Alcoholism is a common comorbid condition of HIV infection. Both conditions have been independently associated with significant brain damage. Mounting evidence suggests that excessive alcohol use may exacerbate HIV-associated brain damage, yet few studies are available that directly address their combined effects. The proposed research will examine the structural and functional brain integrity in HIV-infected individuals and HIV seronegative controls with and without history of heavy alcohol use. Specifically, Diffusion tensor imaging will be used to examine the integrity of brain white matter and structural connectivity. Functional MRI will be used to examine functional brain response to cognitive task. In addition, an exploratory analysis of functional connectivity based on BOLD/FMRI data will provide additional measures of brain connectivity. Using this novel approach of combining multiple neuroimaging and neurocognitive measures, the study will help achieve a better understanding of how functional cortical brain abnormality and neurocognitive impairment associated with alcohol use and HIV infection are linked to degradation of white matter pathways that connect these brain regions. The applicant has received extensive training in neuroimaging investigation of HIV- associated brain dysfunction. The proposed training and research plans represents a natural extension of his work to examine the impact of alcohol use on HIV-associated brain dysfunction, utilizing multiple MRI modalities. To achieve the goal of conducting independent research in this area, the K99 training plan will emphasize 1) the behavioral and biological consequences of alcohol use, 2) the analysis and application of BOLD/FMRI data, and 3) advancing the applicant's current knowledge in neuroAIDS and analysis of diffusion- weighted MRI data. A comprehensive training plan is proposed, combining mentored research and structured didactic activities guided by established researchers in the field, formal coursework and workshops, and participation in seminars at Brown University and The Miriam Hospital.

Public Health Relevance

Results from this study will promote a better understanding of the biological mechanisms underlying alcohol/HIV-related neurocognitive dysfunction, which will help to guide behavioral and pharmacological interventions. In addition, the novel neuroimaging measures may serve as more sensitive biomarkers than those currently available for identifying individuals at risk for neurocognitive dysfunction. Ultimately, successful prevention and treatment of neurocognitive deficits will to help to improve the quality of life and health outcome of HIV-infected individuals.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Transition Award (R00)
Project #
4R00AA020235-03
Application #
8603965
Study Section
Special Emphasis Panel (NSS)
Program Officer
Matochik, John A
Project Start
2013-03-01
Project End
2016-02-29
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
3
Fiscal Year
2013
Total Cost
$248,897
Indirect Cost
$88,318
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Daiello, Lori A; Gongvatana, Assawin; Dunsiger, Shira et al. (2015) Association of fish oil supplement use with preservation of brain volume and cognitive function. Alzheimers Dement 11:226-35
Caldwell, J Z K; Gongvatana, A; Navia, B A et al. (2014) Neural dysregulation during a working memory task in human immunodeficiency virus-seropositive and hepatitis C coinfected individuals. J Neurovirol 20:398-411
Seider, Talia R; Luo, Xi; Gongvatana, Assawin et al. (2014) Verbal memory declines more rapidly with age in HIV infected versus uninfected adults. J Clin Exp Neuropsychol 36:356-67
Gongvatana, Assawin; Correia, Stephen; Dunsiger, Shira et al. (2014) Plasma cytokine levels are related to brain volumes in HIV-infected individuals. J Neuroimmune Pharmacol 9:740-50
Harezlak, J; Cohen, R; Gongvatana, A et al. (2014) Predictors of CNS injury as measured by proton magnetic resonance spectroscopy in the setting of chronic HIV infection and CART. J Neurovirol 20:294-303
Iudicello, Jennifer E; Morgan, Erin E; Gongvatana, Assawin et al. (2014) Detrimental impact of remote methamphetamine dependence on neurocognitive and everyday functioning in older but not younger HIV+ adults: evidence for a legacy effect? J Neurovirol 20:85-98
Gongvatana, Assawin; Morgan, Erin E; Iudicello, Jennifer E et al. (2014) A history of alcohol dependence augments HIV-associated neurocognitive deficits in persons aged 60 and older. J Neurovirol 20:505-13
Correia, Stephen; Cohen, Ronald; Gongvatana, Assawin et al. (2013) Relationship of plasma cytokines and clinical biomarkers to memory performance in HIV. J Neuroimmunol 265:117-23
Hua, Xue; Boyle, Christina P; Harezlak, Jaroslaw et al. (2013) Disrupted cerebral metabolite levels and lower nadir CD4 + counts are linked to brain volume deficits in 210 HIV-infected patients on stable treatment. Neuroimage Clin 3:132-42
Gongvatana, Assawin; Harezlak, Jaroslaw; Buchthal, Steven et al. (2013) Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy. J Neurovirol 19:209-18

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