Boettiger Charlotte A, Kelley Elizabeth A, Mitchell Jennifer M, D'Esposito Mark, Fields Howard L
Department of Psychology, Biomedical Research Imaging Center, University of North Carolina, Chapel Hill 27599-3270, United States.
Pharmacol Biochem Behav. 2009 Sep;93(3):291-9. doi: 10.1016/j.pbb.2009.02.008. Epub 2009 Feb 28.
Previously, we found that distinct brain areas predict individual selection bias in decisions between small immediate ("Now") and larger delayed rewards ("Later"). Furthermore, such selection bias can be manipulated by endogenous opioid blockade. To test whether blocking endogenous opioids with naltrexone (NTX) alters brain activity during decision-making in areas predicting individual bias, we compared fMRI BOLD signal correlated with Now versus Later decision-making after acute administration of NTX (50 mg) or placebo. We tested abstinent alcoholics and control subjects in a double-blind two-session design. We defined regions of interest (ROIs) centered on activation peaks predicting Now versus Later selection bias. NTX administration significantly increased BOLD signal during decision-making in the right lateral orbital gyrus ROI, an area where enhanced activity during decision-making predicts Later bias. Exploratory analyses identified additional loci where BOLD signal during decision-making was enhanced (left orbitofrontal cortex, left inferior temporal gyrus, and cerebellum) or reduced (right superior temporal pole) by NTX. Additional analyses identified sites, including the right lateral orbital gyrus, in which NTX effects on BOLD signal predicted NTX effects on selection bias. These data agree with opioid receptor expression in human frontal and temporal cortices, and suggest possible mechanisms of NTX's therapeutic effects.
此前，我们发现不同的脑区可预测在小的即时奖励（“现在”）和大的延迟奖励（“稍后”）之间进行决策时的个体选择偏差。此外，这种选择偏差可通过内源性阿片类物质阻断来操纵。为了测试用纳曲酮（NTX）阻断内源性阿片类物质是否会改变预测个体偏差的脑区在决策过程中的脑活动，我们比较了急性给予NTX（50毫克）或安慰剂后与“现在”和“稍后”决策相关的功能磁共振成像（fMRI）血氧水平依赖（BOLD）信号。我们采用双盲两阶段设计对戒酒者和对照受试者进行了测试。我们以预测“现在”与“稍后”选择偏差的激活峰值为中心定义了感兴趣区域（ROIs）。给予NTX后，右侧眶外侧回ROI在决策过程中的BOLD信号显著增加，该区域在决策过程中活动增强预示着“稍后”偏差。探索性分析确定了其他一些位点，在这些位点，决策过程中的BOLD信号在给予NTX后增强（左侧眶额皮质、左侧颞下回和小脑）或减弱（右侧颞上极）。进一步分析确定了包括右侧眶外侧回在内的一些位点，其中NTX对BOLD信号的影响预示着NTX对选择偏差的影响。这些数据与人类额叶和颞叶皮质中的阿片受体表达一致，并提示了NTX治疗作用的可能机制。
