Elliot T. Berkman - US grants

DESCRIPTION (provided by applicant): The proposed program of research seeks to understand how the neural processes involved in basic goal pursuit processes are linked to the behavioral outcomes and phenomenological experience of real-world smoking cessation. In the proposed model, smoking cessation is a complex goal pursuit, occurring over months and years, that requires the coordination of many component processes. As such, neuroscience and social psychology have studied different aspects of smoking cessation. On one hand, neuroscience studies to date have made important contributions toward understanding component parts of smoking cessation (e.g. response inhibition, attention control), but have yet to clarify how those neural processes are related to everyday outcomes and experiences. On the other hand, social psychologists have focused on broad theories of everyday goal pursuit, but little is know about the associated neural systems. The proposed program of research seeks to link these two levels of analysis in two ways: first, by combining fMRI with experience sampling, and second, by bringing an approach-avoidance motivation theoretical framework that bridges both neural and behavioral research. Approach-avoidance motivation refers to the extent to which an individual, situation, or task is oriented toward approaching incentives and avoiding threats, and has been shown to be relevant goal pursuit at affective, cognitive, behavioral, and neural levels. In Experiment 1, participants who are smokers [ENROLLED IN A SMOKING CESSATION PROGRAM BUT WHO ARE NOT YET ABSTINENT] complete a basic goal pursuit task in the fMRI scanner. This task assess neural responses to various parts of the goal pursuit process such as goal representation, response inhibition, and progress monitoring, and has both approach and avoidance conditions. [EXPERIMENT 2 TRACKS THOSE SAME PARTICIPANTS DURING THEIR CESSATION ATTEMPT] for 14 days using personal digital assistants. Cigarette consumption and purchase is monitored eight times each day, along with affect and motivation to quit. The data collected in these two experiments is then analyzed together, using neural responses to predict later behavioral, emotional, and motivational outcomes. This approach achieves the project objectives by examining the impact of the neural systems examined in lab-based studies of goal pursuit on the outcomes of a real-world goal pursuit, and by brining an overarching theoretical perspective to the study of goal pursuit and smoking cessation. PUBLIC HEALTH RELEVANCE: The proposed studies advance scientific knowledge on the neural systems involved in smoking cessation, and their connection to behavioral outcomes during a quitting attempt. Results potentially inform quitting interventions and individual differences in quitting strategies.

DESCRIPTION (provided by applicant): Eating energy-dense foods when one is not hungry is a contributor to overweight and obesity, which are risk factors for a range of cancers. Excessive eating of a subset of these foods, such as red meat or foods with a high glycemic index, is an additional risk factor for cancer, separate from overweight and obesity. We refer to foods that are linked to cancer through either or both routes as cancer-promoting foods. The goal of this project is to reduce cancer risk by improving cognitive self-regulation of cravings for cancer-promoting foods. We focus on craving of cancer-promoting foods as one proximal determinant of their consumption. Craving consists of a subjective sense of wanting to eat a food, a motivation to seek out the food, and recurrent or intrusive thoughts related to the food. Considerable research shows that craving is a strong predictor of eating, even in the absence of hunger. Thus, enhancing a simple, low-cost and easily disseminated tool to reduce craving for cancer-promoting foods would advance cancer prevention and related research. Studies from affective science and social neuroscience have identified cognitive self-regulation strategies that are effective in reducing craving and their associated neural systems. This work has focused mostly on craving for other appetitive stimuli (e.g., drug cues), and has only begun to study regulation of food craving. Recent results from our laboratory validated four strategies that are effective in reducing cravings for energy-dense foods. This work relies upon self-reports of craving, which provide an empirical starting point but do not demonstrate the validity of the strategies on their own. Thus, the goals of the proposed project are to provide additional support for the effectiveness of cognitive self-regulation of food cravings using other measures beyond self-report, and to validate a theoretically grounded means to further increase the efficacy of those strategies-strategy choice. These goals will be accomplished in the context of a single study with two sessions. First, participants will be randomly assigned to choose their regulation strategy or to have one selected for them. In Session 1, their self-reported cravings and neural responses will be recorded while they alternately view images of energy- dense foods and regulate their responses to those foods. These data will be used to examine the effects of food regulation on neural activation and self-reports of craving, and to compare the effect of strategy choice on those measures. In Session 2, participants will visit our behavioral laboratory three days following Session 1 for a session in which their actual intake of energy-dense food will be measured in a naturalistic and unobtrusive manner. The difference in energy-dense food intake between the two groups will provide a behavioral measure of the efficacy of strategy choice on eating. Also, brain activity during food cue reactivity and regulation from Session 1 will be used to predict intake during Session 2. Psychological theory and previous neuroscience data suggest that neural activity, particularly in the medial prefrontal cortex, might explain variance in energy-dense food intake above and beyond self-report, and might mediate the effect of strategy choice on intake.

? DESCRIPTION (provided by applicant): Early adversity (EA) in humans is a major contributing factor to a range of deleterious physical and mental health outcomes extending through adulthood such as depression and anxiety, obesity and heart disease, and premature death. In addition to detracting significantly from individual well-being and quality of life, these conditios also consume considerable resources from federal, state, and community organizations. The mechanisms through which EA exerts its effects on these outcomes are increasingly well understood, and include neurocognitive pathways related to executive function. An intervention that can successfully target, engage with, and alter the functioning of one or more of these mechanisms would be a promising way of mitigating the impact of EA on deleterious outcomes later in life. The proposed research focuses on one such pathway-deficits in inhibitory control (IC)-and tests the feasibility and efficacy of an intervention to increase functioning in that pathway in a sample of individuals who experienced EA. The intervention is grounded in a neurally informed model of change that specifies deficits in IC as an underlying causal factor common to several health-risking behaviors (HRBs). These IC deficits emerge during development as a result of a range of EA, and, critically, can be remediated in mid-life through targeted intervention. Research from our laboratory has validated an intervention that can increase IC performance and alter its underlying neural systems in young adults (Berkman, Kahn, & Merchant, 2014). The next step in this program of research, proposed here, is to test the efficacy of that intervention in a sample of mid-life individuals who have experienced EA and the extent to which our intervention generalizes to HRBs that are prevalent in that sample. The first Aim is to test whether the intervention alters the IC system in tasks both similar to and dissimilar from the training task in terms of both behavioral performance and neural functioning. The second Aim is to test whether alterations in the functioning of the underlying neural systems mediate the effect of the intervention on performance and The two Aims will be accomplished within the context of a single RCT with two arms (IC training vs. active control) and pre-post measurements of IC performance, IC neural systems, and HRBs. All participants (N = 110) come to the lab for an initial assessment of behavioral / neural measures of IC and HRBs, among other measures. Then, participants are randomly assigned to receive a Person-Centered Inhibitory Control (PeCIC) training or active control training, every other day for 3-4 weeks. The PeCIC systematically pairs IC engagement with alcohol, tobacco, and/or energy-dense food cues, depending on each participant's reports of disinhibited behavior in those domains. The active control task uses personalized cues and response time tasks but does not involve IC. Finally, participants return to the laboratory for an endpoint assessment where all baseline measures are repeated. The two Aims will be robustly tested in a series of analyses comparing the behavioral and neural change from pre- to post-intervention between the groups disinhibition-related HRBs.

7. Abstract Obesity and intake of certain foods increases cancer risk, but the most common treatment (behavioral weight loss programs) rarely produces lasting weight loss and eating behavior change, apparently because caloric restriction increases the reward value of food and prompts energy-sparing adaptations. Interventions that reduce the implicit valuation of cancer-risk foods (e.g., red meats, refined sugar) may be more effective. Emerging data suggest that behavioral response training and cognitive reappraisal training reduce valuation of such foods, which leads to decrease intake of these foods and weight loss. Internalized incentive value is reflected in a ventromedial prefrontal/orbitofrontal cortex valuation system (?vmPFC?), which encodes the implicit reward value of food and is central to a reinforcement cycle that perpetuates unhealthy eating. Thus, the vmPFC valuation system is a promising target for intervention because changes to the system might disrupt the unhealthy reinforcement cycle. Interestingly, various interventions influence the vmPFC through distinct pathways. Behavioral training alters motor input to valuation regions, whereas cognitive training relies on lateral prefrontal ?top-down? regions. The proposed translational neuroscience experiment will compare the efficacy with which two novel treatments cause lasting change in food valuation, and whether a composite of theory-based baseline individual differences in relevant processes (such as response tendencies and cognitive styles) moderate treatment effects. We will randomize 300 overweight/obese adults who are at risk for eating- and obesity-related cancers to behavioral response training toward healthy foods and away from cancer-risk foods, a cognitive reappraisal intervention focused on cancer-risk foods, or non?food inhibitory control training. Aim 1 compares the efficacy and mechanisms of action of these two interventions to reduce valuation of cancer-risk foods relative to the active control condition, using neural, behavioral, self-report, and physiological measures of the process and outcomes. Aim 2 is to establish the temporal pattern and durability of the effects across time ; food intake and habits , body fat, BMI, and waist-to-hip ratio will be measured pre, post, and at 3-, 6-, and 12-month follow-up. Aim 3 uses machine learning to build and validate a low-cost, easy-to-administer composite that predicts whether and for how long an individual is likely to respond to intervention, and to which treatment. We hypothesize that self-report measures specifically related to valuation (e.g., willingness-to-pay) and to intervention-specific pathways to valuation (e.g., behavioral response tendencies, cognitive style) will predict differential response. Discovering these individual differences will provide a practical, low-cost tool to help interventionists ?match? a given person to an effective treatment for that person . This project is very innovative because no study has directly compared the distinct and common effects of these treatments on valuation, used brain imaging to study the mechanism of effects, tested whether these interventions produce a lasting change in food valuation and body fat, or built and validated a composite that moderates response .

7. Project Summary/Abstract The Pilot & Training Core serves a vital function in the Center by providing the ability to conduct smaller projects that can lay the foundation for cutting-edge, multidisciplinary, and scientifically innovative prevention and intervention research at the interface of opioid use and parenting. The Pilot & Training Core will also serve as the engine for training and career development of ?Generation 2.0? prevention researchers within the context of the Center's Research Projects and Pilot Studies. This Core will have primary responsibility for overseeing the generation, review, selection, and administration of Pilot Studies led by Early Career Scientists that will complement and enhance the thematically integrated aims of the Center. Each year, at least two new Pilot Studies will be selected following rigorous peer review. Pilot Studies must be linked to the overall aims of the Center and will be judged on their scientific quality, their potential to lead to a proposal for a larger-scale project or a key scientific breakthrough, their potential to increase internal and external collaborations, and their ability to serve the needs of parents with opioid misuse. Three pilot studies have undergone initial review and will begin in the first two years of the Center. They showcase the full spectrum of Early Career Scientists that we will mentor through the Pilot & Training Core of the Center. Pilot 1 is led by an assistant professor (Zalewski) who is close to going up for tenure. Pilot 2 is led by a graduate student with the career goal of becoming an independent substance use researcher (Cioffi), mentored by a Senior Scientist (DeGarmo). Pilot 3 is led by a postdoctoral scholar who is now transitioning to a tenure track position. These Pilot Studies were selected to also reflect the breadth of research across the translational spectrum that the Core will support. Pilot 1 uses a transactional framework to understand how maternal psychopathology and opioid use can contribute to harmful parenting practices, which in turn maintain psychopathology and opioid use. Pilot 2 seeks to understand the impacts of opioid use on parenting among fathers and how that use influences uptake of an evidence-based parenting program. Pilot 3 examines the influence of opioid use on basic social-cognitive processes that are critical to parenting and potential intervention targets such as mentalizing. This Core will interface with the other Cores and to provide transdisciplinary training to Early Career Scientists following our early-senior partnership and co-mentorship training models. External and internal trainees will learn approaches across the translational prevention cycle through hands-on, project-based mentorship as well as workshops and webinars. The Core will also serve as a national resource via regular webinars, social media presence, and field building activities.

7. Project Summary/Abstract Lung cancer is the leading major cause of preventable death in the United States, and cigarette smoking is a contributor to lung cancer in 80%?90% of cases. Though adult cigarette smoking rates have declined substantially during the past 50 years, they remain as high as 30% in certain groups, such as individuals living in poverty. Quitting is difficult: a given quit attempt results in cessation in fewer than 10% of cases, and most adult cigarette smokers have attempted and failed to quit, and often many times. What is urgently needed are novel interventions for cigarette smoking cessation that operate through different mechanisms from those targeted by existing interventions, which are likely to have been unsuccessful for persistent smokers. A barrier to progress is that the mechanisms of action of most treatments are not known, which makes it difficult to know which treatment will work best for whom. We turn to affective science to identify a candidate technique that could serve as the basis for a novel intervention. Research on affect regulation typically focuses on down- regulation of affective states, such as craving for cigarettes, using effortful strategies such as cognitive reappraisal. However, a new insight in affect regulation is that people can construe, or subjectively understand, events with varying levels of abstraction, and that construing health-related behaviors in high- versus low-level terms promotes health behavior in several domains. For example, smokers who want to quit are more likely to resist a cigarette when they construe the same event (e.g., ?abstinence?) in more abstract, high-level terms (e.g., ?becoming a better me?) versus more concrete, low-level terms (e.g., ?not smoking this cigarette?). There is some evidence that high-level construal might rely on distinct mechanisms from traditional affect regulation and smoking reduction interventions, but its mechanisms of action are unknown. Directly comparing its mechanisms to those of alternative affect regulation strategies and developing tools to induce high-level construal are the next steps on the path toward developing a novel intervention. Also, establishing individual differences in the effects of high-level construal will allow future interventions to be targeted to the individuals for whom they will be maximally effective. We identified two candidate mechanisms through which high-level construal might operate: down-regulation of craving and up-regulation of goal energization (i.e., motivation to quit). Functional magnetic resonance imaging (fMRI) revealed the neural systems engaged by those processes to be distinct. So, we will use multivariate analyses of fMRI data to quantify the similarity of high-level construal to each candidate (Aim 1). This will be done in a longitudinal translational experiment with 4 conditions?high- level construal, down-regulation of craving, up-regulation of goal energization, and treatment-as-usual?in a sample of persistent smokers in poverty, who are the most likely to benefit from a novel, theory-based treatment. The sample size (N = 240) affords an examination of individual differences in the effect of high-level construal on neural activity and craving, and the degree to which they predict smoking reduction (Aim 2).