Precision functional MRI mapping reveals distinct connectivity patterns for depression associated with traumatic brain injury
Abstract
Depression associated with traumatic brain injury (TBI) is believed to be clinically distinct from primary major depressive disorder (MDD) and may be less responsive to conventional treatments. Brain connectivity differences between the dorsal attention network (DAN), default mode network (DMN), and subgenual cingulate have been implicated in TBI and MDD. To characterize these distinctions, we applied precision functional mapping of brain network connectivity to resting-state functional magnetic resonance imaging data from five published patient cohorts, four discovery cohorts ( n = 93), and one replication cohort ( n = 180). We identified a distinct brain connectivity profile in TBI-associated depression that was independent of TBI, MDD, posttraumatic stress disorder (PTSD), depression severity, and cohort. TBI-associated depression was independently associated with decreased DAN–subgenual cingulate connectivity, increased DAN-DMN connectivity, and the combined effect of both. This effect was stronger when using precision functional mapping relative to group-level network maps. Our results support the possibility of a physiologically distinct “TBI affective syndrome,” which may benefit from individualized neuromodulation approaches to target its distinct neural circuitry.
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Individual resting-state fMRI-based network mapping has revealed different patterns of functional connectivity in patients with TBI plus depression symptoms compared with patients with TBI without depression symptoms or patients with depression symptoms in the absence of TBI.
“Notably, individual resting state fMRI-based network mapping has revealed different patterns of functional connectivity in patients with TBI plus depression symptoms compared with patients with TBI without depression symptoms or patients with depression symptoms in the absence of TBI (16).”
Those with a history of concussion may have unique disruptions in functional networks and a complex neurobehavioral clinical presentation, making standard scalp-based DLPFC targeting even less optimal for this population.
“Compounding the variability in functional brain circuitry seen in the general population, those with a history of concussion may have unique disruptions in functional networks and a complex neurobehavioral clinical presentation (16, 33, 34) making standard scalp-based DLPFC targeting even less optimal for this population.”
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- Authors
- Siddiqi, S. H., Kandala, S., Hacker, C. D., Bouchard, H., Leuthardt, E. C., Corbetta, M., Morey, R. A., & Brody, D. L.
- Affiliations
- Brigham and Women's Hospital (US)
- Washington University in St. Louis (US)
- Duke University (US)
- University of Padua (IT)
- Uniformed Services University of the Health Sciences (US)
- Corresponding author
- Siddiqi, Shan H.
- Morey, Rajendra A.
- Brody, David L.
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2023-07-05
- Volume
- 15
- Issue
- 703
- Pages
- eabn0441-eabn0441
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- OpenAlex
- W4383198682
- Cited by
- 50
- References
- 47
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 15 · 2023: 5
- FWCI
- 7.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 CX002293)
- National Institute of Mental Health (K23MH121657)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- traumatic brain injury, major depressive disorder, post-traumatic stress disorder, dorsal attention network, default mode network, subgenual cingulate, brain network connectivity, resting-state functional connectivity, neuromodulation
- MeSH terms
- Brain Injuries, Traumatic, Brain, Brain Mapping, Depression, Major Depressive Disorder, Humans, Magnetic Resonance Imaging, Neural Pathways
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