In a meta-analysis of 83 functional magnetic resonance imaging (fMRI) studies that included more than 5000 patients, exposure to adversity was associated with higher amygdala reactivity and lower prefrontal cortical reactivity across a range of task domains.
The altered responses were only observed in studies including adult participants and were clearest in participants who had been exposed to severe threat and trauma. Children and adolescents did not show significant adversity-related differences in brain function.
“By integrating the results from 83 previous brain imaging studies, we were able to provide what is arguably the clearest evidence to date that adults who have been exposed to early life trauma have different brain responses to psychological challenges,” senior author Marco Leyton, PhD, professor of psychiatry and director of the Temperament Adversity Biology Lab at McGill University in Montreal, Quebec, Canada, said in a press release. “This includes exaggerated responses in a region that processes emotionally intense information (the amygdala) and reduced responses in a region that helps people regulate emotions and associated behaviors (the frontal cortex).”
The findings were published in JAMA Network Open.
Changes in Reactivity
“One big issue we have in psychology, and especially in neuroscience, is that single-study results are often not reproducible,” lead author Niki Hosseini-Kamkar, PhD, neuroimaging research associate at Atlas Institute for Veterans and Families at Royal Ottawa Hospital, said in an interview.
“It was very important to me to use a meta-analysis to get an overall picture of what brain regions are consistently reported across all these different studies. That is what we did here,” she added. Dr. Hosseini-Kamkar conducted this analysis while she was a postdoctoral research fellow at McGill University in Montreal.
She and her group examined adversity exposure and brain function in the following four domains of task-based fMRI: emotion processing, memory processing, inhibitory control, and reward processing. Their study included 5242 participants. The researchers used multilevel kernel density analyses (MKDA) to analyze the data more accurately.
Adversity exposure was associated with higher amygdala reactivity (P < .001) and lower prefrontal cortical reactivity (P < .001), compared with controls with no adversity exposure.
Threat types of adversity were associated with greater blood-oxygen-level-dependent (BOLD) responses in the superior temporal gyrus and lower prefrontal cortex activity in participants exposed to threat, compared with controls.
Analysis of studies of inhibitory control tasks found greater activity in the claustrum, anterior cingulate cortex, and insula in the adversity-exposed participants, compared with controls.
In addition, studies that administered emotion processing tasks showed greater amygdala reactivity and lower prefrontal cortex (superior frontal gyrus) reactivity in the adversity exposure group, compared with controls.
“The main takeaway is that there’s an exaggerated activity in the amygdala, and diminished prefrontal cortex activity, and together, this might point to a mechanism for how a history of adversity diminishes the ability to cope with later stressors and can therefore heighten susceptibility to mental illness,” said Dr. Hosseini-Kamkar.
‘Important Next Step’
“Overall, the meta-analysis by Dr. Hosseini-Kamkar and colleagues represents an important next step in understanding associations of adversity exposure with brain function while highlighting the importance of considering the role of development,” wrote Dylan G. Gee, PhD, associate professor of psychology at Yale University in New Haven, Connecticut, and Alexis Brieant, PhD, assistant professor of research or creative works at the University of Vermont in Burlington, in an accompanying commentary.
They also applauded the authors for their use of MKDA. They noted that the technique “allows inferences about the consistency and specificity of brain activation across studies and is thought to be more robust to small sample sizes than activation likelihood estimation (ALE) meta-analysis.”
Dr. Gee and Dr. Brieant also observed that a recent ALE meta-analysis failed to find a link between adversity and brain function. “Although it is important to note that the file drawer problem — by which researchers are less likely to publish null results — presents challenges to the inferences that can be drawn in the current work, the current study may provide complementary information to prior ALE meta-analyses.”