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Transdiagnostic Multimodal 7 Tesla MRI of the Locus Coeruleus in Human Pathological Anxiety

人类病理性焦虑中蓝斑的跨诊断多模态 7 特斯拉 MRI

基本信息

批准号：
10535458
负责人：
Priti Balchandani
金额：
$ 52.04万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-15 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10535458
关键词：
Address Anatomy Animal Model Anxiety Anxiety Disorders Architecture Arousal Brain Cell Nucleus Characteristics Clinical Collaborations Data Diagnosis Diagnostic Diffusion Magnetic Resonance Imaging Dimensions Disease Fright Functional Magnetic Resonance Imaging Functional disorder Generalized Anxiety Disorder Human Image Laboratories Link Magnetic Resonance Imaging Maps Measurement Measures Medial Metric System Midbrain structure Modeling Multimodal Imaging National Institute of Mental Health Negative Valence Neurites Neuroanatomy Norepinephrine Panic Disorder Pathological anxiety Patients Post-Traumatic Stress Disorders Pre-Clinical Model Prefrontal Cortex Psychopathology Questionnaires Regulation Research Research Domain Criteria Resolution Role Source Structure Subgroup System Translational Research United States Variant Work anxiety symptoms anxious clinical anxiety clinical diagnosis clinical predictors connectome density design diagnostic strategy human disease human imaging human model in vivo in-vivo diagnostics innovation locus ceruleus structure mood symptom multimodality neural circuit neuropsychiatric disorder neuropsychiatry non-invasive imaging novel novel therapeutics patient population precision medicine response stress related disorder tractography ultra high resolution

项目摘要

Anxiety and stress-related disorders, including panic disorder (PD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD), are among the most disabling neuropsychiatric conditions in the United States. A core feature of these disorders is pathological anxiety (i.e., maladaptive arousal and fear). Animal models point strongly towards shared mechanisms underlying pathological anxiety to involve the locus coeruleus (LC), the primary source of norepinephrine in the CNS, and modulator of the regulation of arousal and response to threat. However, the specific role of the LC in human pathological anxiety is not known, due in part to past technical limitations of non-invasive imaging for small nuclei such as the LC. Thus, despite the prevailing hypothesis of the role of the LC, the pathophysiology of anxiety disorders remains largely undiscovered. This gap impedes translational research aimed at developing more biologically based models of human anxiety and stress-related disorders, precluding precision medicine for these disorders. In order to address this gap, we propose to the first transdiagnostic in vivo study of LC in anxiety, leveraging cutting-edge 7 Tesla (7 T) MRI in patients with PD, PTSD, GAD. Our central hypothesis is that LC dysregulation underlies shared dimensions of psychopathology across neuropsychiatric disorders that are characterized by pathological anxiety. Here we develop and apply MRI innovations for 7 T structural, connectomic, and functional characterization of the LC in terms of drivers of pathological anxiety across diagnostic boundaries. Our 7 T MRI approach affords on the order of three-fold higher resolution and sensitivity over 3 T MRI for multi- modal imaging the LC in patient populations. Our preliminary 7 T MRI data demonstrate the neuroanatomical and functional architecture of LC and connected cortico-subcortical circuitry robustly characterized in both patients and controls. Using quantitative magnetization transfer (MT) imaging and neurite orientation dispersion density imaging (NODDI), our proposal will allow for the precise localization, quantification and microstructural characterization of the LC in humans. Building on our pilot data, Aim 1 will establish the role of LC microstructure in pathological anxiety. Aim 2 will establish the relationship between LC functional and anatomical connectivity and pathological anxiety. Aim 3 will establish the role of LC in functional response to threat in pathological anxiety. In each case, co-variance between imaging measures of the LC and dimensional measures of anxiety will be examined trans-diagnostically across four study groups [PTSD (n=30), PD (n=30), GAD (n=30), healthy controls (N=30)] in a cross-sectional design. Secondarily, between-group differences will be examined. Finally, in Aim 4, we will use a data-driven approach to explore how specific measures of LC microstructure, connectivity, and function relate to specific dimensional clinical features across diagnoses.

焦虑和压力相关障碍，包括恐慌症（PD）、广泛性焦虑症（GAD）、