INHIBITORY CONTROL AND METHAMPHETAMINE DEPENDENCE MODAFINIL EFFECTS

慢性甲基苯丙胺（MA）滥用与额纹状体功能标志物的缺陷有关。 现有数据表明，各种行为障碍，包括反应能力下降， 抑制，伴随着这种功能障碍。反应抑制能力受损可能影响治疗 结果，并有助于从MA滥用到成瘾的异常快速进展。在申请人 实验室，我们最近开始工作，使用功能和结构磁共振成像， 确定与MA滥用者的反应抑制缺陷相关的神经系统，2）将行为 赤字额纹状体灰质使用新的计算脑映射技术，和3）评估 莫达非尼（200 mg）对MA依赖和对照参与者的表现和脑功能的影响 在需要反应抑制的任务期间（“神经系统，抑制控制，和甲基苯丙胺 依赖性”R 01 DA 020726，E.伦敦，PI）。这项正在进行的工作将纳入拟议的 项目1的翻译中心，这样，完成认知测试的MA依赖参与者， 项目1中的结构和功能MRI（n = 30）将直接进入中心项目2（“抑制控制 和MA自我管理：莫达非尼效应”），以允许跨 项目项目1将通过对另外11名受试者实施相同的方案来扩展R 01， 增加目前计划完成研究的19名MA依赖受试者的R 01样本 在翻译中心研究期间，共30例受试者接受了研究方案。项目1将能够 探索现有R 01尚未解决的研究问题。新的分析在 项目1包括评估莫达非尼对MA自我给药的影响之间的关系（项目1）。 2），以及莫达非尼对抑制控制期间脑激活的影响（项目1）。我们也会用大脑 表面匹配技术，将MA自我管理和MA主观反应（项目2）与当地 先验感兴趣区域的体积（额下回、尾状核和壳核;项目1）。通过增加 我们正在进行的成像项目的样本量，并将这项工作与其他翻译中心 项目1的大脑成像和行为结果将促进跨部门的进一步富有成效的联系。 实验室，从而大大提高了我们理解MA滥用的神经生物学的能力， 制定有效的干预措施。

Chronic methamphetamine (MA) abuse is associated with deficits in markers for frontostriatal function. Available data suggest that a variety of behavioral impairments, including diminished capacity for response inhibition, accompany this dysfunction. Impaired capacity for response inhibition may compromise treatment outcomes, and contribute to the unusually rapid progression from MA abuse to addiction. In the applicant laboratories, we have recently initiated work, using functional and structural magnetic resonance imaging, to identify the neural systems associated with response inhibition deficits in MA abusers, 2) to relate behavioral deficits to frontostriatal gray matter using novel computational brain-mapping techniques, and 3) to assess effects of modafinil (200 mg) on performance and brain function of MA-dependent and control participants during tasks that require response inhibition ("Neural Systems, Inhibitory Control, and Methamphetamine Dependence" R01DA020726, E. London, PI). This ongoing work will be integrated within the proposed Translational Center by Project 1, such that MA-dependent participants who complete cognitive tests and structural and functional MRI in Project 1 (n = 30) will proceed directly to Center Project 2 ("Inhibitory Control & MA Self-Administration: Modafinil Effects") in sufficient numbers to allow correlation analyses across projects. Project 1 will extend the R01 by administering the same protocol to 11 additional subjects, augmenting the R01 sample of 19 MA-dependent subjects currently scheduled to complete the research protocol during the Translational Center study period to a total of 30 subjects. Project 1 will thereby be able to explore research questions currently not addressed by the existing R01. New analyses carried out in Project 1 include assessing the relationship between effects of modafinil on MA self-administration (Project 2), and effects of modafinil on brain activation during inhibitory control (Project 1). We will also employ brain surface matching techniques to relate MA self-administration and MA subjective response (Project 2) to local volumes in a priori regions of interest (inferior frontal gyrus, caudate, and putamen; Project 1). By increasing the sample size of our ongoing imaging project, and integrating this work with the other Translational Center projects, the brain imaging and behavioral results of Project 1 will facilitate further productive linkages across laboratories, resulting in substantial gains in our ability to understand the neurobiology of MA-abuse and develop effective interventions.