Neural Mechanisms of Enhancing Emotion Regulation in Bereaved Spouses

This study investigates the underlying mechanisms of a novel emotion regulation intervention among recently bereaved spouses. More specifically, this study examines how thinking about an emotional stimulus in a more adaptive way can affect the relationship between psychological stress, psychophysiological biomarkers of adaptive cardiac response, and brain activity. The emotion regulation strategy targeted is reappraisal, specifically reappraisal-by-distancing (i.e., thinking about a negative situation in a more objective, impartial way) versus reappraisal-by-reinterpretation (i.e., thinking about a better outcome for a negative situation than what initially seemed apparent).

The study seeks to determine if relatively brief, focused reappraisal training in bereaved spouses will result in reduction of self-reported negative affect, increases in respiratory sinus arrhythmia (RSA; a measure of heart rate variability reflecting adaptive cardiac vagal tone), reduction in blood-based inflammatory biomarkers, and changes in neural activity over time. Reappraisal-by-distancing is expected to lead to greater changes in these variables relative to reappraisal-by-reinterpretation. Additionally, it is expected that across time decreases in self-reported negative affect, increases in RSA, reductions in blood-based inflammatory biomarker levels, and changes in neural activity will in turn lead to reductions in depressive symptoms and grief rumination. Finally, it is expected that distancing training will lead to reductions in depressive symptoms and grief rumination that are mediated by changes in the targeted neurobiological and behavioral mechanisms.

Study Overview

• Status: Completed
• Conditions: Depressive Symptoms; Emotions; Grief; Bereavement; Affect
• Intervention / Treatment: Behavioral: Cognitive Emotion Regulation Training

Detailed Description

The objective of this study is to use an experimental medicine approach to evaluate the basic psychological, psychophysiological, and neural mechanisms underlying a novel cognitive emotion regulation intervention aimed at improving psychological outcomes (e.g., reducing depressive symptoms and grief rumination) in recently bereaved spouses. 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 bereavement. 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 current study builds upon promising preliminary work to investigate the effectiveness and underlying neurobiological mechanisms of a novel, five-session cognitive reappraisal intervention in bereaved spouses.

Recently bereaved participants (i.e. approximately 6 months post-spousal loss) will be randomly assigned to receive training in either distancing or reinterpretation, with five sessions occurring every 1-3 days, with longitudinal collection of affective, psychophysiological, physiological (i.e., blood draws to assess inflammatory biomarkers) and functional magnetic resonance imaging (fMRI) data. Follow-up questionnaire assessments will occur at one- and two-months post-intervention. The study aims to mechanistically relate changes in psychological, psychophysiological, physiological, and neural function during a novel emotion regulation intervention never before implemented in this stressed, high risk group. This research represents a Phase I, Stage I clinical trial. The primary endpoints are the assessments of the psychological, psychophysiological, physiological, and neural mechanisms mediating behavior change as a function of the cognitive emotion regulation intervention. The secondary endpoint is testing the efficacy of the intervention via assessment of psychological outcomes (i.e., the behavior change, as represented in changes in depressive symptoms, stress, and grief rumination).

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Rice University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Recent loss of romantic partner within the past 5-7 months
• At least 18 years of age
• Minimum score of 25 on the Inventory for Complicated Grief
• Must be able to speak, read, and write in English
• Must be eligible to safely complete MRI scanning

Exclusion Criteria:

• Death of a second close family member/friend in the past year
• Currently receiving psychotherapy
• Diagnosed with obstructive pulmonary and/or heart disease, diabetes, liver failure, or kidney failure
• Significant visual, auditory, or cognitive impairment
• Divorced within the last year
• Prior participation in a similar emotion regulation training protocol in Dr. Denny's lab
• Any contraindication of MRI scanning (e.g., pregnancy, presence of any non-removable metal on or in the body, implanted medical devices, tattoos, medication patches, orthodontic braces or permanent retainers, hearing aids, history of claustrophobia or breathing disorders)

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: Distancing; Participants will receive structured cognitive emotion regulation training from an experimenter during an approximately 10-minute interaction in which detailed instructions for implementation of the distancing strategy is explained (i.e. appraising an emotional stimulus as an objective, impartial observer).	Behavioral: Cognitive Emotion Regulation Training; Cognitive emotion regulation training via cognitive reappraisal involves the ability to modify the trajectory of an emotional response by thinking about and appraising emotional information in an alternative, more adaptive way. Reappraisal to down-regulate negative emotion can be operationalized via two tactics: psychological distancing and reinterpretation. The current study will randomly assign participants to receive a brief course of reappraisal training using either psychological distancing or reinterpretation.
Active Comparator: Reinterpretation; Participants will receive structured cognitive emotion regulation training from an experimenter during an approximately 10-minute interaction in which detailed instructions for implementation of the reinterpretation strategy is explained (i.e. imagining a better outcome than what initially seemed apparent).	Behavioral: Cognitive Emotion Regulation Training; Cognitive emotion regulation training via cognitive reappraisal involves the ability to modify the trajectory of an emotional response by thinking about and appraising emotional information in an alternative, more adaptive way. Reappraisal to down-regulate negative emotion can be operationalized via two tactics: psychological distancing and reinterpretation. The current study will randomly assign participants to receive a brief course of reappraisal training using either psychological distancing or reinterpretation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-reported Negative Affect	Self-reported negative affect data collected during the emotion regulation task on a 1-4 scale, with 1 meaning "not negative at all" and 4 meaning "very negative".	Sessions 1 (baseline/initial session), 2, 3, 4, and 5, which were conducted approximately every 2-3 days over the course of 2 weeks.
Respiratory Sinus Arrhythmia	Heart rate variability, or variability in time intervals between heart beats, as measured by the log of the root mean square of the successive RR interval differences (ln(RMSSD)). RR intervals are interbeat intervals between consecutive heartbeats. Average ranges for ln(RMSSD) for 30 to over 75 years of age range from 3.2 to 3.9 for women and 3.2 to 3.8 for men.	Sessions 1 (baseline/initial session), 2, 3, 4, and 5, which were conducted approximately every 2-3 days over the course of 2 weeks.
Neural Activity	Picture Induced Negative Emotion Signature (PINES) is an independently-defined, validated whole-brain neural pattern map for negative appraisal, with positive weights for areas like the amygdala and insula. PINES Correspondence Scores (PCS) are correlation coefficients derived for each trial type (Look Neutral, Look Negative, Reappraise Negative) per participant by correlating each participant's whole-brain pattern during the task to PINES. PCS correlation coefficients range from -1 to 1, and higher values reflect greater correlation to PINES and thus greater negative affect.	Sessions 1 (baseline/initial session) and 5, which were conducted approximately 2 weeks apart.
Grief Rumination	Grief rumination assessed via Utrecht Grief Rumination Scale (UGRS) and the Inventory for Complicated Grief (ICG). UGRS items are rated from 1 (never) to 5 (very often). Scores range from 15 to 75; higher numbers represent higher grief rumination. These are summed from 3-item subscales Reactions, Injustice, Counterfactuals, Meaning, and Relationships, which all have score ranges of 3-15. Higher scores represent greater grief rumination. The ICG assesses grief via 19 first-person statements on a scale of 0 (Never) to 4 (Always) with a range from 0-76. Higher numbers reflect greater grief.	Sessions 1 (baseline/initial session) and 5, which were conducted approximately 2 weeks apart, and at the 1- and 2-month follow-ups.
Depressive Symptoms	Symptoms of depression assessed via the Center for Epidemiological Studies Depression (CES-D) scale, which asks participants to rate how often in the past week they have experience symptoms of depression, ranging from 0 (Rarely or none of the time) to 3 (Most of the time). Scores range from 0 to 60, with higher scores indicating higher levels of depressive symptoms.	Sessions 1 (baseline/initial session) and 5, which were conducted approximately 2 weeks apart, and at the 1- and 2-month follow-ups.
Perceived Stress	Perceived stress assessed via the Perceived Stress Scale (PSS), consisting of 10 self-reported items asking participants how often they felt or thought a certain way, ranging from 0 (Never) to 4 (Very Often). Total range is 0 to 40, with higher scores indicate higher levels of perceived stress.	Sessions 1 (baseline/initial session), 2, 3, 4, and 5, which were conducted approximately every 2-3 days over the course of 2 weeks, and at the 1- and 2- month follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Reappraisal Usage	Overall reappraisal usage frequency assessed via the Emotion Regulation Questionnaire Reappraisal facet score. Participants report using a 7-point Likert-type scale ranging from 1 (strongly disagree) to 7 (strongly agree). Reappraisal facet scores may range from 6-42. Higher scores represent greater habitual reappraisal usage.	Sessions 1 (baseline/initial session) and 5, which were conducted approximately 2 weeks apart, and at the 1- and 2-month follow-ups.
Physical Health	Physical health and quality of life assessed via the RAND 36-Item Short Form Health Survey (SF-36) which assesses 8 subscales: physical functioning, social functioning, role limitations due to physical health problems, body pain, role limitations due to personal or emotional problems, emotional well-being, energy/fatigue, and general health perceptions. Each subscale ranges from 0 to 100, higher scores referring to more adaptive health outcomes.	Sessions 1 (baseline/initial session) and 5, which were conducted approximately 2 weeks apart, and at the 1- and 2-month follow-ups.
Inflammatory Biomarkers	Inflammatory biomarkers (e.g., serum IL-6, sIL-6R, IL-10, and TNF- α) measured via blood draw	Sessions 0 and 6, which were conducted approximately 2-3 weeks apart.

Collaborators and Investigators

• Sponsor: Bryan Denny
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Bryan Denny, Ph.D., William Marsh Rice University

Publications and helpful links

General Publications

• Denny BT, Ochsner KN. Behavioral effects of longitudinal training in cognitive reappraisal. Emotion. 2014 Apr;14(2):425-33. doi: 10.1037/a0035276. Epub 2013 Dec 23.
• Denny BT. Getting better over time: A framework for examining the impact of emotion regulation training. Emotion. 2020 Feb;20(1):110-114. doi: 10.1037/emo0000641.
• Fagundes CP, Brown RL, Chen MA, Murdock KW, Saucedo L, LeRoy A, Wu EL, Garcini LM, Shahane AD, Baameur F, Heijnen C. Grief, depressive symptoms, and inflammation in the spousally bereaved. Psychoneuroendocrinology. 2019 Feb;100:190-197. doi: 10.1016/j.psyneuen.2018.10.006. Epub 2018 Oct 11.
• Bonanno GA, Kaltman S. Toward an integrative perspective on bereavement. Psychol Bull. 1999 Nov;125(6):760-76. doi: 10.1037/0033-2909.125.6.760.
• Denny BT, Inhoff MC, Zerubavel N, Davachi L, Ochsner KN. Getting Over It: Long-Lasting Effects of Emotion Regulation on Amygdala Response. Psychol Sci. 2015 Sep;26(9):1377-88. doi: 10.1177/0956797615578863. Epub 2015 Jul 31.
• Ochsner KN, Silvers JA, Buhle JT. Functional imaging studies of emotion regulation: a synthetic review and evolving model of the cognitive control of emotion. Ann N Y Acad Sci. 2012 Mar;1251:E1-24. doi: 10.1111/j.1749-6632.2012.06751.x.
• Fagundes CP, Murdock KW, LeRoy A, Baameur F, Thayer JF, Heijnen C. Spousal bereavement is associated with more pronounced ex vivo cytokine production and lower heart rate variability: Mechanisms underlying cardiovascular risk? Psychoneuroendocrinology. 2018 Jul;93:65-71. doi: 10.1016/j.psyneuen.2018.04.010. Epub 2018 Apr 13.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2022
• Primary Completion (Actual): May 22, 2024
• Study Completion (Actual): May 22, 2024

Study Registration Dates

• First Submitted: March 25, 2021
• First Submitted That Met QC Criteria: March 25, 2021
• First Posted (Actual): March 30, 2021

Study Record Updates

• Last Update Posted (Actual): July 9, 2025
• Last Update Submitted That Met QC Criteria: June 18, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: emotion regulation; affective neuroscience; bereavement; social cognitive neuroscience
• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression
• Other Study ID Numbers: IRB-FY2017-90; 1R21AG061597-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pursuant to the NIH Data Sharing Policy, we have created a Data Sharing Plan for the proposed research. Under this plan, and pursuant to IRB regulations, fully de-identified raw data (defined below) will be made publicly available. Available data will include a compendium of de-identified training condition assignments; raw (i.e. individual subject-by-condition level) negative affect self-reports; questionnaire data; raw heart rate variability data; and raw subject-level brain data (i.e. unpreprocessed functional and structural MRI data, converted to the widely-sharable Brain Imaging Data Structure [BIDS] standard).
• IPD Sharing Time Frame: De-identified data will be made available after the analysis process is complete and research manuscripts are finalized. There is no fixed end date for data access.
• IPD Sharing Access Criteria: Data will be publicly available on OpenNeuro (https://openneuro.org), a free, open- science neuroinformatics data repository.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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