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

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $245,700

## Abstract

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.

## Key facts

- **NIH application ID:** 9920120
- **Project number:** 5R01DA045716-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** BARBARA J KNOWLTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $245,700
- **Award type:** 5
- **Project period:** 2018-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920120

## Citation

> US National Institutes of Health, RePORTER application 9920120, The Effects of Early Life Stress on the Neural Mechanisms Supporting Instrumental Behavior (5R01DA045716-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9920120. Licensed CC0.

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