Prediction Error and Affective Salience Abnormalities in Aging and Late-Life Depression

项目概要 K01 指导研究科学家职业发展奖的目标是为候选人提供 追求独立研究生涯所需的概念知识和技术技能 计算认知神经科学家专注于衰老和晚年情绪障碍。候选人有一个 认知范式设计和功能神经影像方法论的深厚背景，以及不断发展的 对抑郁老年人认知和情感功能障碍的计算模型感兴趣。的 研究将使用计算方法来阐明奖励和显着性的破坏机制 过程并可能产生可以作为未来个性化治疗的数据驱动目标的发现。 拟议的培训包括正式课程、结构化教程和实践方法指导 旨在加强考生对研究计算模型的理解和开发 衰老和晚年抑郁症中的正价系统（PVS）异常。她的导师团队 由经验丰富的研究人员组成，他们将提供神经生物学和神经生物学方面的指导和培训 研究奖励和显着性异常的计算方法。 该研究补充了候选人的培训计划，因为它重点关注可能导致PVS功能障碍的PVS功能障碍。 有助于正常衰老和晚年抑郁症中的奖励处理异常。它基于 预测奖励回路中与衰老相关的异常与神经生物学异常相互作用 抑郁症可能会改变奖励预期和奖励反应性，导致抑郁的老年人分配 对负面刺激的情感更加突出。因此，本研究建议调查 衰老和抑郁症状对三岁时情感显着刺激的预测误差编码的影响 分析层次：回路、行为和自我报告。参与者将是60-85岁的老年人 重度抑郁症（N = 34，分为两个严重程度级别）或没有精神病史或没有精神病史（N = 34）。 拟议的研究将使用基于任务的功能磁共振成像和计算模型来检查动态如何 年龄和晚年抑郁症状的相互作用影响神经网络功能和 由此产生的奖励和显着性处理行为。这项研究和后续研究有望确定 个性化的行为和神经生物学目标，以进行急需的干预措施。这项工作是及时的，因为 认知矫正、大脑刺激和有针对性的行为干预方面的进展正在成为 越来越有能力影响选择性神经生物学功能和相关行为。

PROJECT SUMMARY The goal of this K01 Mentored Research Scientist Career Development Award is to provide the candidate with the conceptual knowledge and technical skills needed to pursue an independent research career as a computational cognitive neuroscientist focused on aging and late-life mood disorders. The candidate has a strong background in cognitive paradigm design and functional neuroimaging methodology, and an evolving interest in computational modeling of cognitive and affective dysfunctions in depressed older adults. The research study will use computational approaches to clarify disrupted mechanisms of reward and salience processes and may lead to findings that can serve as data-driven targets for future personalized treatments. The proposed training consists of formal courses, structured tutorials, and hands-on methodological instruction intended to strengthen the candidate's understanding and development of computational models for the study of Positive Valence Systems (PVS) abnormalities in aging and late-life depression. Her mentoring team consists of accomplished investigators who will provide guidance and training in neurobiological and computational approaches for the study of reward and salience abnormalities. The research study complements the candidate's training plan, as it focuses on PVS dysfunctions that may contribute to reward processing abnormalities in normal aging and late-life depression. It is based on the prediction that aging-related abnormalities in reward circuits interacting with neurobiological abnormalities of depression may alter reward expectancy and reward responsiveness, leading depressed older adults to assign greater affective salience to negative stimuli. Accordingly, the study proposes to investigate the impact of the effects of aging and depressive symptoms on prediction error encoding of affectively salient stimuli at three levels of analysis: circuits, behavior, and self-report. The participants will be older adults aged 60-85 years with major depression (N = 34, stratified into two levels of severity) or no history or presence of psychopathology (N = 34). The proposed study will use task-based fMRI and computational modeling to examine how the dynamic interaction of age and late-life depressive symptomatology influences neural network functions and the resulting reward and salience processing behaviors. This study and the studies to follow promise to identify personalized behavioral and neurobiological targets for much-needed interventions. This work is timely, as advances in cognitive remediation, brain stimulation, and targeted behavioral interventions are becoming increasingly capable of influencing selective neurobiological functions and associated behaviors.