Study pinpoints neural changes from adversity

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In a recently published study, Dr JAMA Network OpenThe researchers assessed links between adverse life experiences and changes in brain response using the multilevel kernel density analysis (MKDA) method in task-based functional magnetic resonance imaging (fMRI) studies.

Study: Adverse life experiences and brain function: a meta-analysis of functional magnetic resonance imaging findings.  Image credit: Tushchakorn/ Study: Adverse life experiences and brain function: a meta-analysis of functional magnetic resonance imaging findings. Image credit: Tushchakorn/


Negative life experiences can alter brain function, thereby increasing the risk of mental illness. The main brain regions affected include the prefrontal cortex (PFC), amygdala and hippocampus.

Although animal studies confirm this, human data are variable due to differences in definitions of adversity, measurement of its effects, and differences in study methods. Variability also arises from the use of different image acquisition and analysis techniques.

A meta-analysis using the MKDA method, which accounts for these variations, provides more reliable insights than the activation likelihood estimation (ALE) method. However, due to inconsistencies in human studies on the brain’s response to adversity, further research is essential to understand long-term neuroplastic changes from adverse experiences.

About the study

The current study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. A comprehensive literature search was conducted across databases including PsycINFO, Medline, EMBASE and Web of Science until May 2022. Brainmap databases and gray literature were also additionally searched.

The search combined terms related to trauma, adversity, neuroimaging, and various cognitive processes. Articles were selected based on specific criteria, thereby excluding conference abstracts, books and some other types of publications.

From the initial 2,016 abstracts identified, 336 met the criteria for further in-depth review. Two reviewers assessed these articles, and a third reviewer resolved any discrepancies.

Brain activation coordinate data were accurately extracted and validated. To account for varying definitions of adversity across studies, these data were categorized by criteria such as threat or deprivation and severity of adversity.

For statistical analysis, the researchers extracted activation coordinates and grouped them based on task type and participant group. The MKDA method was used to determine whether activation was consistent across studies.

Simulations were used to verify the validity of the results. The data was analyzed between August and November 2022 using specialized software tools.

Study results

In a comprehensive analysis of 83 studies involving 5,242 participants, significant changes in blood-oxygen-level-dependent (BOLD) responses to exposure to adversity were observed. When data from 67 studies were examined, those exposed to adversity exhibited increased right amygdala reactivity compared to their counterparts. In comparison, 47 other studies found that the adversity group exhibited consistently reduced responses in the medial frontal gyrus.

Among 50 studies on emotion processing, the adversity-exposed group demonstrated higher amygdala activity and decreased superior frontal gyrus activity. In 11 studies that focused on inhibitory control, those who experienced adversity demonstrated increased activity in the claustrum, anterior cingulate cortex, and insula. No differences were observed in studies of memory or reward-processing tasks.

When examining threats as adversity, there was an amplified BOLD response in the superior temporal gyrus and decreased medial frontal gyrus activity for the adversity group. This pattern persisted across different task domains.

When mixed adversities were studied, individuals exposed to these mixed adversities exhibited higher activity in all domains of the right amygdala, precuneus, and superior frontal gyrus. In studies focusing only on deprivation type adversity, no significant results were reported, thus making firm conclusions challenging.

Individuals exposed to trauma-type adversity had significantly greater bilateral amygdala activation and decreased activity in areas such as the medial frontal gyrus and anterior cingulate cortex. Meanwhile, moderate odds were not associated with any significant associations.

The relationship between trauma and psychopathological conditions such as post-traumatic stress disorder (PTSD) was also examined. To this end, individuals diagnosed with PTSD exhibited significantly greater left amygdala activation but reduced activity in regions such as the hippocampus, orbitofrontal cortex, and insula.

The study considered developmental stages by classifying participants into adults, adolescents, and children. Data from adults, drawn from 34 studies, revealed that exposure to adversity during adulthood was associated with increased right amygdala activation but decreased activity in the middle frontal gyrus.


Individuals with a history of severe adversity have increased amygdala response and decreased PFC response to psychological challenges. 83 studies showed possible PFC impairment in controlling MKDA amygdala activity.

The amygdala, which is essential for threat detection, has demonstrated increased activity as a PTSD biomarker. Individuals with PTSD or those who had experienced severe adversity exhibited stronger amygdala and weaker PFC responses across all tasks.

Specific adversity increased insula and anterior cingulate cortex (ACC) activity. Traumatic adversity specifically increased amygdala activity.

Notably, individuals with PTSD demonstrated significant left amygdala activity, which contrasts with some previous studies and reduced activity in other brain regions.

Journal Reference:

  • Hosseini-Kamkar, N., Farahani, M. V., Nikolic, M., etc (2023). Adverse life experiences and brain function: a meta-analysis of functional magnetic resonance imaging findings. JAMA Network Open. doi:10.1001/jamanetworkopen.2023.40018

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