Neural Mechanisms of Enhancing Emotion Regulation in Bereaved Spouses
Phase: NA
Conditions: Affect, Bereavement, Emotions, Depressive Symptoms, Grief
Sponsor: Bryan Denny

Study Protocol 
 
Study Title: Neural Mechanisms of Enhancing Emotion Regulation in Bereaved Spouses 
ClinicalTrial.gov Identifier: NCT04822194 
Sponser: The National Institute on Aging 
Intervention: Cognitive Emotion Regulation Training 
Protocol Number: 1 
Phase: Phase 1 
May 21, 2025 
Principal Investigator: Bryan Denny 
Rice University 
6500 Main St, MS-663 
Houston, TX 77030 
United States of America 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study Protocol 
 
 
Objectives: 
 
The objective of this research study is to examine the efficacy and behavioral and neural 
mechanisms of a cognitive emotion regulation training intervention aimed at improving 
psychological outcomes such as reducing depressive symptoms and grief rumination in bereaved 
spouses. Training efficacy will be assessed through psychological and neural indices of negative 
affect, and physiological indices including respiratory sinus arrhythmia (RSA), a measure of 
heart-rate variability. Cognitive reappraisal (i.e. the ability to modify the trajectory of an 
emotional response by thinking about and appraising emotional information in an alternative, 
more adaptive way) represents a highly promising target for psychological intervention in 
bereavement1. Reappraisal can be operationalized via two primary tactics: psychological 
distancing (i.e. appraising an emotional stimulus as an objective, impartial observer) and 
reinterpretation (i.e. imagining a better outcome than what initially seemed apparent). The 
project builds upon promising preliminary work to investigate the effectiveness and underlying 
neurobiological mechanisms of a novel, five-session cognitive reappraisal intervention in 
bereaved spouses. The study aims to mechanistically relate changes in psychological, 
psychophysiological, and neural function during a novel emotion regulation intervention never 
before implemented in this stressed, high risk group. The goal is to inform future interventions 
that can reduce negative psychological outcomes in bereaved spouses. 
 
 
Design: 
 
Recently-bereaved participants (i.e. approximately 6 months post-spousal loss) will be screened 
for eligibility, then randomly assigned to receive training in either distancing or reinterpretation, 
with five sessions occurring every 1-3 days, with longitudinal collection of affective, 
psychophysiological, and functional magnetic resonance imaging (fMRI) data. During the five 
sessions (T1-T5), participants will undergo cognitive emotion regulation training and an emotion 
regulation task in their respective training groups, complete questionnaires, and take a 5 minute 
RSA reading. Functional MRI scans will be acquired at T1 and T5. Follow-up questionnaire 
assessments of perceived stress, depressive symptoms and grief rumination will occur at one and 
two months post-intervention. We propose to recruit 84 participants in this study (i.e., 42 
participants per intervention cell). 
 
 
 
 

Methods:  
 
 
Reappraisal Intervention Procedure. At sessions T1-T5, participants will complete a 
widely used image-based reappraisal task2-5. In the task, participants view non-violent images 
from the IAPS6 with themes relevant to grief and loss in bereavement. Task images are distinct 
from training images but contain the same themes. Neutral images contain at least one person but 
are emotionally neutral. All images at every session will be unique, presented in a randomized 
order, and counterbalanced across sessions and negative trial types. In the task, images are 
preceded by a cue word (either “LOOK” or “DECREASE”). On LOOK trials, participants will 
be asked to look at the image to-follow and respond naturally to it. On DECREASE trials, 
participants will be instructed to apply the appropriate regulation strategy (i.e., either distancing 
or reinterpretation) to decrease their emotional response to the image. Participants trained in 
distancing will be asked to alter the way they think about a personal connection to situations by 
viewing the photos with a rational, impartial mindset or imaging the events happened a long time 
ago, whereas participants trained in reinterpretation will be asked to tell themselves a story about 
the photos that whatever is going on will soon be better than it is now or the pain the person is 
feeling will be easier to bear with time. The resulting three trial types are: LOOK paired with a 
neutral image (“Look Neutral”), LOOK paired with a negative image (“Look Negative”), and 
DECREASE paired with a negative image (“Reappraise Negative”). One hundred and eighty 
total negative and 90 total neutral images are used in the task, with 18 trials per trial type per 
session, distributed evenly among 3 task runs. Following the presentation of each image, 
participants will be asked to rate their negative affect on a scale of 1 (least negative) to 4 (most 
negative). 
 
Self-report Questionnaires. Negative affect ratings will be assessed at T1 through T5. 
Perceived stress will be assessed using the Perceived Stress Scale (PSS)7 at T1 through T5 and 
both follow-ups. Participants will complete additional self-report questionnaires at T1, T5, and 
both follow-ups measuring depressive symptoms using the Center for Epidemiologic Studies 
Scale (CES-D)8, intensity and nature of grief-related cognitive processes using the Utrecht Grief 
Rumination Scale (UGRS)9, and emotion regulation strategy use using the Emotion Regulation 
Questionnaire (ERQ)10.   
 
Functional Magnetic Resonance Imaging. Participants will complete the picture task at 
sessions T1 and T5, while undergoing functional magnetic resonance imaging (fMRI) using a 
simultaneous multislice (SMS)-accelerated (3x) EPI acquisition protocol (63 axial slices; TR=1.2 
s; TE=27 ms, 2-mm cubic voxels). Participants will be scanned in a 3.0T Siemens Vida MRI 
scanner at the Houston Methodist Research Institute outfitted with an MR-compatible LCD 
display and an MR-compatible 4-response button box. Participants will be screened for metal 
and other MR-contraindications before entering the scanner.  
 
RSA. RSA will be continuously measured during sessions T1 through T5 non-invasively 
using a Corsense heart rate variability monitor by Elite HRV. RSA will be measured during a 5-
minute resting epoch while seated. 

References 
 
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