Sex Differences in Functional Connectivity during Emotion Regulation and Implications for Healthy Cognitive Aging

Natalie Fletcher, BS

Massachusetts General Hospital – Research Assistant
Natalie Fletcher

Scientific Abstract

Background: The ability to regulate emotional response to negative/stressful events is critical to maintaining mental health and healthy aging. Maladaptive responses to negative affective stimuli are implicated in most psychiatric disorders, including Major Depressive Disorder (MDD), which is a risk factor for cognitive decline. Cognitive reappraisal is one technique used to regulate emotion and consists of consciously reframing a negative stimulus to change emotional response. In this study we examined sex differences in functional connectivity during an emotion regulation task in participants with or without a history of MDD.

Methods: fMRI data were collected from 56 adults (28 M: 28 F) ages 52-61 with long-term history of MDD (“cases”) and without MDD (“controls”). Participants were taught techniques of cognitive reappraisal. Then in a 3T scanner, they were shown negative or neutral images and told to either “maintain” or “decrease” their emotional response. Seed-based functional connectivity analyses were conducted comparing trials between sexes and between cases and controls (within sex). Results were analyzed in relation to performance on Face-Name associative memory task.

Results: Female controls showed increased connectivity between inhibitory stress regions (HIPP, mPFC) and regions in the DMN (ACC, PCC, precuneus) and prefrontal cognitive control regions (dlPFC, vlPFC) compared to female cases and male controls during the negative decrease condition. Connectivity values in both males and females were strongly correlated with performance on the Face-Name task.

Conclusions: Increased connectivity during emotion regulation is strongly associated with performance on a memory measure used to detect signs of early changes in memory performance with age. Results from this study show that healthy women in later midlife are better able to recruit regions involved in cognitive control to attenuate their response to negative events and that this may be protective during cognitive aging.

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research Areas


Natalie Fletcher, BS, Justine E. Cohen, PhD, Hannah Shields, BS, Laura M. Holsen, PhD, Sarah Aroner, PhD, Harlyn Aizley, EdM, Anne Remington, MA, Jill M. Goldstein, PhD

Principal Investigator

Jill M. Goldstein, PhD

Affiliated Website