Modulators of maladaptive decision-making in methamphetamine dependence

甲基苯丙胺依赖中适应不良决策的调节因素

• 批准号: 8547630
• 负责人: Milky Kohno
• 金额: $ 1.57万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8547630
• 关键词: Affect; Anisotropy; Behavior; Behavioral; Biological Neural Networks; Brain; Brain region; Cognitive; Communication; Control Groups; Corpus striatum structure; Decision Making; Dependence; Development; Diffusion Magnetic Resonance Imaging; Disease; Drug usage; Evaluation; Event; Exhibits; Fiber; Functional Magnetic Resonance Imaging; Gambling; Goals; Image Analysis; Impaired cognition; Individual; Insula of Reil; Knowledge; Laboratories; Lead; Link; Measures; Medial; Mediating; Methamphetamine; Methamphetamine dependence; Methods; Modeling; Neurophysiology - biologic function; Nucleus Accumbens; Parietal Lobe; Participant; Pattern; Performance; Prefrontal Cortex; Probability; Process; Pump; Rewards; Risk; Risk-Taking; Signal Transduction; Statistical Methods; Substance abuse problem; Superior temporal gyrus; Task Performances; Testing; Time; Training; Uncertainty; Ventral Striatum; Ventral Tegmental Area; Work; addiction; analog; behavior measurement; behavior observation; design; discounting; effective intervention; experience; frontal lobe; improved; indexing; insight; meetings; neural circuit; neuroimaging; neuromechanism; relating to nervous system; response; success; virtual; white matter

DESCRIPTION (provided by applicant): Addiction is linked to faulty decision-making (1, 2), which may reflect maladaptive strategies in evaluation of rewards. When performing gambling tasks, methamphetamine-dependent individuals exhibit greater risk-taking than healthy control subjects in order to increase the size of rewards (3). On choices that involve the time when a reward is received, however, they prefer smaller, sooner rewards over larger, later ones (4, 5). While these observations indicate that task contingencies influence the subjective valence of reward, the neural mechanisms by which this influence is exerted are not known. The Neuroanatomical Model of Decision-making (6) postulates that dopaminergic afferents from the ventral tegmental area to the nucleus accumbens signal the occurrence of motivationally salient events, and that ventral tegmental area projections to the striatum and prefrontal cortex modulate the expression of subsequent behavior. Building on this model, the Impaired Response Inhibition and Salience Attribution model of addiction (7) posits that repeated drug use leads to adaptations in frontal white matter (8) and in glutamatatergic projections from the prefrontal cortex to the striatum (9), resulting in deficits in decision-making. The proposed work aims to extend our understanding of faulty decision-making processes in MA-dependent individuals, while investigating the potential contributions of deficits in evaluation of reward and associated neural circuitry. Two tasks will be used to examine the influence of different contingencies on decision-making in healthy and MA-dependent individuals. Relationships between performance on these tasks and the structural and functional integrity of regions implicated in the Neuroanatomical Model of Decision-making will be tested with functional MRI (fMRI) and diffusion tensor imaging (DTI). Responses during decision-making under risk, reward or delay will be examined using the Delay Discounting Task (DDT) (10) and the Balloon Analog Risk Task (BART) (11). The BART presents options to take risk in order to increase reward size, or to cash out and retain smaller rewards. Using the BART with fMRI, a goal of the study is to relate the proclivity for risk-taking and temporal discounting to brain function, and to examine differences in neural activation during risk-taking between groups. As performance deficits may also reflect reduced integrity of white matter connecting regions involved in the evaluation of reward, we will examine the extent to which white matter tracts connecting the striatum and prefrontal cortex modulate neural activity and performance on the BART and DDT. Behavioral approaches are the main treatments for MA abuse, but neural deficits that can affect their success are not well delineated. Knowledge of how different contingencies affect neural function subserving decision- making, and the structural connectivity that supports these functions in MA-dependent individuals may lead to a better understanding of MA dependence, and may help improve treatment for this disorder.

描述（由申请人提供）：成瘾与错误的决策有关（1、2），这可能反映了奖励评估中的适应不良策略。在执行赌博任务时，为了增加奖励的规模，甲基苯丙胺依赖者比健康对照受试者表现出更大的冒险精神 (3)。然而，在涉及收到奖励时间的选择中，他们更喜欢较小、较早的奖励，而不是较大、较晚的奖励 (4, 5)。虽然这些观察结果表明任务偶然性会影响奖励的主观效价，但产生这种影响的神经机制尚不清楚。决策的神经解剖模型 (6) 假设从腹侧被盖区到伏隔核的多巴胺能传入信号表示动机显着事件的发生，并且腹侧被盖区投射到纹状体和前额皮质调节后续行为的表达。在此模型的基础上，成瘾反应抑制受损和显着归因模型 (7) 假设，重复吸毒会导致额叶白质 (8) 和从前额皮质到纹状体的谷氨酸能投射发生适应 (9)，从而导致决策缺陷。拟议的工作旨在扩展我们对 MA 依赖个体的错误决策过程的理解，同时调查奖励和相关神经回路评估缺陷的潜在贡献。将使用两项任务来检查不同突发事件对健康和 MA 依赖个体决策的影响。这些任务的表现与决策神经解剖模型所涉及区域的结构和功能完整性之间的关系将通过功能 MRI (fMRI) 和扩散张量成像 (DTI) 进行测试。将使用延迟贴现任务 (DDT) (10) 和气球模拟风险任务 (BART) (11) 检查风险、奖励或延迟决策过程中的响应。 BART 提供了承担风险的选项，以增加奖励规模，或兑现并保留较小的奖励。该研究的目标是将 BART 与 fMRI 结合使用，将冒险倾向和时间贴现与大脑功能联系起来，并检查各组之间冒险期间神经激活的差异。由于表现缺陷也可能反映出参与奖励评估的白质连接区域的完整性降低，因此我们将检查连接纹状体和前额皮质的白质束在多大程度上调节 BART 和 DDT 的神经活动和表现。行为方法是 MA 滥用的主要治疗方法，但影响其成功的神经缺陷尚不清楚。了解不同的突发事件如何影响支持决策的神经功能，以及支持 MA 依赖个体的这些功能的结构连接可能会导致更好地理解 MA 依赖，并可能有助于改善这种疾病的治疗。