Interoceptive Dysregulation in Amphetamine Dependent Individuals

安非他明依赖者的内感受失调

• 批准号: 8234858
• 负责人: MARTIN P. PAULUS
• 金额: $ 12.34万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8234858
• 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; addiction; 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：继大麻之后，安非他明是世界范围内和最近使用最广泛的非法药物类别 有证据表明，甲基苯丙胺在美国每年造成约895人死亡， 每年经济负担235亿美元。内感受包括对生理信号的感知。 身体的状况，在持续活动的背景下有意识地代表这种内部状态， inifiating mofivated行动，以稳态调节这种状态。此前的调查显示， 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， 减弱的活化与复发倾向的增加有关。虽然这一链接 内感受对岛叶功能异常对药物成瘾的影响，内感受在药物成瘾中的确切作用 上瘾是不明确的。为了验证安非他明导致岛叶皮质功能失调的假设， 依赖性（AD）个体导致对干扰的不充分、不稳定或非适应性调整， 内部状态，我们将使用事件相关功能磁共振成像检查的神经加工：（1）直接内感受性 在正价和负价内感受性刺激期间的刺激，和（2）内部 使用线索反应性范例产生内感受性刺激。行为和大脑反应 将在（a）预期、（B）刺激和（c）刺激后处理期间检查特征。 具体目标是：（1）确定内部监督制度的地位， AD成人、完全持续缓解成人和健康成人中的负价内感受性sfimuli （2）确定内感受系统对内部刺激的敏感性。 在AD个体中使用线索反应性产生内感受性sfimulafion，这些个体处于完全持续缓解期， （3）根据动物的行为改变神经影像学范式， 研究（项目3）和第1波人体研究的结果，以确定是否为阴性或阳性 效价interocepfive刺激调节线索反应性在AD个体在不同阶段的药物使用。 脑内和岛叶皮质在苯丙胺不同阶段的作用 依赖性将有助于确定一个“脆弱性窗口”，即个人复发的高风险。 确定AD中内感受系统是否存在改变的价特异性敏感性， 帮助选择特定的sfimulus材料进行认知和情感干预。Elucidafing 甚至内感受性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， 将有助于将内感受与现有的药物成瘾理论联系起来。