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: 8791346
• 负责人: Jonathan E Posner
• 金额: $ 24.54万
• 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 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8791346
• 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; Health; 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 behavior; Obsessive-Compulsive Disorder; Outcome; Patients; Perfusion; Phase; Research; Research Domain Criteria; 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; relating to nervous system; research study; restoration; severe mental illness; trait; white matter

DESCRIPTION (provided by applicant): 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 relationshp 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.

描述（由申请人提供）：神经性厌食症（AN）是一种严重的疾病，发病率和死亡率在所有精神疾病中最高。疾病通常发生在青春期，目前的治疗方法令人失望，高达50%的患者在出院后一年内需要再次住院。 共病率很高，高达66%的人也患有强迫症（OCD）。我们以前提出了一个神经行为模型的AN，从已知的机制强迫症，表明皮质纹状体异常，包括中皮层系统（MCS），根据高度强迫症的特征AN，反过来，介导刚性，仪式化的饮食行为，促进体重不足的状态。MCS包括腹侧纹状体（VS）和眶额皮质（OFC）。在初步实验中，我们成功地使用了一种新型的静息状态功能连接性MRI（rs-fcMRI）方法来证明MCS中的功能连接性与强迫症患者的强迫症状之间的负相关关系。我们的早期数据也表明了AN中的这一发现。 在这个建议中，我们正在研究一个多模式的战略，以前没有被应用到AN。我们将检查功能连接（通过rs-fcMRI）和白色物质的完整性（通过DTI），并探讨灌注（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急性期以及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。具体而言，我们将评估与健康同龄人相比，AN个体是否具有通过rs-fcMRI测量的腹侧纹状体（VS）和眶额皮质（OFC）之间的功能连接性降低，通过减少的眶额白色物质的各向异性分数（FA）以及VS和OFC的灌注减少来指示的白色物质完整性降低。我们将测量MCS连接是否与强迫症状的程度相关，使用进食障碍特异性强迫测量。我们将纵向研究连接性，评估急性治疗前后的AN患者。此外，我们将收集初步数据，以研究这种潜在的生物标志物和长期病程之间的关系。 拟议的研究采取了创新的方法来研究AN，重点是MCS，并通过实施新的神经影像学技术的领域。这种方法的显著优点是可以从整体上评估神经回路，从而改善对神经功能的推断。这项研究将为在大规模R 01中使用这些技术奠定基础，从而能够明确识别神经生物标志物并将神经成像与临床结果相结合。因此，这项研究的数据将为AN的一项研究计划提供新的基础，该计划将研究神经模型作为理解和治疗这种毁灭性疾病的基础。