Characterizing constructs of motivation and the midbrain dopaminergic system in depression with ultra-high field MRI

用超高场 MRI 表征抑郁症患者的动机和中脑多巴胺能系统的结构

• 批准号: 10439716
• 负责人: Laurel Sophia Morris
• 金额: $ 12.59万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10439716
• 关键词: Address; Anhedonia; Anterior; Biological; Clinical Research; Cognitive; Cognitive Therapy; Complex; Computer Models; Data; Dimensions; Disease; Etiology; Expenditure; Foundations; Goals; Human; Image; Incentives; Individual; Insula of Reil; Link; Magnetic Resonance Imaging; Major Depressive Disorder; Maps; Measures; Medial; Mediation; Mental Depression; Mental disorders; Mentorship; Midbrain structure; Modeling; Motivation; Neurites; Neurocognitive; Noise; Nucleus Accumbens; Patients; Pharmacologic Substance; Prefrontal Cortex; Protocols documentation; Psychology; Public Health; Research Domain Criteria; Research Methodology; Research Project Grants; Resolution; Rewards; Rodent Model; Signal Transduction; Symptoms; System; Technology; Testing; Therapeutic; Therapeutic Intervention; Training; Ventral Tegmental Area; Volition; Work; base; career development; clinical diagnostics; clinical phenotype; cognitive neuroscience; cognitive training; cohort; density; digital; disabling symptom; effective therapy; indexing; individual patient; insight; multimodality; neural correlate; neural network; neurobiological mechanism; neuroimaging; neuropsychiatry; next generation; noninvasive brain stimulation; novel; patient oriented research; pre-clinical; relating to nervous system; skill acquisition; skills; stem; targeted treatment; two-dimensional

Project Summary/Abstract This research project aims to characterize the broad cognitive construct of motivation in healthy individuals and patients with major depressive disorder (MDD) and to examine underlying dopaminergic network connectivity stemming from the ventral tegmental area (VTA) using ultra-high field 7-Tesla MRI. Motivational deficits represent a core feature of MDD and are associated with the debilitating symptom of anhedonia. An established measure of motivation, the Effort Expenditure for Rewards Task (EEfRT), which maps onto the reward valuation construct of the Research Domain Criteria (RDoC) framework, does not capture internally-generated motivation, known as volition in classic psychology models. Therefore the dimensional construct of internally-generated motivation has not yet been empirically explored in MDD. Neurally, motivation for rewards, a subjective measure of volition and anhedonia have each been separately linked to VTA projections to nucleus accumbens and medial prefrontal cortex, and insula. However, VTA circuitry has not been fully examined in relation to motivation constructs in MDD, partly due to the limited feasibility of discerning VTA with 3-Tesla MRI. We therefore aim to address these scientific gaps in our understanding of the construct of motivation and VTA circuitry in MDD. We will employ a novel objective measure of internally-generated motivation, an established measure of external motivation (EEfRT) and a validated ultra-high field 7- Tesla MRI protocol for imaging VTA circuitry in patients with MDD and healthy individuals. This combination of novel and established cognitive measures, and high- resolution MRI will allow precise insight into the neurocognitive mechanisms of MDD. Accompanying career development training plans will fine-tune skills in neuroimaging and cognitive neuroscience and facilitate new skills in clinical research methods. With diverse expert mentorship, specific training goals include: 1) Development of skills in clinical diagnostics and phenotyping for translational patient-oriented research; 2) Refinement of existing skills in multi-modal ultra-high field MRI; 3) Refinement of skills in cognitive and computational neuropsychiatry.

项目总结/摘要 本研究项目旨在描述动机的广泛认知结构， 健康个体和重度抑郁症（MDD）患者，并检查 源自腹侧被盖区的潜在多巴胺能网络连接 (VTA)使用超高场7特斯拉核磁共振成像动机缺陷代表了一个核心特征， MDD和与快感缺乏的衰弱症状相关。一个既定 奖励任务的努力支出（EEfRT），它映射了 在研究领域标准（RDoC）框架的奖励评估结构上， 并不能捕捉到内在产生的动机，在经典心理学中被称为意志 模型因此，内部产生的动机的维度结构没有 但在MDD中进行了实证研究。神经学上，奖励的动机，主观的 意志力和快感缺乏的测量分别与VTA预测有关 前额叶皮层内侧核和前额叶皮层内侧核。然而，VTA电路 还没有充分研究MDD中的动机结构，部分原因是 使用3-Tesla MRI识别VTA的可行性有限。因此，我们旨在解决这些问题 我们对动机和VTA电路结构的理解存在科学差距， MDD。我们将采用一种新的客观衡量内部产生的动机， 外部动机的既定措施（EEfRT）和验证超高场7- 用于MDD患者和健康患者VTA电路成像的Tesla MRI方案 个体这种新颖的和既定的认知措施的结合，以及高- 分辨率MRI将允许对MDD的神经认知机制的精确洞察。 伴随的职业发展培训计划将微调神经成像技能 和认知神经科学，促进临床研究方法的新技能。与 不同的专家指导，具体的培训目标包括：1）发展技能， 临床诊断和表型分析，用于转化型患者导向研究; 2） 完善多模式超高场MRI的现有技能; 3）完善 认知和计算神经精神病学