2017 — 2021 |
Porges, Eric |
K01Activity Code Description: For support of a scientist, committed to research, in need of both advanced research training and additional experience. |
Cognitive and Functional Deficits Associated With Reduced Cortical Gaba in Hiv-Infected Heavy Drinkers
Project Summary/Abstract This project will investigate important hypotheses regarding the relationship between regional cerebral ?- aminobutyric acid (GABA) concentrations and cognitive flexibility in HIV+ heavy drinkers. To ensure an independent career post award, two critical areas of training will be addressed: 1) Behavioral and biological consequences of alcohol use in the context of HIV and 2) the development of expertise in the measurement of ?-Aminobutyric acid (GABA), the principal inhibitory neurotransmitter, using Magnetic Resonance Spectroscopy (MRS). The PI is a cognitive neuroscientist with a strong research background in aging, cognition, experimental design, autonomic measurement, and magnetic resonance imagining (fMRI & MRI). The K01 will provide protected time and training for the PI to focus his research agenda firmly in alcohol and HIV. Specifically, the K01 will enable the PI to conduct cutting edge non-invasive research investigating the biological foundations of the well documented behavioral, cognitive, and health alterations resulting from HIV and heavy drinking. This training will provide the skills and knowledge required to translate the PI's basic science skills into clinical translational applications exploring the interaction between HIV+ and heavy drinking. The proposed research will investigate: (A) the relationship between GABA concentrations and heavy alcohol use in individuals with HIV, and (B) the relationship between GABA and cognitive flexibility in individuals with HIV. To investigate these research questions, cognitive capabilities and cortical GABA concentrations will be examined. 35 million people have contracted HIV worldwide, more than 1.2 million people have HIV in the US, with more than 50,000 new diagnoses each year. HIV+ individuals exhibit almost twice the rate of heavy alcohol consumption in contrast to the general population. Heavy alcohol consumption in HIV+ adults, impacts on health outcomes by increasing the occurrences of high-risk behaviors and is associated with increased severity of brain dysfunction. Thus, heavy alcohol consumption in HIV+ is a major public health concern. To assess GABA, GABA concentrations will be measured using MEGA-PRESS MRS in 2 frontal regions that have been implicated in cognitive flexibility and a posterior region of the brain. Measures of Cognitive flexibility will be measured via neuropsychological testing. We hypothesize that: 1) Lower GABA concentrations will be related to heavy drinking and HIV, with hazardous drinking HIV+ adults having the lowest concentrations of GABA 2) Reduced GABA concentrations in frontal regions will be associated with reduced cognitive flexibility.
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0.915 |
2021 |
Porges, Eric |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Cognitive and Inflammation Targeted Gut-Brain Interventions in People Living With Hiv Who Are High-Risk Alcohol Users
RC2 Summary The overarching goal of Research Component 2 (RC2) is to determine whether two non-invasive biological interventions, transcutaneous vagal nerve stimulation (tVNS) and a probiotic supplementation intervention (PBI), will improve cognitive and brain functioning, systemic and neuroinflammation, and gut microbiome health in people living with HIV (PWLH) who are high risk users of alcohol. The study will also delineate mechanisms of the gut-brain axis, which is particularly relevant, given that the factors underlying adverse cognitive and brain effects of alcohol use among PLWH remains unresolved. There is also considerable public health significance if beneficial effects of tVNS and/or PBI can be demonstrated, as cognitive disturbances that adversely impact health outcomes, functional abilities and quality of life are common (~ 50% prevalence), despite marked reductions in mortality in the era of antiretroviral therapies (ART). Among PLWH with reconstituted immune function and undetectable viral loads, comorbid conditions remain common and can have adverse functional consequences. High risk alcohol use, prevalent among PLWH, not only contributes to cognitive and brain dysfunction, but also further exacerbates comorbidities (e.g. liver disease, hepatitis coinfection, obesity, and cardiovascular and gastrointestinal dysfunction), and reduces treatment adherence while increasing the propensity for high risk sexual behaviors, worse health outcomes, and transmission of the virus. The study?s clinical significance is strong given the need for effective interventions to improve cognition and health outcomes in PLWH. To test these hypotheses, we will conduct a hybrid randomized clinical trial that will enroll 80 PLWH who are high risk drinkers from our existing research infrastructure supported by the Southern HIV Alcohol Research Consortium (SHARC). In a 2x2 factorial design, participants will be randomly assigned to one of 4 conditions (tVNS+placebo, sham- stimulaiton+placebo, tVNS+probiotic, sham-stimulation+probiotic). We will obtain data on alcohol consumption, cognitive assessments, blood biomarkers, stool microbiome, and neuroimaging at three timepoints (baseline, 30-days, 90 days).
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0.915 |