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.

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.

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

1. 30 Patients that have suffered a close-head TBI with associated DOC and that are admitted to neurorehabilitation at the TBI unit of Glostrup Hospital.
2. 20 Healthy participants without history of neurological disorders, age-, gender-, and socioeconomically-matched to the included patients.