Adverse Life Experiences and Brain Function: A Meta-Analysis of Functional Magnetic Resonance Imaging Findings

Abstract

Importance: Adverse life experiences have been proposed to contribute to diverse mental health problems through an association with corticolimbic functioning. Despite compelling evidence from animal models, findings from studies in humans have been mixed; activation likelihood estimation (ALE) meta-analyses have failed to identify a consistent association of adverse events with brain function.

Objective: To investigate the association of adversity exposure with altered brain reactivity using multilevel kernel density analyses (MKDA), a meta-analytic approach considered more robust than ALE to small sample sizes and methodological differences between studies.

Data sources: Searches were conducted using PsycInfo, Medline, EMBASE, and Web of Science from inception through May 4, 2022. The following search term combinations were used for each database: trauma, posttraumatic stress disorder (PTSD), abuse, maltreatment, poverty, adversity, or stress; and functional magnetic resonance imaging (fMRI) or neuroimaging; and emotion, emotion regulation, memory, memory processing, inhibitory control, executive functioning, reward, or reward processing.

Study selection: Task-based fMRI studies within 4 domains (emotion processing, memory processing, inhibitory control, and reward processing) that included a measure of adverse life experiences and whole-brain coordinate results reported in Talairach or Montreal Neurological Institute space were included. Conference abstracts, books, reviews, meta-analyses, opinions, animal studies, articles not in English, and studies with fewer than 5 participants were excluded.

Data extraction and synthesis: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline, 2 independent reviewers assessed abstracts and full-text articles for entry criteria. A third reviewer resolved conflicts and errors in data extraction. Data were pooled using a random-effects model and data analysis occurred from August to November 2022.

Main outcomes and measures: Peak activation x-axis (left-right), y-axis (posterior-anterior), and z-axis (inferior-superior) coordinates were extracted from all studies and submitted to MKDA meta-analyses.

Results: A total of 83 fMRI studies were included in the meta-analysis, yielding a combined sample of 5242 participants and 801 coordinates. Adversity exposure was associated with higher amygdala reactivity (familywise error rate corrected at P < .001; x-axis = 22; y-axis = -4; z-axis = -17) and lower prefrontal cortical reactivity (familywise error rate corrected at P < .001; x-axis = 10; y-axis = 60; z-axis = 10) across a range of task domains. These altered responses were only observed in studies that used adult participants and were clearest among those who had been exposed to severe threat and trauma.

Conclusions and relevance: In this meta-analysis of fMRI studies of adversity exposure and brain function, prior adversity exposure was associated with altered adult brain reactivity to diverse challenges. These results might better identify how adversity diminishes the ability to cope with later stressors and produces enduring susceptibility to mental health problems.

Figure 1.. PRISMA Flowchart

DTI indicates diffusion tensor imaging; MKDA, multilevel kernel density analysis; PET, positron emission tomography; PRISMA, preferred reporting items for systematic reviews and meta-analyses; PTSD, posttraumatic stress disorder; ROI, region of interest; TBI, traumatic brain injury.

Figure 2.. Coordinates Indicating Blood-Oxygen-Level-Dependent (BOLD) Responses for Adversity Group vs Comparison Group for All 4 Neurocognitive Domains

Panel A shows collective images of studies that reported greater BOLD responses in the adversity group compared with the comparison group (67 studies; 523 coordinates) across all task domains (emotion processing, memory processing, inhibitory control, and reward processing). Right amygdala activation was consistently reported across studies in adversity groups compared with comparisons (familywise error rate corrected P < .001). Panel B shows collective images of studies that reported greater BOLD responses in the comparison group compared with the adversity group (47 studies; 278 coordinates). Greater prefrontal cortex activation was consistently reported across studies in comparison groups compared with adversity-exposed individuals (familywise error rate corrected P < .001).

Figure 3.. Coordinates Indicating Blood-Oxygen-Level-Dependent (BOLD) Responses for Threat-Type Adversity Group vs Comparison Group

Panel A shows collective images of studies that reported greater BOLD responses in threat-exposed adversity groups compared with comparison groups (32 studies; 294 coordinates). Greater superior temporal gyrus activation was consistently reported across studies in individuals exposed to threat types of adversity as compared with controls (familywise error rate corrected P < .05). Panel B shows collective images of studies that reported greater BOLD responses in the comparison group compared with threat-exposed adversity group (18 studies; 133 coordinates). Lower prefrontal cortex (medial frontal gyrus) activity was seen in participants exposed to threat compared with comparisons (familywise error rate corrected P < .05).