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Cocaine and HIV are independently associated with neural activation in response to gain and loss valuation during economic risky choice.

ABSTRACT: Stimulant abuse is disproportionately common in HIV-positive persons. Both HIV and stimulants are independently associated with deficits in reward-based decision making, but their interactive and/or additive effects are poorly understood despite their prevalent co-morbidity. Here, we examined the effects of cocaine dependence and HIV infection in 69 adults who underwent functional magnetic resonance imaging while completing an economic loss aversion task. We identified two neural networks that correlated with the evaluation of the favorable characteristics of the gamble (i.e. higher gains/lower losses: ventromedial prefrontal cortex, anterior cingulate, anterior and posterior precuneus and visual cortex) versus unfavorable characteristics of the gamble (i.e. lower gains/higher losses: dorsal prefrontal, lateral orbitofrontal, posterior parietal cortex, anterior insula and dorsal caudate). Behaviorally, cocaine and HIV had additive effects on loss aversion scores, with HIV-positive cocaine users being the least loss averse. Cocaine users had greater activation in brain regions that tracked the favorability of gamble characteristics (i.e. increased activation to gains, but decreased activation to losses). In contrast, HIV infection was independently associated with lesser activation in regions that tracked the unfavorability of gamble characteristics. These results suggest that cocaine is associated with an overactive reward-seeking system, while HIV is associated with an underactive cognitive control system. Together, these alterations may leave HIV-positive cocaine users particularly vulnerable to making unfavorable decisions when outcomes are uncertain.

SUBMITTER: Meade CS

PROVIDER: S-EPMC6706251 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Cocaine and HIV are independently associated with neural activation in response to gain and loss valuation during economic risky choice.

Meade Christina S CS Addicott Merideth M Hobkirk Andrea L AL Towe Sheri L SL Chen Nan-Kuei NK Sridharan Sriramkumar S Huettel Scott A SA

Addiction biology 20170706 2

Stimulant abuse is disproportionately common in HIV-positive persons. Both HIV and stimulants are independently associated with deficits in reward-based decision making, but their interactive and/or additive effects are poorly understood despite their prevalent co-morbidity. Here, we examined the effects of cocaine dependence and HIV infection in 69 adults who underwent functional magnetic resonance imaging while completing an economic loss aversion task. We identified two neural networks that c ...[more]

PMID: 28682013

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Project description:Both normative and many descriptive theories of decision making under risk are based on the notion that outcomes are weighted by their probability, with subsequent maximization of the (subjective) expected outcome. Numerous investigations from psychology, economics, and neuroscience have produced evidence consistent with this notion. However, this research has typically investigated choices involving relatively affect-poor, monetary outcomes. We compared choice in relatively affect-poor, monetary lottery problems with choice in relatively affect-rich medical decision problems. Computational modeling of behavioral data and model-based neuroimaging analyses provide converging evidence for substantial differences in the respective decision mechanisms. Relative to affect-poor choices, affect-rich choices yielded a more strongly curved probability weighting function of cumulative prospect theory, thus signaling that the psychological impact of probabilities is strongly diminished for affect-rich outcomes. Examining task-dependent brain activation, we identified a region-by-condition interaction indicating qualitative differences of activation between affect-rich and affect-poor choices. Moreover, brain activation in regions that were more active during affect-poor choices (e.g., the supramarginal gyrus) correlated with individual trial-by-trial decision weights, indicating that these regions reflect processing of probabilities. Formal reverse inference Neurosynth meta-analyses suggested that whereas affect-poor choices seem to be based on brain mechanisms for calculative processes, affect-rich choices are driven by the representation of outcomes' emotional value and autobiographical memories associated with them. These results provide evidence that the traditional notion of expectation maximization may not apply in the context of outcomes laden with affective responses, and that understanding the brain mechanisms of decision making requires the domain of the decision to be taken into account.

Project description:BackgroundRisky decision-making is commonly observed in persons at risk for and infected with HIV and is associated with executive dysfunction. Yet it is currently unknown whether HIV alters brain processing of risk-taking decision-making.MethodsThis study examined the neural substrate of a risky decision-making task in 21 HIV seropositive (HIV+) and 19 seronegative (HIV-) comparison participants. Functional magnetic resonance imaging was conducted while participants performed the risky-gains task, which involves choosing among safe (20 cents) and risky (40/80 cent win or loss) choices. Linear mixed effects analyses examining group and decision type were conducted. Robust regressions were performed to examine the relationship between nadir CD4 count and Kalichman sexual compulsivity and brain activation in the HIV+ group. The overlap between the task effects and robust regressions was explored.ResultsAlthough there were no serostatus effects in behavioral performance on the risky-gains task, HIV+ individuals exhibited greater activation for risky choices in the basal ganglia, i.e. the caudate nucleus, but also in the anterior cingulate, dorsolateral prefrontal cortex, and insula relative to the HIV- group. The HIV+ group also demonstrated reduced functional responses to safe choices in the anterior cingulate and dorsolateral prefrontal cortex relative to the HIV- group. HIV+ individuals with higher nadir CD4 count and greater sexual compulsivity displayed lower differential responses to safe versus risky choices in many of these regions.ConclusionsThis study demonstrated fronto-striatal loop dysfunction associated with HIV infection during risky decision-making. Combined with similar between-group task behavior, this suggests an adaptive functional response in regions critical to reward and behavioral control in the HIV+ group. HIV-infected individuals with higher CD4 nadirs demonstrated activation patterns more similar to seronegative individuals. This suggests that the severity of past immunosuppression (CD4 nadir) may exert a legacy effect on processing of risky choices in the HIV-infected brain.

Dataset Information

Cocaine and HIV are independently associated with neural activation in response to gain and loss valuation during economic risky choice.

Publications

Cocaine and HIV are independently associated with neural activation in response to gain and loss valuation during economic risky choice.

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