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

描述(申请人提供)：DLPFC和杏仁核对可卡因成瘾患者相对偏好的影响的成像研究摘要最近，关于大脑结构测量和奖赏/厌恶加工的关系的研究开始出现。研究表明，大脑结构的改变与上瘾时改变的方法和回避行为有关，但面临的一个挑战是，很难解释这些发现是否与(I)易感因素、(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涌现，这些结果表明我们可以开发和测试假设，以权衡对脆弱性、药物暴露/损害或补偿的解释。我们建议评估大脑结构与相对偏好的按键测量的关系，包括强烈厌恶的测量，并确定研究结果是否可以扩展到健康对照，或与易感因素、药物暴露迹象或可卡因依赖多物质滥用(CDPA)受试者的代偿反应有关。我们将专门针对杏仁核、脑岛(INS)和背外侧前额叶皮质(DLPFC)，因为这些区域中的每一个在功能上都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：(1)杏仁核与易损性有关，(2)INS与药物暴露有关，(3)DLPFC与代偿反应有关。这些假设将通过行为测试和高分辨率MRI扫描进行验证，匹配组(N=80)是(1)活跃的CDPA受试者、(2)长期禁欲的CDPA受试者和(3)健康志愿者。大脑结构和行为将被专门测试这三组之间的差异，以及结构和行为之间的变化关系，以得出以下推断：(A)DLPFC、INS和杏仁核中的结构测量是否可以与健康对照组的按键行为联系起来，以接近和避免目标对象，以及(B)CDPA受试者的异常是否可以从脆弱性、药物暴露或代偿反应的角度进行解释。 公共卫生相关性：DLPFC和杏仁核对可卡因成瘾相对偏好的影响成像吸毒成瘾的一个基本特征，如可卡因依赖，是成瘾者对其兴趣的范围和深度减少；被称为成瘾的“受限行为曲目”，这一关键特征可以比喻为只购买一只股票的投资者，而不是将投资风险分散到广泛的股票上。开创性的研究表明，这种临床特征可能与涉及对奖励做出判断和决定的大脑结构异常有关，这种行为-结构关系可能是药物使用的倾向。目前的项目将直接测试参与奖励决策的广泛大脑结构是否在结构上也是异常的，并与可卡因成瘾的行为异常有关。该项目还将寻求确定这种行为结构异常是否与药物使用本身有关，或者可能具有表明其早于药物使用的特征。

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.