Neural Correlates of the Shift in Social Buffering of Social Evaluative Threat

Not Applicable

Completed

Conditions: Social Stress
Adolescent Behavior

Interventions: Other: Questionnaires
Other: MRI

Registration Number: NCT04211155

Lead Sponsor: University of Minnesota

Brief Summary: The purpose of this experiment is to determine the mechanisms through which parental buffering of stress physiology in response to social evaluative threat diminishes with pubertal development and whether this diminution of effectiveness extends to social buffering by peers (best friends) and/or other unfamiliar social partners (e.g., experimenters).

Detailed Description: On visit one, the participant will 1) be seen by a nurse who will complete a pubertal assessment exam, 2) complete questionnaires, including ones on pubertal development, screening for MRI safety, and quality of relations with parents and friends. The participant will also have a chance to experience a simulated MRI in order to determine whether they will be comfortable in an actual MRI.

Within 2 weeks the participant will return to the University where undergo the following protocol. Participants will be randomly assigned to one of 4 conditions that differ by who is with them in the scanner room: Primary Parent, Close Friend, Experimenter, No Social Partner. (N=50 per condition, 25 male, 25 female).

Once at the Center for Magnetic Resonance Research, participants and the individual who will be with the participant in the scanning room will undergo an MRI safety screening (the repeat of what the investigators completed over the phone). Girls will be shown to a changing room where the investigators will privately question them about any possibility of pregnancy. Participants will be shown into the scanning control room and one more safety check will be performed before they enter the scanner room and the scanner. If they are in one of the social buffering conditions, the social buffering partner will also enter the scanning room and will sit to the side of the scanner.

The scanning bed will then be moved into the barrel of the MRI machine. The participant will be wearing head phones to protect his/her hearing and to receive instructions from the control room. The participant will also be able to see two judges and hear the judges instructions when the participant is in the scanning control room. The participant will then complete a variant or the Trier Social Stress Test, a social evaluative stressor, which produces elevations in heart rate and cortisol.

When saliva is collected, the scanning bed is withdrawn from the barrel of the MRI machine and the participant will be able to see and briefly interact with the social partner while saliva is sampled for steroid collection. Once the scan is over the participant will return to a waiting area and complete additional questionnaires, provide additional saliva samples, and another urine sample.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 208

Inclusion Criteria

sufficient vision to complete assent and study procedures
sufficient hearing to complete assent and study procedures
sufficient language skills to provide verbal and written assent

Exclusion Criteria

Premature birth (less than 37 weeks)
congenital and/or chromosomal disorders (e.g. cerebral palsy, FAS, mental retardation, Turner Syndrome, Down Syndrome, Fragile X)
Autism Spectrum Disorders
history of serious medical illness (e.g., cancer, organ transplant)
youth taking systemic glucocorticoids
youth taking beta-adrenergic medications
diagnoses of psychiatric illness, seizure disorder or other neurological disorders
contraindications for MRI (implanted medical device; presence of non-removal metal in or on the body, including piercings, orthodontic braces or certain permanent retainers)
known pregnancy
tattoos
history of significant claustrophobia

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Primary Parent	Questionnaires	Participants will be randomly assigned to one of 4 conditions that differ by who is with them in the MRI scanner room: Primary Parent, Close Friend, Experimenter, No Social Partner.
Experimenter	MRI	Participants will be randomly assigned to one of 4 conditions that differ by who is with them in the MRI scanner room: Primary Parent, Close Friend, Experimenter, No Social Partner.
Close Friend	MRI	Participants will be randomly assigned to one of 4 conditions that differ by who is with them in the MRI scanner room: Primary Parent, Close Friend, Experimenter, No Social Partner.
Experimenter	Questionnaires	Participants will be randomly assigned to one of 4 conditions that differ by who is with them in the MRI scanner room: Primary Parent, Close Friend, Experimenter, No Social Partner.
No Social Partner	MRI	Participants will be randomly assigned to one of 4 conditions that differ by who is with them in the MRI scanner room: Primary Parent, Close Friend, Experimenter, No Social Partner.
Primary Parent	MRI	Participants will be randomly assigned to one of 4 conditions that differ by who is with them in the MRI scanner room: Primary Parent, Close Friend, Experimenter, No Social Partner.
Close Friend	Questionnaires	Participants will be randomly assigned to one of 4 conditions that differ by who is with them in the MRI scanner room: Primary Parent, Close Friend, Experimenter, No Social Partner.
No Social Partner	Questionnaires	Participants will be randomly assigned to one of 4 conditions that differ by who is with them in the MRI scanner room: Primary Parent, Close Friend, Experimenter, No Social Partner.

Primary Outcome Measures

Name	Time	Method
Amygdala-vmPFC Connectivity: fMRI Functional Connectivity (Speech Prep vs. Rest)	2 hours	For each participant, signal intensity (unitless measure) will be measured using fMRI in the bilateral amygdala over a five-minute recording period. Signal intensity will also be measured using fMRI in the ventromedial prefrontal cortex (vmPFC) over the same period of time. A bivariate correlation will be conducted for these two data sets to determine functional connectivity, which will be reported as the r value of the correlation. This outcome measure will be reported as the mean difference in functional connectivity value (r, or correlation coefficient) for each buffering condition/group.
Change in Cortisol AUCi	2 hours, approx	Area under the curve from initial (baseline) will be calculated and used in the analyses. Description = 9 saliva samples are collected during the course of the assessment. These samples are collected at (1) arrival for training purposes; T=0, (2) scan preparation; T=35 minutes, (3) entering scanner; T=55 minutes, (4) pre-TSST; T=75 minutes, (5) post-TSST; T=100 minutes, (6) pre-math alone; T=110 minutes, (7) post-math alone; T=120 minutes, (8) exiting scanner; T=130 minutes, (9) departure; T=140 minutes. Area under the curve at intercept (AUCi) is calculated using samples 2-7 with sample 2 as the intercept.
Change Heart Rate Response	2 hours	Heart rate will be derived from the EKG signal collected during periods of stress (social evaluation) and non-stress (no evaluation) during the course of the assessment. The variable, heart rate response, is a numeric output (reported in beats per minutes) from validated software (BIOPAC) which is calculated using a regression algorithm. The outcome measure will be reported as the difference between heart rate response during the period of stress and period of non-stress.
Dorsal Anterior Cingulate: Task-related Brain Activity (Judged Math vs. Math Alone)	2 hours	The difference in fMRI BOLD signal intensity in the bilateral dorsal anterior cingulate cortex (dACC) between the social evaluative stress condition (judged math) and non-stress condition (math without judges). Mean group differences in signal intensity between the two math tasks were extracted from a brain region defined by the Harvard-Oxford brain atlas anterior cingulate cortex thresholded at 50% confidence and dorsal to the genu of the corpus callosum.
Left Anterior Insula: Task-related Brain Activity (Judged Math vs. Math Alone)	2 hours	The difference in fMRI BOLD signal intensity in the left anterior insula between the social evaluative stress condition (judged math) and non-stress condition (math without judges). Mean group differences in signal intensity between the two math tasks were extracted from a brain region defined by the Harvard-Oxford brain atlas left insula thresholded at 50% confidence and anterior to the region's midpoint.
Right Anterior Insula: Task-related Brain Activity (Judged Math vs. Math Alone)	2 hours	The difference in fMRI BOLD signal intensity in the right anterior insula between the social evaluative stress condition (judged math) and non-stress condition (math without judges). Mean group differences in signal intensity between the two math tasks were extracted from a brain region defined by the Harvard-Oxford brain atlas right insula thresholded at 50% confidence and anterior to the region's midpoint.
Ventromedial Prefrontal Cortex: Task-related Brain Activity (Judged Math vs. Math Alone)	2 hours	The difference in fMRI BOLD signal intensity in the bilateral ventromedial prefrontal cortex (vmPFC) between the social evaluative stress condition (judged math) and non-stress condition (math without judges). Mean group differences in signal intensity between the two math tasks were extracted from a brain region defined by the combination of Harvard-Oxford brain atlas frontal pole, frontal medial cortex, and subcallosal cortex thresholded at 50% confidence and ventral to the genu of the corpus callosum and medial to the lateral edges of the Harvard-Oxford brain atlas frontal medial cortex.
Left Dorsolateral Prefrontal Cortex: Task-related Brain Activity (Judged Math vs. Math Alone)	2 hours	The difference in fMRI BOLD signal intensity in the left dorsolateral prefrontal cortex (left dlPFC) between the social evaluative stress condition (judged math) and non-stress condition (math without judges). Mean group differences in signal intensity between the two math tasks were extracted from a brain region defined by the Harvard-Oxford brain atlas left middle frontal gyrus thresholded at 50% confidence.
Right Dorsolateral Prefrontal Cortex: Task-related Brain Activity (Judged Math vs. Math Alone)	2 hours	The difference in fMRI BOLD signal intensity in the right dorsolateral prefrontal cortex (right dlPFC) between the social evaluative stress condition (judged math) and non-stress condition (math without judges). Mean group differences in signal intensity between the two math tasks were extracted from a brain region defined by the Harvard-Oxford brain atlas right middle frontal gyrus thresholded at 50% confidence.
Amygdala-left dlPFC Connectivity: fMRI Functional Connectivity (Speech Prep vs. Rest)	2 hours	For each participant, signal intensity (unitless measure) will be measured using fMRI in the amygdala over a five-minute recording period. Signal intensity will also be measured using fMRI in the left dorsolateral prefrontal cortex (dlPFC) over the same period of time. A bivariate correlation will be conducted for these two data sets to determine functional connectivity, which will be reported as the r value of the correlation. This outcome measure will be reported as the mean difference in functional connectivity value (r, or correlation coefficient) for each buffering condition/group.
Amygdala-right dlPFC Connectivity: fMRI Functional Connectivity (Speech Prep vs. Rest)	2 hours	For each participant, signal intensity (unitless measure) will be measured using fMRI in the amygdala over a five-minute recording period. Signal intensity will also be measured using fMRI in the right dorsolateral prefrontal cortex (dlPFC) over the same period of time. A bivariate correlation will be conducted for these two data sets to determine functional connectivity, which will be reported as the r value of the correlation. This outcome measure will be reported as the mean difference in functional connectivity value (r, or correlation coefficient) for each buffering condition/group.
Hypothalamus-vmPFC Connectivity: fMRI Functional Connectivity (Speech Prep vs. Rest)	2 hours	For each participant, signal intensity (unitless measure) will be measured using fMRI in the hypothalamus over a five-minute recording period. Signal intensity will also be measured using fMRI in the bilateral ventromedial prefrontal cortex (vmPFC) over the same period of time. A bivariate correlation will be conducted for these two data sets to determine functional connectivity, which will be reported as the r value of the correlation. This outcome measure will be reported as the mean difference in functional connectivity value (r, or correlation coefficient) for each buffering condition/group.
Hypothalamus-left dlPFC Connectivity: fMRI Functional Connectivity (Speech vs. Rest)	2 hours	For each participant, signal intensity (unitless measure) will be measured using fMRI in the hypothalamus over a five-minute recording period. Signal intensity will also be measured using fMRI in the left dorsolateral prefrontal cortex (dlPFC) over the same period of time. A bivariate correlation will be conducted for these two data sets to determine functional connectivity, which will be reported as the r value of the correlation. This outcome measure will be reported as the mean difference in functional connectivity value (r, or correlation coefficient) for each buffering condition/group.
Hypothalamus-right dlPFC Connectivity: fMRI Functional Connectivity (Speech vs. Rest)	2 hours	For each participant, signal intensity (unitless measure) will be measured using fMRI in the hypothalamus over a five-minute recording period. Signal intensity will also be measured using fMRI in the right dorsolateral prefrontal cortex (dlPFC) over the same period of time. A bivariate correlation will be conducted for these two data sets to determine functional connectivity, which will be reported as the r value of the correlation. This outcome measure will be reported as the mean difference in functional connectivity value (r, or correlation coefficient) for each buffering condition/group.
Change in Salivary Alpha Amylase, AUCi	2 hours	salivary Alpha Amylase is used to index autonomic/sympathetic function. 9 saliva samples are collected during the course of the assessment. These samples are collected at (1) arrival; T=0, (2) scan preparation; T=35 minutes, (3) entering scanner; T=55 minutes, (4) pre-TSST; T=75 minutes, (5) post-TSST; T=100 minutes, (6) pre-math alone; T=110 minutes, (7) post-math alone; T=120 minutes, (8) exiting scanner; T=130 minutes, (9) departure; T=140 minutes. 4 samples (3-6) are assayed for salivary alpha amylase in micrograms per milliliter (sAA). Area under the curve at intercept (AUCi) is calculated using samples 3-6 with sample 3 as the intercept.

Secondary Outcome Measures

Name	Time	Method
Quality of Relationship With Primary Parent, BSV Positive Attachment Scale	Youth report, collected over course of 30 minutes	Network of Relationships Inventory (NRI) reported by youth for their primary parent on how much they experience various emotions or incidents (e.g. How much free time do you spend with this person?), reported on a 5-point scale: (1) Little or None, (2) Somewhat, (3) Very Much, (4) Extremely Much, (5) The Most. Mean scores calculated from all positive attachment items, range 1-5. Potential Covariate.
Quality of Relationship With Close Friend, BSV Positive Attachment Scale	Youth reported, collected over course of 30 minutes	Network of Relationships Inventory (NRI) reported by youth for their close friend on how much they experience various emotions or incidents (e.g. How much free time do you spend with this person?), reported on a 5-point scale: (1) Little or None, (2) Somewhat, (3) Very Much, (4) Extremely Much, (5) The Most. Mean scores calculated from all positive attachment items, ranging 1-5. Potential Covariate.
Self Report of Stress	2 hours	Self-report of stress using a Likert-type scale with 5 levels of stress felt: (1) Not At All, (2) A Little, (3) Some, (4) A Lot, (5) A Whole Lot. Level of stress was reported for 4 points during the assessment: (1) How stressed did you feel when you first arrived at the University and we were walking into the building, (2) How stressful was the period of time when you were preparing your speech and thinking about what to say?, (3) How stressful was giving the speech?, (4) How stressful was the math with judges?. Mean Stress reactivity was calculated as the mean of (2, 3, 4) minus the value at arrival (1).
Peer Acceptance/Rejection	Parent report of child's general experience, collected over 30 minutes	Scale on the MacArthur Health and Behavior Questionnaire, Potential Covariate, 5pt Scale (1-5), High Scores Indicate Peer Acceptance
Behavioral Inhibition	Parent report of child's general experience, collected over 30 minutes	Scale on the MacArthur Health and Behavior Questionnaire. Potential Covariate, 3pt scale (0,1,2), high scores indicate inhibition
Internalizing Symptoms	Parent report of child's general experience, collected over 30 minutes	Higher Order Measure From the MacArthur Health and Behavior Questionnaire. Potential Covariate 3pt scale (0,1,2), high scores indicate Internalizing
Externalizing Symptoms	Parent report of child's general experience, collected over 30 minutes	Higher Order Measure From the MacArthur Health and Behavior Questionnaire. Potential Covariate 3pt scale (0,1,2), high scores indicate externalizing
Time Since Awakening	reported at the beginning of the 2 hour session	Participants self-report the clock time that they woke up on the day of the assessment, and the clock time when the imaging test was done. The difference between these times was calculated and reported in hours. This is only a potential covariate for cortisol, which follows a circadian rhythm.
Pretax Family Income. Potential Covariate	Parent report, collected over 30 minutes	Parents report on gross family income on an 11-point ordinal scale: (1) Less than $15,000, (2) $15,001 to $25,000, (3) $25,001 to $35,000, (4) $35,001 to $50,000, (5) $50,001 to $75,000, (6) $75,001 to $100,000, (7) $100,001 to $125,000, (8) $125,001 to $150,000, (9) $150,001 to $175,000, (10) $175,001 to 200,000, (11) $200,001 or more.
Parental Average Education Level. Potential Covariate	Parent report, collected over 30 minutes	Parents report education level for both parents on a 6-point ordinal scale: (1) Less than high school degree, (2) High school or GED, (3) Associate degree, college academia program, (4) Bachelor's degree, (5) Master's degree, (6) Professional and/or Doctorate degree. Average of parents' education is calculated and reported.
Caffeine or Nicotine Within 1 Hour of Testing. Potential Covariate	Youth report, at start of 2 hour session	Youth report on whether they consumed caffeine or nicotine in the 1-2 hours prior to the assessment. Coded as no=0, yes=1. Used as a potential covariate for heart rate and neuroendocrine measures.
Granger Score	Youth report at the beginning of the 2 hour session	The Granger score (ordinal, modeled continuously) is a score based on work by Doug Granger of medications that can affect activity of the HPA axis, weighted by significance of potential impact (Granger, Hibel, Fortunato, \& Kapelewski, 2009). Each medication taken is given a score of 0, 1, or 2, and all medication scores for a participant is summed, resulting in scores from 0 to infinity. Lower scores are less likely to influence cortisol. Potential Covariate