Neural Injury in Adolescents With Concussion

Study Overview
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Brief Summary
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This study utilizes multimodal brain imaging to obtain quantitative biomarkers of brain injury and to improve understanding of the biological basis of brain pathology in adolescents with concussion. Adolescents with a concussion will undergo neuroimaging and neuropsychology assessments acutely and four months after injury.

Detailed Description
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Concussion is a highly prevalent condition in adolescence, but it remains a clinical diagnosis that largely relies on subjective patient report with no reliable objective biomarkers for diagnosis. Traditional clinical brain imaging has not been found useful for concussion as the pathology is generally not visible on conventional acute MRI or CT. The proposed study addresses this gap in concussion diagnosis and management by examining the sensitivity of magnetoencephalography (MEG) for identifying areas of brain injury through detection of abnormal neural activity (slowing) in adolescents with concussion compared to healthy controls. Adolescents with a concussion will complete neuroimaging (MEG and MRI) and neuropsychology assessments at two time points within ten days and then again 4 months post-injury. Healthy controls will complete neuroimaging and neuropsychology assessments at a single time point.

Official Title
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Neural Injury in Adolescents With Concussion

Conditions
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Mild Traumatic Brain Injury, Concussion, Mild, Acute Brain Injury

Intervention / Treatment
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* Device: MEG
* Device: MRI
* Behavioral: Neuropsychology assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of concussion and within 2 weeks of injury (case subjects) No history of diagnosed concussion (control subjects) Exclusion Criteria: Head injury within 1 year of recent concussion (case subjects) History of neurologic, psychiatric, developmental or learning disorders (all subjects)

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adolescents With Concussion<br>Adolescents with a concussion (n=120) will undergo neuroimaging (MEG and MRI) and neuropsychology assessments at two time points in the acute and chronic periods after injury, respectively. Brain imaging injury measures will be compared to a control normative database we will create. These brain measures will also be associated with cognitive and clinical outcomes. | Device: MEG<br>* MEG is a non-invasive functional imaging technique that can measure slow-wave neural activity.<br>Device: MRI<br>* MRI is a non-invasive imaging modality that provides measures of brain structure.<br>Behavioral: Neuropsychology assessment<br>* A battery of tests will be administered by a neuropsychologist to evaluate the cognitive function of adolescents with concussion compared to healthy controls.<br>|
| Adolescents Without Concussion<br>Age- and gender-matched healthy controls (n=160) will be recruited to establish a normative database of whole-brain slow-wave maps from MEG resting-state data as well as white-matter diffusion measures from MRI. | Device: MEG<br>* MEG is a non-invasive functional imaging technique that can measure slow-wave neural activity.<br>Device: MRI<br>* MRI is a non-invasive imaging modality that provides measures of brain structure.<br>Behavioral: Neuropsychology assessment<br>* A battery of tests will be administered by a neuropsychologist to evaluate the cognitive function of adolescents with concussion compared to healthy controls.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in MEG Whole-Brain Slow-Wave Sensitivity between Controls and Concussion Patients | Whole-brain, resting-state slow-wave maps of whole brain activity will be obtained from the MEG imaging in both adolescents with a concussion and healthy controls. Control images will be analyzed to determine a whole brain z-score value that includes typically developing controls below the 95th percentile, the z-score threshold for this group). Z-score images for the adolescents with concussion will be obtained and the number of adolescents with concussion above this z-score threshold will be determined, and compared to the healthy controls. The sensitivity and specificity of this method determined. | Up to 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in MRI White-Matter Diffusion Measures between Controls and Concussion Patients | MRI diffusion data will be collected to examine associations between abnormal brain slowing and white matter damage in the adolescents with a concussion versus controls. Regions showing abnormal white matter diffusion will be comparing to normative control diffusion data. | Up to 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Magnetoencephalography (MEG), Magnetic resonance imaging (MRI)