Multimodal Imaging of the Mesocortical System in Anorexia Nervosa

神经性厌食症（AN）是一种严重的疾病，与大量的发病率和死亡率 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%的患者在出院后一年内需要再次住院。 共患病率很高，高达66%的人同时患有强迫症 （强迫症）。我们之前已经提出了一个神经行为模型的AN，从已知的机制， 强迫症，这表明皮质纹状体异常，包括中皮质系统（MCS），是 AN的高度强迫性特征，反过来，它介导了刚性的，仪式化的饮食行为， 体重不足的状态。MCS包括腹侧纹状体（VS）和眶额皮质（OFC）。中 初步实验，我们成功地使用了一种新的静息态功能连接MRI（rs-fcMRI） 一种方法来证明MCS的功能连接和强迫症之间的反比关系， 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）和白色物质完整性（通过DTI），并探索灌注 (via 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开始的神经回路，以评估 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与 与健康的同龄人相比，AN的腹侧纹状体（VS）之间的功能连接减少 和眶额皮质（OFC），如通过rs-fcMRI测量的，减少的白色物质完整性，如通过减少的 眶额白色物质的各向异性分数（FA），VS和OFC的灌注减少。我们将 测量MCS连通性是否与强迫症状的程度相关，使用进食 强迫症的具体措施。我们将纵向研究连通性，评估 急性治疗前后的AN患者。此外，我们将收集初步数据， 这种潜在的生物标志物与长期病程之间的关系。 拟议的研究采取了创新的方法来研究AN，重点是MCS，并通过 在这个领域应用新的神经成像技术。这种方法具有以下显著优点： 评估神经回路作为一个整体，从而改善有关神经功能的推断。本研究将 为在大规模R 01中使用这些技术奠定基础， 神经生物标志物和整合神经影像学与临床结果。因此，本研究的数据将提供 一个新的基础，为一个研究计划，研究神经模型的基础上， 了解和治疗这种毁灭性的疾病。

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.