Neurocircuitry of impaired insight in addiction: relevance to aberrant self-related processing

成瘾洞察力受损的神经回路：与异常自我相关处理的相关性

• 批准号: 8948519
• 负责人: Scott J Moeller
• 金额: $ 25.13万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8948519
• 关键词: Acquaintances; Affective; Alcohols; Amygdaloid structure; Anterior; Awareness; Basic Science; Behavior; Behavior Control; Behavior assessment; Behavioral; Brain; Brodmann' s area; Choice Behavior; Chronic; Clinical; Cocaine; Cognitive; Color; Conflict (Psychology); Consummatory Behavior; Contrast Media; Control Groups; Corpus striatum structure; Data; Disease; Drug Addiction; Drug Use Disorder; Drug usage; Eating; Emotional; Emotions; Environment; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Health; Hippocampus (Brain); Human; Impairment; Individual; Intervention Studies; Interviewer; Investigation; Judgment; Link; Manic; Maps; Marijuana; Measures; Mediating; Monitor; Morbidity - disease rate; Motivation; Neurobiology; Neurocognitive Deficit; Participant; Patient Self-Report; Pattern; Pharmaceutical Preparations; Prefrontal Cortex; Process; Psychopathology; Psychotic Disorders; Relative (related person); Reporting; Research; Rest; Scanning; Schizophrenia; Seeds; Self Perception; Self-control as a personality trait; Severities; Severity of illness; Subgroup; Symptoms; Testing; Time; Treatment outcome; Validation; addiction; base; behavioral impairment; cingulate cortex; cocaine use; cognitive function; cognitive process; improved; indexing; insight; instrument; interest; neural circuit; neural correlate; neuropsychiatry; public health relevance; response; social; theories

 DESCRIPTION (provided by applicant): Impaired self-awareness of illness severity (insight) is associated with increased morbidity and poorer treatment outcome across multiple neuropsychiatric diseases. Although the study of insight has traditionally been limited to psychotic disorders (e.g., schizophrenia, mania), emerging theory and evidence suggest that this construct may also be highly relevant to drug addiction. In particular, addicted individuals often overestimate their addiction-related self-control, underestimate their neurocognitive impairments, and fail to seek treatment when it is warranted. In this R21 application, we provide the first direct investigation of insight impairment in drug addiction and its underlying neurobiology. Individuals with cocaine use disorder (CUD) and matched healthy controls (HC) will complete a brand-new functional magnetic resonance imaging (fMRI) insight task, during which they will respond to probes about the severity of their drug use. Specific Aims include uncovering the behavioral and neural correlates (both task and baseline resting-state) of impaired insight in CUD, and then validating this task via measures of social-cognitive functioning (self-awareness and emotional awareness) and drug use. We hypothesize that this fMRI insight task will identify a subpopulation of CUD with impaired insight into their addiction severity, which in these individuals will be associated with focal- and network-related deficits of the rostral anterior cingulate cortex extending into the ventromedial prefrontal cortex (rACC/vmPFC). This region, insofar as it mediates personal relevance and is disrupted in addiction and other psychopathologies, indeed provides a plausible candidate region for studying insight. We further hypothesize that this insight impairment and its underlying functional deficits will correlate with reduced social-cognitive functioning and increased drug use. Taken together, in this project we map a newly appreciated addiction- related symptom (insight) onto functional deficits of corticolimbic circuitry that mediate self-related processing. This approach can then be applied to other diseases of impaired insight (e.g., schizophrenia, mania), with the goal of identifying a common thread (insight) that links drug addiction with these other disorders. Even more broadly, studying impaired insight vis-à-vis general abnormalities of core social-cognitive functioning (i.e., tagging behavior and emotions with personal relevance and emotional salience in association with rACC/vmPFC function) could even help illuminate the basic science of social-cognitive processing in health.

 描述（由申请人提供）：对疾病严重程度（洞察力）的自我意识受损与多种神经精神疾病的发病率增加和治疗结局较差相关。虽然洞察力的研究传统上仅限于精神障碍（例如，精神分裂症，躁狂症），新兴的理论和证据表明，这种结构也可能与药物成瘾高度相关。特别是，成瘾者往往高估了他们与成瘾相关的自我控制能力，低估了他们的神经认知障碍，并且在必要时不寻求治疗。在这个R21应用程序中，我们提供了第一个直接调查药物成瘾及其基础神经生物学的洞察力障碍。患有可卡因使用障碍（CUD）的个体和匹配的健康对照（HC）将完成一项全新的功能性磁共振成像（fMRI）洞察任务，在此期间，他们将对有关其药物使用严重程度的探针做出反应。具体目标包括揭示CUD中洞察力受损的行为和神经相关性（任务和基线静息状态），然后通过社会认知功能（自我意识和情绪意识）和药物使用的测量来验证此任务。我们假设这个fMRI洞察力任务将识别一个CUD亚群，他们对成瘾严重程度的洞察力受损，在这些个体中，这将与局部和网络相关的缺陷有关， 前扣带皮层延伸到腹内侧前额叶皮层（rACC/vmPFC）。这个区域，因为它调节个人相关性，并且在成瘾和其他精神病理学中被破坏，确实为研究洞察力提供了一个合理的候选区域。我们进一步假设，这种洞察力障碍及其潜在的功能缺陷将与社会认知功能下降和药物使用增加相关。总之，在这个项目中，我们将一个新认识的成瘾相关症状（洞察力）映射到介导自我相关处理的皮质边缘回路的功能缺陷上。 然后，这种方法可以应用于其他洞察力受损的疾病（例如，精神分裂症，躁狂症），目的是确定一个共同的线索（洞察力），连接药物成瘾与这些其他疾病。更广泛地说，研究受损的洞察力与核心社会认知功能的一般异常（即，用与rACC/vmPFC功能相关的个人相关性和情绪显著性来标记行为和情绪）甚至可以帮助阐明健康中的社会认知处理的基础科学。