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The Effects of Early Life Stress on the Neural Mechanisms Supporting Instrumental Behavior

早期生活压力对支持工具行为的神经机制的影响

基本信息

批准号：
9920120
负责人：
BARBARA J KNOWLTON
金额：
$ 24.57万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9920120
关键词：
Addictive Behavior Address Adult Affect Alcohol consumption Alcohol or Other Drugs use Amygdaloid structure Anatomy Animal Model Animals Anterior Avoidance Learning Behavior Behavioral Behavioral Mechanisms Behavioral Paradigm Corpus striatum structure Cues Dependence Development Dose Drug usage Exhibits Fright Functional Magnetic Resonance Imaging Goals Habits Health Hippocampus (Brain)Human Hypertrophy Impairment Individual Laboratories Lateral Learning Life Light Link Literature Measures Medial Mediator of activation protein Memory Meta-Analysis Methods Modeling Neurocognitive Obesity Onset of illness Operant Conditioning Participant Pattern Performance Population Reporting Research Resolution Response to stimulus physiology Risk Factors Role Sampling Signal Transduction Smoking Stimulus Stress Study Subject System Testing Training Work addiction base behavioral response caudate nucleus early experience early life stress experience habit learning human subject indexing innovation interest neural circuit neuroimaging neuromechanism putamen reinforcer relating to nervous system response stressor theories tractography

项目摘要

Early life stress (ELS) is strongly associated with a host of negative health consequences in adulthood, including addiction and obesity. However, there is a critical gap in our understanding of the mechanism underlying these relationships.. We propose to test an innovative set of hypotheses linking behavioral and neurocognitive mechanisms of habit vs. goal-directed learning with ELS. We further propose to evaluate the role of conditional fear cues as potentiators of habit learning, via Pavlovian-Instrumental Transfer in individuals who experienced ELS. This study will test a model by which reminders of past fearful experiences enhance habit learning in individuals already vulnerable to addiction. These studies apply the rigor of learning theory concepts to understand behavioral vulnerabilities resulting from ELS. We will link work in experimental animals on neural circuits of habit learning with human subject studies using functional connectivity methods and neuroimaging. We will test a young, healthy population to maximize the isolation of risk factors associated with ELS prior to the onset of disease. Participants will be grouped based on no major early life stressors, one or two early life stressors, and three or more early life stressors, to evaluate the dose relationship between stress and propensity for habit learning over goal- directed learning. We propose to measure habit learning using an instrumental task that we have adapted for use in the fMRI scanner. By assessing whether the learned response is sensitive to devaluation, we will test whether learning is habitual vs. goal- directed. We hypothesize that individuals who experienced ELS will show greater rates of habit learning, and the presence of a fear CS will accentuate this difference between the groups. We will use the same behavioral paradigm to assess neural mechanisms of habit responding using high-resolution fRMI that will enable us to assess BOLD signal activation in striatal subregions during instrumental learning. Based on work in experimental animals, we hypothesize that individuals who experienced ELS will show activation in more lateral regions of the striatum including the putamen, while in control participants, activation will be more medial, in the caudate nucleus. We will be able to achieve greater anatomical precision in our analyses by our use of our meta-analysis of striatal activation in habit learning tasks in the literature. We will also be able to assess functional connectivity with the amygdala and other regions, thus integrating our findings with work linking early-life stress to amygdala hypertrophy. An array of addiction-related behaviors (e.g., smoking, drug use, alcohol use ) will be tested as correlates of behavioral and neural indices of habit learning to validate the model.

早期生活压力（ELS）与许多负面健康后果密切相关成年期，包括成瘾和肥胖。然而，我们的理解存在严重差距这些关系背后的机制。我们建议测试一组创新的将习惯的行为和神经认知机制与目标导向学习联系起来的假设与ELS。我们进一步建议评估条件恐惧线索作为习惯增强剂的作用通过巴甫洛夫工具迁移在经历过 ELS 的个体中进行学习。这项研究将测试一个模型，通过该模型提醒过去的恐惧经历可以增强个人的习惯学习已经很容易上瘾。这些研究将学习理论概念的严谨性应用于了解 ELS 导致的行为漏洞。我们将把实验动物的工作联系起来使用功能连接研究习惯学习的神经回路与人类受试者研究方法和神经影像学。我们将对年轻、健康的人群进行测试，以最大限度地隔离发病前与 ELS 相关的危险因素。参与者将根据没有重大的早期生活压力源，一到两个早期生活压力源，以及三个或更多早期生活压力源压力源，评估压力与习惯学习倾向之间的剂量关系目标导向的学习。我们建议使用我们的工具性任务来衡量习惯学习已适用于功能磁共振成像扫描仪。通过评估学到的反应是否敏感贬值，我们将测试学习是习惯性的还是目标导向的。我们假设经历过 ELS 的人会表现出更高的习惯学习率，并且存在担心 CS 会加剧群体之间的这种差异。我们将使用相同的行为使用高分辨率 fRMI 评估习惯反应神经机制的范式使我们能够在工具学习期间评估纹状体分区中的 BOLD 信号激活。根据对实验动物的研究，我们假设经历过 ELS 的个体会在控制状态下，包括壳核在内的纹状体更外侧区域显示出激活参与者，激活将更内侧，在尾状核。我们将能够实现通过使用纹状体激活的荟萃分析，我们的分析具有更高的解剖学精度文献中的习惯学习任务。我们还能够评估功能连接与杏仁核和其他区域结合，从而将我们的发现与早期生命联系起来的工作结合起来压力导致杏仁核肥大。一系列与成瘾相关的行为（例如吸烟、吸毒、酒精使用）将作为习惯学习的行为和神经指数的相关性进行测试验证模型。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Value-directed remembering in first-episode schizophrenia.

DOI：
10.1037/neu0000840
发表时间：
2022-09
期刊：
NEUROPSYCHOLOGY
影响因子：
2.4
作者：
Patterson, Tara K.;Nuechterlein, Keith H.;Subotnik, Kenneth L.;Castel, Alan D.;Knowlton, Barbara J.
通讯作者：
Knowlton, Barbara J.

Early-life stress is associated with a preponderance of habitual responding in a novel instrumental avoidance learning paradigm.