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（EL）与许多负面的健康后果密切相关成年，包括成瘾和肥胖。但是，我们的理解存在关键的差距这些关系的基础机制。我们建议测试一组创新的假设习惯与目标学习的行为和神经认知机制联系起来与Els。我们进一步建议评估条件恐惧线索作为习惯的增强者的作用通过Pavlovian-trumstrumental Transcoms学习经历了ELS的个人。这项研究会测试一个模型，通过该模型提醒过去的恐惧体验可以增强个人的习惯学习已经容易受到成瘾的影响。这些研究将学习理论概念的严格性应用于了解由EL产生的行为漏洞。我们将链接实验动物的工作使用功能连通性进行人类学科研究的习惯学习神经回路方法和神经影像学。我们将测试年轻，健康的人群，以最大化疾病发作之前与EL相关的危险因素。参与者将基于分组在没有重大的早期压力源，一个或两个早期的生活压力和三个或更多的早期生活压力源，以评估压力与习惯学习倾向之间的剂量关系目标定向学习。我们建议使用我们的工具任务来衡量习惯学习已适用于fMRI扫描仪。通过评估学习的响应是否对贬值，我们将测试学习是否是习惯性与目标。我们假设这一点经历过EL的个人将显示出更大的习惯学习率，并且存在恐惧CS会突出两组之间的差异。我们将使用相同的行为使用高分辨率FRMI评估习惯反应的神经机制的范式使我们能够评估仪器学习过程中纹状体子区域中的大胆信号激活。根据实验动物的工作，我们假设经历了ELS的个人将在纹状体的更外侧区域中显示激活，包括壳壳参与者在尾状核中的激活将更加内侧。我们将能够实现通过使用纹状体激活的荟萃分析，我们的分析中有更高的解剖学精度在文献中的习惯学习任务中。我们还将能够评估功能连接与杏仁核和其他地区一起，将我们的发现与链接早期生活的工作相结合压力杏仁核肥大。一系列与成瘾相关的行为（例如吸烟，吸毒，饮酒）将被测试为习惯学习的行为和神经指数的相关性验证模型。

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.