Interoceptive Dysregulation in Amphetamine Dependent Individuals

安非他明依赖者的内感受失调

• 批准号: 7797726
• 负责人: MARTIN P. PAULUS
• 金额: $ 15.31万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7797726
• 关键词: Address; Adolescent; Adult; Amphetamine Dependence; Amphetamines; Amygdaloid structure; Animals; Anterior; Attenuated; Behavior; Behavioral; Brain; Breathing; C Fiber; Cessation of life; Characteristics; Chronic; Cognitive; Cues; Dependence; Development; Disease remission; Drug Addiction; Drug usage; Economic Burden; Emotional; Etiology; Event; Exhibits; Feeling; Functional Magnetic Resonance Imaging; Functional disorder; Human; Illicit Drugs; Impulsivity; Individual; Insula of Reil; Intervention; Investigation; Lesion; Link; Marijuana; Methamphetamine; Modeling; Pattern; Pharmaceutical Preparations; Physiological; Play; Population; Process; Property; Relapse; Relative (related person); Reporting; Research; Role; Self Destructive Behavior; Self Efficacy; Smoke; Staging; Stimulus; Stroke; Structure; Substance Addiction; System; Testing; Ventral Striatum; Visual; base; comparison group; craving; cue reactivity; experience; flexibility; high risk; neuroimaging; psychologic; relating to nervous system; research study; response; sobriety; stimulus processing; theories

Project 2: After marijuana, amphetamines are the most widely used illicit drug class woridwide and recent evidence shows that methamphetamine causes about 895 deaths per year in the U.S. and is responsible for an annual economic burden of $23.5 billion. Interoception comprises the sensing of the physiological condition of the body, consciously representing this internal state within the context of ongoing activities, and inifiating mofivated action to homeostatically regulate this state. Previous investigations have shown that individuals with insular lesions reported they had "lost the urge to smoke," and our results indicate that attenuated activation in insula was related to an increase propensity to relapse. Although this links interoception to insular functioning abnormalities to drug addiction, the precise role of interoception in drug addiction is unclear. To test the hypothesis that dysregulated insular cortex function in amphetamine dependent (AD) individual results in an insufficient, instable, or non-adaptive adjustment to perturbations of the internal state, we will examine using event-related fMRI the neural processing of: (1) direct interoceptive stimulation during positively valenced and negatively valenced interoceptive stimuli, and (2) internally generated interoceptive stimulation using cue reactivity paradigms. The behavioral and brain response characteristics will be examined during: (a) anticipation, (b) stimulation, and (c) post-stimulus processing. The specific aims are: (1) To determine the status of the interocepfive system in response to positively and negatively valenced interoceptive sfimuli in adults with AD, adults in full sustained remission, and healthy comparison subjects; (2) To determine the sensifivity of the interoceptive system in response to internally generated interoceptive sfimulafion using cue reactivity in AD individuals, those in full sustained remission, and healthy comparison subjects; (3) To modify the neuroimaging paradigms in response to the animal studies (Project 3) and results from Wave 1 human studies to determine whether negafive or positively valenced interocepfive stimulation modulates cue reactivity in AD individuals at various stages of drug use. The clarification of the role of interocepfion and insular cortex functioning in various stages of amphetamine dependence would help to identify a "vulnerability window" when individuals are at high risk for relapse. Determining whether there is an altered valence-specific sensitivity of the interoceptive system in AD would help to select specific sfimulus materials for cognitive and emotional intervention approaches. Elucidafing the relationship betiA/een interoceptive dysfunctions and other psychological constructs, e.g. craving and selfefficacy, will help to relate interoception to existing theories of drug addiction.

项目 2：安非他明是继大麻之后全球范围内最近使用最广泛的非法药物类别 有证据表明，甲基苯丙胺每年在美国导致约 895 人死亡，并导致 每年经济负担达235亿美元。内感受包括生理感觉 身体状况，在正在进行的活动的背景下有意识地表现这种内部状态，以及 启动动机行动来稳态调节这种状态。此前的调查表明 患有岛叶病变的个体报告说他们“失去了吸烟的冲动”，我们的结果表明 岛叶激活减弱与复发倾向增加有关。虽然这个链接 内感受对岛叶功能异常和药物成瘾的影响，内感受在药物中的精确作用 成瘾情况尚不清楚。检验安非他明中岛叶皮质功能失调的假设 依赖（AD）个体会导致对扰动的调整不足、不稳定或非适应性 对于内部状态，我们将使用事件相关的功能磁共振成像来检查以下神经处理：（1）直接内感受 正价和负价内感受刺激期间的刺激，以及（2）内部 使用线索反应范式产生内感受刺激。行为和大脑反应 将在以下过程中检查特征：（a）预期，（b）刺激，以及（c）刺激后处理。 具体目标是：（1）确定内感受系统的状态，以响应积极和 AD 成人、完全持续缓解的成人和健康人的负价内感受刺激 比较对象； (2) 确定内感受系统对内部反应的敏感性 使用 AD 个体、完全持续缓解的个体的提示反应性产生内感受刺激， 和健康的对照受试者； (3) 修改神经影像范式以响应动物 研究（项目 3）和第一波人体研究的结果，以确定是消极的还是积极的 价间感受器刺激调节 AD 个体在药物使用的各个阶段的提示反应性。 澄清间脑皮质和岛叶皮质在安非他命各个阶段的功能 当个体处于复发高风险时，依赖性将有助于确定“脆弱窗口”。 确定 AD 中内感受系统的价特异性敏感性是否发生改变 帮助选择用于认知和情绪干预方法的特定刺激材料。阐明 内感受功能障碍与其他心理结构之间的关系，例如渴望和自我效能感， 将有助于将内感受与现有的毒瘾理论联系起来。