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J Neurotrauma. 2017 Apr 15;34(8):1546-1557. doi: 10.1089/neu.2016.4752. Epub 2017 Jan 13.

Resting-State Functional Connectivity Alterations Associated with Six-Month Outcomes in Mild Traumatic Brain Injury.

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1 Department of Radiology and Biomedical Imaging, University of California , San Francisco, California.
2 Brain and Spinal Cord Injury Center, San Francisco General Hospital and Trauma Center , San Francisco, California.
3 Department of Neurological Surgery and Brain and Spinal Injury Center, University of California , San Francisco, California.
4 Department of Psychology, University of Texas , Austin, Texas.
5 Department of Neurological Surgery and Neurotrauma Clinical Trials Center, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
6 Department of Neurosurgery, Virginia Commonwealth University , Richmond, Virginia.
7 Department of Rehabilitation Medicine, Ichan School of Medicine at Mount Sinai , New York, New York.
8 Department of Neurosurgery, Antwerp University Hospital , Edegem, Belgium .


Brain lesions are subtle or absent in most patients with mild traumatic brain injury (mTBI) and the standard clinical criteria are not reliable for predicting long-term outcome. This study investigates resting-state functional MRI (rsfMRI) to assess semiacute alterations in brain connectivity and its relationship with outcome measures assessed 6 months after injury. Seventy-five mTBI patients were recruited as part of the prospective multicenter Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) pilot study and compared with matched 47 healthy subjects. Patients were classified following radiological criteria: CT/MRI positive, evidence of lesions; CT/MRI negative, without evidence of brain lesions. rsfMRI data were acquired and then processed using probabilistic independent component analysis. We compared the functional connectivity of the resting-state networks (RSNs) between patients and controls, as well as group differences in the interactions between RSNs, and related both to cognitive and behavioral performance at 6 months post-injury. Alterations were found in the spatial maps of the RSNs between mTBI patients and healthy controls in networks involved in behavioral and cognition processes. These alterations were predictive of mTBI patients' outcomes at 6 months post-injury. Moreover, different patterns of reduced network interactions were found between the CT/MRI positive and CT/MRI negative patients and the control group. These rsfMRI results demonstrate that even mTBI patients not showing brain lesions on conventional CT/MRI scans can have alterations of functional connectivity at the semiacute stage that help explain their outcomes. These results suggest rsfMRI as a sensitive biomarker both for early diagnosis and for prediction of the cognitive and behavioral performance of these patients.


TBI; cognitive and behavioral outcome; rsfMRI

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