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Clinical Study Protocol ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2018.01012

Consciousness in neurocritical care cohort study using fMRI and EEG (CONNECT-ME): Protocol for a longitudinal prospective study and a tertiary clinical care service

 Anine P. Skibsted1, Moshgan Amiri2, Patrick M. Fisher1,  Annette S. Sidaros2, Melita H. Hribljan2, Vibeke A. Larsen3, Joan L. Højgaard4, Miki Nikolic2, John Hauerberg5, Martin E. Fabricius2, Gitte M. Knudsen1, Kirsten Møller6 and  Daniel Kondziella4*
  • 1Neurobiology Research Unit, Rigshospitalet, Denmark
  • 2Department of Clinical Neurophysiology, Rigshospitalet, Denmark
  • 3Clinic of Radiology, Rigshospitalet, Denmark
  • 4Department of Neurology, Rigshospitalet, Denmark
  • 5Department of Neurosurgery, Rigshospitalet, Denmark
  • 6Department of Neuroanaesthesiology, Rigshospitalet, Denmark

Aims and objectives: To facilitate individualized assessment of unresponsive patients in the intensive care unit for signs of preserved consciousness after acute brain injury.
Background: Physicians and neuroscientists are increasingly recognizing a disturbing dilemma: Brain-injured patients who appear entirely unresponsive at the bedside may show signs of covert consciousness when examined by functional MRI (fMRI) or electroencephalography (EEG). According to a recent meta-analysis, roughly 15% of behaviorally unresponsive brain-injured patients can participate in mental tasks by modifying their brain activity during EEG- or fMRI-based paradigms, suggesting that they are conscious and misdiagnosed. This has major ethical and practical implications, including prognosis, treatment, resource allocation and end-of-life decisions. However, EEG- or fMRI-based paradigms have so far typically been tested in chronic brain injury. Hence, as a novel approach, CONNECT-ME will import the full range of consciousness paradigms into neurocritical care.
Methods: We will assess intensive care patients with acute brain injury for preserved consciousness by serial and multimodal evaluation using active, passive and resting state fMRI and EEG paradigms, as well as state-of-the-art clinical techniques including pupillometry and sophisticated clinical rating scales. In addition, we are establishing a biobank to facilitate genomic and microbiomic research to search for signatures of consciousness recovery.
Discussion: We anticipate that this multimodal approach will add vital clinical information, including detection of preserved consciousness in patients previously thought of as unconscious, and improved (i.e. personalized) prognostication of individual patients. Our aim is twofold: We wish to establish a cutting-edge tertiary care clinical service for unresponsive patients in the intensive care unit and lay the foundation for a fruitful multidisciplinary research environment for the study of consciousness in acute brain injury. Of note, CONNECT-ME will not only enhance our understanding of consciousness disorders in acute brain injury but it will also raise awareness for these patients who, for obvious reasons, have lacked a voice so far.
Trial registration: The study is registered with ( Identifier: NCT02644265).

Keywords: Coma, disorders of consciousness, electroencephaelography, Functional MR (fMR), locked-in syndrome, Magnetic resonace imaging, unresponsive wakefulness syndrome, vegetative state

Received: 07 Sep 2018; Accepted: 09 Nov 2018.

Edited by:

Rajeev K. Garg, Rush University, United States

Reviewed by:

Rita Formisano, Fondazione Santa Lucia (IRCCS), Italy
Benjamin Rohaut, Columbia University, United States
Lauren Koffman, Rush University Medical Center, United States
Starane Shepherd, Rush University Medical Center, United States  

Copyright: © 2018 Skibsted, Amiri, Fisher, Sidaros, Hribljan, Larsen, Højgaard, Nikolic, Hauerberg, Fabricius, Knudsen, Møller and Kondziella. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Daniel Kondziella, Department of Neurology, Rigshospitalet, Copenhagen, 2100, Denmark,