Habenula Developmental Trajectories in the ABCD Study

ABCD 研究中的缰核发育轨迹

• 批准号: 10378700
• 负责人: Benjamin Adam Ely
• 金额: $ 25.2万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10378700
• 关键词: Address; Adolescence; Adolescent; Adolescent Development; Adult; Affective; Age; Amygdaloid structure; Anhedonia; Anxiety; Anxiety Disorders; Area; Behavior Disorders; Brain; Child Health; Chronic; Clinical; Clinical Data; Data; Development; Disease; Epithalamic structure; Exhibits; Family; Functional Magnetic Resonance Imaging; Future; Habenula; Human; Hypersensitivity; Image; Insula of Reil; Knowledge; Laboratories; Life; Link; Longevity; Machine Learning; Magnetic Resonance Imaging; Measures; Mental Depression; Mental Health; Mental disorders; Methodology; Methods; Modeling; Mood Disorders; Morbidity - disease rate; Motivation; Motor; National Institute of Mental Health; Neurosciences; Nonparametric Statistics; Nucleus Accumbens; Onset of illness; Outcome; Pattern; Pharmaceutical Preparations; Play; Population; Prevalence; Procedures; Process; Psychiatric Diagnosis; Public Health; Recording of previous events; Research; Resolution; Rest; Rewards; Role; Sampling; Scheme; Severities; Shock; Signal Transduction; Socioeconomic Status; Stimulus; Strategic Planning; Structure; Surface; Symptoms; System; Techniques; Time; Ventral Tegmental Area; Visceral; Work; Youth; animal data; anxiety symptoms; automated segmentation; behavior measurement; clinically significant; cognitive development; cohort; comorbidity; connectome; critical period; denoising; early adolescence; high dimensionality; human data; improved; in vivo; interest; mood symptom; neuroimaging; novel; psychiatric symptom; response; reward circuitry; subclinical depression; substance use; tv watching

PROJECT SUMMARY/ABSTRACT Converging evidence has linked the habenula (Hb), a small epithalamic structure that inhibits dopaminergic reward signaling, to a wide range of affective, motivational, and motor functions. Abnormalities in Hb circuitry are increasingly implicated in psychiatric and behavioral disorders. In vivo Hb research has proceeded slowly, however, due to technical constraints in magnetic resonance imaging (MRI) that make it difficult to define and characterize this small region. Understanding of the Hb is especially limited in adolescence, a critical period marked by rapid maturation of the reward system and, often, the first emergence of psychiatric disorders. To address these gaps in basic and clinical neuroscience, our proposal leverages the unprecedented scale and quality of high-resolution neuroimaging data available through the Adolescent Brain Cognitive Development (ABCD) study to investigate the development of Hb function in early adolescence and its role in psychiatric illness onset. The proposed research builds on extensive work by our group to develop and refine Hb imaging methodology, including automated segmentation and a region of interest optimization approach that significantly improves Hb fMRI sensitivity, and is supported by substantial data from our laboratory. In independent samples of adult and adolescent healthy controls (HCs), we found a highly consistent pattern of positive Hb intrinsic functional connectivity (iFC) with the dopaminergic ventral tegmental area (VTA), downstream nucleus accumbens (NAc), and cortical salience network (SN), as well as negative Hb iFC throughout the default mode network (DMN). Adults with high vs. low subclinical depression scores exhibited distinct iFC patterns with regions associated with anxiety and depression, including the amygdala and insula. Moreover, adolescents with mood and anxiety disorders had positive Hb iFC with the DMN, and this abnormal Hb-DMN iFC pattern was associated with anxiety severity across both healthy and clinical adolescents, while hyperconnectivity with SN and other expected Hb targets correlated with anhedonia. Building on our compelling findings to date, we propose to study Hb function at Baseline and Year 2 ABCD neuroimaging timepoints in relation to normative (Aim 1) and clinical (Aim 2) developmental trajectories. Subjects will comprise two cohorts of ~3000 adolescents each: clinical subjects, with significant past or current mood and anxiety symptoms, and HCs, with no history of psychiatric diagnoses or clinically significant symptoms. Study procedures will incorporate sophisticated preprocessing and denoising, optimized subject-level Hb definition, neuroanatomically accurate cortical surface mapping, and rigorous non-parametric statistics. Analyses will encompass both resting-state and task fMRI to characterize Hb iFC and activation during specific reward, loss, and inhibitory control processes. We will examine both group differences and associations with psychiatric symptom severity using hypothesis-driven as well as machine learning approaches.

项目摘要/摘要 融合证据与Habenula（HB）联系在一起，HB（HB）是一种抑制多巴胺能的小上皮结构 奖励信号传导，从而达到各种情感，动机和运动功能。 HB电路异常是 越来越多地涉及精神病和行为障碍。体内HB研究的进行缓慢， 但是，由于磁共振成像（MRI）的技术限制，因此难以定义和 表征这个小区域。对HB的了解在青春期特别有限，这是一个关键时期 以奖励系统的快速成熟为特征，通常是精神疾病的第一个出现。到 在基本和临床神经科学中解决这些差距，我们的建议利用了前所未有的规模和 通过青少年脑认知发展获得的高分辨率神经影像学数据的质量 （ABCD）研究青春期早期HB功能的发展及其在精神病中的作用 发作。拟议的研究基于我们小组开发和完善HB成像的广泛工作 方法论，包括自动分割和感兴趣的优化方法，这些方法显着 提高HB fMRI敏感性，并得到我们实验室的大量数据支持。在独立样品中 成人和青少年健康对照（HCS），我们发现了高度一致的阳性Hb固有模式 功能连通性（IFC）与多巴胺能腹侧盖区（VTA），下游核 在默认模式中 网络（DMN）。高与低亚临床抑郁评分的成年人表现出不同的IFC模式 与焦虑和抑郁症有关，包括杏仁核和岛状。而且，有心情的青少年 焦虑症与DMN具有阳性HB IFC，并且这种异常的HB-DMN IFC模式相关 在健康和临床青少年的焦虑严重程度上，而SN和其他的过度连接性 预期的HB靶标与Anhedonia相关。在我们迄今为止令人信服的发现的基础上，我们建议学习 基线和2年级的HB功能与规范（AIM 1）和临床有关的ABCD神经影像时间 （目标2）发展轨迹。受试者将包括两个〜3000名青少年的队列：临床 具有重大过去或当前的情绪和焦虑症状以及HC的受试者，没有精神病学史 诊断或临床上重要的症状。研究程序将结合复杂的预处理，并 降级，优化的主题级HB定义，神经解剖学上精确的皮质表面映射和 严格的非参数统计。分析将包括静止状态和任务fMRI以表征HB 在特定奖励，损失和抑制控制过程中的IFC和激活。我们将检查两个小组 使用假设驱动和机器的差异和与精神病症状严重程度的差异和关联 学习方法。