Todd F. Heatherton - US grants

The methods of cognitive neuroscience will be used to examine a social psychological theory of self-regulation. According to the strength model, self-regulation is governed by a limited resource that allows people to control impulses and desires. Self-regulatory resources can be depleted or fatigued by self-regulatory demands. Hence, the active effort required to control behavior in one domain leads to diminished capacity for self-regulation in other domains. Because people have a limited reservoir of self-regulatory resources, they can be overwhelmed by both self-initiated and situational demands, thereby resulting in self-regulation failure. Preliminary studies using social psychological methods have found consistent support for the strength model. The new studies use methods from cognitive neuroscience to more fully elucidate the underlying brain mechanisms involved in self-regulation. A first project examines whether performing an initial self-regulatory task leads to alterations in performance on a subsequent test of frontal lobe functioning. Tasks such as the Tower of London, Stroop Task, and negative priming have been shown to reflect frontal lobe activity. A second project uses functional magnetic resonance imaging (fMRI) to assess brain activity correlated with self-regulatory effort. Together these studies should provide substantial evidence about the neural correlates of self-regulation. In addition, this research allows for an examination of the strength model of self-regulation that is not possible using traditional social psychological methods. More generally, this research will demonstrate the usefulness of cognitive neuroscience methods for examining social psychological phenomena.

Support is provided for three educational workshops to be held at the Society of Personality and Social Psychology's (SPSP) First Annual Meeting in Nashville, TN, February 6, 2000. The workshops include (1) Capturing the Vicissitudes of Life: Electronic Experience-Sampling; (2) Functional Neuroimaging in Personality and Social Psychology; and (3) Using the Web for Research in Social and Personality Psychology. The workshops will provide an interdisciplinary focus on the use of cutting-edge technologies in social and personality psychology research.

DESCRIPTION (adapted from investigator's abstract): This research explores the basic dynamics of the effect of self-esteem and threat on social evaluation. Recent evidence suggests that individuals with high self-esteem may have interpersonal and self-regulatory difficulties when self-image is threatened or challenged. Three preliminary laboratory studies are described demonstrating that dyadic interaction partners negatively evaluate high self-esteem targets who have received an ego threat. By contrast, those with low self-esteem are evaluated more positively following an ego threat. The proposed studies explore the interpersonal consequences of having high or low self-esteem, especially under conditions of threat. The first series consists of four laboratory studies that examine the interpersonal context of this asymmetric evaluative pattern. The questions addressed include: How are people behaving in the dyadic interactions (verbally and nonverbally)? What role does the rater's self-esteem play? Is this asymmetric liking effect limited to strangers? Is this effect limited to an intimacy task? Studies in the second series examine the motivational basis of interpersonal evaluation following ego threat. The general proposition is that people with low self-esteem focus on affirming social bonds whereas people with low self-esteem affirm personal competence. These motivational differences have social consequences such that low self-esteem individuals act in ways that lead people to like them whereas high self-esteem individuals act in ways that lead people to dislike them. Three studies assess the sort of information people are motivated to obtain, their memory for dyad partners, and the extent they expect to be accepted or rejected. The third series tries to directly test the proposed mediators of the asymmetrical liking pattern. Questions asked in this series include: Does ego threat change degree of self-focus? Does ego threat lead to differential patterns of interpersonal comparisons? Do the effects of self-esteem in comparisons and self-focus correlate with evaluations made by raters? The final series considers the possibility that the putative negative consequences of high self-esteem are due primarily to defensive or fluctuating self-esteem. Measures of implicit self-esteem and self-esteem stability are collected to examine their role in interpersonal evaluation. Considered together, there studies will provide important information regarding the interpersonal consequences of having high or low self-esteem, especially under situations that involve ego threat.

The Center for Cognitive and Educational Neuroscience (C-CEN) at Dartmouth, under the direction of Michael Gazzaniga and funded under the NSF Science of Learning Program, will bring together the fields of cognitive neuroscience and education. Education changes the brain, and understanding this complex process will be fundamental to creating a science of learning. Based on our understanding of how the brain encodes, stores, and activates knowledge, what are the barriers to learning, and how can ways around those barriers be implemented? What is the brain-basis of core content areas of learning, including language, math, science, and literacy? How do social/cultural cues impact the ability to learn? And how is learning regulated by genetic factors? To explore these and related questions, C-CEN will advance basic discovery in cognitive and educational neuroscience, foster a dialogue between researchers and educators, and create learning deliverables that will enhance and transform education for diverse participants.

The research core of C-CEN will advance basic discovery of the brain basis of human learning by conducting research on (a) core content areas of learning: language, reading, science, and math; and (b) fundamental aspects of learning: transfer of learning , brain lateralization, social aspects of learning, and brain development. This research will be conducted by (a) using multiple techniques including functional Magnetic Resonance Imaging, Near Infra-Red Spectrography, Evoked Response Potentials, genetic and behavioral measures; (b) across several ages, infants, children, adolescents, and young adults, and (c) using multiple contexts including the laboratory, formal classrooms, and informal learning environments.

[unreadable] DESCRIPTION (provided by applicant): Background: For addicts, exposure to drug-relevant stimuli produces significant emotional and motivational reactions, such as pleasure and craving that encourage immediate substance use and undermine efforts to abstain or control drug use. Recent neuroimaging research has identified a distributed network of brain regions that contribute to this reactivity. However, results across studies have been vexingly inconsistent, perhaps in part because researchers have failed to pay sufficient attention to the psychological contexts that influence drug craving. Outside of the laboratory, the mental state of the addict, the availability of ready substances, the social environment, and the environmental context in which cues are encountered are likely to make vital contributions to psychological and behavioral reactions to drug cues. Delineating the nature of these factors may help resolve extant discrepancies in the literature, thereby helping to elucidate the neural substrates responsible for drug cue reactivity and their role in addiction. Specific Aims: The overarching goal of this research is to identify key social and contextual factors that affect the propensity to engage in drug-seeking behavior. Specific aims include (i) understanding how social context influences neural activity associated with cue reactivity (ii) examining how the emotional and mental state of research participants influences reactions to cue exposure, (iii) predicting self-regulatory behavior following cue exposure, and (iv) examining whether social conformity depletes self-regulatory resources. This research will make use of a unique resource of movies that have been rigorously computer-coded for drug, tobacco, and alcohol use, as well as for social context, drug use motivations, and character features. The database consists of the top 100 movies each year since 1995. The stimulus materials for each study will be carefully selected from the database. To accomplish our research goals, we will use functional magnetic resonance imaging. Significance: Because exposure to drug cues plays a prominent role in drug use and relapse, understanding the neural mechanisms that contribute to these reactions will provide insights into the addicted brain. Understanding the social context of drug cue exposure has the potential to illuminate treatment of addictive behaviors. [unreadable] [unreadable] [unreadable]

DESCRIPTION (Provided by applicant): This application seeks matching funds for five years to support the Summer Institute in Cognitive Neuroscience, an annual, multidisciplinary training program in cognitive neuroscience. The broad, long-term objectives of the Summer Institute are to advance the studies of mind and brain that will lead to our better understanding mental functioning, mental health, and mental disorders. Education Program Plan: The Institute brings together senior graduate students, postdoctoral fellows, physician fellows, psychiatrists, psychologists, and junior faculty of the wide variety of disciplines that intersect in the study of human consciousness and cognition. The topics and faculty change yearly to allow rapid responses to areas of mind/brain research that show promise for advancing the research agenda. Together, the fellows and faculty address problems in the science of the mind, defining questions, presenting hypotheses, exploring existing experimental results, and developing each participant's ability to carry on innovative and important research into mind and brain mechanisms and disorders. The format includes formal lectures, laboratory exercises, and demonstrations by faculty, as well as constant interaction fostered by social events and proximity of the fellows in a residential setting. In a five-year cycle, four of the five Summer Institutes run for 2 weeks and train 70 fellows. Every five years the program carries a comprehensive review of the field of cognitive neuroscience. The information synthesized and evaluated at the Summer Institute is then published as The Cognitive Neurosciences. The Cognitive Neurosciences is widely used as the primary and standard reference book in the field. Curricula for the Institute are set one year in advance. As an example, the upcoming Summer Institute 2001 will feature cognition reward, and learning. The first week will examine issues of imaging and development, imaging and neuropathology, imaging and computational modeling, imaging and vision, as well as explore the feasibility of combining of fMRI, MEG, TMS, and ERP techniques. The second week will continue to push forward with current topics in cognitive neuroscience by addressing the process of reward. The course will examine reward from a broad perspective including anatomic, systems, social and computational approaches. Additionally, beginning with week one the Fellows will be formed into several groups that will conceive of, design, implement, analyze, and present topical TMS, ERP &/or FMRI experiments. We continue to work hard at making the Summer Institute in the most up-to-date, interactive and informative course of study for cognitive neuroscience.

DESCRIPTION (provided by applicant): This application examines the functional neuroanatomy of interpersonal distress. Based on the premise that humans have a fundamental need to belong, this research is concerned with understanding how people process information when they believe that their interpersonal relations are at risk. This topic is important because there is overwhelming evidence of physical and mental health problems resulting from and contributing to interpersonal distress (e.g., depression, social anxiety). Using multiple methodologies, and working across levels of analysis, the proposed research has the potential to provide new insights into how interpersonal distress changes how people process information in a way that affects their mental health. Although some research examining the neural correlates of rejection is beginning to emerge, there are ambiguities in the literature regarding the involvement of specific brain regions (i.e., anterior cingulate cortex) in feelings of rejection. Given the importance of interpersonal distress to mental health, research is needed to delineate the brain processes involved in feelings of rejection and how this impacts emotion, cognition, and behavior. Specific Aims - The overarching goal of this research is to understand the impact of interpersonal distress on the brain and behavior. Specific aims include (a) characterizing the neural mechanisms for detecting and responding to interpersonal distress, which includes examining a network of brain regions including ventral and dorsal anterior cingulate cortex, amygdala, and medial prefrontal cortex, (b) examining individual differences in responsiveness to interpersonal distress by testing the hypothesis that some individuals are particularly sensitive to cues of social exclusion, and (c) identifying the effects of interpersonal distress on cognition, affect, and behavior, such as greater attention to rejection cues, increased social memory, and greater adherence to social norms. Significance - Because interpersonal distress has been implicated in many mental and physical health disorders, this research will contribute to a better understanding of its neural correlates, as well as how it impacts cognition, affect, and behavior. Ultimately, this may inform psychological treatments for many mental health disorders, including depression, post-traumatic stress disorder and social phobia. PUBLIC HEALTH RELEVANCE: Because interpersonal distress plays a prominent role in many mental health disorders, understanding its functional neuroanatomy will provide insights into the cognitive, affective and behavioral consequences of social distress. As such, the results of this research have the capacity to provide insights into the psychological aspects of interpersonal distress, which are likely to inform psychological treatment.

Summary Although humans have an impressive capacity for self-regulation, failures are common and people sometimes have difficulty controlling their behavior across a wide variety of circumstances. Such failures are implicated in many preventable health problems associated with death and disease, including obesity, poor nutrition, inadequate exercise, alcoholism and addiction, and risky sexual activity. The overarching goal of this research is to better understand the neural basis of individual differences in the extent to which people are susceptible to self-regulatory failure. The proposed research examines a recent model of self-regulatory failure developed by the investigators that that builds on three decades of social psychological research. Specifically, the model examines the situational and contextual factors under which self-regulation fails in light of the current neuroscience literature on brain mechanisms underlying executive control and reward sensitivity. This model indicates that successful self-regulation is dependent on top-down control from frontal regions over subcortical regions involved in reward and emotion and that botom-up subcortical activity contributes to self-regulation failure. This project uses recently developed applications of network analysis to assess resting state connectivity (rs-fcMRI) and its relation to self-regulatory success and failure. Network-based rs-fcMRI allows for the examination of functional coupling of brain networks, patterns of statistical coherence across brain regions that arise throughout development, in a manner that permits assessment of a network's integrity (i.e., strength of connections between nodes in the network). When subjects are not performing an explicit task, coherent activity within several separable and reproducible brain networks can be identified. One of these is the fronto-parietal network-preliminary research shows that activity in this network at rest predicts body weight and aerobic capacity (in separate studies). The guiding hypothesis of this research is that individual differences in the integrity of this fronto-parietal network are associated with long-term success or failure in self-regulation. The target self-regulatory behavior in this research is dieting because it is amenable to functional imaging research and it can be manipulated in behavioral laboratory experiments. Three studies are proposed to test the specific aims of this project, which include assessing rs-fcMRI and brain reward activity to predict (1) eating behavior in laboratory assessments of food consumption following dietary challenges, (2) functional brain activity following self-regulatory depletion, and (3) long-term outcomes in dietary success. Examining resting state connectivity in the fronto-parietal network and brain reward activity will provide novel insights into individual differences in self-regulatory success and failure. !

DESCRIPTION (provided by applicant): This R01 application is written in response to PA-11-015, Alcohol Marketing and Youth Drinking, which aims to answer whether there is a direct causal relation between exposure to alcohol marketing and alcohol attitudes/behaviors among youth. The application supports a multi-disciplinary team of epidemiologists, neuroscientists and psychologists that will rapidly accumulate evidence for important causality prerequisites: a) a content analysis will establish whether the themes included in contemporary alcohol advertising could be salient to adolescents and promote hazardous drinking (theoretical plausibility), b) fMRI experiments will assess whether alcohol ad exposure engages brain patterns consistent with a marketing effect (biological plausibility), c) population based survey research will assess whether there is an association between alcohol marketing and adolescent behavior, assessing causal constructs of strength, dose-response, independence, and specificity (epidemiologic plausibility), and d) whether that association is mediated through marketing- specific cognitions (psychological plausibility). The proposal revolves around an innovative heuristic model that the association between alcohol marketing exposure and hazardous/harmful drinking among experimental drinkers is mediated through marketing-specific cognitions-drinker identity and having a favorite alcohol brand-tested using cutting-edge analyses. The content analysis involves a thematic and image-based assessment of over 700 alcohol ads televised nationally over a two-year period, ads that also form the basis for cues presented in the neuroscience and epidemiologic research. Proposed brain imaging studies examine the neural correlates of cue reactivity to dynamic viewing of alcohol brand advertisements among underage undergraduates. Reward activity and activation of drinking-relevant motor planning circuitry is expected in response to viewing the ads, and response levels should predict future drinking behavior. Consistent with our model of marketing effects proposing favorite brand to drink as a key mediating cognition, activity in brain regions associated with self-relevance is expected for favorite vs. other alcohol brand ads-evidence that the brain is processing favorite brand in the context of self. The proposed population-based research builds on ARRA-funded research that recruited 3342 subjects aged 15 to 23 from across the United States in 2010. In this cohort, we have employed an innovative cue-based assessment of alcohol marketing exposures across entertainment media (TV programming, movies and music), advertising on TV and the internet, in which adolescents respond to images randomly drawn from large samples of contemporary media. Our initial findings demonstrate an association between cued responses to alcohol ads and binge drinking and expected mediation paths. A comprehensive review of the published literature will be conducted in year 5. Taken together, the proposed research allows us to rapidly propel the science forward and make significant advances in our understanding of whether the relation between alcohol marketing and drinking behavior is causal.

DESCRIPTION (provided by applicant): Impaired self-control is a defining feature of addiction. Indeed, self-regulation failures are implicated in many of the most vexing problems facing contemporary society, from drug abuse and addiction, to smoking and cancer, to overeating and obesity, to impulsive sexual behavior and HIV/AIDS. One reason that people may be prone to engaging in unwanted behaviors is because of heightened sensitivity to cues related to those behaviors. Researches findings from the prior award period (R01 DA022582) demonstrate that incidental exposure to drug cues activate brain reward regions (i.e., the nucleus accumbens [NAcc] as well as those involved in motor planning) for subsequent consumption. We also found that heightened NAcc responsively to food and sexual cues is associated with indulgence in overeating and sexual activity, respectively, and provides evidence for a common neural mechanism associated with addictive and appetitive behaviors. The overarching goal of this research is to identify neural predictors of self-regulatory failure and success using a model developed by the investigators that integrates what is known from three decades of social psychological research into the situational and contextual factors under which self-regulation fails with the neuroscience literature on brain mechanisms underlying executive control and reward sensitivity. This model argues that successful self- regulation is dependent on top-down control from cortical brain networks over subcortical regions involved in reward and emotion. This project uses recently developed applications of network analysis to assess resting state connectivity (rs-fcMRI) in brain circuitry and its relation to health-relevant outcomes. Complementary to stimulus-driven fMRI activation studies, network-based rs-fcMRI allows for the examination of functional coupling of brain circuits in a manner that permits assessment of a network's integrity. When individuals are not performing an explicit task, several separable and reproducible brain circuits can be identified and have been demonstrated to predict, for example, brain maturity, body weight and aerobic capacity. The guiding hypothesis of this research is that individual differences in the integrity of these networks can predict success or failure in self-regulation leading to markedly different outcomes when self-regulation is challenged by daily temptations, self-regulatory strength depletion, negative moods, or minor indulgences. The target self- regulatory behaviors in this research are smoking and dieting because they are amenable to functional imaging research and can be manipulated in behavioral laboratory experiments. Studies are proposed to test the specific aims of this project, which include using rs-fcMRI and brain reward activity to predict (1) long-term outcomes in smoking cessation, dietary success, and daily resistance to impulses, (2) functional brain activity following self-regulatory depletion, and (3) to test whether self-regulatory training can strengthen resting-state connectivity and in so doing enhance long-term self-regulatory behavior. Collectively, these studies will provide novel insights into individual differences in sef-regulatory success and failure.

Project Summary How the self is experienced is central to healthy emotional functioning as well as many disturbances in psychological functioning. This competing renewal uses structural, functional, and resting-state neuroimaging, coupled with passive smartphone sensing technology and ecological momentary assessments, to examine the affective components of self. Understanding the factors that contribute to changes in the affective aspects of self that result from environmental stressors has the potential to provide important insights into the development of mental disorders and help identify individuals who might be in greatest need of early intervention or treatment. Research findings during the prior two award periods (R01 MH059282) revealed several key brain regions involved in processing information related to self. Moreover, we discovered that structural and functional connectivity between these regions and other brain regions known to be involved in emotional processes are associated with measures of self-affect. The overarching goal of this research is to examine how brain connectivity and activity is related to change in subjective distress and associated functional impairment. An exciting aspect of the proposed work is that we will take advantage of the university setting to follow a large cohort of participants over their four years of college to assess how changes in self- affect are predicted by relevant brain networks as well as how those networks change over time. Tasks assessing self-affect will be performed during scanning. Given that approximately 30% of participants are likely to develop a significant subjective distress, one goal is to examine whether there are biomarkers that predict these outcomes. Additional scanning studies will induce interpersonal distress to examine the temporary inductions of affect on task performance. This project will use recently developed applications of network analysis to assess resting state connectivity in brain circuitry and its relation to self-affect and health- relevant outcomes. The guiding hypothesis of this research is that individual differences in the integrity of these networks can predict individual differences in vulnerability to stress and their relation to self-affect. The specific aims of the study are: (1). Characterize neural networks that give rise to self-affect using diffusion tensor imaging, resting state functional connectivity, and task-related functional imaging. In addition, multivariate pattern analysis and representation similarity analysis will be used to classify participants as having high or low self-affect (e.g., self-esteem, depression, anxiety); (2). Examine how changes in self-affect that occur over time are reflected by changes within relevant brain networks and are predicted by baseline network connectivity; and (3). Examine how induced interpersonal distress impacts self-affect and related functional connectivity across networks. Understanding the factors that contribute to changes in self-affect that result from environmental stressors has the potential to provide important insights into the development of mental disorders and help identify individuals who might be in greatest need of early intervention or treatment.