In recent years, advances in emergency medicine and reanimation have considerably increased the number of patients surviving prolonged cardiac arrest or severe motor vehicle accidents (Laureys and Boly, 2008
). An important proportion of these surviving patients are left with severe brain damage, leading to the presence of disorders of consciousness. Among disorders of consciousness, coma is defined by ‘unarousable unresponsiveness’; and ‘vegetative state’ by preserved behavioural sleep–wake cycles and reflexive but not purposeful behaviours (Laureys and Boly, 2007
). Minimally conscious patients, though unable to communicate, show inconsistent non-reflexive behaviours, interpreted as signs of awareness of self or environment (Giacino et al.
). The locked-in syndrome describes patients who are awake and conscious but have no means of producing speech, limb or facial movements (American Congress of Rehabilitation Medicine, 1995
). A particular problem in patients with disorders of consciousness is that the clinical diagnosis is very challenging at the bedside, and several studies have reported high rates of misdiagnosis, reaching up to 40% (Majerus et al.
; Schnakers et al.
). It is now increasingly recognized that diagnosing these distinct conditions correctly is critical, both for ethical reasons and in order to improve the clinical management of these patients. Indeed, several studies have shown that brain activation in response to auditory or painful stimuli is very limited when in a vegetative state, while this activation is virtually normal in patients who are minimally conscious (Boly et al.
), suggesting the possibility of residual external stimuli perception in the latter patient population. Furthermore, preliminary data show that patients in the minimally conscious state have a much better functional prognosis than patients in a vegetative state, independently of the aetiology (Giacino, 2005
). These concerns raise the need for reliable paraclinical markers as a complement to the clinical assessment in differentiating patients in a vegetative state from patients in a minimally conscious state.
Over the last 8 years, increasing attention has been paid to the study of spontaneous brain activity and its significance for cognition and behaviour (Raichle, 2006
). In particular, the concept of a ‘default mode network (DMN) of brain function’ was introduced by Raichle et al.
), after observing that a number of areas including the precuneus, bilateral temporo-parietal junctions and medial prefrontal cortex, were more active at rest than when the subjects were involved in an attention-demanding cognitive task. This network of areas, now commonly referred to as the ‘DMN’, has been replicably implicated in cognitive processes like ‘daydreaming’ or ‘mind-wandering’, stimulus-independent thoughts or self-related thoughts (Laureys et al.
; Mason et al.
; Buckner et al.
). Though the functional significance of the DMN remains a matter of debate, it has been suggested as a candidate for the network subserving basic functions related to consciousness (Boly et al.
; Greicius et al.
). Studying this network in patients with disorders of consciousness is, at first glance, a very challenging undertaking, due to the highly subjective and complex cognitive functions reported to be supported by this network.
Several studies in healthy volunteers have shown the ability of resting state functional magnetic resonance imaging (fMRI) to identify structured patterns of functional connectivity among defined neuroanatomical systems reliably, including the DMN (Cavanna and Trimble, 2006
; Damoiseaux et al.
; Cavanna, 2007
; Shehzad et al.
). Of potentially major interest from the clinical point of view, is the fact that resting state fMRI connectivity studies allow the investigation of higher order cognitive networks like the DMN, without requiring the patients’ collaboration. This fact is particularly important in non-communicative patients such as those with disorders of consciousness. Resting state fMRI acquisitions are also very easy to perform compared with standard task-based fMRI paradigms, and could thus have a potentially broader and faster translation into clinical practice. However, to date, the functional significance of resting state connectivity patterns remain unclear. Some authors have even questioned the value and interpretability of spontaneous brain activity fluctuations as recorded by fMRI (Morcom and Fletcher, 2007
The aim of this study was to investigate DMN resting state fMRI connectivity in a cohort of patients with disorders of consciousness including coma, vegetative state, minimally conscious state and locked-in syndrome. We hypothesized that DMN connectivity strength would be related to the level of consciousness of non-communicative brain-damaged patients, as assessed by standardized behavioural scales. Furthermore, we expected a particularly strong link between the level of consciousness and connectivity in the precuneus, reported to be a central node in the DMN (Fransson and Marrelec, 2008
), and potentially the most connected area in the brain (Hagmann et al.