Change in Connectivity After mTBI Depending on Cognitive Reserve

Study Overview
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Brief Summary
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The purpose of this study is to investigate the role of cognitive reserve in change in connectivity in the brain (measured with functional magnetic resonance imaging, fMRI) and how this is related to symptoms and symptom resolution.

Detailed Description
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The population-based rate of mild traumatic brain injury (mTBI) is estimated to exceed 600/100000 population per year in total, if including only patients seeking emergency care the estimated rate is approximately 100-300/100000. Many patients recover within 3 months after injury but a sustainable proportion suffer from persisting symptoms, for instance fatigue, headaches, irritability. As conventional neuroimaging techniques have failed to detect the subtle alterations that may be important for prognosis and long-term outcome after mTBI, studies using fMRI have shown some interesting results. Other variables, for instance demographic and cognitive variables, also need to be incorporated with imaging biomarkers when investigating the relationship between fMRI biomarkers with outcome after mTBI. A marker related to demographic status and cognition that have shown to be relevant for outcome in brain injury or pathology is cognitive reserve. Cognitive reserve is defined as an aspect of the brain's function or structure that impacts the relationship between injury/pathology and outcome. Higher cognitive reserve is related to better outcome in conditions ranging from Alzheimer, MS and mTBI. In this study 15 patients with mTBI and 15 patients with minor orthopedic injury underwent assessment, including cognitive testing, self-assessment of symptoms, testing of visual functions and resting-state fMRI at approximately one week after injury and 4 months after injury. Cognitive reserve was assessed with a lexical decision test designed to measure pre-morbid IQ. Descriptive statistics will be used to depict demographics, injury characteristics, results on neuropsychological tests and psychological screening instruments. Multi-subject and multi-session analysis based on general linear model will be performed and assessed using statistical tools including regression analysis and 2-way ANOVA.

Official Title
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Different Courses of Change in Connectivity After mTBI Depending on Cognitive Reserve and How This is Related to Symptoms and Symptom Resolution?

Conditions
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Mild Traumatic Brain Injury

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria mTBI group: presenting at the emergency departement between January 2015 and April 2016 due to an mTBI to such an extent that CT was indicated. mTBI was defined by a Glasgow Coma Scale score between 13-15 and one or more of the following symptoms: <30 minutes loss of consciousness, <24 hours post-traumatic amnesia and/or a transient neurological deficit according to the WHO Collaborating center of Neurotrauma Task Force Inclusion Criteria orthopedic group: presenting at the emergency departement between January 2015 and April 2016 due to minor traumatic injuries to the hand, foot, arm or leg that did not require surgical intervention. Exclusion Criteria: uncertain duration of loss of consciousness contraindications to MR previously acquired brain injury, a progressive neurological disorder or another injury/illness with short expected survival were dependent of help in daily living before the current damage severe visual impairment non-Swedish speaking.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Mild traumatic brain injury<br>15 consecutive patients presenting at the emergency departement with mild traumatic brain injury | |
| Minor orthopedic injury<br>15 patients, recruited during the same time-frame as the mTBI-patients, presenting at the emergency departement with a minor orthopedic injury | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| State fatigability | Difference between score during the first 60 and the last 60 seconds of the Digit Symbol Substitution Test/Coding (DSST). The lower the score, the stronger the indication of fatigability | Measured at approximately one week after injury | 
| State fatigability | Difference between score during the first 60 and the last 60 seconds of the Digit Symbol Substitution Test/Coding (DSST). The lower the score, the stronger the indication of fatigability | Measured at approximately 4 months after injury | 
| Self rated post-concussion symptoms | For assessment of self-rated symptoms The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) was used. RPQ is based on a Likert scale and includes 16 items with ratings from 0 to 4. Higher score indicates more symptoms | Measured at approximately one week after injury | 
| Self rated post-concussion symptoms | For assessment of self-rated symptoms The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) was used. RPQ is based on a Likert scale and includes 16 items with ratings from 0 to 4. Higher score indicates more symptoms | Measured at approximately 4 months after injury | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trait fatigability | The Fatigue Severity Scale (FSS) was used to measure trait fatigue. FSS consists of 9 questions and is based on a 7 point Likert scale A high score implies a higher level of fatigue. | Measured at approximately one week after injury | 
| Trait fatigability | The Fatigue Severity Scale (FSS) was used to measure trait fatigue. FSS consists of 9 questions and is based on a 7 point Likert scale A high score implies a higher level of fatigue. | Measured at approximately 4 months after injury | 
| Anxiety and depression | Hospital Anxiety and Depression (HADS) scale was used to screen for depression and anxiety, range (0-42) higher scores indicate more severe problems | Measured at approximately one week after injury | 
| Anxiety and depression | Hospital Anxiety and Depression (HADS) scale was used to screen for depression and anxiety, range (0-42) higher scores indicate more severe problems | Measured at approximately 4 months after injury | 
| Self-rated visual symptoms in near work | Convergence Insufficiency Symptom Survey (CISS) was used to assess near work-related visual symptoms. Total score is 60 and a value above 21 indicates a high level of symptoms. | Measured at approximately one week after injury | 
| Self-rated visual symptoms in near work | Convergence Insufficiency Symptom Survey (CISS) was used to assess near work-related visual symptoms. Total score is 60 and a value above 21 indicates a high level of symptoms. | Measured at approximately 4 months after injury | 
| Convergence | A visual examination performed by a licensed optometrist, using standard optometric clinical methods. Diagnosis of visual dysfunction were based on established diagnostic criteria | Measured at approximately one week after injury | 
| Convergence | A visual examination performed by a licensed optometrist, using standard optometric clinical methods. Diagnosis of visual dysfunction were based on established diagnostic criteria | Measured at approximately 4 months after injury | 
| Accommodation | A visual examination performed by a licensed optometrist, using standard optometric clinical methods. Diagnosis of visual dysfunction were based on established diagnostic criteria | Measured at approximately one week after injury | 
| Accommodation | A visual examination performed by a licensed optometrist, using standard optometric clinical methods. Diagnosis of visual dysfunction were based on established diagnostic criteria | Measured at approximately 4 months after injury | 
| Fusional vergence | A visual examination performed by a licensed optometrist, using standard optometric clinical methods. Diagnosis of visual dysfunction were based on established diagnostic criteria | Measured at approximately one week after injury | 
| Fusional vergence | A visual examination performed by a licensed optometrist, using standard optometric clinical methods. Diagnosis of visual dysfunction were based on established diagnostic criteria | Measured at approximately 4 months after injury | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognitive reserve, rs-fMRI, Fatigue, Visual disturbances