Alterations in the Brain's Connectome After Severe Traumatic Brain Injury

Study Overview
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Brief Summary
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This study explores the changes in whole-brain connectivity that occur during recovery from severe Traumatic Brain Injury and how these changes are related to the recovery of consciousness. Multimodal neuroimaging techniques will be used in a longitudinal fashion while patients are undergoing neurorehabilitation and after one-year of the TBI episode.

Detailed Description
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Severe Traumatic Brain Injury (TBI) can result in a long-lasting altered state of consciousness. At present, the underlying neurological determinants of recovery in patients with disorders of consciousness (DOC) after a severe TBI are not well understood, and individual prognosis is very limited. Moreover, the rate of misdiagnosis between different states of altered consciousness by standard clinical scales is high, which further impacts on the clinical prognosis. In this project, multimodal neuroimaging measures will be applied and whole-brain data will be obtained from patients recovering from severe TBI in a longitudinal fashion. Patients will be examined at four time points during the sub-acute stage: immediately after admission to the neurorehabilitation unit, after ten weeks of admission, at discharge, and after one year of the TBI episode. Brain connectivity will be assessed with functional Magnetic Resonance Imaging (fMRI) combined with electroencephalography (EEG), structural MRI, diffusion MRI, high-density EEG (hdEEG) alone, and hdEEG combined with Transcranial Magnetic Stimulation (EEG-TMS), and [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). The overall aim of the study is to find reliable biomarkers for the recovery of consciousness based on changes in cortico-cortical and cortico-subcortical brain connectivity. In order to explore this, patients that suffered a severe TBI as well a matched healthy participants group will be included in the study.

Official Title
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Alterations in the Brain's Connectome in Severe Traumatic Brain Injury

Conditions
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Traumatic Brain Injury, Disorders of Consciousness

Intervention / Treatment
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* Procedure: MRI
* Procedure: TMS-EEG
* Procedure: FDG-PET
* Other: Clinical scales


Participation Criteria
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Eligibility Criteria
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Patient's inclusion criteria: - closed-head injury Patient's exclusion criteria: high level of consciousness after coma ventricular shunt for hydrocephalus large intracerebral hemorrhages or infarctions structural lesions in the brain stem locked-in syndrome due to motor pathway lesions contraindications for MR contraindications for TMS Healthy participant's inclusion criteria: - no prior history of neurological disorders and / or head injury Healthy participant's exclusion criteria: contraindications for MR contraindications for TMS

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| 1<br>Patients with TBI and DOC. Experimental measures (MRI, TMS-EEG, and clinical scales) will be performed at 4 time points: within 2 weeks of admission, 6-10 weeks after admission, at discharge, 1-year follow-up after TBI episode. FDG-PET will be performed in a subset of 25 patients at 3 time points: at admission, at discharge, and at 1-year follow-up. | Procedure: MRI<br>* EEG-functional MRI, structural MRI, diffusion MRI<br>* Other names: Magnetic Resonance Imaging;Procedure: TMS-EEG<br>* Single pulse TMS combined with EEG, resting-state EEG, noise masking (auditory stimulation), electrical stimulation<br>* Other names: Transcranial Magnetic Stimulation-Electroencephalogram;Procedure: FDG-PET<br> <br> * Other names: [18F]-fluorodeoxyglucose positron emission tomography;Other: Clinical scales<br>* Evaluation of DOC: Coma recovery scale-Revised (CRS-R) and Rancho Los Amigos Scale (RLAS). Evaluation of function: Functional Independent Measure (FIMTM), and Early Functional Assessment (EFA).<br>|
| 2<br>Healthy patient-matched controls. Experimental measures (MRI, TMS-EEG, and FDG-PET) will be performed at 2 time points: within patient admission, and within patient discharge. | Procedure: MRI<br>* EEG-functional MRI, structural MRI, diffusion MRI<br>* Other names: Magnetic Resonance Imaging;Procedure: TMS-EEG<br>* Single pulse TMS combined with EEG, resting-state EEG, noise masking (auditory stimulation), electrical stimulation<br>* Other names: Transcranial Magnetic Stimulation-Electroencephalogram;Procedure: FDG-PET<br> <br> * Other names: [18F]-fluorodeoxyglucose positron emission tomography;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in whole brain connectivity as a measure of recovery of consciousness |  | up to 32 months |