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: 10166618
• 负责人: Laurel Sophia Morris
• 金额: $ 12.84万
• 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/10166618
• 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; Structure; 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.

项目摘要/摘要 该研究项目旨在表征动机的广泛认知结构 健康的个体和患有重度抑郁症（MDD）的患者并检查 腹侧换段区域的潜在多巴胺能网络连通性 （VTA）使用超高场7-Tesla MRI。动机赤字代表了 MDD，与Anhedonia的衰弱症状有关。建立 衡量动机，奖励任务的努力支出（EEFRT），该任务映射 进入研究领域标准（RDOC）框架的奖励估值结构， 不会捕捉内部产生的动机，被称为经典心理学中的意志 型号。因此，内部产生动机的维度结构尚未 然而，在MDD中得到了经验探索。神经，奖励的动力，主观 意志和阿尼多尼亚的度量已分别与VTA预测相关 给伏隔核和内侧前额叶皮层和岛。但是，VTA电路 尚未与MDD中的动机结构有关，部分原因是 使用3-Tesla MRI辨别VTA的可行性有限。因此，我们旨在解决这些问题 科学差距我们对动机和VTA电路的构建的理解 MDD。我们将采用一种新颖的客观衡量内部动机的目标 既定的外部动机（EEFRT）和经过验证的超高领域的衡量标准7- Tesla MRI用于成像MDD患者VTA电路的TESLA MRI方案 个人。新颖和建立的认知措施以及高度的这种结合 分辨率MRI将允许精确了解MDD的神经认知机制。 伴随的职业发展培训计划将微调神经影像的技能 认知神经科学并促进了临床研究方法的新技能。和 多样化的专家指导，具体培训目标包括：1）发展技能 临床诊断和以患者为导向的研究的临床诊断和表型； 2） 多模式超高场MRI中现有技能的完善； 3）技能的完善 认知和计算神经精神病学。