Neurocognitive Mechanisms and Recovery from Addiction

描述（由申请人提供）：关于作为成瘾和恢复功能的决策和冲动控制的神经认知机制的知识有限。然而，成瘾和恢复期间大脑变化和认知功能的时间过程可能对我们合理地瞄准新治疗的能力至关重要。建立在长期的 这项试点研究将对申请人前瞻性跟踪超过12年的可卡因依赖者队列进行研究，探索与成瘾和恢复阶段相关的神经认知机制。该项目将使用磁共振成像（MRI）技术来研究已知在决策，冲动控制和奖励处理中发挥关键作用的大脑结构区域，这些区域的结构和功能连接，以及这些相同的关键区域对受试者在不确定条件下做出的决定的反应。将通过高分辨率MRI扫描对每例受试者的脑区体积和灰/白色物质密度进行量化，这些脑区对于处理奖励和情感信息非常重要，包括丘脑核、杏仁核、岛叶和体感皮层、腹内侧前额叶皮层和前扣带回。此外，当受试者执行决策任务时，这些区域的fMRI BOLD反应将被测量。DTI和静息状态功能磁共振成像将使我们能够评估相关大脑区域的结构和功能连接。这些措施将在成瘾和恢复的不同阶段的受试者之间进行比较，以探索关于大脑功能恢复或接近正常所需的可卡因戒断时间的研究问题。具体来说，我们将比较（1）可卡因成瘾者与非可卡因使用者或正常对照者，以及（2）在不同阶段康复的人与未康复的人，这些比较包括：（a）已知在处理情感信息和决策中起关键作用的大脑区域的脑容量和灰质密度;（B）属于“反射”系统的神经系统的活动（例如，VMPFC，前扣带回）;（c）神经系统的活动， 到“脉冲系统”（例如，杏仁核、腹侧纹状体、纹状体），（d）岛叶活动的调节作用，以及（e）相关大脑区域的结构和功能连接。该项目的结果将为更大规模的研究提供信息，以检查更直接受可卡因成瘾影响并参与恢复过程的特定大脑区域的细节，这将对认知训练计划和药物的发展产生影响针对相关的大脑结构。 公共卫生相关性：从成瘾中恢复是一个缓慢的过程，药物滥用的慢性复发是一个公共卫生问题。这项拟议的研究通过提高我们对成瘾和恢复期间大脑变化和认知功能的时间进程的理解来解决这一公共卫生问题，这可能会提出新的治疗方法来促进早期恢复或加快恢复过程。

DESCRIPTION (provided by applicant): Limited knowledge is available regarding the neurocognitive mechanism of decision-making and impulse control as a function of addiction and recovery. Yet the time course of brain changes and cognitive function during addiction and recovery may be critical to our ability to rationally target new treatments. Built upon a long-term cohort of cocaine-dependent users that have been prospectively followed by the applicants for more than 12 years, this pilot study will explore neurocognitive mechanisms associated with stages of addiction and recovery. The project will use Magnetic Resonance Imaging (MRI) techniques to investigate structural areas of the brain known to play a key role in decision-making, impulse control, and reward processing, structural and functional connectivity of these regions, as well as the responses of these same key regions to decisions made by subjects under conditions of uncertainty. The volume and gray/white matter density of brain areas that are important for processing reward and emotional information, including the nucleus accumbens, amygdala, insular and somatosensory cortex, ventromedial prefrontal cortex, and anterior cingulate, will be quantified for each subject from high resolution MRI scans. In addition the fMRI BOLD responses of these regions will be measured when subjects perform decision-making tasks. DTI and resting state fMRI will allow us to assess structural and functional connectivity of the relevant brain regions. These measures will be compared across subjects at different stages of addiction and recovery to explore research questions regarding the length of abstinence from cocaine required for brain functioning to recover or approach normal. Specifically, we will compare (1) cocaine addicts versus non-cocaine-using or normal controls, and (2) those recovered at various stages versus those not recovered in terms of (a) brain volume and gray matter density in brain regions known to play a key role in processing emotional information and decision-making; (b) activity in neural systems belonging to the "reflective" system (e.g., the VMPFC, anterior cingulate); (c) activity in neural systems belonging to the "impulsive system" (e.g., amygdala, ventral striatum, insula) when these participants perform various decision-making tasks, (d) modulatory effects of insular activities, and (e) structural and functional connectivity of the relevant brain regions. The results of this project wll inform the development of a larger study to examine details on specific brain areas that are more directly affected by cocaine addiction and involved in the process of recovery, which will have implications for the development of cognitive training programs and medications that target the relevant brain structures. PUBLIC HEALTH RELEVANCE: Recovery from addiction is a slow process, and chronic relapse to drug abuse is a public health concern. The proposed study addresses this public health problem by improving our understanding of the time course of brain changes and cognitive function during addiction and recovery, which may suggest new treatments to promote early recovery or to speed up the recovery process.