Alterations in the brain's connectome during recovery from severe traumatic brain injury: protocol for a longitudinal prospective study

Virginia Conde, Sara Hesby Andreasen, Tue Hvass Petersen, Karen Busted Larsen, Karine Madsen, Kasper Winther Andersen, Irina Akopian, Kristoffer Hougaard Madsen, Christian Pilebæk Hansen, Ingrid Poulsen, Lars Peter Kammersgaard, Hartwig Roman Siebner, Virginia Conde, Sara Hesby Andreasen, Tue Hvass Petersen, Karen Busted Larsen, Karine Madsen, Kasper Winther Andersen, Irina Akopian, Kristoffer Hougaard Madsen, Christian Pilebæk Hansen, Ingrid Poulsen, Lars Peter Kammersgaard, Hartwig Roman Siebner

Abstract

Introduction: Traumatic brain injury (TBI) is considered one of the most pervasive causes of disability in people under the age of 45. TBI often results in disorders of consciousness, and clinical assessment of the state of consciousness in these patients is challenging due to the lack of behavioural responsiveness. Functional neuroimaging offers a means to assess these patients without the need for behavioural signs, indicating that brain connectivity plays a major role in consciousness emergence and maintenance. However, little is known regarding how changes in connectivity during recovery from TBI accompany changes in the level of consciousness. Here, we aim to combine cutting-edge neuroimaging techniques to follow changes in brain connectivity in patients recovering from severe TBI.

Methods and analysis: A multimodal, longitudinal assessment of 30 patients in the subacute stage after severe TBI will be made comprising an MRI session combined with electroencephalography (EEG), a positron emission tomography session and a transcranial magnetic stimulation (TMS) combined with EEG (TMS/EEG) session. A group of 20 healthy participants will be included for comparison. Four sessions for patients and two sessions for healthy participants will be planned. Data analysis techniques will focus on whole-brain, both data-driven and hypothesis-driven, connectivity measures that will be specific to the imaging modality.

Ethics and dissemination: The project has received ethical approval by the local ethics committee of the Capital Region of Denmark and by the Danish Data Protection. Results will be published as original research articles in peer-reviewed journals and disseminated in international conferences. None of the measurements will have any direct clinical impact on the patients included in the study but may benefit future patients through a better understanding of the mechanisms underlying the recovery process after TBI. TRIAL REGISTRATION NUMBER NCT02424656; PRE-RESULTS.

Keywords: Brain connectivity; Disorders of Consciousness; Longitudinal study; Multimodal study; Neuroimaging; Traumatic Brain Injury.

Conflict of interest statement

Competing interests: None declared.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
Schematic representation of the timeline for the experimental sessions in relation to the clinical rehabilitation of the patients. Please note that the discharge of the patient does not have a fixed week number but can vary across patients due to clinical reasons. Consc. eva. (‘Consciousness evaluation’) refers to the clinical evaluation of the consciousness state of the patient via standardised clinical scales. EEG, electroencephalograph; EFA, early functional abilities; FDG-PET, [18F]-fluorodeoxyglucose positron emission tomography; FIM, functional independent measure; MRI, magnetic resonance imaging; TMS, Ttranscranial magnetic stimulation.
Figure 2
Figure 2
Schematic representation of the workflow. Please notice that some steps overlap due to the requirements of the study (planning on patient recruitment cannot be made in advance since it depends on admission to the rehabilitation department). EEG, electroencephalography; dMRI, diffusion Mangentic resonance imaging; fMRI, functional magnetic resonance imaging; PET, positron emission tomography; MR, Magnetic resonance; TMS, transcranial magnetic stimulation.

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