Frontal Neural Mechanisms and Risk for Substance Abuse

描述(由申请人提供)： 前额叶区域的异常功能被认为会削弱个体监控和抑制行为的能力，因此可能导致更大的开始使用药物的风险，并阻碍药物使用的停止。在神经认知调查以及结构和功能神经成像研究中，已经记录了药物滥用者额叶/执行障碍的证据，为这一系统的缺陷提供了证据。前扣带回皮质(ACC)和背外侧前额叶皮质(DLPFC)有很强的相互联系，并被证明是执行功能的神经网络的一部分。最近的神经成像发现表明，在正常对照组的行为抑制任务中，ACC和DLPFC的亚区具有特定的作用(Gruber等人，2002年)。基于这些发现，我们认为认知控制是由ACC和DLPFC调节的两个互补的交互功能组成的。该项目建议应用两种互补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)，对象为12名正常对照组、12名慢性可卡因滥用者和12名吸食大量大麻的人。虽然BOLD功能磁共振成像技术允许检查不同感兴趣区域内的皮质活动，但DTI提供了对白质完整性的定量估计，这对于解释神经系统内的功能变化至关重要。到目前为止，还没有研究结合使用认知挑战范式和DTI的FMRI BOLD技术来研究额叶执行系统的两个关键组成部分--ACC和DLPFC的功能和潜在结构。这项研究产生的数据可能会为抑制加工和决策的神经机制提供新的见解，这对滥用药物的人有意义。此外，该项目的发现将为未来旨在研究前额叶皮质在药物滥用中的作用的赠款申请提供基础。

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.