Neural substrates of impulsive behavior in methamphetamine dependence

描述（由申请人提供）：尽管存在健康、法律的和社会问题等负面后果，但使用甲基苯丙胺（MA）反映了适应不良的行为，如未经事先考虑就采取行动，未能延迟满足或保留不适当的反应。这些行为可以被广泛地描述为反映冲动，这被认为是导致成瘾的原因。所提出的工作的总体目标是帮助澄清冲动行为的神经网络，并确定这些网络的结构完整性如何影响健康和MA依赖个体的冲动行为。 一个时间折扣任务，这被认为是反映冲动的选择，将被用来衡量一个决策者的主观价值如何减少作为时间的函数。它要求参与者在较小的、更直接的奖励和较大的、延迟的奖励之间做出选择。由于任务表现可能取决于神经回路，这些神经回路对于评估奖励的主观价值、比较呈现的两个选项以及最终选择一个选项而不是另一个选项很重要，因此将使用结构磁共振成像来测量额叶、顶叶和边缘皮质的灰质完整性，这可能有助于这些认知功能。 流程.扩散张量成像将用于确定连接这些结构的通路的白色物质完整性。这项工作的直接目标是确定健康个体的时间折扣和大脑结构之间的关系，以评估MA依赖的参与者是否在牵连的电路中存在结构异常，并确定在潜在的MA诱导的神经病理学条件下，大脑结构和时间折扣之间的正常关系是否成立。最后，特质冲动的自我报告措施将被用来确定是否涉及时间折扣的神经网络的完整性也有助于在更广泛的评估冲动的结构的个体差异。 由于目前还没有药物治疗被批准用于MA依赖，冲动行为尤其成问题，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性疾病的治疗提供信息，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.