CONNECT-ME: CONsciousness in NEurocritical Care cohorT Study Using fMRI and EEG

Searching for consciousness in non-communicating brain-injured patients by clinical examination is essential, yet challenging. The origin of many clinical signs is not entirely clear and their significance as to whether or not the patient is conscious is even less certain. In addition, consciousness may wax and wane within seconds to hours and days to months. Indeed, as many as 40% of patients with disorders of consciousness (DoC) are misclassified as being in a vegetative state (VS). Although these patients may not show any signs of consciousness during clinical examination because of lost motor output, some are able to willfully modulate their brain activity on command, occasionally even answering yes or no questions by performing mental imagery tasks. For patients with acute brain injury and their caregivers, this has significant ethical and practical implications, not least for prognostication, treatment decisions, resource allocation and end-of-life considerations.

Technologies based on functional Magnetic Resonance Imaging (fMRI) and electroencephalography (EEG) have been developed during the last two decades to assist clinical evaluation of patients in VS and minimal conscious states (MCS). There are three main approaches to test for preserved consciousness: (i) Active paradigms in which patients are required to execute cognitive tasks, as outlined above, (ii) passive paradigms relying on the documentation of preserved large-scale functional cortical connectivity, following an external stimulus, and (iii) resting state conditions in which assumptions about the patient's conscious state are made by extrapolation from patterns of spontaneous brain activity. Consciousness paradigms offer exciting opportunities but so far they have been almost exclusively employed in rehabilitation medicine, addressing patients with chronic brain disorders, typically several years following onset of the injury. Moreover, these studies have mainly been restricted to spot assessments, not taking into account that consciousness fluctuates over time. In addition, important methodological issues remain, including uncertainties about the specificity and sensitivity of the different paradigms and about their applicability in brain disorders of various etiologies. Lastly, almost all studies until now have employed either fMRI- or EEG-based paradigms, although the two modalities do not necessarily yield identical results in a given patient but rather complement each other. As the investigators have recently pointed out in a review and meta-analysis, systematic evaluation of the similarities and differences of these technologies is essential, preferentially by multimodal serial assessments.

In the present protocol, as a novel approach the investigators will focus on the evaluation of consciousness in patients in the acute phase of brain injury. The aim is to establish, validate and improve fMRI- and EEG-based consciousness paradigms in intensive care (ICU) and step down units. This will assist clinicians in more precisely estimating the level of consciousness in various acute disorders of the brain. The project will comprise a multidisciplinary approach including expertise from neurology, clinical neurophysiology, anesthesiology and functional neuroimaging. The investigators hypothesize that serial multimodal assessments better reflect changing levels of consciousness than single unimodal evaluations. Within the next two to three years, the investigators wish to establish a full clinical service and a fruitful research milieu covering the entire spectrum of fMRI- and EEG-based consciousness paradigms in acute brain injury. The ability to identify preserved cognitive abilities following acute brain injury is of utmost importance to improve diagnosis, to guide therapeutic decisions and to better predict outcome in non-responsive patients. Eventually, the present research project will lead to more efficient decision making in neurocritical care, thereby optimizing resource allocation and improving quality of life in survivors with acute brain injury.

Study Design:

Due to its complexity, this project is divided into 3 phases, including 9 work packages.