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

早期生活压力（ELS）与儿童的许多负面健康后果密切相关

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.