Emotional Cognition: Establishing Constructs and Neural-Behavioral Mechanisms in Older Adults with Depression (ENSURE)

项目摘要 成人一生中的严重抑郁障碍(MDD)是世界范围内导致残疾的主要原因。 认知功能障碍在MDD中非常普遍，并与功能损害和减少有关 生活质量。人们注意到认知功能障碍存在于非情绪性的、“冷”的认知功能，例如 执行功能、记忆力和注意力，以及情感负荷大、“热”的认知功能，例如 情绪加工、负面注意偏向、奖励加工和社会认知。尽管有足够的 与热的认知功能、行为和相关的神经回路有关的损害的证据， 关于患有MDD的成年人在整个生命周期中的热认知功能的信息有限。给定 认知功能障碍对MDD病程和整体功能的重要性，关键是要确定 改善相关认知功能障碍的作用机制和靶向治疗方法 并达到改善整体病程、功能和生活质量的最终目标。鉴定 与特定的冷热认知功能和治疗相关的区域脑网络改变 修改这些区域将使我们更接近基于机制的个性化医疗并改进 病人的结果。这项R21研究的长期努力和目标的第一个关键步骤是更好地 描述MDD的热认知功能障碍，告知年龄对这些功能障碍的潜在影响， 并阐明与老年人相关的潜在神经回路。在拟议的先导研究中，我们进一步 我们之前在患有MDD和寒冷认知障碍的成年人中所做的工作是通过检查 对热点认知功能研究不足的领域。这一具有临床意义和创新性的为期两年的初步项目 有两个目标：1)建立和整合成年人一生中的冷热认知功能障碍；2) 建立和比较热和冷认知任务背后的特定大脑网络。建议进行的研究 聘请了一个拥有不同专业知识的跨学科团队，包括临床神经心理学， 认知/行为神经科学、神经成像和生物统计学。通过综合临床指标， 热和冷的认知指标和静息状态脑磁图(MEG)，我们将表征热 MDD的认知功能障碍，检查年龄的潜在影响，并告知相关潜在的潜在原因 神经回路。在这项初步研究中获得的新知识将使我们能够制定一个研究计划， 然后将使用非侵入性神经调节技术(例如，经颅磁刺激)来扰动 神经回路，并确认热和冷认知功能的潜在机制。跟随 机制确认，后续调查将制定以机制为基础的靶向治疗(S) 改善认知障碍。这些研究对成人具有很强的临床意义和创新性。 在MDD的整个生命周期中，因为它们将导致新的基于机制的个性化治疗， 纠正认知功能障碍，优化整体健康。

PROJECT ABSTRACT Major depressive disorder (MDD) in adults across the lifespan is a leading cause of disability worldwide. Cognitive dysfunction is highly prevalent in MDD and is associated with functional impairments and reduced quality of life. Cognitive dysfunction has been noted across non-emotional, “cold” cognitive functions, such as executive function, memory, and attention, as well as emotionally-laden, “hot” cognitive functions, such as emotion processing, negative attentional biases, reward processing, and social cognition. Despite ample evidence of impairments associated with hot cognitive function, behaviors, and associated neural circuity, limited information exists regarding hot cognitive function in adults across the lifespan with MDD. Given the importance of cognitive dysfunction on disease course and overall functioning in MDD, it is critical to identify mechanisms of action and targeted treatment approaches that will improve associated cognitive dysfunction and achieve the ultimate goal of improving overall disease course, functioning, and quality of life. Identification of regional brain network alterations associated with particular hot and cold cognitive functions and treatments that modify these regions will move us closer toward mechanism-based personalized medicine and improved patient outcomes. A first critical step in this long-term endeavor and goal of this R21 study is to better characterize hot cognitive dysfunction in MDD, inform potential effects of age on these dysfunctions, and elucidate associated underlying neurocircuitry in older adults. In the proposed pilot study, we further our prior work in adults across the lifespan with MDD and cold cognitive impairment by examining the understudied area of hot cognitive function. This clinically significant and innovative 2-year preliminary project has two aims: 1) Establish and integrate hot and cold cognitive dysfunction in adults across the lifespan, and 2) Establish and compare specific brain networks underlying hot and cold cognitive tasks. The proposed study engages an interdisciplinary team with diverse expertise including clinical neuropsychology, cognitive/behavioral neuroscience, neuroimaging, and biostatistics. Through the synthesis of clinical metrics, hot and cold cognitive metrics, and resting-state magnetoencephalography (MEG), we will characterize hot cognitive dysfunction in MDD, examine potential effects of age, and inform associated underlying neurocircuitry. The new knowledge gained in this pilot study will allow us to develop a program of research that will then use non-invasive neuromodulation technology (e.g., transcranial magnetic stimulation) to perturb neurocircuitry and confirm the mechanisms underlying both hot and cold cognitive function. Following mechanistic confirmation, subsequent investigations will develop mechanism-based targeted treatment(s) to improve cognitive impairments. These investigations have strong clinical significance and innovation for adults across the lifespan with MDD as they will lead to new and mechanism-based personalized therapeutics, remediate cognitive dysfunction, and optimize overall health.