The prevalence of disorders of consciousness (DoC) in the United States (2018)1 – including coma, vegetative state, and minimally conscious state – is estimated to be:
The landscape of DoC management is fraught with challenges. Diagnosis is difficult, with no laboratory nor imaging tests to detect consciousness. Published estimates of misdiagnosis among people with DoC approximate 40% and there are no acute treatments to prevent the secondary effects of primary brain injury. The only one proven post-acute treatment proven to accelerate rate of recovery, amantadine hydrochloride, has narrow indications.
A 2020 Symposium from the Curing Coma Campaign2 identified research targets within six areas: defining endotypes/phenotypes, biomarkers, proof-of-concept clinical trials, prognostication, long-term recovery, and establishing large data sets. Advances in our understanding of brain pathophysiology and biotechnology offer new avenues to improve diagnosis and treatment through research. The table below lists potential areas of exploration for applicants to consider. It is not an exhaustive list, and applicants are not limited to the below topics.
| Knowledge Gap | Area of Exploration |
|---|---|
| Infrastructure for clinical trials and observational studies | Establish infrastructure, such as a multicenter DoC network or model system, focused on a specific research question |
| Understanding of neurobiological mechanisms underlying consciousness/DoC | Connectomics / Circuit mapping |
| Injury classification | Phenotyping / Endotyping |
| Long-term outcome | Trajectory modeling |
| Neuroimaging and blood-based biomarkers | Validation of diagnostic, prognostic, response biomarkers |
| Prognostication | Modeling, large datasets, machine learning |
| Treatments for neuroprotection & post-acute recovery | Innovative proof-of-concept to comparative effectiveness studies (including re-purposed drugs and novel devices) |
1Giacino et al. “Comprehensive systematic review update summary: disorders of consciousness.” Neurology, 2018 Sept. 4; 91(10:461–470)
2Claassen J, Akbari Y, Alexander S, et al. Proceedings of the First Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness. Neurocrit Care. 2021;35(Suppl 1):4-23. doi:10.1007/s12028-021-01260-x
The 2024 grant cycle funded two projects:
Rolston, who is also director of epilepsy surgery at the Brigham, is leading a study that will evaluate the safety and efficacy of applying noninvasive or invasive forms of electrical stimulation to a so-called “sweet spot” deep within the brains’ thalamus, that has been previously identified as a potential treatment target due to it overlapping arousal fibers and being functionally connected to the cortical network. Studying this region more closely and testing different electrical stimulation interventions may one day lead to promising new treatment options.
Rao’s DECIPHER-COMA project seeks to identify unknown biomarkers of coma recovery, in an effort to create a roadmap for recovery that can fill current knowledge gaps within the field of neurocritical care. The researchers plan to utilize cutting edge techniques, including machine learning and AI, to review enrolled patients’ electronic health records and find new markers and patterns that can deepen their understanding of coma recovery. The hope is that in the future, this roadmap can serve as an adaptable platform that powers clinical trials of coma treatments.
View the 2026 grant application instructions.
Shonali Gaudino
sgaudino@mgb.org
(617) 952-6509
