Altered Functional Response to Risky Choice in HIV Infection

Abstract

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.

HIV-1 Transgenic Rat Prefrontal Cortex Hyper-Excitability is Enhanced by Cocaine Self-Administration

“…The hyper-excitability may, however, underpin the enhanced psychological distress and neurological decline reported for the comorbid individual (Gibbie et al, 2007;Meade et al, 2011;Meyer et al, 2013). Outcomes from Tg rats also indicate that mPFC PN remain vulnerable to HIVassociated dysregulation even when viral replication is controlled, thus providing a pathophysiological explanation for the persistent behavioral deficits reported for these individuals (Meyer et al, 2013;Connolly et al, 2014).…”

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models

“…Results from task-based functional MR imaging also support HIV- associated alterations in frontostriatal tracts. Participants (21 HIV+ and 19 HIV–) performed the risky gains task during functional MR imaging (Connolly et al 2014). While the two groups did not differ in terms of their behavior (i.e.…”

Compensatory activation in fronto-parietal cortices among HIV-infected persons during a monetary decision-making task

“…Since then, one published study has examined the effects of HIV on neural processing during a risky decision‐making task [Connolly et al, ]. HIV‐positive participants showed increased activation compared to HIV‐negative participants in the basal ganglia, anterior cingulate, dorsolateral prefrontal cortex, and insula during risky choices, but reduced activation in the anterior cingulate and dorsolateral prefrontal cortices during safe choices [Connolly et al, ]. This pattern of hyperactivity within task‐relevant regions has been interpreted as a compensatory mechanism for maintaining cognitive performance in the context of decreased efficiency due to neural injury or healthy aging [Barulli and Stern, ; Cabeza and Dennis, ; Stern, ], and it has been applied to HIV‐associated increases in brain activation [Chang et al, ; Connolly et al, ; Ernst et al, ; Melrose et al, ].…”