Altered functional response to risky choice in HIV infection

Abstract

Background: Risky 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.

Methods: This 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.

Results: Although 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.

Conclusions: This 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.

Figure 1. An illustration of four different trial types from the risky gains task: (A) lose 80, (B) win 20, (C) win 40 and (D) lose 40.

The blue arrow indicates participant response to select the value on screen.

Figure 2. Brain regions identified by the between-group whole-brain analysis of the general linear test of risky (40, 80) versus safe (20) choices.

The bar charts indicate percentage signal change and are the breakdown of responses within group and by choice (20, 40, 80) in these regions. Error bars indicate the standard error of the mean. L, left; R, right.

Figure 3. Within the HIV+ group, graphs of the relationship between nadir CD4 count and a subset of the voxels in each of the clusters depicted in Figure 2 and Table 2.

The subset of voxels is the overlap between the clusters showing between-group task related functional differences and those clusters identified by the robust regression analysis conducted only within the HIV+ group. The black line is the robust regression line on the difference between risky and safe responses. The red and blue lines are robust regression lines of the safe and risky components of the black line. L, left; R, right; Inf, Inferior; Sup, Superior; Gy, Gyrus.

Figure 4. Within the HIV+ group, graphs of the relationship between Kalichman Sexual Compulsivity Scaled Mean and a subset of the voxels in three of the clusters depicted in Figure 2 and Table 2.

The subset of voxels is the overlap between the clusters showing between-group task related functional differences and those clusters identified by the robust regression analysis conducted only within the HIV+ group. The black line is the robust regression line on the difference between risky and safe responses. The red and blue lines are robust regression lines of the safe and risky components of the black line. L, left; R, right; Sup, Superior; Gy, Gyrus.