Imaging of DLPFC and amygdala impact on relative preference in cocaine addiction

描述（由申请人提供）：DLPFC 和杏仁核的成像对可卡因成瘾相对偏好的影响 摘要 最近，关于大脑结构测量和奖赏/厌恶处理之间关系的研究已经开始出现。研究表明大脑结构的改变与成瘾中接近和回避行为的改变有关，其中一个挑战是很难解释这些发现是否与（i）脆弱因素，（ii）药物暴露/损害的影响，或（iii）对疾病的补偿反应有关。从文献中，关于结构不对称、与行为的相关性以及对禁欲的反应的结果正在出现，这表明我们可以开发和测试假设，这些假设对脆弱性、药物暴露/损害或补偿进行权重解释。我们建议评估大脑结构与相对偏好的按键测量（包括强烈厌恶的按键测量）之间的关系，并确定研究结果是否可以扩展到健康对照，或与脆弱因素、药物暴露迹象或可卡因依赖多物质滥用（CDPA）受试者的补偿反应相关。我们将特别针对杏仁核、脑岛 (INS) 和背外侧前额叶皮层 (DLPFC)，因为这些区域在功能上与基于相对偏好的判断和决策相关的按键任务相关，或者在结构上与 CDPA 受试者的按键任务相关。我们预测以下方面的改变：(1) 杏仁核与脆弱性相关，(2) INS 与药物暴露相关，(3) DLPFC 与补偿反应相关。这些假设将通过按键任务的行为测试和匹配组（每组 N=80）的高分辨率 MRI 扫描来检验，这些组是（1）活跃的 CDPA 受试者，（2）长期禁欲的 CDPA 受试者，以及（3）健康志愿者。将专门测试这三组之间的大脑结构和行为，以及结构和行为之间关系的改变，以得出以下推论：(a) DLPFC、INS 和杏仁核中的结构测量是否可以与按键行为联系起来，以接近和避免健康对照中的目标对象，以及 (b) CDPA 受试者的异常是否可以用脆弱性、药物暴露或补偿反应来解释。 公共卫生相关性：DLPFC 和杏仁核成像对可卡因成瘾相对偏好的影响 药物成瘾（例如可卡因依赖）的一个基本特征是，成瘾者对其兴趣的范围和深度有所减少；这一关键特征被称为成瘾的“受限行为库”，可以类比为只购买一只股票的投资者，而不是在广泛的股票中分配投资风险。开创性研究表明，这种临床特征可能与涉及奖励判断和决策的大脑结构异常有关，并且这种行为-结构关系可能是吸毒的倾向。当前的项目将直接测试涉及奖励决策的一系列广泛的大脑结构是否也在结构上异常，并与可卡因成瘾的行为异常相关。该项目还将寻求确定这种行为结构异常是否与吸毒本身有关，或者是否可能具有表明其早于吸毒的特征。

DESCRIPTION (provided by applicant): Imaging of DLPFC and amygdala impact on relative preference in cocaine addiction Abstract Relatively recently, studies of the relationship of brain structural measures and reward/aversion processing have started to appear. One challenge with studies showing altered brain structure in relationship to altered approach and avoidance behaviors in addiction is that it is difficult to interpret whether the findings relate to (i) vulnerability factors, (ii) effects of drug exposure/damage, or (iii) compensatory responses to the illness. From the literature, results regarding structure asymmetry, correlations with behavior, and responses to abstinence are emerging that suggest we can develop and test hypotheses that weight interpretation toward vulnerability, drug exposure/damage, or compensation. We propose to evaluate the relationship of brain structure with keypress measures of relative preference, including strongly aversive ones, and determine if findings can be extended to healthy controls, or related to vulnerability factors, signs of drug exposure, or compensatory responses in cocaine dependent polysubstance abusing (CDPA) subjects. We will specifically target the amygdala, insula (INS), and dorsolateral prefrontal cortex (DLPFC), given each of these regions has been functionally connected with keypress tasks related to judgment and decision-making based on relative preferences, or structurally connected with keypress tasks in CDPA subjects. We predict that alterations in: (1) the amygdala relate to vulnerability, (2) the INS relate to drug exposure, and (3) the DLPFC relate to compensatory responses. These hypotheses will be tested by behavioral testing with keypress tasks and high- resolution MRI scanning of matched groups (N=80 each) who are (1) active CDPA subjects, (2) long-term abstinent CDPA subjects, and (3) healthy volunteers. Brain structure and behavior will be specifically tested for differences between these three groups, and for altered relationships between structure and behavior to draw inferences on (a) whether structural measures in the DLPFC, INS, and amygdala can be connected to keypress behavior to approach and avoid goal-objects in healthy controls, and (b) whether abnormalities in CDPA subjects can be interpreted in terms of vulnerability, drug exposure, or compensatory responses. PUBLIC HEALTH RELEVANCE: Imaging of DLPFC and amygdala impact on relative preference in cocaine addiction A fundamental feature of drug addiction, such as cocaine dependence, is that the addicted individual shows a reduced range and depth to their interests; referred to as the "restricted behavioral repertoire" of addiction, this critical feature can be analogized to an investor who only buys one stock, as opposed to distributing investment risk across a broad range of stocks. Pioneering studies have suggested this clinical feature may be connected to abnormalities in brain structures involved with making judgments and decisions about reward and that this behavior-structure relationship may be a predisposition to drug use. The current project will directly test if a broad set of brain structures involved with decision-making about reward, are also abnormal structurally, and associated with the behavioral abnormality in cocaine addiction. This project will also seek to determine if this behavior-structure abnormality is related to the drug use itself, or potentially has features indicating it predates the drug-use.