P2: Neural Substrates of Decision-Making The prevalent use of methamphetamine (METH) among individuals with HIV infection.represents a """"""""double epidemic"""""""" that has serious consequences involving neural and behavioral alterations. Both HIV and METH independently alter brain function within dopaminergic regions, and their comorbidity likely preferentially impacts goal-directed behavior and risky decision-making due to altered reward and punishment processing and expectancy. This is supported by our prior work demonstrating an HIV by METH interaction for fMRI BOLD response to reward expectancy within the ventromedial prefrontal cortex and anterior cingulate, as well as impaired responses within anterior cingulate and striatum during risky decision-making. An emerging concern is the possibility that aging might exacerbate neurocognitive dysfunction already prevalent in HIV infected individuals, particularly on reward-related decision-making and learning behaviors. Building from our prior findings, the aims of the current project involve state-of-the-art multimodal MRI methods that will be used to query both functional brain responses (BOLD/FMRI) and the underlying connectivity between brain regions relevant to the decision-making process (diffusion MRI and resting BOLD). We also aim to determine the modulatory^effects of aging on HIV and/or METH effects. We propose to study four groups of 30 well-characterized individuals stratified by HIV serostatus and METH dependence diagnosis from the primary TMARC cohort (total N=120). Participants will undergo functional magnetic resonance imaging (fMRI) to probe limbic and cognitive circuitry using three experimental paradigms: 1) probabilistic associative learning with positive and negative feedback;2) risky decision-making;and 3) resting state (task-free) fMRI. Participants will also undergo diffusion MRI to assess white matter integrity within frontostriatal tracts and to examine the relationship between frontostriatal structural and functional connectivity. We will map our neuroimaging and neurobehavioral task data onto the decision-making data gathered in Project 1. Findings will inform a future NIH application investigating re.al-world consequences (e.g., adherence to treatment and risky behavior) of increased reward sensitivity due to HIV/METH and aging.

Public Health Relevance

Reward processing and risk-taking are important processes that influence behavior, change throughout one's lifespan, and are altered in substance using and HIV+ individuals. This project will examine the neural circuitry of these behaviors in HIV+ and METH dependent individuals. Understanding these relationships and how aging may worsen their dysfunction may inform interventions aimed at altering risky behavior.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZDA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
La Jolla
United States
Zip Code
Kamat, Rujvi; Doyle, Katie L; Iudicello, Jennifer E et al. (2016) Neurobehavioral Disturbances During Acute and Early HIV Infection. Cogn Behav Neurol 29:1-10
Noel, Richard J; Kaul, Marcus (2016) The 22nd Scientific Conference of the Society on Neuroimmune Pharmacology. J Neuroimmune Pharmacol 11 Suppl 1:S1-2
Soontornniyomkij, Virawudh; Umlauf, Anya; Soontornniyomkij, Benchawanna et al. (2016) Lifetime methamphetamine dependence is associated with cerebral microgliosis in HIV-1-infected adults. J Neurovirol 22:650-660
Gianella, Sara; Letendre, Scott (2016) Cytomegalovirus and HIV: A Dangerous Pas de Deux. J Infect Dis 214 Suppl 2:S67-74
Kesby, James P; Markou, Athina; Semenova, Svetlana (2016) The effects of HIV-1 regulatory TAT protein expression on brain reward function, response to psychostimulants and delay-dependent memory in mice. Neuropharmacology 109:205-15
Hoenigl, Martin; Little, Susan J (2016) How can we detect HIV during the acute or primary stage of infection? Expert Rev Mol Diagn 16:1049-1051
Bischoff-Grethe, Amanda; Connolly, Colm G; Jordan, Stephan J et al. (2016) Altered reward expectancy in individuals with recent methamphetamine dependence. J Psychopharmacol :
Brown, Gregory G; Jacobus, Joanna; McKenna, Benjamin (2016) Structural imaging for addiction medicine: From neurostructure to neuroplasticity. Prog Brain Res 224:105-27
Hoenigl, Martin; Chaillon, Antoine; Moore, David J et al. (2016) Clear Links Between Starting Methamphetamine and Increasing Sexual Risk Behavior: A Cohort Study Among Men Who Have Sex With Men. J Acquir Immune Defic Syndr 71:551-7
Pérez-Santiago, Josué; Schrier, Rachel D; de Oliveira, Michelli F et al. (2016) Cell-free mitochondrial DNA in CSF is associated with early viral rebound, inflammation, and severity of neurocognitive deficits in HIV infection. J Neurovirol 22:191-200

Showing the most recent 10 out of 108 publications