A new study linking the location of brain injury to levels of depression in post-injury patients has identified two distinct brain networks; one associated with an increase in depressive symptoms and another with a decrease in depressive symptoms. The large-scale study led by researchers at the University of Iowa Health Care expands 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, the understanding of which areas of the brain should be targeted for the best therapeutic effect is still limited.
The new findings, which are published in the journal Brain, used brain imaging scans and depression scores of 526 patients who had acquired localized areas of brain damage from a stroke or other type of traumatic brain injury. A detailed statistical analysis of the patients’ data allowed the researchers to correlate the locations of the brain injuries with the levels of depression experienced by the patients in the months following the brain injury.
We found really interesting results that identified specific brain structures that were associated with higher levels of post-injury depression and, surprisingly, we also found some areas that were associated with lower than average levels of post-injury depression.”
Nicholas Trapp, MD, UI assistant professor of psychiatry and lead author of the study
Networks of risk and resilience in depression
Using data from functional brain scans of healthy subjects to understand how these structures were interconnected, the researchers discovered that regions of risk and resilience were not randomly scattered within the brain. Instead, the regions most strongly associated with increased depression coincided with nodes in the so-called salience network, which is involved in task reorientation, attention, and emotion processing.
In contrast, the regions of greatest resilience 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 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 can disrupt this circuit in a way that leads people to report less depression.”
Patients whose brain injuries did not fall within any network had an average depression score after their brain injury and provided a comparison group for the study.
strength in numbers
The initial lesion-mapping approach used by Trapp and 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 causes the ability to be lost, the area is likely required for the ability. However, identifying an effect when regions span a network within the brain requires data from many patients, which may have hampered previous smaller studies.
Trapp and his team were able to conduct the study thanks to two large patient registries: the UI-based Iowa Neurological Patient Registry and the Northwestern-affiliated Vietnam Head Injury Study University.
“Being able to identify these brain regions is really a product of having a large sample to study,” says Trapp. “It’s very difficult to recruit these patients and collect the data that is required. The decades of effort here at the University of Iowa (establishing and maintaining the Iowa Neurological Patient Registry) positions us very well to do this kind of studies”.
New potential 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 like TMS, where we could modulate the specific brain areas or networks that we’ve identified, to try to get an antidepressant effect. , or potentially other therapeutic effects,” he says.
In addition to Trapp, the UI research team included Aaron Boes, Joel Bruss, Kenneth Manzel and Dan Tranel of the UI Department of Neurology, and Jordan Grafman of the Shirley Ryan AbilityLab at the Northwestern University Feinberg School of Medicine of 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
Journal reference:
Trapp, NT, et al. (2022) Large-Scale Lesion Symptom Mapping of Depression Identifies Brain Regions for Risk and Resilience. brain doi.org/10.1093/brain/awac361.