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

基本信息

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
项目类别：
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

项目摘要

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) 是一种严重疾病，发病率和死亡率很高是所有精神疾病中最严重的。疾病通常发生在青春期，目前治疗效果令人失望，高达 50% 的患者在出院一年内需要再次住院。合并症发生率很高，高达 66% 的人同时患有强迫症（强迫症）。我们之前提出了 AN 的神经行为模型，该模型是根据已知的机制构建的强迫症，表明皮质纹状体异常，包括中皮质系统（MCS），是导致 AN 的高度强迫性特征，反过来又介导严格的、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) 和眶额皮质 (OFC)。在一个初步实验，我们成功地使用了一种新型的静息态功能连接磁共振成像（rs-fcMRI）方法来证明 MCS 中的功能连接与强迫之间的反比关系强迫症患者的症状。我们的早期数据也表明了 AN 中的这一发现。在本提案中，我们正在研究一种以前未应用于 AN 的多模式策略。我们将检查功能连接（通过 rs-fcMRI）和白质完整性（通过 DTI）并探索灌注（通过美国手语）。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。具体来说，我们将评估个人是否具有与健康同龄人相比，AN 腹侧纹状体 (VS) 之间的功能连接减少和眶额皮质（OFC）（通过 rs-fcMRI 测量），白质完整性降低，以减少为指标眶额白质分数各向异性 (FA)，以及 VS 和 OFC 灌注减少。我们将使用饮食来测量 MCS 连接性是否与强迫症状的程度相关障碍特异性强迫措施。我们将纵向研究连通性，评估急性治疗前后患有 AN 的个体。此外，我们将收集初步数据进行调查这种潜在的生物标志物与长期病程之间的关系。拟议的研究采用创新方法来研究 AN，重点关注 MCS，并通过在该领域实施新的神经影像技术。这种方法的显着优点是评估整个神经回路，从而改善对神经功能的推断。这项研究将为在大规模 R01 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影像学与临床结果相结合。因此，本研究的数据将提供 AN 研究项目的新基础，该项目研究神经模型作为基础了解并治疗这种毁灭性的疾病。