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Recently, the cortical source of blink-related delta oscillations (delta BROs) in resting healthy subjects has been localized in the posterior cingulate cortex/precuneus (PCC/PCu), one of the main core-hubs of the default-mode network. This has been interpreted as the electrophysiological signature of the automatic monitoring of the surrounding environment while subjects are immersed in self-reflecting mental activities. Although delta BROs were directly correlated to the degree of consciousness impairment in patients with disorders of consciousness, they failed to differentiate vegetative state/unresponsive wakefulness syndrome (VS/UWS) from minimally conscious state (MCS). In the present study, we have extended the analysis of BROs to frequency bands other than delta in the attempt to find a biological marker that could support the differential diagnosis between VS/UWS and MCS. Four patients with VS/UWS, 5 patients with MCS, and 12 healthy matched controls (CTRL) underwent standard 19-channels EEG recordings during resting conditions. Three-second-lasting EEG epochs centred on each blink instance were submitted to time-frequency analyses in order to extract the normalized Blink-Related Synchronization/Desynchronization (nBRS/BRD) of three bands of interest (low-alpha, high-alpha and low-beta) in the time-window of 50-550 ms after the blink-peak and to estimate the corresponding cortical sources of electrical activity. VS/UWS nBRS/BRD levels of all three bands were lower than those related to both CTRL and MCS, thus enabling the differential diagnosis between MCS and VS/UWS. Furthermore, MCS showed an intermediate signal intensity on PCC/PCu between CTRL and VS/UWS and a higher signal intensity on the left temporo-parieto-occipital junction and inferior occipito-temporal regions when compared to VS/UWS. This peculiar pattern of activation leads us to hypothesize that resting MCS patients have a bottom-up driven activation of the task positive network and thus are tendentially prone to respond to environmental stimuli, even though in an almost unintentional way.

BACKGROUND:During non-rapid eye movement (NREM) sleep synchronous neural oscillations between neural silence (down state) and neural activity (up state) occur. Sleep Slow Oscillations (SSOs) events are their EEG correlates. Each event has an origin site and propagates sweeping the scalp. While recent findings suggest a SSO key role in memory consolidation processes, the structure and the propagation of individual SSO events, as well as their modulation by sleep stages and cortical areas have not been well characterized so far. METHODOLOGY/PRINCIPAL FINDINGS:We detected SSO events in EEG recordings and we defined and measured a set of features corresponding to both wave shapes and event propagations. We found that a typical SSO shape has a transition to down state, which is steeper than the following transition from down to up state. We show that during SWS SSOs are larger and more locally synchronized, but less likely to propagate across the cortex, compared to NREM stage 2. Also, the detection number of SSOs as well as their amplitudes and slopes, are greatest in the frontal regions. Although derived from a small sample, this characterization provides a preliminary reference about SSO activity in healthy subjects for 32-channel sleep recordings. CONCLUSIONS/SIGNIFICANCE:This work gives a quantitative picture of spontaneous SSO activity during NREM sleep: we unveil how SSO features are modulated by sleep stage, site of origin and detection location of the waves. Our measures on SSOs shape indicate that, as in animal models, onsets of silent states are more synchronized than those of neural firing. The differences between sleep stages could be related to the reduction of arousal system activity and to the breakdown of functional connectivity. The frontal SSO prevalence could be related to a greater homeostatic need of the heteromodal association cortices.