Stress and Decision Making: Effects on Valuation, Learning, and Risk-taking

A wide range of stressful experiences can influence human decision making in complex ways beyond the simple predictions of a fight-or-flight model. Recent advances may provide insight into this complicated interaction, potentially in directions that could result in translational applications. Early research suggests that stress exposure influences basic neural circuits involved in reward processing and learning, while also biasing decisions toward habit and modulating our propensity to engage in risk-taking. That said, a substantial array of theoretical and methodological considerations in research on the topic challenge strong cross study comparisons necessary for the field to move forward. In this review we examine the multifaceted stress construct in the context of human decision making, emphasizing stress’ effect on valuation, learning, and risk-taking

Could dopamine agonists aid in drug development for anorexia nervosa?

Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage-years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight, and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological, and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction, and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction, and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways

Viewing the personality traits through a cerebellar lens. A focus on the constructs of novelty seeking, harm avoidance, and alexithymia

The variance in the range of personality trait expression appears to be linked to structural variance in specific brain regions. In evidencing associations between personality factors and neurobiological measures, it seems evident that the cerebellum has not been up to now thought as having a key role in personality. This paper will review the most recent structural and functional neuroimaging literature that engages the cerebellum in personality traits, as novelty seeking and harm avoidance, and it will discuss the findings in the context of contemporary theories of affective and cognitive cerebellar function. By using region of interest (ROI)- and voxel-based approaches, we recently evidenced that the cerebellar volumes correlate positively with novelty seeking scores and negatively with harm avoidance scores. Subjects who search for new situations as a novelty seeker does (and a harm avoiding does not do) show a different engagement of their cerebellar circuitries in order to rapidly adapt to changing environments. The emerging model of cerebellar functionality may explain how the cerebellar abilities in planning, controlling, and putting into action the behavior are associated to normal or abnormal personality constructs. In this framework, it is worth reporting that increased cerebellar volumes are even associated with high scores in alexithymia, construct of personality characterized by impairment in cognitive, emotional, and affective processing. On such a basis, it seems necessary to go over the traditional cortico-centric view of personality constructs and to address the function of the cerebellar system in sustaining aspects of motivational network that characterizes the different temperamental trait

Neural Correlates of Approach and Avoidance Learning in Behavioral Inhibition

Behavioral inhibition is a temperamental trait characterized in infancy and early childhood by a tendency to withdraw from novel or familiar stimuli. Recent neuroimaging research indicates that BI individuals have atypical neural responses to information regarding reward and punishment in the striatum and amygdala--regions of the brain that receive information about salient stimuli and use it to guide motivated behavior. Activation to rewarding and punishing stimuli in these regions follows a "prediction error" pattern. My research examines whether behaviorally inhibited young adults display atypical prediction error responses, and whether these responses are specific to rewarding or aversive events. Prediction error signals are theorized to be critical for approach and avoidance learning, and a second study examined probabilistic approach and avoidance learning in the same sample, examining differences in approach and avoidance learning between behaviorally inhibited and non-inhibited individuals, and the relation between learning and neural prediction error signals to reward and punishment

How Gains and Losses Influence the Brain and Behavior: Relations to Age, Risk for Depression, and Individual Differences

Behavioral and neural response to rewards and punishments has been the subject of a growing literature with particular interest within developmental, psychopathology, and individual difference domains. There is now mounting evidence suggesting that adolescents show heightened response to reward relative to adults, and that adolescents with Major Depressive Disorder (MDD), elevated depressive symptoms, or at high-risk for depression show reduced response to reward. However, it is unclear whether similar relations between response to incentives and development/psychopathology are observed during childhood. Here we examine behavioral, neural (functional magnetic resonance imaging - fMRI), and self-reported responsiveness to gain and loss of rewards within healthy children and young adults. We relate observed neural/behavioral incentive responsiveness to 1) developmental stage, 2) risk for depression, and 3) self-reported incentive sensitivity. First, studies investigating developmental stage indicated that responsiveness to gain and loss of reward feedback show differing relations with age. Specifically, while children show elevated behavioral and neural (dorsal/posterior insula) response to loss of reward relative to adults, response to reward was similar across age groups. Second, we observed similar levels of both gain approach and loss avoidance behavior between healthy children at relatively high and low-risk for MDD, based on a positive/negative maternal history of MDD respectively. Third, across several studies both elevated gain approach and elevated loss avoidance behavior related to elevated self-reported incentive sensitivity as assessed via different questionnaire types (i.e. hedonic capacity, Behavioral Inhibition System/Behavioral Activation System, and anhedonic depressive scales). Interestingly, gain approach and loss avoidance behavior predicted unique variance in self-reported incentive sensitivity (BAS drive) and relations between incentive sensitivity and behavior did not differ based on age or depression risk status. Together these results highlight the importance of responsiveness to feedback signaling the loss of reward from both developmental and incentive sensitivity perspectives. Future work is needed to examine how gain and loss responsiveness during childhood prospectively predicts changes in incentive responsiveness over development and incidence of depression/changes in depressive symptoms

Interactions Between the Basolateral Amygdala and Ventral Striatum During Probabilistic Learning in Children and Associations with Individual Differences in Free Cortisol

Stress can drastically alter the behavioural and functional correlates of feedback learning; however, the functional correlates of these effects are poorly understood, particularly in children. In the present study, typically developing children between the ages of 9- and 11-years-old completed a probabilistic learning task with both appetitive and aversive outcomes in a magnetic resonance imaging scanner. Anticipatory stress to the experimental environment was measured via salivary cortisol at baseline and prior to completion of the task. Although baseline and pre-MRI cortisol values were not reliably different at the group level, subsequent analyses revealed that the basolateral amygdala was less responsive to positive feedback in children with higher pre-MRI cortisol levels. Furthermore, individual differences in feedback-related basolateral amygdala activity were positively associated with differences in striatal activity. Thus, the basolateral amygdala may be particularly sensitive to individual differences in active cortisol levels, and may also modulate striatal feedback sensitivity

The development of sensitivity to threat among children and adolescents

Several theories of adolescent brain development suggest that adolescence is a sensitive period of development characterized by the onset of internalizing problems, such as anxiety. Sensitivity to threat, a heightened responsiveness to aversive situations, has been suggested to be a precursor to anxiety, highlighting the importance of understanding sensitivity to threat among children and adolescents. Yet relatively little is known about the development of sensitivity to threat. Further, identifying the neural indicators that are associated with heightened sensitivity to threat would help classify which youth are most at risk for anxiety. The primary goals of my dissertation were: 1) to explore whether adolescents, compared to children, have heightened sensitive to threat, 2) assess which neural indicators are associated with heightened sensitivity to threat, and 3) assess whether individual differences (e.g., in consistency of sensitivity to threat across time and situation) help predict which youth are most at risk for anxiety-related problems. Study 1 of my dissertation examined, with concurrent data, whether adolescents have greater neural sensitivity to negative feedback compared to children. Study 2 examined whether children and adolescents differ in their longitudinal trajectories of sensitivity to threat (e.g., consistency across time). I also was interested in whether these trajectories were associated with frontal asymmetry, a neural indicator associated with avoidance motivations. Study 3 extended the findings from Study 2 to examine consistency across threatening situations. While Studies 1 through 3 investigated whether adolescence is a period of heightened sensitivity to threat, Study 4 of my dissertation used a latent class analysis to investigate whether individual differences in sensitivity to threat, impulsivity, and emotion dysregulation are associated with anxiety and/or risk taking. Results indicated that adolescence (especially when defined by pubertal status), may be a normative period for sensitivity to threat. At the same time, not all youth who are sensitive to threat go on to develop anxiety; thus, it may be that for many adolescents, sensitivity to threat is an adolescent-limited phenomenon, meaning that threat sensitivity may peak in adolescence, but then tapers off into adulthood. Importantly, neural indicators associated with threat sensitivity helped identify which youth may have the highest levels of threat sensitivity. Overall, my dissertation shows that while some level of sensitivity to threat is normative, it is less common for youth to be consistently sensitive to threats and importantly, these youth who are consistently sensitive appear to be most at risk. Taken together, the four studies of my dissertation incorporate EEG, longitudinal designs, multiple indicators of development (age and pubertal status), and self-report data to gain a holistic understanding of sensitivity to threat from childhood to adolescence

Neurocognitive Mechanisms of Learning and Decision-Making in Adolescent-OCD: A Computational Approach

Early-onset obsessive-compulsive disorder (OCD) is substantially less researched than adult-OCD, resulting in prevalent equivocation surrounding the neurocognitive profile of child-OCD. Research into this area is pivotal as population studies report that youths with OCD struggle significantly in academic settings. In the General Introduction of this thesis, I reviewed existing literature and found that strikingly, young patients do not show impairment on features that are considered both hallmarks of adult OCD and tightly linked to disorder symptomatology, such as response inhibition and cognitive flexibility. Among the characteristics that are thought to be present in children and adolescents with OCD are abnormal decision-making under uncertainty and impaired learning, and I decided to focus on these features as they may be driving poor academic attainment in young people with the disorder. In addition, I sought to investigate other cognitive processes that have not been well-researched in adolescent-OCD but are found to be robustly altered in adult OCD such as goal directed/model-based reasoning, meta-cognition, and feedback sensitivity. I aimed to delineate these various processes using a battery of suitably complex cognitive tasks. Moreover, I highlighted that majority of past studies fail to find differences between young patients and controls due to behavioural signatures being too subtle to be uncovered by standard statistical analyses. Hence, I employed computational modelling of cognitive task data to disentangle latent decision-making processes displayed by adolescents with OCD. In Chapter 2, I modelled data from the Wisconsin Card Sorting task, a frequently used paradigm of cognitive flexibility, and confirmed that youths with OCD show equivalent performance on the task to controls. Only patients on serotonergic medication showed increased response latencies and a tendency to make unique errors (choosing a deck associated with no rule present on the test card). Next, in Chapter 3, I sought to understand instrumental and Pavlovian learning, and whether adolescents with OCD show increased punishment sensitivity on a novel aversive Pavlovian-to Instrumental Transfer paradigm. Once again, patient performance was equivalent to that of controls. Hence, the remaining chapters were dedicated to probing behaviour on probabilistic paradigms. In Chapter 4, I formally investigated model-based and model-free learning using a well-validated two step decision-making task, and fit a reinforcement learning drift diffusion model to both choice and reaction time data. Patients showed increased exploration on the task as well as faster and more erratic decisions compared to controls. Nonetheless, model-based learning was equivalent between groups. In the penultimate chapter, I demonstrate on a predictive-inference task that patients with OCD update their choices more frequently compared to controls independent of prediction error magnitude. Finally, in Chapter 6, I administered a probabilistic reversal learning paradigm to a large sample of 50 adolescent patients and 53 matched controls. Standard analyses revealed a significant reversal learning deficit in patients with OCD, wherein they displayed more errors and a lower propensity to repeat choices following positive feedback during the post-reversal phase. Crucially, computational modelling revealed striking group differences where adolescents with OCD displayed elevated reward learning and lower punishment learning, increased exploration, and decreased perseveration compared to controls. In the General Discussion, I emphasise that atypical learning and decision-making in adolescent-OCD are more pronounced on probabilistic tasks, where task environments are more volatile. Results are partly discussed in the context of the uncertainty model of OCD, where subjective feelings of doubt experienced by patients drive compulsive behaviours such as checking and certainty-seeking in daily life, alongside excessive exploration on probabilistic tasks. I also consider various explanations for cognitive distinctions between adult- and adolescent OCD. More general implications of the findings are discussed for understanding OCD in the context of adolescent development and for treatment/support strategies.WELLCOME TRUST (104631/Z/14/Z

Adolescent rats are resistant to forming ethanol seeking habits

AbstractEarly age of onset alcohol drinking is significantly more likely to lead to alcohol use disorders (AUDs) than alcohol drinking that begins after the age of 18. Unfortunately, the majority of people in the United States begin drinking in adolescence. Therefore, it is important to understand how early alcohol drinking leads to increased risk for AUDs so that better treatments and prevention strategies can be developed. Adolescents perceive greater rewarding properties of alcohol, and adolescents may be more likely to form alcohol-seeking habits that promote continued use throughout the lifetime. Therefore, we compared the development of alcohol seeking habits in adolescent and adult male, Sprague-Dawley rats. Rats were trained to lever press to receive 10% ethanol+0.1% saccharin on a schedule that promotes habit formation. Rats were tested using a contingency degradation procedure at different points in training. Adult rats formed ethanol-seeking habits with only moderate training, while adolescents remained goal-directed even with extended training. Nevertheless, adolescents consumed more ethanol than adults throughout the experiment and continued to consume more ethanol than adults when they reached adulthood. Therefore, early onset alcohol use may promote AUD formation through establishment of high levels of drinking that becomes habitual in adulthood

Addictions NeuroImaging Assessment (ANIA): Towards an integrative framework for alcohol use disorder.

Alcohol misuse and addiction are major international public health issues. Addiction can be characterized as a disorder of aberrant neurocircuitry interacting with environmental, genetic and social factors. Neuroimaging in alcohol misuse can thus provide a critical window into underlying neural mechanisms, highlighting possible treatment targets and acting as clinical biomarkers for predicting risk and treatment outcomes. This neuroimaging review on alcohol misuse in humans follows the Addictions Neuroclinical Assessment (ANA) that proposes incorporating three functional neuroscience domains integral to the neurocircuitry of addiction: incentive salience and habits, negative emotional states, and executive function within the context of the addiction cycle. Here we review and integrate multiple imaging modalities focusing on underlying cognitive processes such as reward anticipation, negative emotionality, cue reactivity, impulsivity, compulsivity and executive function. We highlight limitations in the literature and propose a model forward in the use of neuroimaging as a tool to understanding underlying mechanisms and potential clinical applicability for phenotyping of heterogeneity and predicting risk and treatment outcomes