Summary: Researchers have identified two distinct brain regions, one linked to increased and the other with decreased depressive symptoms, associated with the location of brain injuries.
Source: University of Iowa
A new study that links the location of brain injury to levels of depression in patients following the injury has identified two distinct brain networks; one associated with increased depression symptoms and one associated with decreased depression symptoms.
The large-scale study led by researchers with University of Iowa Health Care expands on previous findings and suggests that these brain networks might 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 get the best therapeutic effect is still limited.
The new findings, which are published in the journal Brain, 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, UI assistant professor of psychiatry and lead author of the study.
Risk and resilience networks in depression
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.”
Patients whose brain lesions did not fall within either network had an average score of depression following their brain injury and provided 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 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 and his team were able to conduct they study thanks to two large patient registries: the Iowa Neurological Patient Registry based at the UI, and the Vietnam head injury study, which is affiliated with researchers at Northwestern University.
“Being able to identify these brain regions is really a product of having a large sample to study,” Trapp says. “It’s very challenging to recruit these patients and collect the data that’s required. The decades of efforts here at the University of Iowa (establishing and maintaining the Iowa Neurological Patient Registry) positions us extremely well to do these types of 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.
Large-scale lesion symptom mapping of depression identifies brain regions for risk and resilience
Understanding neural circuits that support mood is a central goal of affective neuroscience, and improved understanding of the anatomy could inform more targeted interventions in mood disorders.
Lesion studies provide a method of inferring the anatomical sites causally related to specific functions, including mood.
Here, we perform a large-scale study evaluating the location of acquired, focal brain lesions in relation to symptoms of depression. 526 individuals participated in the study across 2 sites (356 male, average age 52.4 +/- 14.5 years).
Each subject had a focal brain lesion identified on structural imaging and an assessment of depression using the Beck Depression Inventory-II, both obtained in the chronic period post-lesion (>3 months). Multivariate lesion-symptom mapping was performed to identify lesion sites associated with higher or lower depression symptom burden, which we refer to as “risk” versus “resilience” regions.
The brain networks and white matter tracts associated with peak regional findings were identified using functional and structural lesion network mapping, respectively.
Lesion-symptom mapping identified brain regions significantly associated with both higher and lower depression severity (r = 0.11; p = 0.01).
Peak “risk” regions include the bilateral anterior insula, bilateral dorsolateral prefrontal cortex, and left dorsomedial prefrontal cortex. Functional lesion network mapping demonstrated that these “risk” regions localized to nodes of the salience network.
Peak “resilience” regions include the right orbitofrontal cortex, right medial prefrontal cortex, and right inferolateral temporal cortex, nodes of the default mode network.
Structural lesion network mapping implicated dorsal prefrontal white matter tracts as “risk” tracts and ventral prefrontal white matter tracts as “resilience” tracts, although the structural lesion network mapping findings did not survive correction for multiple comparisons.
Taken together, these results demonstrate that lesions to specific nodes of the salience network and default mode network are associated with greater risk versus resiliency for depression symptoms in the setting of focal brain lesions.