1997 — 2003 |
Bates, Marsha E |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neurocognitive Impairment and Alcohol Use Disorders @ Rutgers the St Univ of Nj New Brunswick
Neurocognitive impairment is believed to affect alcoholism treatment process and outcome. However, alcohol researchers have had difficulty empirically validating this relationship between impairment and outcome, often finding weak and inconsistent support. This competitive renewal application seeks to extend a Rutgers CAS research program studying neurocognitive impairment in persons treated for alcohol use disorders. The unmet need to examine neurocognitive moderation models has often been highlighted by alcohol researchers and is strongly supported by the literature on the relation of neuropsychological impairment to behavioral outcomes following treatment for brain injuries of multiple etiologies. We have found support for a hypothesized model wherein neurocognitive impairment moderated the relation of robust change processes to intensity of alcohol and other drug use 6 months after treatment. Self-efficacy, commitment to abstinence, and AA affiliation were strong predictors of outcome in unimpaired persons, but only weak predictors of outcome in those who were impaired. Results supported a threshold model of impairment which suggests that only severe neurocognitive impairments may affect moderation. The goal of this competitive renewal application is to develop heuristic models of brain-behavior relations that adequately characterize the effect of alcohol-related neurocognitive impairment on treatment outcome through secondary analysis of three existing longitudinal data bases which overlap substantively in constructs and measures. We will use two convergent analytic methods to contrast direct effect, mediation, and moderation models of neurocognitive influences on alcohol- and drug-specific, and psychosocial outcomes within a conceptual framework informed by the traumatic brain injury rehabilitation literature. By examining the generality of results across different addictions treatment populations, we can provide a more robust test of putative neurocognitive models of treatment outcome than otherwise would be possible without costly collection of new longitudinal data. Results will advance understanding of mechanisms which support good outcomes in neurocognitively impaired individuals and will have theoretical implications for cognitive models of relapse.
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0.969 |
2001 — 2005 |
Bates, Marsha E |
K02Activity Code Description: Undocumented code - click on the grant title for more information. |
Complex Brain Behavior Relations in Alcohol Studies @ Rutgers the St Univ of Nj New Brunswick
APPLICANT'S ABSTRACT: This is a proposal for an Independent Scientist Award (KO2) to expand the applicant's research program on alcohol-associated neuropsychological impairment and treatment-outcome. The aim is to develop a multilevel neuroscience approach for studying these complex brain-behavior relations by pursuing specialized collaboration and advanced training in quantitative and neuroimaging methodologies. The first career objective is to develop further expertise in complex variable-centered and person-centered quantitative methods, as well as methods for integrating these two analytic approaches. Specialized quantitative skills will be developed through collaboration with experts and participation in advanced training institutes. These skills will be used to test complex mediation and moderation models of the effects of alcohol-related neuropsychological impairment on treatment outcomes in three existing NIAAA and private data bases. The second career objective is to gain expertise in magnetic resonance imaging (MRI) and functional MRI (fMRI) methods. Career development in neuroimaging will comprise formal course work, hands-on training, and collaboration with experts. Neuroimaging training will be applied to a preliminary study of the influence of family histories of alcoholism and depression on neuropsychological impairment and neuroanatomical changes in youth with psychiatric diagnoses compared to a control group with no psychiatric diagnoses. Hypotheses of heightened neurocognitive vulnerability and symptom severity in high-risk FH+ youth will be tested.
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0.969 |
2004 — 2009 |
Bates, Marsha E |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Alcohol, Memory and Affective Regulation @ Rutgers the St Univ of Nj New Brunswick
Automatic and implicit memory processes, and difficulties in the regulation of negative affect, are thought to be importantly involved in the development and maintenance of alcohol and other drug use disorders (Koob & Le Moal; 1997; O'Brien et al., 1992; Robinson & Berridge, 1993; Tiffany, 1990). Studies comparing persons with a multigenerational family history of alcohol use disorders (FHP) to those with no such family history (FHN) suggest that there are differences in memory functioning and affective regulation, although these differences have yet to be linked to specific mechanisms that underlie variance in addiction liability. Understanding has been limited in preclinical human populations because research has seldom included measures of both psychophysiological arousal and memory disruption in the same paradigm, and has not examined the extent to which alcohol selectively disrupts explicit versus implicit memory processing of emotionally valenced stimuli that are and are not distressing. The goal of this application is to better understand the influence of alcohol on implicit and explicit memory for, and psychophysiological reactivity to, neutral, positive, and emotionally distressing stimuli in FHP and FHN persons. A sequence of three experiments is proposed: Experiment 1 examines whether alcohol's dissociation of multiple forms of implicit and explicit memory processes differs in high versus low risk family history groups. Experiment 2 examines alcohol's selective effects on implicit and explicit memory for emotionally arousing versus neutral word stimuli, assesses psychophysiological reactivity during stimulus encoding, and tests differential influences on long term memory consolidation in FHP and FHN persons. Experiment 3 examines these questions using emotionally arousing picture stimuli that have been further characterized as having distinct positive versus negative affective valences. Data from Experiments 2 and 3 will further be used to explore whether heart rate variability measures of autonomic balance and adaptability can characterize alcohol effects on dynamic affective self-regulation processes in high and low risk persons. The proposed sequence of experiments builds systematically on our previous alcohol and memory research in a way that should yield further knowledge about alcohol effects on implicit and explicit, immediate and longer term memory processes, and how these covary with arousal responses to both verbal and picture stimuli that vary in emotional salience. The findings will be useful in examining the predictions of "stress response dampening" models of alcohol effects in high and Iow risk groups, and may ultimately help to refine, from a human behavioral perspective, addiction models that posit the operation of unintentional memory processes and difficulties in the regulation of negative affect in contributing to addiction vulnerability.
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0.969 |
2007 |
Bates, Marsha E |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Memory, Emotion, Developmental Stage-Drug Use Exposure @ Rutgers the St Univ of Nj New Brunswick |
0.969 |
2007 — 2011 |
Bates, Marsha E |
K02Activity Code Description: Undocumented code - click on the grant title for more information. |
Novel Mechanisms of Behavior Change in Alcoholism Treatment @ Rutgers, the State Univ of N.J.
DESCRIPTION (provided by applicant): Current treatments for alcohol use disorders vary in theoretical foundation and approach, yet are often equally effective across clients who differ substantially in clinical features. Limited progress in client treatment matching, based on our current understanding of mechanisms of behavior change (MOBC), argues strongly for basic to clinical science translation research to provide innovation (Willenbring, 2005). Better understanding of mechanisms that support behavioral flexibility is essential for progress in developing more effective treatments. It would facilitate client-treatment matching by helping to classify clients with different underlying capacities for behavior change, clarify fundamental change processes ctivated by current treatments, and suggest potentially new treatment targets. This K02 competitive renewal application seeks to build upon the knowledge, research skills, and quantitative training the applicant gained during the previous award period to further understand neurobiological and neurocognitive processes that subserve emotional regulation and can act to support or hinder adaptive behavioral change. The overarching goal is to gain expertise in methods that promote translation between basic and clinical science to characterize novel MOBC. Structured, multidisciplinary collaborative expertise and new quantitative skills will be applied to data from the applicant's ongoing research program. NIAAA supported experiments focus on alcohol and placebo challenge effects on implicit memory for, and autonomic nervous system reactivity to, neutral, emotionally valenced and alcohol-related cues in young adult drinkers who are not alcohol dependent. The NIDA supported study focuses on memory and reactivity to the same stimuli, and to drug-related cues, in clinical and high risk samples, and examines the relation of implicit memory and autonomic regulatory processes to intervention outcomes. Skills will also be applied to data from pilot fMRI and genetic studies that recruit participants from these NIH projects to characterize cognitive control processes that operate in bidirectional feedback loops with autonomic reactivity during cue exposure and memory tasks, and test for genetic markers of intermediary phenotypes related to regulatory processes. Support of this application will allow the PI to cross-fertilize theories and methods needed to conduct productive translation research to improve understanding of MOBC in alcoholism treatment, and maximize her contributions to the field.
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0.969 |
2011 |
Bates, Marsha E |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Marijuana Cues, Arousal and the Central Autonomic Network @ Rutgers, the State Univ of N.J.
DESCRIPTION (provided by applicant): This application is in response to PAR-09-073 to facilitate the entry of two addiction researchers into the area of functional magnetic resonance imaging (fMRI). We are currently characterizing moment-to-moment changes in cardiovascular arousal in response to emotionally-valenced and appetitive visual cues. This research focus is of substantial public health significance due to the fundamental role of cue reactivity and drug craving in motivating alcohol and drug seeking, use, and relapse following treatment. Visceral changes in autonomic nervous system (ANS) functions contribute significantly to the phenomenal experience of emotional arousal through extensive ANS and central nervous system (CNS) interconnections and the baroreflex. Yet, understanding of dynamic mechanisms that control cue reactivity has been hampered by conceptualizing ANS functions in isolation from the neural system(s) within which they operate. We seek to apply a neurophysiological systems approach to characterize how intra-individual changes in functional, regulatory aspects of emotional arousal in response to environmental cues are integrated across the ANS and CNS. The specific aims are to gain expertise in fMRI methodology and analysis, and to apply this expertise to study a dynamic neural system that modulates cardiovascular response to drug cues. As proof-of-concept, an experiment merging psychophysiological and neuroimaging methodologies is proposed as a fMRI and connectivity analysis learning vehicle (Aim 1) and to examine substantive differences in integrated brain and cardiovascular system response to marijuana-related picture cues in regular marijuana users compared to matched controls who do not use marijuana (Aim 2). fMRI data during cue exposure will be gathered using a 3-Tesla magnet, and the spread of activation between brain regions involved in arousal modulation will be examined using brain connectivity analysis. Activation and connectivity of three brain regions (medial prefrontal cortex, amygdala, brain stem) will be quantitatively linked to cardiovascular modulation within a graph theoretical connectivity model. If successful, this application will yield (1) preliminary support for a new approach wherein ANS reactivity can be linked dynamically (in a time-varying manner, not as a correlation) to neural systems that modulate cue reactivity, (2) new knowledge about how activation in three brain regions interrelates with baroreflex modulation of cardiovascular response to cues, and (3) the groundwork for translational research aimed at evaluating whether biofeedback interventions that improve specific cardiovascular functions can be used to affect inhibition in brain systems that control arousal in response to drug cues. PUBLIC HEALTH RELEVANCE: Cues in the environment, such as the sight of someone smoking, can produce a powerful emotional reaction that increases the likelihood that susceptible individuals will seek or use a drug of choice, even following periods of abstinence. The visceral experience of emotional arousal is an important component of reactivity to drug cues. This application seeks to characterize how the autonomic nervous system works together with the brain to control visceral response to marijuana cues.
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0.934 |
2013 — 2017 |
Bates, Marsha E |
K24Activity Code Description: To provide support for the clinicians to allow them protected time to devote to patient-oriented research and to act as mentors for beginning clinical investigators. |
The Baroreflex Mechanism: Translation to Aud Treatment and Prognostic Models @ Rutgers, the State Univ of N.J.
DESCRIPTION (provided by applicant): The critical importance of two-way communication between the brain and the heart during thought, emotion, and behavior has been known for over 100 years, but this knowledge had little impact on alcohol use disorder (AUD) treatment .This revised K24 application by a mid-career translational clinical scientist addresses this gap by translating a new model of neurocardiac signaling (called the baroreflex [BAR] model) into behavioral interventions for AUDs. The research goal is to refine and test interventions based on her basic research supporting the BAR as an active behavioral change mechanism. Interventions that affect the BAR mechanism increase feedback between the brain and cardiovascular system. The overarching hypothesis of this K24 is that enhancing BAR functioning will increase behavioral flexibility towards alcohol as evidenced by reduced drinking, relapse prevention, decreased depression, and other positive psychosocial outcomes. The first specific aim is to use data from four ongoing clinical trials to evaluate the efficacy of two established (aerobic exercise, meditation) and one new (heart rate variability biofeedback) intervention and determine whether the BAR is a common mechanism of action in each intervention. The second aim is to examine whether treatment responders show different patterns of neural connectivity compared to those who do not respond. The third exploratory aim is to build prognostic models using clinical, cardiovascular, and neural indicators to predict which persons are most likely to benefit from interventions that target the BAR mechanism. Whether genetic indicators can improve prediction will also be explored the career development goal is to move the Candidate's patient oriented research program from early to late stage clinical translation. Training aims are to gain expertise in the design, conduct, and analysis of randomized clinical trials, the use of neuroimaging and neurocardiac tools to differentiate treatment responders versus non-responders, and the application of nonlinear sensitivity and uncertainty analysis to build a multi-level prognostic model. The proposed research and career development strategy will provide a unique training opportunity for five rising junior faculty and one graduate student with shared interests in translational clinical science, emotion regulation, and alcohol use disorders. The mentees bring to the team unique backgrounds and collaborations in the clinical psychopathology of emotional dysregulation and interpersonal violence, psychophysiology and exercise science, neuroimaging, and genetics. Attainment of research and training milestones will be gauged formally from yearly conference presentations, peer-reviewed publications, and patient-oriented research grant submissions.
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0.934 |
2014 — 2015 |
Bates, Marsha E |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Fmri and Integrated Neurocardiac Control of Alcohol Cue Reactivity @ Rutgers, the State Univ of N.J.
DESCRIPTION (provided by applicant): This R21 application is in response to PA-10-256: Behavioral Regulation Mechanisms of Alcohol Dependence and Related Phenotypes. In persons with alcohol use disorders, conscious attempts to regulate drinking behavior are often undermined by automatic processes that capture attention and instigate arousal in the context of alcohol cues. The persistence of heightened cue reactivity, even following treatment, contributes significantly to the public health burden of the chronic, relapsing disorder of alcohol dependence. Cue reactivity processes involve dynamic feedback loops between the brain and other bodily organs such as the heart. Yet, very little is known about how the brain and heart work together to give rise to heightened alcohol cue reactivity. We propose to address this gap by examining the neurocardiac feedback loop during exposure to alcohol picture cues (Aim 1). Further, there remains a need to develop interventions that effectively diminish reactivity in persons for whom automatic processes, such as those supported by the neurocardiac feedback loop, maintain alcohol cue salience. Thus, we further test whether a brief behavioral manipulation can significantly diminish neural and cardiovascular reactivity to alcohol cues (Aim 2). We will use functional magnetic resonance imaging (fMRI) to capture reactivity of the brain's central autonomic network (CAN) while simultaneously assessing cardiovascular changes during presentation of alcohol-related and neutral picture cues in a group of 24 non-treatment seeking emerging adults with alcohol dependence (DEP) compared to a matched sample of moderate drinking controls (MOD). Activation in selected CAN structures (medial prefrontal cortex, insula, brain stem) and neurocardiac signal variability (heart rate variability and blood pressure variability) in response to alcohol cues will be simultaneously assessed. Specific Aim 1 will examine differences in alcohol cue reactivity between DEP and MOD young adults in terms of brain activation, effective connectivity, and physiological measures of neurocardiac signaling. Specific Aim 2 will explore whether a behavioral manipulation of breathing at 0.1 Hz reduces neural and/or cardiovascular reactivity to alcohol cues. If successful, this application will yield support for a new approach wherein neurocardiac signaling can be linked in a time-varying manner to neural systems that modulate cue reactivity. Its potential public health significance is in exploring a behavioral regulation intervention that would be amenable to large scale dissemination and could be used within the treatment context or ad lib during moments of heightened vulnerability to relapse.
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0.934 |
2015 — 2019 |
Bates, Marsha E Buckman, Jennifer F. Mezic, Igor (co-PI) [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Project Impact: in-the-Moment Protection From Automatic Capture by Triggers @ Rutgers, the State Univ of N.J.
DESCRIPTION (provided by applicant): There are effective behavioral interventions to treat alcohol use disorders, but over time, treatment gains are often lost when clients find themselves unable to resist drinking because of negative emotions and appetitive cues. The power of internal and environmental triggers to elicit relapse, even among clients with conscious abstinence goals and extended abstinence, is compelling and well-documented. Thus, bolstering clients' ability to withstand drinking triggers and craving in real time could have tremendous public health impact. This application proposes translational research that focuses on the a priori defined and malleable baroreflex (BAR) mechanism. The BAR is a dynamic mechanism that helps to regulate automatic-visceral reactivity to triggers of alcohol and other drug use by regulating bidirectional communication between the heart and brain. A key feature of the BAR mechanism is that it can be consciously manipulated using a simple behavioral breathing technique called resonance breathing. This manipulation can occur in the moment and outside of the treatment context as triggers are anticipated or encountered. This application proposes a randomized clinical trial of a BAR-based intervention (added to behavioral treatment as usual) in conjunction with laboratory assessments (pre-post intervention design), and computational modeling to validate the operation of the BAR as a biobehavioral change mechanism. The sample comprises women with young children from an empirically supported, intensive outpatient behavioral treatment program (IOP). The intervention involves daily use of iPhone applications (apps) during IOP treatment weeks 4-12. Those randomized to the active intervention will be trained to use an existing resonance breathing app to activate the BAR mechanism as they anticipate or confront emotions or cues that can trigger relapse. Participants in the placebo group will use an app that does not affect the BAR. Aim 1 will address whether activating the BAR mechanism accelerates and stabilizes positive behavior change, specifically change in alcohol and drug use, anxiety, craving, depression during and after treatment. Aim 2 will compare natural versus manipulated changes in BAR functioning pre- to post- intervention using physiological, and, for a subset of women, fMRI data to correlate biological and behavioral change. Aim 3 will characterize how and for whom the BAR mechanism supports behavior change using computational modeling to capture change across multiple interacting biological systems within a person. The novelty of this study comes from focusing on a well-specified automatic-physiological mechanism, capturing change in the dynamic space of real life replete with triggers and affective changes, characterizing the BAR mechanism across biobehavioral levels using variable-and person-centered quantitative strategies, and focusing on an understudied population whose positive behavior change can have important immediate and long-term health implications. If successful, the proposed research will set the stage for a new generation of mechanism-based intervention approaches and personalized prognostic models.
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0.934 |