Certain brain networks could be potential targets for neuromodulation therapies to treat depression

Certain brain networks could be potential targets for neuromodulation therapies to treat depression

A new study linking the location of brain injury to the level of depression in post-injury patients has identified two distinct brain networks; one was associated with increased depression symptoms and one was associated with decreased depression symptoms. The large-scale study, conducted by researchers at the University of Iowa Health Care, builds on previous findings and suggests that these brain networks could be potential targets for neuromodulation therapies to treat 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 achieve the best therapeutic effect is still limited.

The new findings, published in the journal Brain, are based on brain imaging studies and depression results from 526 patients who suffered local brain injuries from a stroke or other type of traumatic brain injury. Detailed statistical analysis of patient data allowed researchers to correlate the locations of brain lesions with the level of depression patients experienced in the months following brain injury.

We found some really interesting results identifying specific brain structures that were associated with higher levels of post-lesion depression, and surprisingly, we also found some areas that were associated with lower than average levels of post-lesion depression.”

Nicholas Trapp, MD, UI assistant professor of psychiatry and lead author of the study

Risk and resilience networks in depression

To understand how these structures are connected, the researchers used data from functional brain scans of healthy volunteers and then found that the risk and resilience regions were not randomly scattered throughout the brain. Instead, the regions most strongly associated with increasing depression coincided with the nodes of the so-called salience network, which is involved in task reorientation, attention and emotion processing.

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

“Previous studies have shown that nodes in this network may be hyperactive in people with depression who are prone to rumination,” says Trapp, who is also a member of the Iowa Neuroscience Institute. "It's possible that lesions within this network alter this circuitry so that people report less depression."

Patients whose brain lesions did not fall into either network had average depression scores after their brain injury and formed a comparison group in the study.

Strength in numbers

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

Trapp and his team were able to conduct their study thanks to two large patient registries: the Iowa Neurological Patient Registry at UI and the Vietnam Head Injury Study, which is affiliated with researchers at Northwestern University.

“In order to be able to identify these brain regions, it is really necessary to be able to examine a large sample,” says Trapp. "It is a significant challenge to recruit these patients and collect the necessary data. The decades-long effort here at the University of Iowa (establishing and maintaining the Iowa Neurological Patient Registry) positions us well to conduct these types of studies."

Possible new targets for neuromodulation

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

“This could open the door to potential studies looking at deep brain stimulation or non-invasive forms of stimulation such as TMS, where we may be able to modulate the specific brain areas or networks we have identified to produce an antidepressant effect.” or possibly other therapeutic effects,” he says.

In addition to Trapp, the UI research team also included Aaron Boes, Joel Bruss, Kenneth Manzel and Dan Tranel from the UI Department of Neurology, and Jordan Grafman from the Shirley Ryan AbilityLab at the Feinberg School of Medicine at Northwestern University in Chicago

The study was funded in part by grants from the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the Kiwanis Neuroscience Research Foundation.

Source:

University of Iowa Health Care

Reference:

Trapp, N.T., et al. (2022) Large-scale mapping of lesion symptoms in depression identifies brain regions for risk and resilience. Brain. doi.org/10.1093/brain/awac361.

.