Neural substrates of impulsive behavior in methamphetamine dependence

描述(由申请人提供)：尽管存在健康、法律和社会问题等负面后果，但仍使用甲基苯丙胺(MA)反映了不适应行为，如未经事先考虑就采取行动，未能推迟满足或不适当的反应。这种行为可以广泛地描述为反映冲动，这被认为是导致上瘾的原因之一。这项拟议工作的首要目标是帮助澄清冲动行为背后的神经网络，并确定这些网络的结构完整性如何影响健康和MA依赖者的冲动行为。时间折扣任务被认为反映了冲动的选择，它将被用来衡量增强剂的主观价值如何随着时间的变化而减少。它要求参与者在更小的、更直接的奖励和更大的、延迟的奖励之间做出选择。由于任务表现可能依赖于神经回路，神经回路对评估奖励的主观价值很重要，比较两个选项，并最终选择一个选项，结构磁共振成像将用于测量额叶、顶叶和边缘皮质的灰质完整性，这可能有助于这些认知 流程。扩散张量成像将被用来确定连接这些结构的路径的白质完整性。这项工作的近期目标是确定健康个体的时间折现和脑结构之间的关系，评估MA依赖参与者是否在涉及的回路中存在结构性异常，并确定在潜在的MA诱导的神经病理条件下，脑结构和时间折现之间的正常关系是否成立。最后，将使用特质冲动性的自我报告测量来确定时间折现所涉及的神经网络的完整性是否也有助于在更广泛的冲动性结构的评估中的个体差异。由于目前还没有被批准用于MA依赖的药物治疗，冲动行为尤其有问题，因为它们破坏了药物依赖行为治疗的成功。这些信息可以为成瘾障碍的治疗提供信息，从而改善治疗保留率和降低复发率。

DESCRIPTION (provided by applicant): The use of methamphetamine (MA) despite negative consequences such as health, legal and social problems reflects maladaptive behaviors, such as acting without forethought and failure to delay gratification or to withhold inappropriate responses. Such behaviors can broadly be characterized as reflecting impulsivity, which is thought to contribute to addictions. The overarching goal of the proposed work is to help clarify the neural networks that underlie impulsive behavior and to determine how the structural integrity of these networks influences impulsive behaviors in healthy and MA-dependent individuals. A temporal discounting task, which is thought to reflect impulsive choice, will be used to measure how the subjective value of a reinforcer diminishes as a function of time. It requires that participants choose between smaller, more immediate rewards and larger, delayed rewards. As task performance likely depends on neural circuitry important for assessing subjective value of rewards, comparison of two options presented, and ultimately selecting one option over the other, structural magnetic resonance imaging will be used to measure the gray matter integrity of frontal, parietal, and limbic cortices, which may contribute to these cognitive processes. Diffusion tensor imaging will be used to determine white matter integrity of the pathways connecting these structures. The immediate goals of this work are to determine the relationship between temporal discounting and brain structure in healthy individuals, to assess whether MA-dependent participants have structural abnormalities in the implicated circuitry, and to determine whether the normal relationship between brain structure and temporal discounting holds under conditions of potential MA-induced neuropathology. Lastly, a self-report measure of trait impulsivity will be used to determine if the integrity of the neural networks implicated in temporal discounting also contribute to individual differences in a broader assessment of the construct of impulsivity. As there are currently no pharmacological treatments approved for MA-dependence, impulsive behaviors are especially problematic because they undermine the success of behavioral treatments for drug dependence. This information could inform treatments for addictive disorders resulting in improved treatment retention and lower rates of relapse.