Mauricio Delgado - US grants

The association of rewards with specific actions is a common learning mechanism observed in day to day life that lead to predictions about potential rewards and shaping of behaviors. Over the years, research has suggested that one particular brain structure, the striatum, is a central region involved in how humans learn what decisions are advantageous (e.g., lead to reward). The goal of this proposal is to explore the neural substrates of human reward learning and decision-making processes drawing on two distinct methodologies in cognitive neuroscience: functional neuroimaging and experimental neuropsychology. Functional neuroimaging in healthy individuals can show whether a brain region is normally involved in a cognitive function; neuropsychological studies of individuals with damage localized to the same brain region can show whether or not that region is also necessary for that function. With support from the National Science Foundation, Drs. Mark Gluck, Mauricio Delgado and colleagues at Rutgers University propose to integrate both methodologies to investigate the role of the human striatum during (1) learning when reinforcement is directly contingent on actions as opposed to learning from passive observation, (2) learning when there is a delay between action and reinforcement. Parallel studies will be conducted in patients with striatal dysfunction due to lack of dopaminergic input that occurs in Parkinson's disease (PD) and neuroimaging studies of striatal function in healthy subjects.

Results from this research will contribute to a deeper understanding of the role of the striatum in decision making and in reward prediction, and of how the striatum, and related brain regions, utilize prediction-error feedback. This research builds on prior studies of the role of the basal ganglia in feedback learning, but also expands into new and more complex cognitive domains, including the creation of chains of linked predictions about sequences of actions. Learning to predict future rewards and other positive outcomes is fundamental to our survival in a complex, dynamic and uncertain world; it provides essential knowledge for making decisions that critically affect our lives, and the lives of those around us. The findings could influence interdisciplinary research in economics and neuroscience concerned about the mechanisms of how humans make decisions. Further, the research will give us a deeper understanding of the non-motoric, more motivational deficits associated with PD, eliciting new ideas for future research directions. Finally, the proposal aims to increase training opportunities for undergraduate, graduate and post-doctoral trainees in both neuropsychology and functional neuroimaging.

[unreadable] DESCRIPTION (provided by applicant): Risk-taking and reward-seeking behaviors are staples of compulsive gambling, a progressive addiction that affects many aspects of life. In a society that encourages consumption and immediate rewards, a risk-taking individual is constantly presented with salient conditioned cues representing risk-taking opportunities. Such salient conditioned cues lead to craving - broadly defined as an urge or desire for an appetitive stimulus or event. As craving grows in intensity, an increase in consumption of the addictive substance (e.g., cocaine) or behavior (e.g., risk-taking or gambling behavior) can be observed. Thus, it is imperative that treatment options exist not only to cope with the consequences of addictions such as compulsive gambling, but also to curtail reward seeking behavior. One potential treatment is the use of antecedent-focused cognitive strategies to regulate craving elicited by conditioned cues, in order to decrease reward-seeking or risk-taking behavior. The goal of this proposal is to investigate the effects of emotion regulation strategies on the neural systems of reward processing. Cognitive strategies are successful in modulating both physiological (as measured by skin conductance) and neural (as measured by neuroimaging) responses elicited by an inherently emotional stimulus or a conditioned stimulus. Thus, such strategies may also be successful in reducing the anticipatory feelings or craving associated with a more salient conditioned stimulus (e.g., a slot machine), subsequently influencing behavior (e.g., decreased risk-taking or gambling), while modulating neural circuits involved in reward processing (e.g., striatum). The proposed studies will use fMRI, in conjunction with physiological and behavioral measures, to investigate two aims outlined below. AIM 1: To examine the influence of cognitive strategies on physiological arousal elicited by salient stimuli, risk-taking behavior & the neural mechanisms underlying reward processing. AIM 2: To examine the influence of cognitive strategies on the neural mechanisms of reward processing and risk-taking behavior when immediate reinforcement is presented. The general hypothesis is that using emotion regulation during an appetitive conditioning gambling task will modulate the human reward circuitry while engaging regions of the brain involved in cognitive control. Accordingly, such strategies will lead to decreases in craving or levels of arousal elicited by the conditioned stimulus, thus influencing risky economic decision-making (i.e., choosing a safe vs. the risky option). This proposal serves as an initial step towards a long-term research plan aimed at investigating techniques that may help curtail risk-taking or reward seeking behavior before social and psychological problems occur. The studies described in the proposal have the potential of supporting techniques that may help curtail risk-taking or gambling behavior by focusing on the reduction of craving, before social & psychological problems occur. Although the proposed studies target gambling behavior, the potential results can be translated to other addictions, suggesting the use of antecedent focused strategies in reducing risk-taking behavior. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Motivated or goal-directed behaviors often abide by simple rules of reinforcement. That is, actions that lead to positive consequences tend to be repeated at a greater frequency, while actions that lead to negative consequences tend to be avoided. Fundamental research in non-human animals, complemented by an array of human neuroimaging studies, has delineated a basic neurocircuitry underlying reward-related learning and motivated behaviors. Such research has specifically identified circuits linking cortical structures and the basal ganglia, particularly its input unit - the striatum, a heterogeneous structure in terms of connectivity and functionality - as an interface for the processing of motor and motivational information. However, it is unclear how these basic mechanisms characterized by simple behaviors (e.g., learning that a button press leads to a reward) extend to more complex motivated behaviors typically displayed in society (e.g., learning that an individual is trustworthy and interactions will lead to rewards). The availability of social information and the prospects of social interactions are factors that challenge current thinking of how the brain processes reward and punishment feedback and how it uses such information to make decisions. The goal of this proposal is to use fMRI to investigate how social factors modulate the basic behavioral and neural mechanisms underlying reward-related processing as a precursor to understanding how social influences on motivated behavior impact well-being and mental health. Specifically, the proposed studies attempt to build on a solid and existing research foundation on the neural circuitry of reward-related processing by first: establishing the behavior and neural correlates of a simple task modeled after animal research and second: adding a social component to a similar task to investigate overlap in mechanisms. This approach allows for a translational method that, in future research, can also be further extended to developmental (e.g., the role of social feedback from a social network during adolescence) and clinical settings (e.g., social feedback during observational learning in autism). The proposed studies will investigate two aims. Specific Aim 1 - We will investigate how socially relevant feedback, such as reward feedback from a social network of peers, is processed in the brain and how it compares to non-social feedback. Specific Aim 2 - We will investigate how socially relevant feedback creates social expectations that influence mechanisms of reward-related learning and if such mechanisms are unaffected by non-social feedback. The studies outlined in the proposal will build on our knowledge of the role of corticostriatal systems during simple motivated behavior to probe the antecedents and consequences of social motivation, as a platform to understand how social behavior breaks down in clinical disorders in the future.

DESCRIPTION (provided by applicant): Avoiding potentially negative outcomes is a common practice in human society. For instance, a person may drive to work earlier to avoid the negative consequences and stress associated with rush-hour traffic. In such circumstances, the traffic acts as a negative reinforcer, eliciting negative affect and strengthening the action of driving earlier. Negative reinforcers can have beneficial short-term influences on behavior by prompting one to actively cope with negative affect (e.g. avoiding traffic stress). However, an avoidance response can also become maladaptive if it prevents an individual from directly addressing the stressful event, causing long-term consequences such as fostering an addictive behavior (e.g., avoiding work deadlines and stress with drug use). These responses are difficult to extinguish and can become habitual, creating a burden for the individual and society. Thus, it is imperative to understand how aversive outcomes influence human brain and behavior. Non-human animal models of aversive learning highlight the role of striatal circuits, commonly implicated in reinforcement learning, in the acquisition of avoidance or coping responses (e.g., Salamone, 1994; LeDoux & Gorman, 2001). Yet, less is known about 1) human mechanisms of avoidance learning; 2) alternative means of coping with negative affect that are dependent on higher-order cognition and control and; 3) the influence of a pre-existing negative emotional state or stress on active coping strategies. The goal of this application is to investigate how negative reinforcement influences human brain and behavior as a precursor to understanding how humans learn to cope with potential negative outcomes that can influence decision-making in maladaptive ways (e.g., drug abuse to alleviate negative affect). The proposed studies will build on a solid and existing research foundation on affective learning in animals, which links the striatum and avoidance behavior, by first: establishing in humans the behavior and neural correlates of simple negative reinforcement tasks modeled after animal research; and second: examining alternative means of active coping with negative reinforcement that are more common to humans, such as higher-order cognitive strategies. Finally, proposed studies will examine the influence of a pre-existing acutely stressful state on active coping through avoidance or emotion regulation strategies. This approach allows for a translational method that can also be further extended to developmental (e.g., avoidance learning during adolescence) and clinical settings (e.g., mechanisms of active coping via emotion regulation during drug craving) in future research.

This award from the Major Research Instrumentation program is for the acquisition of a functional magnetic resonance imaging scanner to be housed at Rutgers University main campus in Newark in the Center for Molecular and Behavioral Neuroscience. It will be available to researchers from all three Rutgers campuses (Newark, New Brunswick, and Camden) as well as to those from nearby institutions, especially New Jersey Institute of Technology, University of Medicine and Dentistry of New Jersey, and the Kessler Foundation Research Center. The scanner will allow work to proceed on investigating brain-behavior relationships. The specific questions addressed are organized around six clusters of research: 1) neuroeconomics, 2) learning, memory, and plasticity, 3) human development, 4) perception and sensation, 5) mechanisms of mental illness, and 6) computational neuroimaging. The overarching theme that links the clusters is that they all broadly relate to the learning sciences.

Progress rarely comes without the experience of a failure along the way, but some failures can undermine progress entirely. Students in Science, Technology, Engineering, and Math (STEM) fields face a difficult choice when they encounter an academic failure: persist or give up. In the best case, a student will persist after interpreting a failed test as feedback to change studying habits. In the worst case, a student may give up after interpreting a failed test as a reason to switch to a less challenging major. Institutions can improve the participation and success of underrepresented groups in STEM by better understanding the factors that determine a student's response to failure and the interventions that may promote academic persistence rather than giving up. Negative outcomes, such as failed tests, can change behavior in two distinct manners that have disparate consequences for a student. In one manner, a student persists when a failed test spurs behavioral change to better pursue an original learning goal. In another manner, a student gives up when a failed test spurs a change in the learning goal itself (e.g., switch to a non-STEM field or drop out).

Intellectual Merit:

Research on the neural basis of incentive processing provides a foundation for understanding how the brain responds to negative outcomes and how those responses may be linked to behavioral changes. However, research has yet to address how the brain processes negative outcomes in ways that lead to different manners of behavior change: persistence versus giving up. The current research builds from the foundations of incentive processing research to understand how the brain responds to failure in ways that lead to persistence versus giving up. This research then examines how certain aspects of learning environments may alter a student?s response to failure. In particular, does stress harmfully influence neural and behavioral responses to failure? This proposal addresses two specific aims towards understanding neural responses to failure and their relation to decisions to persist or give up on a goal. The first aim understands the neural responses that underlie two distinct roles that negative outcomes can play in learning. The current research examines neural responses to negative outcomes that lead to (a) change in behavior to reach an original goal (persistence), or (b) change in choice of the goal (giving up). This research forms the foundation for understanding neural responses to failure that promote persistence versus giving up. The second aim understands the impact of stress on responses to failure. Specifically, the research examines how acute stress may influence decisions to persist or give up on a goal by altering neural responses to failure. More specifically, the proposed aims set up future examinations of how different cognitive interpretations of failure can beneficially influence neural responses and decisions to persist with a goal.

This project's research takes a novel approach to understand how people change their behavior in response to failure. In particular, this research examines two distinct manners in which negative outcomes can change behavior to (a) promote persistence or (b) give up on a goal. These different roles of negative outcomes in learning can be the difference between graduation and dropping out in an academic learning context. Furthermore, the research promises insight into relationships between acute stress, neural responses, and the decisions students make after failure. The research program lays a foundation to translate neuroscience research on incentive processing into a model of academic persistence that includes a more complete understanding of conditions that may impair or promote academic success.

Broader Impacts:

This project bridges a gap between research on the mechanisms of basic learning and research on factors contributing to academic diversity and the success of underrepresented students. This research promotes teaching, training, and learning by providing a better understanding of academic feedback and the ways that it can influence student behaviors and eventual success. The research program contributes to broadening participation of underrepresented groups in STEM by examining the influence of acute stress on responses to failure. This research examines a specific biological mechanism by which stress may impair the likelihood of achieving academic goals and sets up future examinations of cognitive interventions targeted to ameliorate undesirable effects of stress. The increased understanding of relationships between acute stress, neural responses, and decisions after failure helps to refine the strategies that educational institutions can implement to broaden the participation of underrepresented groups in STEM.

This award provides a state of the art MRI scanners, such as the SIEMENS PRISMA magnetic resonance imager to the Rutgers University Newark. This model has ultra-fast collection times in 100s of milliseconds and sharp detail in (0.1mm) spatial resolution. The combination of these features and many other recent innovations in MRI will provide for novel research and fundamental breakthroughs in brain research, impacting on the characterization and basic understanding of mental health disease (e.g. Schziophrenia, Depression, Autism) as well as furthering more general understanding of areal connectivity within the human brain.

RUBIC is a core research center for all Rutgers campuses and a regional resource for institutions and research groups throughout the northeast corridor. Specific areas of research are immediately enabled by the PRISMA and other core areas are strengthened. These research areas include (1) Human connectome research and network neuroscience, (2) Decision science and reward learning (3). Basic research on Alzheimer's and characterization of various types of dementia. RUBIC has 25-30 PI researchers in any given research cycle, and has an active growing community of researchers at RUTGERS and in nearby institutions.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

ABSTRACT The mission of the proposed G-RISE Program is to increase the number of PhDs underrepresented in the diverse fields of Biology, Chemistry, Neuroscience and Psychology who will proceed to postdoctoral research fellowships/positions, on a trajectory to enter the biomedical/behavioral research workforce. To accomplish this goal, our main program objectives are: 1) to foster in each trainee: self-efficacy in their chosen specialty, self-identification as a research scientist, and the confidence that they are integral, contributing members of their scientific community; 2) to develop our trainees? technical and professional skills required to conduct research in an ethically responsible and rigorous manner; 3) to develop our trainees? didactic, research, mentoring, and career development skills; 4) to promote our trainees? timely fulfillment of the institutional requirements for the Ph.D.; 5) to foster and facilitate each trainee?s appointment to a postdoctoral position in preparation for entering the biomedical/behavioral research workforce in their specialty. The rationale for the current G-RISE proposal is to build on the success of our current IMSD Program (24 PhDs in the last 3 grant cycles and 5 more expected this year) and take the opportunity to develop programmatic innovations within the G-RISE format. The following key activities comprise part of the design of the proposed G-RISE Program: 1) Research Communication Workshop to develop the trainees? skills in communicating their scientific research to a multidisciplinary audience, 2) Fellowship Writing Workshop to foster a knowledge base to develop a fellowship application, 3) Research Career Preparation seminar series and 4) Responsible Conduct of Research and Research Reproducibility seminar series. A mentor-training component is included in the proposed G-RISE program with a healthy balance between established and early career investigators. The proposed program measurable outcomes are: 1) Earning the PhD degree; 2) Applying for at least one predoctoral fellowship, 3) Successfully vying for a postdoctoral research fellowship/position by the completion of the doctorate. Taken together, the proposed G-RISE Program will continue the development of a successful training program aimed at fostering the entrance of the trainees into fields of behavioral/biomedical research in which they have been traditionally underrepresented.