Social Buffering During Aversive Conditioning

Study Overview
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Brief Summary
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The purpose of this experiment is to determine the mechanisms through which parental buffering of stress physiology during aversive conditioning 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
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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 they will 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 was completed over the phone). Girls will be shown to a changing room where the investigators will privately question them about any possibility of pregnancy. All participants will provide a urine sample for oxytocin assessment. Then 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 then complete two aversive (fear) conditioning paradigms, none using a social and one using a non-social stimulus. The investigators will use a 3T Siemens Prisma scanner with a standard 32-channel phased array head coil.

Official Title
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Social Buffering During Aversive Conditioning

Conditions
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Social Stress, Adolescent Behavior

Intervention / Treatment
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* Other: Questionnaires
* Other: MRI


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Primary Parent<br>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. | Other: Questionnaires<br>* The participant will complete questionnaires, including ones on pubertal development and quality of relations with parents and friends.<br>Other: MRI<br>* Within 2 weeks of the first study visit, the participant will return to the University where they will undergo MRI.<br>|
| Experimental: Close Friend<br>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. | Other: Questionnaires<br>* The participant will complete questionnaires, including ones on pubertal development and quality of relations with parents and friends.<br>Other: MRI<br>* Within 2 weeks of the first study visit, the participant will return to the University where they will undergo MRI.<br>|
| Experimental: Experimenter<br>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. | Other: Questionnaires<br>* The participant will complete questionnaires, including ones on pubertal development and quality of relations with parents and friends.<br>Other: MRI<br>* Within 2 weeks of the first study visit, the participant will return to the University where they will undergo MRI.<br>|
| Experimental: No Social Partner<br>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. | Other: Questionnaires<br>* The participant will complete questionnaires, including ones on pubertal development and quality of relations with parents and friends.<br>Other: MRI<br>* Within 2 weeks of the first study visit, the participant will return to the University where they will undergo MRI.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cortisol AUCi | 8 samples will be taken during the course of the assessment. Area under the curve from initial (baseline) will be calculated and used in the analyses. | 2 hours | 
| Change Heart Rate Response | 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 (beats per minute) from validated software (BIOPAC). The outcome measure will be reported (in beats per minute) as the difference between heart rate response during the period of stress and period of non-stress. | 2 hours | 
| Left amygdala: Task-related brain activity during threat conditioning | The difference in fMRI signal intensity (unitless measure) in the left amygdala between the threat and safety cues during the acquisition of conditioned threat. | 2 hours | 
| Right amygdala: Task-related brain activity during threat conditioning | The difference in fMRI signal intensity (unitless measure) in the right amygdala between the threat and safety cues during the acquisition of conditioned threat. | 2 hours | 
| Left insula: Task-related brain activity during threat conditioning | The difference in fMRI signal intensity (unitless measure) in the left insula between the threat and safety cues during the acquisition of conditioned threat. | 2 hours | 
| Right insula: Task-related brain activity during threat conditioning | The difference in fMRI signal intensity (unitless measure) in the right insula between the threat and safety cues during the acquisition of conditioned threat. | 2 hours | 
| Dorsomedial prefrontal cortex (dmPFC): Task-related brain activity during threat conditioning | The difference in fMRI signal intensity (unitless measure) in the bilateral dorsomedial prefrontal cortex (dmPFC) between the threat and safety cues during the acquisition of conditioned threat. | 2 hours | 
| Amygdala-vmPFC by Task: Psychophysiological interaction (PPI) functional connectivity during threat conditioning | 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 functional connectivity value (r, or correlation coefficient) for each task condition/group. | 2 hours | 
| Amygdala-dmPFC by Task: Psychophysiological interaction (PPI) functional connectivity during threat conditioning | 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 bilateral dorsomedial prefrontal cortex (dmPFC) 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 functional connectivity value (r, or correlation coefficient) for each task condition/group. | 2 hours | 
| Conditioning Effect: Stimulus valence | Conditioning effect will be measured as the difference in self-reported stimulus valence, defined as pleasure or aversion to the study stimulus, between CS+ and CS- tasks over time. Stimulus valence will be measured on a 5-point Likert scale for each of 40-50 trials for each the CS+ and CS+ conditions. The mean of all CS+ trials and CS- trials is calculated and outcome is reported has the difference between the two. | 2 hours | 
| Conditioning Effect: Stimulus arousal | Conditioning effect will be measured as the difference in self-reported stimulus arousal, defined as the intensity of pleasure or aversion to the study stimulus, between CS+ and CS- tasks over time. Stimulus arousal will be measured on a 5-point Likert scale for each of 40-50 trials for each the CS+ and CS+ conditions. The mean of all CS+ trials and CS- trials is calculated and outcome is reported has the difference between the two. | 2 hours | 
| Conditioning Effect: Mean Unconditioned Stimulus (UCS) expectancy | Conditioning effect will be measured as the difference in self-reported UCS expectancy, defined as how likely a task is to cause pleasure or aversion, between CS+ and CS- tasks over time. Stimulus arousal will be measured on a 7-point Likert scale for each of 40-50 trials for each the CS+ and CS+ conditions. The mean of all CS+ trials and CS- trials is calculated and outcome is reported has the difference between the two. | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Self Report of Stress | The Self Report of Stress is an 8-item questionnaire assessing participant level of stress at various time points across the session. Items are rated on a 5 point Likert scale. Total score is the unweighted mean of item scores. Total scores range from 0 to 40, with higher scores indicating greater stress. The assessment will be administered at baseline (no stress) and during a period of stress. The outcome will be reported as the difference between the baseline period and experimental stress period. | 2 hours |