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      Dynamic functional network connectivity discriminates mild traumatic brain injury through machine learning

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          Abstract

          Mild traumatic brain injury (mTBI) can result in symptoms that affect a person's cognitive and social abilities. Improvements in diagnostic methodologies are necessary given that current clinical techniques have limited accuracy and are solely based on self-reports. Recently, resting state functional network connectivity (FNC) has shown potential as an important imaging modality for the development of mTBI biomarkers. The present work explores the use of dynamic functional network connectivity (dFNC) for mTBI detection. Forty eight mTBI patients (24 males) and age-gender matched healthy controls were recruited. We identified a set of dFNC states and looked at the possibility of using each state to classify subjects in mTBI patients and healthy controls. A linear support vector machine was used for classification and validated using leave-one-out cross validation. One of the dFNC states achieved a high classification performance of 92% using the area under the curve method. A series of t-test analysis revealed significant dFNC increases between cerebellum and sensorimotor networks. This significant increase was detected in the same dFNC state useful for classification. Results suggest that dFNC can be used to identify optimal dFNC states for classification excluding those that does not contain useful features.

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          Highlights

          • Dynamic functional connectivity and support vector machine classified traumatic brain injury patients and healthy controls.

          • Out of 4 dynamic brain states, we identified 1 state useful for classification.

          • Classification performance of the dynamic state of interest achieved a performance of 92% area under the curve method.

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          Most cited references37

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          Network dysfunction after traumatic brain injury.

          Diffuse axonal injury after traumatic brain injury (TBI) produces neurological impairment by disconnecting brain networks. This structural damage can be mapped using diffusion MRI, and its functional effects can be investigated in large-scale intrinsic connectivity networks (ICNs). Here, we review evidence that TBI substantially disrupts ICN function, and that this disruption predicts cognitive impairment. We focus on two ICNs--the salience network and the default mode network. The activity of these ICNs is normally tightly coupled, which is important for attentional control. Damage to the structural connectivity of these networks produces predictable abnormalities of network function and cognitive control. For example, the brain normally shows a 'small-world architecture' that is optimized for information processing, but TBI shifts network function away from this organization. The effects of TBI on network function are likely to be complex, and we discuss how advanced approaches to modelling brain dynamics can provide insights into the network dysfunction. We highlight how structural network damage caused by axonal injury might interact with neuroinflammation and neurodegeneration in the pathogenesis of Alzheimer disease and chronic traumatic encephalopathy, which are late complications of TBI. Finally, we discuss how network-level diagnostics could inform diagnosis, prognosis and treatment development following TBI.
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            Detection of blast-related traumatic brain injury in U.S. military personnel.

            Blast-related traumatic brain injuries have been common in the Iraq and Afghanistan wars, but fundamental questions about the nature of these injuries remain unanswered. We tested the hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging (DTI), an advanced form of magnetic resonance imaging that is sensitive to axonal injury. The subjects were 63 U.S. military personnel who had a clinical diagnosis of mild, uncomplicated traumatic brain injury. They were evacuated from the field to the Landstuhl Regional Medical Center in Landstuhl, Germany, where they underwent DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mechanism of injury (e.g., being struck by a blunt object or injured in a fall or motor vehicle crash). Controls consisted of 21 military personnel who had blast exposure and other injuries but no clinical diagnosis of traumatic brain injury. Abnormalities revealed on DTI were consistent with traumatic axonal injury in many of the subjects with traumatic brain injury. None had detectable intracranial injury on computed tomography. As compared with DTI scans in controls, the scans in the subjects with traumatic brain injury showed marked abnormalities in the middle cerebellar peduncles (P<0.001), in cingulum bundles (P=0.002), and in the right orbitofrontal white matter (P=0.007). In 18 of the 63 subjects with traumatic brain injury, a significantly greater number of abnormalities were found on DTI than would be expected by chance (P<0.001). Follow-up DTI scans in 47 subjects with traumatic brain injury 6 to 12 months after enrollment showed persistent abnormalities that were consistent with evolving injuries. DTI findings in U.S. military personnel support the hypothesis that blast-related mild traumatic brain injury can involve axonal injury. However, the contribution of primary blast exposure as compared with that of other types of injury could not be determined directly, since none of the subjects with traumatic brain injury had isolated primary blast injury. Furthermore, many of these subjects did not have abnormalities on DTI. Thus, traumatic brain injury remains a clinical diagnosis. (Funded by the Congressionally Directed Medical Research Program and the National Institutes of Health; ClinicalTrials.gov number, NCT00785304.).
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              Functional connectivity in mild traumatic brain injury.

              Research suggests that the majority of mild traumatic brain injury (mTBI) patients exhibit both cognitive and emotional dysfunction within the first weeks of injury, followed by symptom resolution 3-6 months postinjury. The neuronal correlates of said dysfunction are difficult to detect with standard clinical neuroimaging, complicating differential diagnosis and early identification of patients who may not recover. This study examined whether resting state functional magnetic resonance imaging (fMRI) provides objective markers of injury and predicts cognitive, emotional, and somatic complaints in mTBI patients semiacutely (<3 weeks postinjury) and in late recovery (3-5 month) phases. Twenty-seven semiacute mTBI patients and 26 gender, age, and education-matched controls were studied. Fifteen of 27 patients returned for a follow-up visit 3-5 months postinjury. The main dependent variables were spontaneous fluctuations (temporal correlation) in the default-mode (DMN) and fronto-parietal task-related networks as measured by fMRI. Significant differences in self-reported cognitive, emotional, and somatic complaints were observed (all P < 0.05), despite normal clinical (T1 and T2) imaging and neuropsychological testing results. Mild TBI patients demonstrated decreased functional connectivity within the DMN and hyper-connectivity between the DMN and lateral prefrontal cortex. Measures of functional connectivity exhibited high levels of sensitivity and specificity for patient classification and predicted cognitive complaints in the semi-acute injury stage. However, no changes in functional connectivity were observed across a 4-month recovery period. Abnormal connectivity between the DMN and frontal cortex may provide objective biomarkers of mTBI and underlie cognitive impairment. Copyright © 2011 Wiley-Liss, Inc.
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                Author and article information

                Contributors
                Journal
                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                Elsevier
                2213-1582
                15 March 2018
                2018
                15 March 2018
                : 19
                : 30-37
                Affiliations
                [a ]The Mind Research Network and Lovelace Biomedical and Environmental Research Institute, 1101 Yale Blvd. NE, Albuquerque, NM 87106, United States
                [b ]Dept of ECE, University of New Mexico, Albuquerque, NM 87131, United States
                [c ]Department of Psychology, University of New Mexico, Albuquerque, NM 87131, United States
                [d ]Department of Neurology, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States
                [e ]Department of Psychiatry and Behavioral Sciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States
                Author notes
                [* ]Corresponding author at: The Mind Research Network, 1101 Yale Blvd. NE, Albuquerque, NM 87106, United States. vvergara@ 123456mrn.org
                Article
                S2213-1582(18)30087-1
                10.1016/j.nicl.2018.03.017
                6051314
                30034999
                901950d5-4e2e-4435-9f30-9c87d0522260
                © 2018 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 July 2017
                : 22 February 2018
                : 14 March 2018
                Categories
                Regular Article

                traumatic brain injury,magnetic resonance imaging,dynamic functional network connectivity

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