Learning, Spatial, Stress
Conditions
Keywords
memory
Brief summary
The purpose of this study is to investigate the neural mechanisms by which acute stress influences statistical learning and episodic encoding.
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.
Interventions
BEHAVIORALSocially Evaluated Cold Pressor Test
The SECPT is a brief validated laboratory-based stress induction containing both physical and social elements
BEHAVIORALControl
This is matched to the SECPT but with warm instead of cold water
Sponsors
National Institute of Mental Health (NIMH)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in fMRI Signal | 1-2 hours | 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. |
| Statistical Learning | 1-2 hours | Online measures of statistical learning ( mean reaction time) based on item predictability during task for condition A, B or x. |
| Retention of Statistical Learning | 1 hour | Offline measure of statistical learning assessed through familiarity tests the next day (comparison of accurate recognition of previously-studied pairs to chance, 50%) |
| Episodic Memory | 1 hour | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cortisol Reactivity | 1-2 hours | Change in salivary cortisol levels following the SECPT/control procedure |
| Alpha-amylase Reactivity | 1-2 hours | Change in salivary alpha-amylase levels following the SECPT/control procedure |
Countries
United States
Participant flow
Pre-assignment details
106 participants were randomized, 9 participants withdrew prior to receiving any intervention therefore 97 started
Participants by arm
| Arm | Count |
|---|---|
| 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
Socially Evaluated Cold Pressor Test: The SECPT is a brief validated laboratory-based stress induction containing both physical and social elements | 49 |
| No Stress Participants complete a matched condition with no stress-related exposure involving submerging an arm in warm water
Control: This is matched to the SECPT but with warm instead of cold water | 47 |
| Total | 96 |
Baseline characteristics
| Characteristic | Acute Stress | No Stress | Total |
|---|---|---|---|
| Age, Continuous | 23 years | 24 years | 24 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 6 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants | 41 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 17 Participants | 20 Participants | 37 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 6 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 17 Participants | 37 Participants |
| Region of Enrollment United States | 49 participants | 47 participants | 96 participants |
| Sex: Female, Male Female | 29 Participants | 28 Participants | 57 Participants |
| Sex: Female, Male Male | 20 Participants | 19 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 47 |
| other Total, other adverse events | 0 / 50 | 0 / 47 |
| serious Total, serious adverse events | 0 / 50 | 0 / 47 |
Outcome results
Primary
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.
Time frame: 1-2 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acute Stress | Changes in fMRI Signal | 0.261 Pearson's rho |
| No Stress | Changes in fMRI Signal | -0.264 Pearson's rho |
p-value: 0.023t-test, 1 sided
p-value: 0.068t-test, 1 sided
Primary
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.
Time frame: 1 hour
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Stress | Episodic Memory | X condition | 0.615 proportion of items | Standard Deviation 0.071 |
| Acute Stress | Episodic Memory | A condition | 0.067 proportion of items | Standard Deviation 0.076 |
| Acute Stress | Episodic Memory | B condition | 0.590 proportion of items | Standard Deviation 0.079 |
| No Stress | Episodic Memory | A condition | 0.639 proportion of items | Standard Deviation 0.072 |
| No Stress | Episodic Memory | B condition | 0.619 proportion of items | Standard Deviation 0.094 |
| No Stress | Episodic Memory | X condition | 0.611 proportion of items | Standard Deviation 0.073 |
Comparison: A conditionp-value: <0.0001t-test, 2 sided
Comparison: B conditionp-value: <0.0001t-test, 2 sided
Comparison: X conditionp-value: <0.0001t-test, 2 sided
Primary
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%)
Time frame: 1 hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acute Stress | Retention of Statistical Learning | 0.537 correct pairs | Standard Deviation 0.247 |
| No Stress | Retention of Statistical Learning | 0.477 correct pairs | Standard Deviation 0.188 |
p-value: 0.143t-test, 1 sided
p-value: 0.797t-test, 1 sided
p-value: 0.087t-test, 2 sided
Primary
Statistical Learning
Online measures of statistical learning ( mean reaction time) based on item predictability during task for condition A, B or x.
Time frame: 1-2 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Stress | Statistical Learning | A condition | 0.692 minutes | Standard Deviation 0.092 |
| Acute Stress | Statistical Learning | B condition | 0.694 minutes | Standard Deviation 0.094 |
| Acute Stress | Statistical Learning | X condition | 0.686 minutes | Standard Deviation 0.087 |
| No Stress | Statistical Learning | A condition | 0.698 minutes | Standard Deviation 0.078 |
| No Stress | Statistical Learning | B condition | 0.694 minutes | Standard Deviation 0.074 |
| No Stress | Statistical Learning | X condition | 0.693 minutes | Standard Deviation 0.07 |
Comparison: Within-group A - B (null \>0)p-value: 0.281t-test, 1 sided
Comparison: Within-group A - B (null \>0)p-value: 0.645t-test, 1 sided
Comparison: Between-group comparisonp-value: 0.245t-test, 2 sided
Secondary
Alpha-amylase Reactivity
Change in salivary alpha-amylase levels following the SECPT/control procedure
Time frame: 1-2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acute Stress | Alpha-amylase Reactivity | -0.286 log nmol/L | Standard Deviation 1.27 |
| No Stress | Alpha-amylase Reactivity | -0.281 log nmol/L | Standard Deviation 1.199 |
p-value: 0.083t-test, 1 sided
p-value: 0.088t-test, 1 sided
Secondary
Cortisol Reactivity
Change in salivary cortisol levels following the SECPT/control procedure
Time frame: 1-2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acute Stress | Cortisol Reactivity | 0.636 log nmol/L | Standard Deviation 0.655 |
| No Stress | Cortisol Reactivity | -0.252 log nmol/L | Standard Deviation 0.475 |
p-value: <0t-test, 1 sided
p-value: 0.0008t-test, 1 sided