Abstract
Disorder of consciousness (DoC) refers to a group of clinical conditions that may emerge after brain injury, characterized by a varying decrease in the level of consciousness that can last from days to years. An understanding of its neural correlates is crucial for the conceptualization and application of effective therapeutic interventions. Here we propose a quantitative meta-analysis of the neural substrate of DoC emerging from functional magnetic resonance (fMRI) and positron emission tomography (PET) studies. We also map the relevant networks of resulting areas to highlight similarities with Resting State Networks (RSNs) and hypothesize potential therapeutic solutions leveraging network-targeted noninvasive brain stimulation. Available literature was reviewed and analyzed through the activation likelihood estimate (ALE) statistical framework to describe resting-state or task-dependent brain activation patterns in DoC patients. Results show that task-related activity is limited to temporal regions resembling the auditory cortex, whereas resting-state fMRI data reveal a diffuse decreased activation affecting two subgroups of cortical (angular gyrus, middle frontal gyrus) and subcortical (thalamus, cingulate cortex, caudate nucleus) regions. Clustering of their cortical functional connectivity projections identify two main altered functional networks, related to decreased activity of (i) the default mode and frontoparietal networks, as well as (ii) the anterior salience and visual/auditory networks. Based on the strength and topography of their connectivity profile, biophysical modeling of potential brain stimulation solutions suggests the first network as the most feasible target for tES, tDCS neuromodulation in DoC patients.
Highlights
Brain injury is one of the major causes of death and disability in the world [1]
Several patients suffer from disorder of consciousness (DoC), a condition that can be divided into four states: (i) coma, (ii) vegetative state/unresponsiveness wakefulness syndrome (VS/UWS; patients are able to stay awake spontaneously or after stimulation, but they have no awareness of themselves or of the environment; [4,5]), (iii) minimally conscious state (MCS; patients show some behavioral evidence of consciousness; [6]) and (iv) patients emerging from MCS (EMCS; patients recover the ability to use objects in a functional manner, [7])
We intentionally excluded (i) review papers, (ii) studies not mentioning any of the keywords in the abstract, (iii) studies not reporting fMRI/positron emission tomography (PET) activations coordinates in Montreal Neurological Institute (MNI) or Talairach space, (iv) studies not reporting activation foci in table format or reporting statistical values without corresponding coordinates, (v) studies that used predefined regions of interest (ROIs), (vi) studies reporting results obtained with small volume correction (SVC), (vii) studies not in the English language
Summary
Brain injury is one of the major causes of death and disability in the world [1]. As a consequence, several patients suffer from disorder of consciousness (DoC) (for specific statistics see [2]), a condition that can be divided into four states: (i) coma (patients are not able to spontaneously open their eyes and to be awakened even with strong sensory stimulation; [3]), (ii) vegetative state/unresponsiveness wakefulness syndrome (VS/UWS; patients are able to stay awake spontaneously or after stimulation, but they have no awareness of themselves or of the environment; [4,5]), (iii) minimally conscious state (MCS; patients show some behavioral evidence of consciousness; [6]) and (iv) patients emerging from MCS (EMCS; patients recover the ability to use objects in a functional manner, [7]). Awareness can be divided in two distinct and negatively correlated networks: the ‘external awareness’ network, which includes bilateral fronto-temporo-parietal cortices, and the ‘internal awareness’ network, consisting of midline posterior cingulate cortex/precuneus and anterior cingulate/medial prefrontal cortices [9]. In support of this hypothesis, several neuroimaging and electrophysiological studies showed the presence of a structural and functional disconnection between these brain areas in DoC patients [10,11,12]. A decrease in functional MRI resting-state low frequency fluctuations and regional voxel homogeneity [18] has been shown in DMN regions in patients with DoC. The DMN has been associated with conscious and self-related cognitive processes [19,20] such as inner or task-unrelated thoughts [21] and self-reflection [22], with a progressive decrease in the functional connectivity (FC) of DMN regions alongside the spectrum of consciousness [15,17,23,24,25]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
