Frontal Neural Mechanisms and Risk for Substance Abuse

额叶神经机制和药物滥用风险

• 批准号: 6674640
• 负责人: STACI A GRUBER
• 金额: $ 20.57万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2005-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6674640
• 关键词: behavioral /social science research tag; brain imaging /visualization /scanning; cingulate gyrus; clinical research; cocaine; cognition; decision making; disease /disorder proneness /risk; drug abuse; functional magnetic resonance imaging; human subject; interview; marijuana abuse; neural information processing; prefrontal lobe /cortex; substance abuse related behavior

DESCRIPTION (provided by applicant): Anomalous functioning of the prefrontal regions have been hypothesized to impair an individual's ability to monitor and inhibit behavior, and therefore may lead to greater risk for initiation of substance use as well as hinder the discontinuation of substance use. Evidence for frontal/executive impairments in individuals who are substance abusers has been documented in neurocognitive investigations, as well as structural and functional neuroimaging studies, offering evidence for deficits in this system. The anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) share strong reciprocal connections, and have been shown to be part of the neural network underlying executive functioning. Recent neuroimaging findings indicate specific roles for subdivisions of the ACC and DLPFC in normal controls during a task of behavioral inhibition (Gruber et al., 2002). Based on these findings, we propose that cognitive control is comprised of two complementary interactive functions mediated by the ACC and the DLPFC. This project proposes the application of two complementary techniques to examine the integrity of the frontal lobes: functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to 12 normal control subjects, 12 chronic cocaine abusers and 12 heavy marijuana smokers. While BOLD fMRI techniques allow for the examination of cortical activity within discrete regions of interest, DTI provides a quantitative estimate of white matter integrity, crucial to the interpretation of functional changes within neural systems. To date, no study has incorporated focal fMRI BOLD techniques using cognitive challenge paradigms and DTI to examine the function and underlying structure of subdivisions of the ACC and DLPFC, two key components of the frontal executive system. Data generated from this investigation may provide new insights into the neural mechanisms of inhibitory processing, and decision-making, which has implications for substance abusing individuals. Additionally, findings from this project will provide the foundation for future grant applications aimed at examining the role of the prefrontal cortex in substance abuse.

描述（由申请人提供）： 前额叶区域的异常功能被假设为损害个体的监测和抑制行为的能力，因此可能导致更大的开始使用物质的风险，以及阻碍停止使用物质。在神经认知调查以及结构和功能神经影像学研究中，已经记录了药物滥用者的额叶/执行功能障碍的证据，为该系统的缺陷提供了证据。前扣带皮层（ACC）和背外侧前额叶皮层（DLPFC）有着很强的相互联系，并且已经被证明是执行功能神经网络的一部分。最近的神经影像学发现表明，在行为抑制任务期间，正常对照中ACC和DLPFC的亚类具有特定作用（Gruber et al.，2002年）。基于这些发现，我们提出，认知控制是由两个相互补充的互动功能，ACC和DLPFC介导的。该项目提出了两个互补的技术来检查额叶的完整性：功能磁共振成像（fMRI）和扩散张量成像（DTI）的应用程序，以12名正常对照组，12名慢性可卡因滥用者和12名重度大麻吸烟者。虽然BOLD功能磁共振成像技术允许检查感兴趣的离散区域内的皮质活动，DTI提供了一个定量的估计白色物质的完整性，神经系统内的功能变化的解释至关重要。到目前为止，没有研究纳入局灶性fMRI BOLD技术使用认知挑战范式和DTI检查的功能和底层结构的分区的ACC和DLPFC，两个关键组成部分的额叶执行系统。从这项调查中产生的数据可能会提供新的见解的神经机制的抑制处理和决策，这对药物滥用的个人的影响。此外，该项目的研究结果将为未来的拨款申请提供基础，旨在研究前额叶皮层在药物滥用中的作用。

项目成果

Age of onset of marijuana use and executive function.

• DOI: 10.1037/a0026269
• 发表时间: 2012-09
• 期刊: PSYCHOLOGY OF ADDICTIVE BEHAVIORS
• 影响因子: 3.4
• 作者: Gruber, Staci A.;Sagar, Kelly A.;Dahlgren, Mary Kathryn;Racine, Megan;Lukas, Scott E.
• 通讯作者: Lukas, Scott E.

Why so impulsive? White matter alterations are associated with impulsivity in chronic marijuana smokers.

为什么这么冲动？白质改变与慢性大麻吸烟者的冲动有关。

• DOI: 10.1037/a0023034
• 发表时间: 2011-06
• 期刊: EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY
• 影响因子: 2.3
• 作者: Gruber, Staci A.;Silveri, Marisa M.;Dahlgren, Mary Kathryn;Yurgelun-Todd, Deborah
• 通讯作者: Yurgelun-Todd, Deborah

Age of onset of marijuana use impacts inhibitory processing.

• DOI: 10.1016/j.neulet.2012.01.039
• 发表时间: 2012-03-09
• 期刊: Neuroscience letters
• 影响因子: 2.5
• 作者: Gruber SA;Dahlgren MK;Sagar KA;Gönenc A;Killgore WD
• 通讯作者: Killgore WD

Altered affective response in marijuana smokers: an FMRI study.

• DOI: 10.1016/j.drugalcdep.2009.06.019
• 发表时间: 2009-11-01
• 期刊: DRUG AND ALCOHOL DEPENDENCE
• 影响因子: 4.2
• 作者: Gruber, Staci A.;Rogowska, Jadwiga;Yurgelun-Todd, Deborah A.
• 通讯作者: Yurgelun-Todd, Deborah A.