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，具有相当高的发病率和死亡率，是所有精神疾病中最高的。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(OCD)。我们之前已经提出了一个强迫症的神经行为模型，建立在已知的强迫症机制的基础上，认为包括中皮质系统(MCS)在内的皮质纹状体异常是强迫症高度强迫特征的基础，而这反过来又介导了促进体重不足状态的僵硬、仪式化的进食行为。MCS包括腹侧纹状体(VS)和眶前叶皮质(OFC)。在初步实验中，我们成功地使用了一种新的静息状态功能连接性磁共振成像(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症状之间存在反向关系。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。我们将检查功能连接(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，我们将评估与健康同龄人相比，患有AN的患者是否存在rs-fcMRI测量的腹侧纹状体(VS)和眼眶额叶皮质(OFC)之间的功能连接降低，以减少的分数各向异性(FA)为指标的眼眶前额白质白质完整性降低，以及VS和OFC的血流灌注减少。我们将使用进食障碍专用强迫症测量MCS连接性是否与强迫症的程度相关。我们将纵向研究连接性，评估急性治疗前后的个体。此外，我们将收集初步数据，以调查这一潜在的生物标志物与长期病程之间的关系。这项拟议的研究采用了一种创新的方法来研究AN，重点放在MCS上，并为该领域实施了新的神经成像技术。这种方法具有评估神经回路作为一个整体的显著优势，从而改进了对神经功能的推断。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，这项研究的数据将为AN的研究计划提供新的基础，该计划调查神经模型，作为理解和治疗这种毁灭性疾病的基础。