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

DLPFC 和杏仁核成像对可卡因成瘾相对偏好的影响

• 批准号: 7776495
• 负责人: HANS C BREITER
• 金额: $ 42.84万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7776495
• 关键词: Abstinence; Amygdaloid structure; Animals; Aversive Stimulus; Behavior; Behavioral; Brain; Clinical; Cocaine; Cocaine Dependence; Complex; Data; Decision Making; Deltastab; Development; Disease; Drug Addiction; Drug Exposure; Drug usage; Financial compensation; Functional Imaging; Goals; Human; Image; Individual; Insula of Reil; Intelligence; Investments; Judgment; Literature; MRI Scans; Matched Group; Measures; Pharmaceutical Preparations; Predisposition; Prefrontal Cortex; Process; Relative (related person); Resolution; Rewards; Risk; Structure; Testing; Thick; Weight; Work; abstracting; active control; addiction; approach avoidance behavior; base; behavior test; healthy volunteer; interest; neuroimaging; polysubstance abuse; preference; public health relevance; response

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.

描述（由申请人提供）：DLPFC和杏仁核的成像对可卡因成瘾的相对偏好摘要相对较最近，对大脑结构测量与奖励/厌恶处理的关系的研究开始出现。研究表明，在成瘾中与改变方法和回避行为的关系发生变化的研究之一是，很难解释发现与（i）脆弱性因素相关，（ii）药物暴露/损害的影响，或（iii）对疾病的补偿性反应。从文献中，出现了有关结构不对称性，与行为的相关性以及对禁欲的反应的结果，这表明我们可以开发和检验假设对脆弱性，药物暴露/损害或补偿的重量解释。我们建议评估大脑结构与键键率的相对偏好度量的关系，包括强烈厌恶，并确定发现是否可以扩展到健康对照，或与脆弱性因素，药物暴露的迹象或可卡因依赖性多进取的滥用滥用（CDPA）受试者中的疾病相关。我们将特别针对杏仁核，岛（INS）和背外侧前额叶皮层（DLPFC），鉴于这些区域中的每个区域都与基于相对偏好或与CDPA主题中的键盘任务相关的与判断和决策有关的关键任务进行了功能连接。我们预测：（1）杏仁核与脆弱性有关，（2）INS与药物暴露有关，以及（3）DLPFC与补偿性反应有关。这些假设将通过按键任务进行行为测试和高分辨率的MRI扫描（n = 80）（每个）为（1）主动CDPA受试者，（2）长期禁止CDPA受试者和（3）健康志愿者。将对这三组之间的差异进行特殊测试，以及结构和行为之间的关系改变，以提出（a）DLPFC，INS和杏仁核中的结构测量是否可以连接到Keypress行为，以接近接近并避免对健康控制中的目标对象进行依靠CDPA型在CDPA中的侵蚀性，并且是否可以对CDPA进行反应，以示意CDPA的反应。 公共卫生相关性：DLPFC和杏仁核对可卡因成瘾的相对偏好的影响，例如可卡因依赖性的药物成瘾的基本特征，即上瘾的个体对他们的利益显示出降低的范围和深度；这一关键特征被称为成瘾的“行为库”，可以类似于仅购买一张股票的投资者，而不是在广泛的股票上分配投资风险。开创性的研究表明，这种临床特征可能与大脑结构的异常有关，涉及判断和决定奖励，并且这种行为结构关系可能是药物使用的倾向。当前的项目将直接测试与奖励决策有关的一系列大脑结构，在结构上也异常，并且与可卡因成瘾中的行为异常有关。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，或者可能具有可能早于药物使用的特征。