Luke J. Chang, PhD - US grants

DESCRIPTION (provided by applicant): Understanding the nature of social cooperative behavior has received considerable attention over the past few decades spanning multiple domains of inquiry. People have been demonstrated to weigh the value of utility gained from positive social interactions higher then that associated with self-serving monetary payoffs. A variety of explanations have been proposed to explain this phenomenon including: people are inequity averse, people care about other's intentions, people receive social utility from positive social interactions, and people experience negative emotional reactions in response to norm violations. Recent research in the emerging field of Social Neuroeconomics has supported the notion that cooperation can lead to increased positive moods and increased activity in regions ofthe brain associated with reward processing, suggesting that indeed people find utility in positive social interactions. However, another possible mechanism underlying this behavior is that people are guilt averse and make decisions that minimize their anticipated guilt. This idea, based on notions of guilt from social psychology, has found support in recent economic models in which beliefs about other's beliefs are incorporated into individual utility functions. Despite its extensive theoretical development in clinical and social psychology, guilt has surprisingly generated little compelling empirical work. Psychological Game Theory provides an ideal combination of methods and theories from economics and psychology to explore how guilt impacts actual behavior in the context of social interactions. Study 1.1 will address the hypothesis that guilt is only experienced if you believe that your partner believes that you were at fault. Study 1.2 will address the hypothesis that guilt can be relinquished by taking reparative action. Finally, study 2 will attempt to use a sophisticated economic model of guilt to predict brain activity associated with processes involved in the experience of guilt. Consistent with the NIMH's mission to advance the integration of behavior and brain science to provide a greater understanding of mental disorders, this proposal combines theories and methods from the diverse fields of psychology, economics, and neuroscience to gain a greater understanding of the role of guilt in social interactive decision-making, which can yield insight into the socio-emotional impairment associated with a multitude of neuropsychiatric disorders including psychopathy, depression, traumatic brain injury, and fronto-temporal dementia. My long-term goal is to pursue an academic career as a clinical neuroscientist, in which I will use neuroimaging as my primary research methodology to investigate the nature of decision-making impairments in neuropsychiatric disorders. I believe that the most important advances in both basic and applied research arise out of an interdisciplinary approach, which necessitates finding a balance between breadth of interests and depth of knowledge. Ultimately, I hope to make advances in the application of imaging techniques, which will facilitate a better understanding ofthe functional impairment associated with neuropsychiatric pathology and lead to improved diagnostic and treatment procedures. My training proposal incorporates the necessary tools for me to achieve my career goal. First, I am actively pursuing a doctorate in clinical psychology with a minor in clinical neuropsychology. A considerable amount of my coursework consists of seminars, practica, and externships that are focused on understanding the nature of psychopathology in psychiatric and neurological disorders and gaining proficiency in the most current empirically supported psychological assessment and treatment techniques. Second, my research proposal focuses on integrating cutting edge techniques in neuroscience, economics, and psychology to develop novel paradigms that isolate the role of belief and emotion in decision-making. These paradigms will be critical in understanding the nature of decision-making impairment associated with various neuropsychiatric pathologies. I am fortunate to have access to faculty that have pioneered theory and methods that are directly relevant to my proposal. Through,courses, direct one-on-one interactions, laboratory meetings, and communications with their students, I will be able to enhance my proficiency in concepts and skills pertaining to Neuroeconomics from Dr. Alan Sanfey, emotion from Dr. John Allen, Psychological Game Theory from Dr. Martin Dufwenberg, dynamic reinforcement learning models from Dr. Michael Frank, neuroimaging from Drs. Alan Sanfey, Lee Ryan, and Ted Trouard, and in multivariate statistics from Dr. Aurelio Figueredo. Third, my training plan also highlights the excellent mentoring and guidance I will receive from my sponsor. Dr. Alan Sanfey, which directly relates to my career goals. Receiving didactic training in the responsible conduct of research, the development of an independent program of research, writing of manuscripts and grants, and in developing effective posters and presentations will be instrumental in preparing for an academic career. I will also receive valuable teaching experience by mentoring undergraduate research assistants. This training program provides an ideal path for an individual pursuing an ambitious academic career in the field of Neuroeconomics as a clinical neuroscientist. The unique integration of formal clinical training with a research focus extending into the diverse fields of psychology, economics, and neuroscience will provide me with the optimal training to produce high impact research consistent with the NIMH's priority of "Advancing the integrative science of brain and behavior science which provides the foundation for understanding mental disorders and their treatments.

Emotions play a critical role in organizing human experience and behavior, and emotion dysregulation lies at the heart of psychopathology and functional impairment across disorders. To measure and understand emotion dysregulation, advances in understanding the fundamentals of how the brain generates and represents emotional states are vitally needed. This proposal develops and validates models of the brain representations that give rise to emotional states in naturalistic, narrative contexts. This will provide normative models of emotion to ground future translational studies, measurement models for specific emotional brain representations, and targets for interventions. We combine Functional Magnetic Resonance Imaging (fMRI), multi-dimensional measures of behavior, and pattern recognition techniques to develop models of brain activity that characterize and differentiate discrete categories of emotion experience (joy, anger, sadness, pride, and others) and blends of emotion. We place particular emphasis on the predictive validity (sensitivity and specificity) and generalizability of these models across sensory modalities, evaluative judgments, contextual narratives, and populations. We elicit emotional experiences in an ecologically valid paradigm using narratives (stories) experienced via listening, reading, or watching video. We measure multiple types of emotional experience in parallel with fMRI, using innovative collaborative filtering approaches to infer continuous moment-by-moment experience. The resulting brain models of specific emotion categories afford several potentially transformative advantages. Such models can (a) provide insight into which systems are necessary and sufficient for emotion generation (Aim 1); (b) be shared and tested across studies, allowing us to evaluate their generalizability across contexts (Aim 2); and (c) provide targets for psychological and neurological interventions (Aim 3). Six experiments focus on developing and validating emotional brain representations that are generalizable across individuals, research sites (Dartmouth and Colorado), and populations (college students and more diverse community samples). Expt. 1 develops models that predict the intensity of discrete emotional states. Expts. 2-4 establish the context sensitivity and generalizability of these. Expt. 2 examines the role of evaluative judgments in shaping emotional experience. Expt. 3 assesses the impact of background contextual narratives. Expt. 4 evaluates the role of sensory processing in emotion representations. Expts. 5-6 establish whether or not the brain models mediate emotional experiences. Expt. 5 uses cognitive appraisal and Expt. 6 uses real-time fMRI neurofeedback to manipulate emotion category-specific brain representations, testing for causal effects of these psychological and brain manipulations on emotional experience. Together, these studies will yield generalizable models of the dynamic brain patterns underlying specific emotional experiences. Such models could transform clinical research by allowing investigators to test emotion- focused interventions and assess emotion-related risk factors, permitting early detection and intervention.

PROJECT SUMMARY This R01 renewal application proposes functional neuroimaging studies with human subjects to elucidate the role of the prefrontal cortex and amygdala in the processing of facial identities and expressions that predict critical social outcomes. Presentations of facial expressions of emotion in neuroimaging studies have proven particularly robust stimuli for activating amygdala and prefrontal regions involved in processing biologically- relevant social cues. Here we propose to further develop our novel structural and functional neuroimaging methods to better understand how the amygdala interacts with reciprocally connected prefrontal areas when such expressions are encountered. Specifically, following up on our previous findings that the structural integrity of an amygdala-prefrontal pathway predicts individual differences in reported anxiety ? we replicated this effect in > 250 subjects and observed an exciting sex difference; this effect is compellingly stronger in females than in males. Here we propose to follow up on this effect with higher resolution DTI methods and to extend it to functional resting state data to see if the same sex difference is observed functionally. In addition, we propose a new mathematical model where we believe we can disentangle the effects of valence from arousal in brain imaging data, a confound the field continues to struggle with. Finally, we propose the development of a new facial expression stimulus set where we record the psychological status of the models posing for the expressions so we can determine any interaction this might have with the psychological status of the our subjects of study. The field can then usefully compare these data to complementary developmental research (i.e., with children and adolescents) and will be amenable to direct translation to clinical populations (e.g., anxiety and depression).