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

 描述(由申请人提供)：对疾病严重性的自我意识受损(洞察力)与多种神经精神疾病的发病率增加和治疗结果较差有关。虽然对自知力的研究传统上仅限于精神障碍(如精神分裂症、躁狂症)，但新兴的理论和证据表明，这一结构可能也与药物成瘾高度相关。特别是，上瘾的人往往高估了他们与毒瘾相关的自我控制能力，低估了他们的神经认知障碍，并且在有必要的时候没有寻求治疗。在这个R21的应用中，我们提供了第一个关于药物成瘾的自知力障碍及其潜在神经生物学的直接调查。可卡因使用障碍(CUD)患者和匹配的健康对照组(HC)将完成一项全新的功能磁共振成像(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测做出反应。具体目标包括揭示CUD自知力受损的行为和神经相关性(任务和基线休息状态)，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这项任务。我们假设，这项fmri洞察任务将识别一组对成瘾严重程度缺乏洞察力的CUD亚群，在这些人中，这将与焦点和网络相关的缺陷有关。 吻侧前扣带回皮质延伸至腹内侧额前皮质(rACC/vmPFC)。这一区域，就其与个人的关联性而言，在成瘾和其他精神病态方面受到干扰，确实为研究洞察力提供了一个看似合理的候选区域。我们进一步假设，这种自知力受损及其潜在的功能缺陷将与社会认知功能降低和药物使用增加相关。综上所述，在这个项目中，我们将一个新认识的成瘾相关症状(洞察力)映射到调节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自知力受损的疾病(例如精神分裂症、躁狂症)，目的是找出一条共同的线索(洞察力)，将吸毒与这些其他障碍联系起来。更广泛地说，研究洞察力受损与核心社会认知功能的一般异常(即，将行为和情绪标记为与个人相关的标签，以及与rACC/vmPFC功能相关的情绪显著)，甚至有助于阐明健康中社会认知过程的基础科学。

 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.