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Investigating Traumatic Brain Injury

Our team at the Laboratory for NeuroImaging of Coma and Consciousness (NICC) at Massachusetts General Hospital studies how patients recover consciousness after a severe traumatic brain injury and how to promote the recovery process.

We use advanced structural and functional imaging techniques to identify brain networks whose connectivity is critical to the restoration of consciousness, communication, and functional independence.

We believe the identification of these brain networks will allow clinicians to provide patients' families with more accurate prognoses and will enable the development of personalized treatments that promote recovery.

Our efforts are dedicated to improving outcomes for civilians and military personnel with traumatic coma and other disorders of consciousness. 

Research Projects

Traumatic Coma RESPONSE Study

RESPONSE (REsting and Stimulus-based Paradigms to detect Organized NetworkS and predict Emergence of consciousness) is an MRI and EEG study of brain network structure and function in patients with acute traumatic coma.

The primary goal of this study is to determine if acute MRI and EEG predict long-term outcomes. 

The secondary goal of this study is to identify longitudinal changes within brain networks that enable recovery of consciousness, communication, and functional independence.

The above figure shows several functional MRI techniques that are being used by NICC researchers to identify brain activity in patients with traumatic disorders of consciousness. Figure adapted from Edlow BL, Giacino JT, Wu O. Functional MRI and outcome in traumatic coma. Current Neurology and Neuroscience Reports. 2013;13:375.

Ex Vivo Connectomics of Traumatic Coma

Ex Vivo Connectomics of Traumatic Coma is a postmortem imaging and histopathological study of brain specimens from patients who die from severe traumatic brain injury.

The primary goal of this study is to identify the circuits within the brainstem arousal network that are essential for recovery of consciousness after traumatic coma.

Secondary goals of this study include:

  • Validation of structural connectivity imaging (i.e. diffusion tractography) with gold-standard histopatholgical data
  • Development of a multimodal autopsy protocol that integrates ex vivo radiologic and histopathological data to advance knowledge about the neuroanatomic basis of coma and consciousness

The above figure shows traumatic hemorrhages in the brainstem of a patient who died from traumatic coma (panel A, arrows).  This brainstem was scanned using an ultra-high resolution MRI technique before it was sectioned and stained for histopathological analysis.  The MRI scan showed severe disruption of brainstem pathways in the coma patient (panel C), as compared to the intact pathways seen in a human control subject (panel D).  Microscopic analysis of the patient's brainstem showed severe traumatic axonal injury (panel B, arrowheads), corresponding to sites of fiber tract disruption that were identified by postmortem MRI.  Figure adapted from Edlow BL, Haynes RL, Takahashi E, Klein JP, Cummings P, Benner T, Greer DM, Greenberg SM, Wu O, Kinney HC*, Folkerth RD*. Disconnection of the ascending arousal system in traumatic coma. Journal of Neuropathology and Experimental Neurology. 2013;72:505-523. (*co-senior authors).

Harvard Ascending Arousal Network Atlas

The ascending arousal network (AAN) is a subcortical neural network that is critical to consciousness. To date, the majority of studies investigating AAN connectivity have utilized animal models. As a result, current knowledge about the connectivity of the human AAN is largely based upon extrapolations from animal data.  

We created an AAN atlas to facilitate research into the structural and functional connectivity of the human AAN. The study of AAN "connectomics" has the potential to increase knowledge about arousal physiology in the human brain, as well as arousal pathology in neurological diseases, such as coma and other disorders of consciousness.

In addition, the study of AAN connectomics may advance knowledge about reciprocal connectivity between this subcortical arousal network and cortically based awareness networks, such as the default mode network.

More information about the Harvard Ascending Arousal Network Atlas can be found at https://www.martinos.org/resources/aan-atlas. In addition, regions of interest for AAN nuclei in MNI152 space can be downloaded at this site.

The above figure shows an anterior (front) view in panel A and a posterior (back) view in panel B of brainstem nuclei that are critical to human consciousness. These nuclei were manually traced on an ultra-high resolution MRI of a human brainstem. The locations and borders of the nuclei on the MRI dataset were correlated with microscopic analysis of the same human brainstem after it was scanned. The neuroanatomic information from this human brainstem, along with neuroanatomic data from standard atlases of the human brainstem, formed the basis for the Harvard Ascending Arousal Network AtlasFigure adapted from Edlow BL, Takahashi E, Wu O, Benner T, Dai G, Bu L, Grant PE, Greer DM, Greenberg SM, Kinney HC, Folkerth RD. Neuroanatomic connectivity of the human ascending arousal system critical to consciousness and its disorders. Journal of Neuropathology and Experimental Neurology. 2012;71:531-546.

EEG-Based Brain Computer Interface in the Intensive Care Unit

The goal of this project is to determine the feasibility of deploying mindBEAGLE (Guger Technologies), a portable bedside EEG-based Brain Computer Interface (BCI) system, in the Intensive Care Unit to detect consciousness and facilitate communication in patients with disorders of consciousness or locked-in syndrome.
 
For more information about this BCI study, please see ClinicalTrials.gov.

Publications

Lee S, Polimeni JR, Price CM, Edlow BL, McNab JA. Characterizing signals within lesions and mapping brain network connectivity after traumatic axonal injury: A 7 Tesla resting-state fMRI study. Brain Connectivity. 2018;8:288-298. PMCID PMC6011808.

Chatelle C, Spencer CA, Cash SS, Hochberg LR, Edlow BL. Feasibility of an EEG-based brain-computer interface in the intensive care unit. Clinical Neurophysiology. 2018;129:1519-1525. PMCID PMC6045427.

Threlkeld ZD, Bodien YG, Rosenthal ES, Giacino JT, Nieto-Castanon A, Wu O, Whitfield-Gabrieli S, Edlow BL. Functional networks reemerge during recovery of consciousness after acute severe traumatic brain injury. Cortex. 2018; in press. doi: 10.1016/j.cortex.2018.05.004.


Patient Resources

In addition to performing research to improve outcomes for patients with severe traumatic brain injury, the NICC aims to provide resources and support for patients and families during each stage of the recovery process. Below is a list of links that have been helpful to our patients and their families. Please contact us at nicc@mgh.harvard.edu if there is additional information that would be helpful to you, or if you have suggestions for other resources.

Brain Trauma Foundation

Brain Trauma Foundation

Conducting clinical research and developing evidence-based guidelines for brain trauma.

Brain Injury Association of America

Brain Injury Association of America

The BIA seeks to be the voice of brain injury in America.

Center for Disease Control

Center for Disease Control

The CDC’s page about severe brain injuries.

Project Mend the Mind

Project Mend the Mind

A community support group for TBI

Injury Prevention Programs

Injury Prevention Programs

Advocates for simple actions that can greatly reduce the risk of TBI.

End Distracted Driving

End Distracted Driving

Simple steps for safe driving

National Institutes of Health

National Institutes of Health

The official page for NIH Research About TBI