Influence of Stress on Encoding and Prediction

Neural Mechanisms of Stress Effects Across Hippocampal Encoding and Prediction

The purpose of this study is to investigate the neural mechanisms by which acute stress influences statistical learning and episodic encoding.

Study Overview

• Status: Completed
• Conditions: Stress; Learning, Spatial
• Intervention / Treatment: Behavioral: Socially Evaluated Cold Pressor Test; Behavioral: Control

Detailed Description

This study aims to assess the neural and behavioral mechanisms by which acute stress modulates episodic encoding (which involves the trisynaptic pathway: entorhinal cortex, dentate gyrus, cornu ammonis [CA] 3, and CA 1) and statistical learning (monosynaptic pathway: entorhinal cortex, CA1) in humans.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18-45 years old
• Fluent in English
• BMI 18-35

Exclusion Criteria:

• Meeting current DSM-V criteria for any substance use disorder (except caffeine)
• Having current significant medical conditions or psychiatric symptoms requiring medication
• Current use of medications/drugs that interfere with physiological stress responses
• Peri and post-menopausal women, pregnant or lactating women, and those with hysterectomies
• Metal in body (for MRI safety) history will be assessed for female participants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acute Stress; Participants complete the socially evaluated cold pressor test (SECPT), a validated laboratory-based stress induction procedure involving submerging an arm in an ice bath	Behavioral: Socially Evaluated Cold Pressor Test; The SECPT is a brief validated laboratory-based stress induction containing both physical and social elements
Active Comparator: No Stress; Participants complete a matched condition with no stress-related exposure involving submerging an arm in warm water	Behavioral: Control; This is matched to the SECPT but with warm instead of cold water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in fMRI Signal	fMRI signal during learning will be assessed using connectivity, multivariate, and univariate approaches over 1-2 hour long learning period. Correlation between change in CA1-EC background connectivity and pair familiarity. rho represents the true correlation within the entire population, with values ranging from -1 to +1; values closer to +1 indicate a strong positive linear relationship, closer to -1 a strong negative one, and closer to 0 indicate no linear relationship.	1-2 hours
Statistical Learning	Online measures of statistical learning ( mean reaction time) based on item predictability during task for condition A, B or x.	1-2 hours
Retention of Statistical Learning	Offline measure of statistical learning assessed through familiarity tests the next day (comparison of accurate recognition of previously-studied pairs to chance, 50%)	1 hour
Episodic Memory	Memory for individual items will be assessed through performance on old/new recognition tests the next day, quantified as hit rates and A' (non-parametric normalized ratio of hits to false alarms). Data presented here is the proportion of studied items attributed to the correct condition (A, B or X) minus the proportion of nonstudied items incorrectly attributed to that same condition.	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortisol Reactivity	Change in salivary cortisol levels following the SECPT/control procedure	1-2 hours
Alpha-amylase Reactivity	Change in salivary alpha-amylase levels following the SECPT/control procedure	1-2 hours

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Elizabeth V Goldfarb, PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2023
• Primary Completion (Actual): October 4, 2024
• Study Completion (Actual): October 4, 2024

Study Registration Dates

• First Submitted: June 15, 2023
• First Submitted That Met QC Criteria: June 15, 2023
• First Posted (Actual): June 27, 2023

Study Record Updates

• Last Update Posted (Estimated): October 15, 2025
• Last Update Submitted That Met QC Criteria: September 26, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: memory
• Additional Relevant MeSH Terms: Behavior; Spatial Behavior; Spatial Learning
• Other Study ID Numbers: 2000030825; 1R21MH128740-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Aggregate data will be shared on NIMH Data Archives

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No