Multimodal Imaging of the Mesocortical System in Anorexia Nervosa

神经性厌食症中皮层系统的多模态成像

• 批准号: 8638552
• 负责人: Jonathan E Posner
• 金额: $ 22.1万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-13 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8638552
• 关键词: Acute; Address; Adolescence; Anisotropy; Anorexia Nervosa; Biological Markers; Biological Neural Networks; Brain; Brain region; Cerebrum; Characteristics; Clinical; Comorbidity; Data; Development; Diffusion Magnetic Resonance Imaging; Eating Behavior; Eating Disorders; Ensure; Foundations; Functional disorder; Grant; Hospitalization; Image; Individual; Inpatients; Link; Literature; Magnetic Resonance Imaging; Measures; Mediating; Methods; Modeling; Morbidity - disease rate; Morphologic artifacts; Multimodal Imaging; Neurophysiology - biologic function; Obsessive-Compulsive Disorder; Outcome; Patients; Perfusion; Phase; Research; Rest; Risk Factors; Ritual compulsion; Spin Labels; Starvation; Structure; Suggestion; Symptoms; System; Techniques; Testing; Underweight; Ventral Striatum; Ventral Tegmental Area; Weight; base; design; follow-up; improved; indexing; innovation; lens; longitudinal design; mortality; neural circuit; neural model; neurobehavioral; neuroimaging; neuromechanism; novel; outcome forecast; peer; prognostic; programs; public health relevance; relating to nervous system; research study; restoration; severe mental illness; trait; white matter

Anorexia nervosa (AN) is a serious illness associated with substantial morbidity and a mortality rate among the highest of any psychiatric illness. Illness commonly develops in adolescence, and current treatments are disappointing, with up to 50% of patients requiring re-hospitalization within a year of discharge. Comorbidity rates are high, with up to 66% of individuals also suffering from obsessive compulsive disorder (OCD). We have previously proposed a neurobehavioral model of AN, building from known mechanisms of OCD, suggesting that corticostriatal abnormalities, including the mesocortical system (MCS), underlie the highly obsessional characteristic of AN which, in turn, mediates rigid, ritualized eating behaviors that promote the underweight state. The MCS includes the ventral striatum (VS), and the orbitofrontal cortex (OFC). In a preliminary experiment, we successfully used a novel resting state functional connectivity MRI (rs-fcMRI) approach to demonstrate an inverse relationship between functional connectivity in the MCS and obsessional symptoms in individuals with OCD. Our early data suggest this finding in AN, as well. In this proposal, we are investigating a multimodal strategy that has not previously been applied to AN. We will examine functional connectivity (via rs-fcMRI) and white matter integrity (via DTI) and explore perfusion (via ASL). By combining imaging approaches, we will integrate functional and structural connectivity. We propose to study neurocircuitry in the acute phase of AN as well as after weight restoration to begin to evaluate the prognostic significance and stability of these findings. Specifically, we will evaluate whether individuals with AN, as compared with healthy peers, have reduced functional connectivity between the ventral striatum (VS) and orbitofrontal cortex (OFC) as measured by rs-fcMRI, reduced white matter integrity, as indexed by reduced fractional anisotropy (FA), in the orbitofrontal white matter, and reduced perfusion to the VS and OFC. We will measure whether MCS connectivity is associated with degree of obsessional symptoms, using an eating disorder specific obsessive-compulsive measure. We will study connectivity longitudinally, evaluating individuals with AN before and after acute treatment. In addition, we will collect preliminary data to investigate the relationship between this potential biomarker and longer-term course. The proposed study takes an innovative approach to the study of AN by focusing on the MCS, and by implementing new neuroimaging techniques for the field. This approach has the significant advantage of evaluating the neural circuit as a whole, thereby improving inferences about neural functioning. This study will create a foundation for using these techniques in a large scale R01 that will be able to definitively identify neural biomarkers and integrate neuroimaging with clinical outcome. Thus the data from this study will provide a new foundation for a program of research in AN that investigates neural models as the basis for understanding and treating this devastating illness.

神经性厌食症（AN）是一种严重的疾病，与大量发病率和死亡率相关 在任何精神病中最高的。疾病通常在青春期发展，并且 治疗令人失望，多达50％的患者需要在出院一年内重新住院。 合并症率很高，多达66％的人也患有强迫症 （OCD）。我们以前曾提出了AN的神经行为模型，该模型是根据已知机制构建的 强迫症，表明皮质纹状体异常，包括中皮层系统（MCS），是 高度痴迷的特征，反过 体重不足状态。 MCS包括腹侧纹状体（VS）和眶额皮层（OFC）。在 初步实验，我们成功使用了一种新型的静止状态功能连通性MRI（RS-FCMRI） 证明MC中功能连接性与痴迷之间的功能连通性之间的反比关系的方法 强迫症患者的症状。我们的早期数据也表明了AN的发现。 在此提案中，我们正在研究一种多模式策略，该策略以前尚未应用于AN。我们 将检查功能连接性（通过RS-FCMRI）和白质完整性（通过DTI）并探索灌注 （通过ASL）。通过结合成像方法，我们将整合功能和结构连接性。我们 提议在重量恢复的急性阶段研究神经记录，以开始评估 这些发现的预后意义和稳定性。具体来说，我们将评估是否有 与健康的同龄人相比，AN的腹侧纹状体（VS）之间的功能连通性降低了 通过RS-FCMRI测量的ORBITROFRONTAL CORTEX（OFC），降低了白质完整性，如降低而索引 分数各向异性（FA），在眶额白质中，并减少了VS和OFC的灌注。我们将 测量MCS连通性是否与痴迷症状相关，并使用饮食 障碍特定的强迫态度。我们将纵向研究连接性，评估 患有急性治疗前后的个体。此外，我们将收集初步数据以调查 这种潜在的生物标志物与长期过程之间的关系。 拟议的研究通过关注MC和通过 为该领域实施新的神经影像技术。这种方法具有重要的优势 整体评估神经回路，从而提高了有关神经功能的推论。这项研究会 为在大规模R01中使用这些技术创建基础 神经生物标志物并将神经影像与临床结果整合。因此，这项研究的数据将提供 研究神经模型的研究计划的新基础 了解和治疗这种毁灭性疾病。