Altered Functional Response to Risky Choice in HIV Infection

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.研究背景：在HIV感染风险人群与HIV感染者中，冒险决策行为较为常见，且该行为与执行功能障碍存在关联。然而目前尚不清楚HIV是否会改变大脑在冒险决策过程中的神经活动模式。 研究方法：本研究纳入21名HIV血清阳性（HIV seropositive，HIV+）受试者与19名HIV血清阴性（HIV seronegative，HIV-）对照受试者，对其完成冒险决策任务时的神经基础进行了考察。受试者执行冒险收益任务（risky-gains task）期间完成功能磁共振成像（functional magnetic resonance imaging）扫描；该任务要求受试者在安全选项（20美分固定收益）与风险选项（40/80美分的赢取或亏损）之间进行选择。本研究采用线性混合效应分析（linear mixed effects analyses）对组别与决策类型的效应进行检验；并通过稳健回归（robust regressions）分析HIV+组受试者的CD4细胞最低计数（nadir CD4 count）、卡利奇曼性强迫量表（Kalichman sexual compulsivity）得分与脑激活水平之间的关联。此外，本研究还探索了任务效应与稳健回归分析结果之间的重叠脑区。 研究结果：尽管两组受试者在冒险收益任务的行为表现上未出现血清状态相关的差异，但与HIV-组相比，HIV+组受试者在进行风险选项选择时，基底神经节（basal ganglia，包括尾状核（caudate nucleus））、前扣带回（anterior cingulate）、背外侧前额叶皮层（dorsolateral prefrontal cortex）以及脑岛（insula）的激活水平显著更高。同时，与HIV-组相比，HIV+组受试者在面对安全选项时，前扣带回与背外侧前额叶皮层的功能响应显著减弱。此外，CD4细胞最低计数更高、性强迫症状更严重的HIV+受试者，在上述多数脑区中对安全选项与风险选项的差异化响应程度更低。 研究结论：本研究证实，HIV感染者在完成冒险决策任务时存在额纹状体环路（fronto-striatal loop）功能异常。结合两组间行为表现无显著差异的结果，这提示HIV+组受试者在奖赏与行为控制关键脑区出现了适应性功能代偿。CD4细胞最低计数更高的HIV感染者，其脑激活模式与HIV-组受试者更为相似。这表明既往免疫抑制的严重程度（以CD4细胞最低计数衡量）可能对HIV感染者大脑的冒险决策加工过程产生遗留效应。