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.

神经性厌食症是一种严重的疾病，其发病率和死亡率都很高。 在所有精神疾病中名列前茅。疾病通常发生在青春期，目前 治疗方法令人失望，多达50%的患者需要在出院一年内再次住院。 共病发生率很高，高达66%的人还患有强迫症 (强迫症)。我们之前已经提出了一个AN的神经行为模型，建立在已知的 强迫症，提示皮质纹状体异常，包括中皮质系统(MCS)，是 强迫症的高度强迫症的特征，反过来，它调解僵化的、仪式化的饮食行为，从而促进 体重不足的状态。MCS包括腹侧纹状体(VS)和眶前叶皮质(OFC)。在一个 初步实验中，我们成功地使用了一种新型的静息功能连接磁共振成像(rs-fcmri)。 MCS中功能连通性与强迫症之间负相关关系的论证方法 强迫症患者的症状。我们的早期数据也表明了这一发现。 在这项提案中，我们正在调查一种以前从未应用过的多式联运战略。我们 将检查功能连通性(通过rs-fcMRI)和脑白质完整性(通过DTI)并探索血流灌注。 (通过ASL)。通过结合成像方法，我们将整合功能和结构连接。我们 建议研究AN急性期和体重恢复后的神经回路以开始评估 这些发现的预后意义和稳定性。具体地说，我们将评估患有 与健康的同龄人相比，AN降低了腹侧纹状体(VS)之间的功能连接 和眼眶前额叶皮质(OFC)，由RS-fcMRI测量，白质完整性降低，以减少为指标 眼眶前部白质的分数各向异性(FA)，VS和OFC的灌注量减少。我们会 使用进食测量MCS连接性是否与强迫症的程度相关 障碍特有的强迫症测量。我们将纵向研究互联互通，评估 治疗前后有急性发作的个体。此外，我们还将收集初步数据进行调查 这一潜在的生物标志物与长期病程之间的关系。 拟议的研究采用了一种创新的方法来研究AN，重点是MCS，并通过 为该领域实施新的神经成像技术。这种方法具有显著的优势，即 将神经回路作为一个整体进行评估，从而改进对神经功能的推断。这项研究将 为在大规模R01中使用这些技术奠定基础，R01将能够明确地识别 神经生物标记物，并将神经成像与临床结果相结合。因此，这项研究的数据将提供 AN研究计划的新基础，该计划调查神经模型作为基础 理解和治疗这种毁灭性的疾病。