Distinct Brain Networks Associated with Risk and Resilience in Depression

Neuromodulation therapies such as transcranial magnetic stimulation, or deep brain stimulation, are emerging as new non-pharmacological treatments for mood disorders. However, understanding which areas of the brain to target to get the best therapeutic effect is still limited.

These new findings used brain imaging scans and depression scores from 526 patients who had acquired localized areas of brain injury from a stroke or other type of traumatic brain injury. A detailed statistical analysis of the patients’ data allowed the researchers to correlate the brain lesion locations with levels of depression experienced by the patients in the months following the brain injury.

“We found some really interesting results identifying specific brain structures that were associated with higher levels of depression post lesion, and surprisingly, also found some areas that were associated with lower-than-average levels of depression post lesion.” says Nicholas Trapp, MD  lead author of the study.

Using data from functional brain scans of healthy subjects to understand how these structures were interconnected, the researchers then discovered that the risk and resilience regions were not randomly scattered within the brain. Instead, regions most strongly associated with increased depression coincided with the nodes of the so-called salience network, which is involved in task reorientation, attention, and emotion processing.

In contrast, peak resilience regions that were associated with less depression, were part of a network known as the default mode network, which is thought to be involved in introspection, or self-referential thinking.

“Previous studies have suggested nodes of this network may be hyperactive in people with depression, who are prone to ruminating,” says Trapp, who also is a member of the Iowa Neuroscience Institute. “It’s possible that lesions within this network may alter that circuit in a way that leads people to report less depression.”

The initial lesion mapping approach used by Trapp and his colleagues is a powerful tool for inferring if a brain region is required for a behavior, emotion, or cognitive ability. If damage to a specific area leads to loss of the ability, the area is most likely required for the ability. However, identifying an effect when the regions are spread across a network within the brain requires data from many patients, which may have hindered earlier smaller studies.

Trapp hopes the findings will improve understanding of the causes of depression and potentially lead to better treatments.

“This could open the doors to potential studies looking at deep brain stimulation, or non-invasive forms of stimulation like TMS, where we might be able to modulate the specific brain areas or networks that we’ve identified, to try to get antidepressant effect, or potentially other therapeutic effects,” he says.


Nicholas T Trapp, Joel E Bruss, Kenneth Manzel, Jordan Grafman, Daniel Tranel, Aaron D Boes. Large-scale lesion symptom mapping of depression identifies brain regions for risk and resilience. Brain, 2022; DOI: 10.1093/brain/awac361

University of Iowa Health Care. “Distinct brain networks associated with risk and resilience in depression.” ScienceDaily. ScienceDaily, 13 October 2022. <www.sciencedaily.com/releases/2022/10/221013145640.htm>.

Materials provided by University of Iowa Health Care. Original written by Jennifer Brown. Note: Content may be edited for style and length.

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Photo by Anthony Tran