Knowledge for the sake of knowledge: Understanding the relationship between curiosity, exploration, and reward

Curiosity has long been a topic of scientific interest, but it encompasses so many potential traits and behaviors that it has been difficult to precisely target the cognitive and neural mechanisms that drive it. Recent work has reinvigorated the scientific approach to this topic by shifting from trait-level questions to a neurobiological perspective that emphasizes behavior, exploration and information-seeking. By viewing information as a reward, this research has leveraged the extensive body of work on reward processing to understand curiosity as a type of intrinsically motivated, goal-directed behavior. However, this information-as-reward framework raises a host of new questions about how curiosity develops and how it drives learning. In this dissertation, I aimed to test this framework and to address a series of questions about how curiosity drives exploration, learning, and memory. Chapter 1 addresses the question of how curiosity changes across the adult lifespan and tests whether these changes mirror well-established declines in dopamine transmission and reward sensitivity. The first study in this chapter found that, rather than showing declines in curiosity, older adults in fact displayed behaviors that reflected increases in curiosity. They were more willing to wait for information than younger adults and were equally able to remember the information they learned. The second study sought to replicate these results and to examine their neural substrates using fMRI. This study found that older and younger adults displayed equal levels of curiosity and memory. Results from fMRI also showed similar effects for both age groups: increased activation in brain regions associated with reward processing, as well as semantic memory, was related to curiosity and to memory. Chapter 2 explored the other end of development and examined changes in curiosity from late childhood into early adulthood. In this study, we focused on two different conceptualizations of curiosity -- willingness to wait (as in Chapter 1) and also a new measure of exploratory visual behavior. Results showed increases in both waiting and visual exploration between childhood and adulthood. These changes in curiosity were also accompanied by improvements in memory. These findings, like those in Chapter 1, provide evidence against the hypothesis that curiosity declines with age, and also expands our understanding of how different measures of curiosity-driven behavior may relate to one another. Chapter 3 addresses a fundamental question about how to evaluate curiosity and how different forms of curiosity cluster together. Using a large online sample, we obtained two separate groups of measures: measures of curiosity-driven behaviors (willingness to wait, ratings of interest about specific questions, curiosity-related memory), and measures of curiosity as a trait. Additionally, we obtained measures of traits and behaviors though to be related to curiosity, including impulsivity, need for cognition and willingness to wait for monetary rewards. Results revealed that different aspects of curiosity-related behavior cluster together, and that while there was a relationship between self-report and behavioral measures, there were also more nuanced differences in the relationships between different behaviors. Overall, the results from these three lines of research advance our understanding of curiosity by examining the extent to which curiosity is similar to reward processing, testing how it changes across the lifespan, and comparing different types of curiosity. The findings also open up new questions about the influence of other cognitive processes on curiosity and suggest ways in which we can better study how curiosity drives exploration and learning

Inferences of Others' Competence Reduces Anticipation of Pain When under Threat

On a daily basis, we place our lives in the hands of strangers. From dentists to pilots, we make inferences about their competence to perform their jobs and consequently to keep us from harm. Here we explore whether the perceived competence of others can alter one's anticipation of pain. In two studies, participants (Receivers) believed their chances of experiencing an aversive stimulus were directly dependent on the performance of another person (Players). We predicted that perceiving the Players as highly competent would reduce Receivers' anxiety when anticipating the possibility of an electric shock. Results confirmed that high competence ratings consistently corresponded with lower reported anxiety, and complementary fMRI data showed that increased competence perception was further expressed as decreased activity in the bilateral posterior insula, a region localized to actual pain stimulation. These studies suggest that inferences of competence act as predictors of protection and reduce the expectation of negative outcomes

Inferences of Others' Competence Reduces Anticipation of Pain When under Threat

On a daily basis, we place our lives in the hands of strangers. From dentists to pilots, we make inferences about their competence to perform their jobs and consequently to keep us from harm. Here we explore whether the perceived competence of others can alter one's anticipation of pain. In two studies, participants (Receivers) believed their chances of experiencing an aversive stimulus were directly dependent on the performance of another person (Players). We predicted that perceiving the Players as highly competent would reduce Receivers' anxiety when anticipating the possibility of an electric shock. Results confirmed that high competence ratings consistently corresponded with lower reported anxiety, and complementary fMRI data showed that increased competence perception was further expressed as decreased activity in the bilateral posterior insula, a region localized to actual pain stimulation. These studies suggest that inferences of competence act as predictors of protection and reduce the expectation of negative outcomes

Moral Chivalry: Gender and Harm Sensitivity Predict Costly Altruism.

Moral perceptions of harm and fairness are instrumental in guiding how an individual navigates moral challenges. Classic research documents that the gender of a target can affect how people deploy these perceptions of harm and fairness. Across multiple studies, we explore the effect of an individual's moral orientations (their considerations of harm and justice) and a target's gender on altruistic behavior. Results reveal that a target's gender can bias one's readiness to engage in harmful actions and that a decider's considerations of harm-but not fairness concerns-modulate costly altruism. Together, these data illustrate that moral choices are conditional on the social nature of the moral dyad: Even under the same moral constraints, a target's gender and a decider's gender can shift an individual's choice to be more or less altruistic, suggesting that gender bias and harm considerations play a significant role in moral cognition

Moral Chivalry: Gender and Harm Sensitivity Predict Costly Altruism

Moral perceptions of harm and fairness are instrumental in guiding how an individual navigates moral challenges. Classic research documents that the gender of a target can affect how people deploy these perceptions of harm and fairness. Across multiple studies, we explore the effect of an individual’s moral orientations (their considerations of harm and justice) and a target’s gender on altruistic behavior. Results reveal that a target’s gender can bias one’s readiness to engage in harmful actions and that a decider’s considerations of harm—but not fairness concerns—modulate costly altruism. Together, these data illustrate that moral choices are conditional on the social nature of the moral dyad: Even under the same moral constraints, a target’s gender and a decider’s gender can shift an individual’s choice to be more or less altruistic, suggesting that gender bias and harm considerations play a significant role in moral cognition

A systematic review of intravenous gamma globulin for therapy of acute myocarditis

BACKGROUND: Intravenous gamma globulin (IVGG) is commonly used in the management of acute myocarditis. The objective of this study was to systematically review the literature evaluating this practice. METHODS: We conducted a comprehensive search (electronic databases, trials registries, conference proceedings, reference lists, contact with authors) to identify studies evaluating the use of IVGG in adults and children with a clinical or histologically proven diagnosis of myocarditis of possible viral etiology and symptoms of less than six months duration. Two reviewers independently screened the searches, applied inclusion criteria, and graded the evidence. RESULTS: Results were described qualitatively; data were not pooled because only one randomized controlled trial (RCT) with 62 patients was identified. The RCT showed no benefit with respect to cardiac function, functional outcome, or event-free survival. A small, uncontrolled trial (n = 10) showed significant improvement in LVEF from a mean of 24% to 41% 12 months after IVGG in nine survivors. A retrospective cohort study of pediatric patients showed improvement in cardiac function and a trend towards improved survival in patients receiving IVGG (n = 21) versus historic controls (n = 25). Ten case reports and two case series (total n = 21) described improvement in cardiac function after administration of IVGG; two case reports showed no benefit of IVGG. One case of hemolytic anemia was attributed to IVGG. CONCLUSION: There is insufficient data from methodologically strong studies to recommend routine use of IVGG for acute myocarditis. Future randomized studies that take into account the etiology of acute myocarditis will be required to determine the efficacy of IVGG

The p53 Inhibitor MDM2 Facilitates Sonic Hedgehog-Mediated Tumorigenesis and Influences Cerebellar Foliation

Disruption of cerebellar granular neuronal precursor (GNP) maturation can result in defects in motor coordination and learning, or in medulloblastoma, the most common childhood brain tumor. The Sonic Hedgehog (Shh) pathway is important for GNP proliferation; however, the factors regulating the extent and timing of GNP proliferation, as well as GNP differentiation and migration are poorly understood. The p53 tumor suppressor has been shown to negatively regulate the activity of the Shh effector, Gli1, in neural stem cells; however, the contribution of p53 to the regulation of Shh signaling in GNPs during cerebellar development has not been determined. Here, we exploited a hypomorphic allele of Mdm2 (Mdm2puro), which encodes a critical negative regulator of p53, to alter the level of wild-type MDM2 and p53 in vivo. We report that mice with reduced levels of MDM2 and increased levels of p53 have small cerebella with shortened folia, reminiscent of deficient Shh signaling. Indeed, Shh signaling in Mdm2-deficient GNPs is attenuated, concomitant with decreased expression of the Shh transducers, Gli1 and Gli2. We also find that Shh stimulation of GNPs promotes MDM2 accumulation and enhances phosphorylation at serine 166, a modification known to increase MDM2-p53 binding. Significantly, loss of MDM2 in Ptch1+/− mice, a model for Shh-mediated human medulloblastoma, impedes cerebellar tumorigenesis. Together, these results place MDM2 at a major nexus between the p53 and Shh signaling pathways in GNPs, with key roles in cerebellar development, GNP survival, cerebellar foliation, and MB tumorigenesis

Subjective Fear Dilutes as Group Size Increases

According to Hamilton’s Selfish Herd Theory, a crucial survival benefit of group living is that it provides a ‘risk dilution’ function against predation. Despite a large literature on group living benefits in animals, few studies have been conducted on how group size alters subjective fear or threat perception in humans, and on what factors drive preferences for being in groups when facing threats. We conducted seven experiments (N=3,838) to test (A) if the presence of others decreases perception of threat under a variety of conditions. In studies 1 to 3, we experimentally manipulated group size in hypothetical and real-world situations, to show that fear responses decreased as group size increased. In studies 4 to 7 we again used a combination of hypothetical, virtual and real-world decisions to test (B) how internal states (e.g. anxiety) and external factors (e.g. threat level, availability of help) affected participants’ preference for groups. Participants consistently chose larger groups when threat and anxiety were high. Overall, our findings show that group size provides a salient signal of protection and safety

Moral Chivalry

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Achievement of Remission in Two Early Rheumatoid Arthritis Cohorts Implementing Different Treat-to-Target Strategies

Objective The objective of this study was to compare achievement of remission in 2 early rheumatoid arthritis (RA) treat‐to‐target (TTT) cohorts, a tight control cohort with a target of stringent remission in a randomized controlled trial and an observational cohort targeting a looser definition of remission in clinical practice. Methods We analyzed data from the Aiming for Remission in Rheumatoid Arthritis: a randomised trial examining the benefit of ultrasound in a Clinical Tight Control regimen (ARCTIC) trial and the Norwegian Very Early Arthritis Clinic (NOR‐VEAC) observational study. Both were Norwegian multicenter studies that included disease‐modifying antirheumatic drug (DMARD)–naive RA patients and implemented TTT. The target in the ARCTIC trial was remission defined as a Disease Activity Score (DAS) of <1.6 plus 0 swollen joints on a 44‐joint count, while the target in the NOR‐VEAC study was the less stringent remission target of a DAS28 of <2.6. We assessed achievement of the study‐specific targets and compared the odds of achieving the American College of Rheumatology(ACR)/European League Against Rheumatism (EULAR) Boolean remission during 2 years of follow‐up. Results We included 189 patients from the ARCTIC trial and 330 patients from the NOR‐VEAC study. The study‐specific target had been achieved in more than half of the patients in each cohort at 6 months, increasing to >60% at 12 and 24 months. The odds of achieving ACR/EULAR Boolean remission during follow‐up were higher in the ARCTIC trial than in the NOR‐VEAC study, with significant differences at 3 months (odds ratio 1.73 [95% confidence interval 1.03–2.89]), 12 months (odds ratio 1.97 [95% confidence interval 1.21–3.20]), and 24 months (odds ratio 1.82 [95% confidence interval 1.05–3.16]). Conclusion A majority of patients in both cohorts reached the study‐specific treatment targets. More patients in the ARCTIC trial than in the NOR‐VEAC study achieved ACR/EULAR Boolean remission during follow‐up, suggesting that targeting a more stringent definition of remission provides further potential for favorable outcomes of a TTT strategy