Neurobehavioral Mechanisms

Age Effects on HIV-associated Brain Dysfunction

This study investigates the effects of HIV in the brain and on neurocognitive functioning as people age. The study incorporates state-of-the-art brain imaging methods along with clinical and laboratory measures of HIV infection. We will examine how neurocognitive outcome and structural brain changes vary as a function of age and these HIV-associated factors. A longitudinal experimental design will be employed with statistical modeling methods to characterize changes over time. Comparing young and older HIV-infected patients (< or > 45 years) with matched cohorts of young and older healthy controls over 36-months on neurocognitive, neuroimaging, and laboratory measures. The results will inform us about the interaction of HIV infection in the brain and aging over time, will provide metrics for assessing structural brain changes, will extend our knowledge of the clinical application of diffusion tensor imaging for brain disorders, and may lead to advances in neurodiagnostics for HIV. This study will provide valuable information about the effects of HIV on the brain as people age. Clinical application of brain imaging methods, most notably in particular MRI diffusion tensor imaging, may occur, which may lead to advances in diagnostics for HIV effects in the brain.

Principal Investigator: Ronald Cohen, PhD

Co-Investigators: Timothy Flanigan, MD; Joseph Hogan, PhD; David Laidlaw, PhD; Karen Tashima, MD

Funding Agency: National Institute of Mental Health

Dates: 2006 - 2011

Cognitive Effects of Bariatric Surgery

This study will examine the cognitive effects of bariatric surgery in participants from the Longitudinal Assessment of Bariatric Surgery (LABS) project. There is growing evidence that obesity is associated with adverse neurocognitive outcome. We are assessing cognitive performance in bariatric surgery patients enrolled in the LABS project and matched controls at four time points: pre-operatively, 12 weeks post-operatively, 12 months post-operatively and 24 months post-operatively. Findings from the proposed study will provide important information regarding the cognitive effects of bariatric surgery, the possible mechanisms for these effects, and the contribution of cognitive performance to short- and long-term outcome of bariatric surgery.

Principal Investigators:Ronald Cohen, PhD (Subcontract) and John Gunstad, PhD (Project PI)

Funding Agency: National Institute of Diabetes and Digestive and Kidney Diseases

Dates: 2006 - 2010

Hemodynamic and Cognitive Function in Cardiovascular Disease

The goal of this project is to use functional magnetic resonance imaging (fMRI) and arterial spin labeling (ASL) to examine how cardiovascular disease (CVD) affects cognitive function and the measurement of brain function. CVD is associated with cognitive deficits; however, it is not understood how abnormal cardiac output associated with severe CVD leads to impaired cognitive function. A potential decoupling of neural demands and observed blood oxygenation level-dependent (BOLD) response needs to be examined to address validity and reliability of fMRI among this population. We will directly examine these possibilities by assessing systemic cardiovascular function, cerebrovascular hemodynamic functions, and cognitive performance among elderly patients with severe CVD and a cohort of age-matched controls. We predict that BOLD response will be diminished during all conditions among the CVD group, and that a significant portion of this reduction will be attributed to vascular hypoperfusion.

Principal Investigators: Ronald Cohen, PhD (Subcontract) and Lawrence Sweet, PhD (Project PI)

Funding Agency: National Heart, Lung, and Blood Institute

Dates: 2007 - 2011

Imaging Individual Differences in Amphetamine Effects

This project investigates the neural mechanisms underlying individual differences in how amphetamine affects mood and behavior. The objective of this study is to investigate the neural foundations of these individual differences and gender effects using a pharmacological challenge design and fMRI neuroimaging methods. The study utilizes a two-session, placebo-controlled amphetamine administration procedure. fMRI scans are timed during the peak period of drug effects. Individual differences in amphetamine-induced blood oxygenation level-dependent (BOLD) signal are assessed on two tasks: the Balloon Analogue Risk Task (BART) and International Affective Picture Set (IAPS), which test behavioral impulsivity and emotional reactivity, respectively. The major aims of the study are to investigate individual differences in amphetamine-induced increase in the neural activity and regions of activation associated with reward-related and punishment-related signal processing relevant to the drug's effects on mood and behavior.

Principal Investigators: Ronald Cohen, PhD (Subcontract) and Tara White, PhD (Project PI)

Funding Agency: National Institute on Drug Abuse

Dates: 2007 - 2011

Proton MRS Studies of Cerebral Injury in HIV Infection

The major goals of this project are to examine the MRS and MRI correlates of cognitive function in the context of antiretroviral therapy.

Principal Investigators: Ron Cohen, PhD (Subcontract) and Brad Navia (Project PI)

Funding Agency: National Institute of Neurological Disorders and Stroke

Dates: 2005 - 2010

Cognitive Benefits of Cardiac Rehabilitation in Heart Failure

The main goal of this project is to study CVD and its effects on the brain, and particularly how cardiac rehabilitation and the effects of vascular conditioning are influenced by the vascular CVD and systemic vascular disease factors.

Principal Investigators: Ron Cohen, PhD (Subcontract) and John Gunstad (Project PI)

Funding Agency: National Heart, Lung, and Blood Institute

Dates: 2008 - 2012

The VETSA Longitudinal Twin Study of Cognition and Aging

This study examines the contribution of genetic and environmental factors to cognitive aging.

Principal Investigators:Jeanne McCaffery, PhD (Subcontract) and Michael Lyons, PhD (Project PI)

Funding Agency: National Institute of Aging

Dates: 2008-2013

Neurocognitive markers of cognitive decline

This study is designed to examine genetic and MRI predictors of cognitive decline.

Principal Investigators:Jeanne McCaffery, PhD (Subcontract)and Robert Paul, PhD (Project PI)

Funding Agency: National Institute of Neurological Disorders and Stroke

Dates: 2007 - 2012

Cardiac Autonomic Regulation Enhancement through Exercise (CARE-E) Trial

This project examines the feasibility, acceptability, and short-term efficacy of a randomized clinical trial examining a 3-month supervised exercise intervention compared to a heart healthy education intervention, designed specifically for patients with implantable cardioverter defibrillators (ICD) with the primary aim of estimating an effect size for change in  parasympathetic activity. Other aims of this study are examining: (1) intervention effects on the frequencies of arrhythmias and ICD therapies, and (2) parasympathetic function in relation to changes in exercise tolerance. The study will also examine changes in psychological well-being and quality of life from pre- to post- intervention (3-months), and short-term follow-up (6-months).

Principal Investigator: Eva R. Serber, PhD

Co-Investigators: Alfred Buxton, MD; Bess Marcus, PhD; Ray Niaura, PhD; Peter Tilkemeier, MD; John Todaro, PhD

Funding Agency: National Heart, Lung, and Blood Institute

Dates: 2008 - 2011

Maternal Smoking, Fetal Behavior and Infant Withdrawal
The BAM BAM (Behavior and Mood in Babies and Mothers) Study

Although Maternal Smoking During Pregnancy (MSDP) has been linked to long-term neurobehavioral deficits in older offspring, relatively little attention has focused on the effects of MSDP on neurobehavioral deficits during the fetal and newborn periods. One key unanswered question is whether exposure to prenatal smoking induces neurobehavioral symptoms of withdrawal/abstinence in newborns. In this study, we are characterizing signs of abstinence and neurobehavior in infants and fetuses exposed and unexposed to MSDP. Specifically, the Behavior and Mood in Babies and Mothers (BAM BAM) study is an intensive, short-term, longitudinal study of signs of abstinence and neurobehavior during the fetal and newborn periods in continuously exposed and unexposed offspring. Results may lead to targeted intervention with newborns, education for parents to improve interactions with exposed newborns, and, potentially, early identification of high-risk infants and novel intervention and prevention efforts for pregnant smokers.

Principal Investigator:Laura Stroud, PhD

Co-Investigators: Raymond Niaura, PhD; George Papandonatos, PhD; Barry Lester, PhD; Amy Salisbury, PhD

Funding Agency:  National Institute on Drug Abuse

Dates: 2005 - 2010

Maternal Depression, Placental HPA Regulation and Fetal-Neonatal Stress Response
The BAMBI (Behavior and Mood in Mothers, Behavior in Infants) Study

Exposure to maternal depression during pregnancy is common and associated with adverse medical and behavioral outcomes in infants. However, little is known about mechanisms underlying early adverse effects. This information is critical for early identification and intervention efforts with high-risk infants. This study is an intensive, longitudinal investigation of maternal major depressive disorder (MDD), maternal-placental neuroendocrine dysregulation, and fetal/neonatal stress response and neurobehavior. Three groups of mothers and offspring will be identified: a) mothers with MDD during pregnancy (including MDD-only and MDD+anxiety disorder), b) mothers with a history of MDD who remain euthymic during pregnancy, and c) mothers with no history of or current psychiatric disorder (controls).

Neonatal assessment will involve cortisol and behavioral response to a neurobehavioral examination at 1-2 and 30 days; fetal assessment will include heart rate and behavioral response to vibroacoustic stimulus. Measures of maternal-placental neuroendocrine regulation will include maternal circadian cortisol, and expression of placental genes regulating stress response. Results may elucidate early markers of risk and help to delineate early pathways to later behavioral dysregulation. Early identification of high-risk fetuses and infants may also lead to education for parents to improve interactions with stressed newborns, and, potentially, novel therapeutic targets to protect fetuses from consequences of maternal depression.

Principal Investigator:Laura Stroud, PhD

Co-Investigators: James Padbury, MD; Amy Salisbury, PhD; Barry Lester, PhD; George Papandonatos, PhD; Thamara Davis, MD

Funding Agency: National Institute of Mental Health

Dates: 2007 - 2012

Maternal Smoking: Fetuses in Withdrawal?

Exposure to maternal smoking during pregnancy is linked to numerous adverse fetal and neonatal health outcomes as well as longer-term neurobehavioral deficits in children and adults. Relatively little attention, however, has focused on effects of maternal smoking on fetal and neonatal neurobehavior. One key unanswered question is whether exposure to maternal cycles of daytime smoking and overnight abstinence results in symptoms of withdrawal/abstinence in the fetus. To examine the possibility of a fetal withdrawal syndrome from exposure to maternal smoking, aims of this study are: a) to characterize differences in fetal behavior including signs of abstinence under conditions of maternal satiation (daytime ad libitim smoking) versus overnight abstinence, b) to characterize links between fetal neurobehavior/withdrawal and newborn neurobehavior/withdrawal and c) to examine the influence of second-hand smoke exposure on fetal and infant neurobehavior/withdrawal (exploratory aim).

Our group has pioneered the use of ultrasound technology to comprehensively evaluate fetal neurobehavior including signs of abstinence. In this study, we apply these techniques to examine the possibility of a fetal withdrawal process in offspring exposed to maternal smoking and second-hand smoke. This study is the first to examine effects of maternal smoking on fetal withdrawal. Results may lead to critical advances in understanding mechanisms underlying long-term effects of maternal smoking exposure. Results also have important clinical and public health implications, including early identification and targeted intervention efforts to protect at-risk offspring, and novel intervention efforts to help pregnant smokers quit.

Principal Investigator:Laura Stroud, PhD

Co-Investigators: Raymond Niaura, PhD; Amy Salisbury, PhD

Funding Agency: Flight Attendant Medical Research Institute

Dates: 2007 - 2010

Stress Response and the Adolescent Transition

Although adolescence represents a critical period of brain plasticity as well as physical and social changes, fundamental knowledge regarding potential developmental shifts in stress response over the adolescent/pubertal transition is lacking. Adolescence also represents a critical period for gender intensification and solidifying of academic and social trajectories for girls and boys. However, basic research examining gender differences in physiological and affective response to academic and social stressors has not been conducted. In this study, we are investigating the influence of pubertal status and gender on physiological (hypothalamic pituitary adrenal and sympathetic adrenal medullary) and affective responses to laboratory stressors (academic and social) over the adolescent transition.

The proposed study will allow fundamental insights into the nature of stress response patterns over the adolescent transition, and will allow discovery of new models for characterizing stress response. Given evidence for continuity of functioning between adolescence and adulthood, elucidating fundamental shifts in stress response across this period of enormous social, academic, and biological change has the potential to identify and improve trajectories of adolescents at risk for poorer functioning. Finally, it is clear that the adolescent/pubertal transition represents a period of heightened vulnerability for girls. An understanding of factors leading to increased vulnerability for girls at this critical period may lead to improved adjustment and acquiring of productive roles that may begin a positive cycle across generations.

Principal Investigator:Laura Stroud, PhD

Funding Agency: National Science Foundation

Dates: 2007 - 2010

Increasing Sleep Duration: A Novel Approach to Weight Control

This project, which establishes the Center for Behavioral Intervention Development (CBID), seeks to translate the basic science on sleep duration into a novel intervention to reduce obesity and obesity-related co- morbidities. The project involves a programmatic series of studies to develop a sleep + weight loss intervention. The target population for these studies will be young adults (age 25 - 45) where the association between sleep duration and obesity appears strongest, who are overweight or obese (BMI 25 - 40), and who currently sleep less than six and a half hours per night. This series of studies will be used to examine the effects of increases in sleep duration alone and in combination with a weight loss program on eating and exercise behaviors (measured objectively), and ultimately on body weight. The effects of increasing sleep duration on physiological, psychological and cognitive changes that may relate to the changes in eating and activity and adherence to weight control recommendations will also be examined. The CBID creates a new interdisciplinary team, including investigators in the areas of behavioral weight control, basic and clinical aspects of sleep, fMRI and neuropsychological assessment of cognitive function, eating and exercise behavior, and physiological changes associated with sleep and weight. (U01 CA150387-01)

Principal Investigator:Rena Wing, PhD

Co-Investigators: Dale Bond, PhD, Mary Carskadon, PhD; Robert Considine, PhD; Ron Cohen, PhD; Joseph Fava, PhD; Chantelle Hart, PhD; Jeanne McCaffery, PhD; Richard Millman, MD; George Papandonatos, PhD; Donn Posner, PhD; Hollie Raynor, PhD; Katherine Sharkey, MD; and Larry Sweet, PhD.

Funding Agency: The National Cancer Institute

Dates: 2009 - 2014