factor for a range of psychiatric disorders. From a cognitive perspective a negative self-image can be maintained through aberrant learning about self-worth derived from social feedback. We previously showed that neural teaching signals that represent the difference between expected and actual social feedback (i.e., social prediction errors) drive fluctuations in self-worth. Here, we used model-based functional magnetic resonance imaging (fMRI) to characterize learning from social prediction errors in 61 participants drawn from a population-based sample (n = 2402) who were recruited on the basis of being in the bottom or top 10% of self-esteem scores. Participants performed a social evaluation task during fMRI scanning, which entailed predicting whether other people liked them as well as the repeated provision of reported feelings of self-worth. Computational modeling results showed that low self-esteem participants had persistent expectations that others would dislike them, and a reduced propensity to update these expectations in response to social prediction errors. Low self-esteem subjects also displayed an enhanced volatility in reported feelings of self-worth, and this was linked to an increased tendency for social prediction errors to determine momentary self-worth. Canonical correlation analysis revealed that individual differences in self-esteem related to several interconnected psychiatric symptoms organized around a single dimension of interpersonal vulnerability. Such interpersonal vulnerability was associated with an attenuated social value signal in ventromedial prefrontal cortex when making predictions about being liked, and enhanced dorsal prefrontal cortex activity upon receipt of social feedback. We suggest these computational signatures of low self-esteem and their associated neural underpinnings might represent vulnerability for development of psychiatric disorder

Using games to understand the mind

Board, card or video games have been played by virtually every individual in the world. Games are popular because they are intuitive and fun. These distinctive qualities of games also make them ideal for studying the mind. By being intuitive, games provide a unique vantage point for understanding the inductive biases that support behaviour in more complex, ecological settings than traditional laboratory experiments. By being fun, games allow researchers to study new questions in cognition such as the meaning of 'play' and intrinsic motivation, while also supporting more extensive and diverse data collection by attracting many more participants. We describe the advantages and drawbacks of using games relative to standard laboratory-based experiments and lay out a set of recommendations on how to gain the most from using games to study cognition. We hope this Perspective will lead to a wider use of games as experimental paradigms, elevating the ecological validity, scale and robustness of research on the mind

Testing Models of Resilience in University Students: A Multi-Site Study

Emerging adulthood is characterized by marked increases in vulnerability to psychiatric illness. As such, understanding how risk and protective factors function to promote, or impede, resilience during early adulthood is critical. This pre-registered work is the first to test four leading models of resilience among emerging adults. A sample of 1,075 participants drawn from four international university sites were followed across two stressors: the transition to university (cross-sectional) and the COVID-19 pandemic (longitudinal). We found support for the compensatory model, which holds that risk and protective factors contribute additively to predict resilience, at both timepoints. Findings also support the risk-protective model, but only during the university transition, indicating that the influence of risk factors on negative outcomes during the university transition is buffered by protective factors. Neither the challenge nor protective-protective models were supported. Results have the potential to guide theory development by highlighting the dynamic nature of resilience and have implications for prevention and intervention efforts by underscoring the powerful influence of protective factors

Measuring self-regulation in everyday life: reliability and validity of smartphone-based experiments in alcohol use disorder

Self-regulation, the ability to guide behavior according to one’s goals, plays an integral role in understanding loss of control over unwanted behaviors, for example in alcohol use disorder (AUD). Yet, experimental tasks that measure processes underlying self-regulation are not easy to deploy in contexts where such behaviors usually occur, namely outside the laboratory, and in clinical populations such as people with AUD. Moreover, lab-based tasks have been criticized for poor test–retest reliability and lack of construct validity. Smartphones can be used to deploy tasks in the field, but often require shorter versions of tasks, which may further decrease reliability. Here, we show that combining smartphone-based tasks with joint hierarchical modeling of longitudinal data can overcome at least some of these shortcomings. We test four short smartphone-based tasks outside the laboratory in a large sample (N = 488) of participants with AUD. Although task measures indeed have low reliability when data are analyzed traditionally by modeling each session separately, joint modeling of longitudinal data increases reliability to good and oftentimes excellent levels. We next test the measures’ construct validity and show that extracted latent factors are indeed in line with theoretical accounts of cognitive control and decision-making. Finally, we demonstrate that a resulting cognitive control factor relates to a real-life measure of drinking behavior and yields stronger correlations than single measures based on traditional analyses. Our findings demonstrate how short, smartphone-based task measures, when analyzed with joint hierarchical modeling and latent factor analysis, can overcome frequently reported shortcomings of experimental tasks

Measuring self-regulation in everyday life: Reliability and validity of smartphone-based experiments in alcohol use disorder

Self-regulation, the ability to guide behavior according to one's goals, plays an integral role in understanding loss of control over unwanted behaviors, for example in alcohol use disorder (AUD). Yet, experimental tasks that measure processes underlying self-regulation are not easy to deploy in contexts where such behaviors usually occur, namely outside the laboratory, and in clinical populations such as people with AUD. Moreover, lab-based tasks have been criticized for poor test-retest reliability and lack of construct validity. Smartphones can be used to deploy tasks in the field, but often require shorter versions of tasks, which may further decrease reliability. Here, we show that combining smartphone-based tasks with joint hierarchical modeling of longitudinal data can overcome at least some of these shortcomings. We test four short smartphone-based tasks outside the laboratory in a large sample (N = 488) of participants with AUD. Although task measures indeed have low reliability when data are analyzed traditionally by modeling each session separately, joint modeling of longitudinal data increases reliability to good and oftentimes excellent levels. We next test the measures' construct validity and show that extracted latent factors are indeed in line with theoretical accounts of cognitive control and decision-making. Finally, we demonstrate that a resulting cognitive control factor relates to a real-life measure of drinking behavior and yields stronger correlations than single measures based on traditional analyses. Our findings demonstrate how short, smartphone-based task measures, when analyzed with joint hierarchical modeling and latent factor analysis, can overcome frequently reported shortcomings of experimental tasks

Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches