Cherie L. Marvel - US grants

DESCRIPTION Schizophrenia patients have difficulty interpreting facial emotions. This proposal examines their ability to implicitly learn facial stimuli. It uses a paradigm developed by Lewicki and his colleagues in which people learn non-salient covariations, or relations between features that are presented together, without having express knowledge of these co-variations. First, subjects will implicitly learn a co-variation between word-emotion pairs and their spatial location on a video screen. Because prior work shows normal implicit learning of verbal material in schizophrenia it is expected that patients will perform normally on this task. Second, pictures of faces replace verbal material. Thus, subjects will associate a covariation between a face- emotion pair and its spatial location on a video screen. Because this task does not require patients to process internal facial features, it is expected that patients will perform normally on this task as well. Finally, subjects will be presented with a covariation between internal facial features and emotion. Because learning the covariation requires perception of internal facial features, it is expected that the patients will be impaired. If patients do not show normal learning, it will be the first demonstration of abnormal implicit learning of faces in this group. If patients perform normally on this implicit learning tasks, then this finding demonstrates an intact system for learning covariations. Further, this method of training would be a potential therapeutic means for teaching schizophrenia patients how to interpret social cues.

DESCRIPTION (provided by applicant): This is an application for a Mentored Research scientist Development Award (K01). The goal of the proposed project is to provide the Candidate with advanced skills needed to establish an independent program of addiction research using advanced neuroimaging methods. The Candidate proposes a comprehensive training plan, combining didactic instruction overseen by her mentors, formal coursework, participation in applied training experiences with individual advisors, and participation in ongoing seminars. Specific training goals include: (1) gaining additional clinical and didactic training in drug addiction, (2) training in advanced neuroimaging methods and data analysis, (3) training in the neurological assessment of movement disorders, and (4) training in the responsible conduct of research. The training plan will be executed in coordination with a proposed set of research studies that are based upon preliminary data collected by the Candidate, which found that abnormal function of the brain's cerebro-cerebellar pathway was associated with executive dysfunction in methadone-maintained opioid-addicted drug users. These findings are directly relevant to drug addiction because impairments of executive control over behavior are thought to lead to risky and impulsive behavior. The proposed research will characterize the function and interdependence of specific nodes within the cerebro-cerebellar pathway, while also defining how disruptions within this pathway contribute to executive dysfunction in drug users, specifically methadone-maintained opioid users. The studies will combine fMRI scanning during executive control tasks with other advanced neuroimaging methods that will (1) assess baseline physiological states so that fundamental group differences in neurophysiology can be factored into the data interpretation, (2) identify nodes within the cerebro-cerebellar pathway that function in synchrony, and (3) determine the integrity of the white matter nerve bundles that subserve the pathway. The proposed application will, therefore, identify neural mechanisms that contribute to executive dysfunction in drug addiction and, at the same time, enable the Candidate to establish an independent research career in the study of drug addiction. PUBLIC HEALTH RELEVANCE: The aim of this study is to examine measures that that identify brain abnormalities involved in drug addiction. The relevance of this research to public health is that results have the potential to identify important targets for therapeutic interventions in drug addiction and relapse.

? DESCRIPTION (provided by applicant): This proposal examines the neurocognitive factors that contribute to risky decision making in HIV + and drug dependent individuals. Because risky behaviors that lead to HIV transmission are often associated with immediate reward, understanding how individuals process reward, in terms of their HIV and drug use status, would shed light on mechanisms involved in risky decision making and inform treatment strategies. Our prior research in HIV+ and drug dependent individuals has indicated that these two populations have a heightened sensitivity to learning a stimulus-reward association. Their ability to subsequently ignore a learned reward when it is presented in a novel, irrelevant context is impaired. This characteristic simulates a real-world situation in which a previously learned reward (e.g., heroin syringe) is viewed out of context (e.g., insulin needle) but cannot be ignored and prompts drug craving. We have found that factors contributing to one's ability to ignore context-irrelevant reward include working memory capacity, drug use history, impulsivity traits, and motor function. Moreover, these factors can predict attention-to-reward behaviors six months beforehand. In order to better understand the mechanisms underlying this relationship, the proposed project will examine the neurocognitive processes that direct one's attention to reward. Methods will combine a cognitive task that measures attentional bias for reward with functional magnetic resonance imaging (fMRI). Data will be obtained from populations that include HIV+ individuals with and without a history of drug dependence, HIV - individuals with a history of drug dependence, and healthy controls. In order to measure how the value of reward changes over time (and becomes more difficult to ignore), volunteers will be assessed at two time points six months apart. The overarching hypothesis is that HIV-related brain changes interfere with reward processing, which is further compounded by drug abuse. This leads to heightened, sustained reward salience and increases a person's vulnerability to risky behaviors. Neuroimaging results will reveal whether strategies for ignoring reward are bottom-up (attached to basic reward salience) or top-down (relying on cognitive control). This information will highlight differences between individuals who can successfully ignore reward when necessary vs. those who cannot, and the factors that contribute to both types of behaviors. Knowing how reward is processed in the brain to influence cognition and behavior (e.g., top-down vs. bottom-up mechanisms) could alter clinical practice in terms of developing harm reduction strategies and teaching self-control techniques to high-risk populations before they acquire HIV.