Background. Transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (lDLPFC) was reported to promote the recovery of signs of consciousness in some patients in a minimally conscious state (MCS), but its electrophysiological effects on brain activity remain poorly understood. Objective. We aimed to assess behavioral (using the Coma Recovery Scale—Revised; CRS-R) and neurophysiological effects (using high density electroencephalography; hdEEG) of lDLPFC-tDCS in patients with prolonged disorders of consciousness (DOC). Methods. In a double-blind, sham-controlled, crossover design, one active and one sham tDCS (2 mA, 20 min) were delivered in a randomized order. Directly before and after tDCS, 10 min of hdEEG were recorded and the CRS-R was administered. Results. Thirteen patients with severe brain injury were enrolled in the study. We found higher relative power at the group level after the active tDCS session in the alpha band in central regions and in the theta band over the frontal and posterior regions (uncorrected results). Higher weighted symbolic mutual information (wSMI) connectivity was found between left and right parietal regions, and higher fronto-parietal weighted phase lag index (wPLI) connectivity was found, both in the alpha band (uncorrected results). At the group level, no significant treatment effect was observed. Three patients showed behavioral improvement after the active session and one patient improved after the sham. Conclusion. We provide preliminary indications that neurophysiological changes can be observed after a single session of tDCS in patients with prolonged DOC, although they are not necessarily paralleled with significant behavioral improvements.

Mind-blanking (MB) is termed as the experience of inability to report mental contents. In contrast to other mental states, such as mind-wandering or sensory perceptions, the neural correlates of MB started getting elucidated only recently. A notable particularity that pertains to MB studies is the way MB is instructed for reports, like by deliberately asking participants to “empty their minds”. Such instructions were shown to induce fMRI activations in frontal brain regions, typically associated with metacognition and self-evaluative processes, suggesting that MB may be a result of intentional mental content suppression. Here, we aim at examining this hypothesis by determining the neural correlates of MB without induction. Using fMRI combined with experience-sampling, univariate analysis of MB reports revealed deactivations in occipital, frontal, somatosensory, and thalamic areas, but no activations in prefrontal regions. In fact, a Bayesian region-of-interest analysis on areas previously shown to be implicated in MB provided evidence for frontal deactivations during MB reports in comparison to other mental states. Further contrast analysis between reports of MB and content-oriented mental states also revealed deactivations in the L angular gyrus. We propose that these effects characterize a cortical profile of MB, where key cortical nodes are unable to communicate and formulate reportable content. Collectively, our results show that study instructions for MB may lead to cortical differences which provide different insights as to the underlying mechanisms leading to the phenomenology of MB. Significance Statement An emergent research paradigm in the study of mental states has focused on periods of complete thought absence, where people report an inability to report mental content, termed mind blanking. The neural correlates supporting mind blanking are still debated and might vary depending on thought-report instructions. By reanalyzing an fMRI dataset utilizing an unguided, free-thinking paradigm, the present study provides critical insights into the neuronal events that preceded mind-blanking reports. Our findings demonstrate that spontaneous mind-blanking occurrences are associated with large-scale cortical deactivations in frontal, occipital, parietal and thalamical sites, with the frontal evaluative sites and the angular gyrus especially differentiating mind-blanking from other mental states associated with the presence of content.

Increasing evidence links disorders of consciousness (DOC) with disruptions in functional connectivity between distant brain areas. However, to which extent the balance of brain network segregation and integration is modified in DOC patients remains unclear. Using high-density electroencephalography (EEG), the objective of our study was to characterize the local and global topological changes of DOC patients’ functional brain networks. Resting state high-density-EEG data were collected and analyzed from 82 participants: 61 DOC patients recovering from coma with various levels of consciousness (EMCS (n=6), MCS+ (n=29), MCS- (n=17) and UWS (n=9)), and 21 healthy subjects (i.e., controls). Functional brain networks in five different EEG frequency bands and the broadband signal were estimated using an EEG connectivity approach at the source level. Graph theory-based analyses were used to evaluate group differences between healthy volunteers and patient groups. Results showed that networks in DOC patients are characterized by impaired global information processing (network integration) and increased local information processing (network segregation) as compared to controls. The large-scale functional brain networks had integration decreasing with lower level of consciousness.

Introduction: Research on severely brain-damaged patients with disorders of consciousness (DOC) recently revealed a wide range of therapeutic possibilities through non-invasive brain stimulation (NIBS)[1-4]. Transcranial direct current stimulation (tDCS) and transcranial pulsed current stimulation (tPCS) are safe and inexpensive NIBS techniques that could be easily implemented in rehabilitative programs. The mechanisms of these NIBS techniques are based on delivering a low-intensity current to the brain via scalp electrodes, modifying neuronal features in different ways according to the type of current applied[5]. TDCS over left dorsolateral prefrontal cortex (DLPFC) has shown to improve cognitive functions in DOC patients as measured by the Coma Recovery Scale-Revised (CRS-R) in about 50% of patients in minimally conscious state (MCS) [6,7]. TPCS has been used to modulate cortical and subcortical neural connectivity within a frequency range comprises of 6-10Hz[8]. It was successfully employed as a tool for enhancing motor skills and cognitive functions in healthy volunteers [9] and has shown promising results on brain activity and connectivity, as measured with quantitative electroencephalogram (qEEG), being theoretically able to reach deeper brain structures than tDCS [10,11] due to specific localization of current delivery. These two NIBS techniques have been shown to induce different neural changes in healthy volunteers and in patients with chronic visceral pain[12]. This experimental protocol aims to compare the effects of tPCS and tDCS on neurophysiological outcomes in one patient with DOC using qEEG. Furthermore, we will also evaluate the effects of tPCS and tDCS on behavioral outcomes (i.e., CRS-R). Methods: This is a double-blind sham-controlled case-report on one MCS+ patient who suffered a subarachnoid haemorrhage 15 months prior. The subject received 3 sessions in a randomized way, with a minimum interval of 5 days between each treatment condition: (i) active tPCS with sham tDCS, (ii) sham tPCS with active tDCS, and (iii) sham tPCS with sham tDCS (see Fig.1). Furthermore, before and after each session we performed CRS-R and recorded 10 minutes of resting EEG using 25 electrodes montage based on 10-20 standard. The stimulation target for tDCS was the left DLPFC with an intensity of 2mA for 20 minutes, while the target for tPCS was on the bimastoid line with an intensity of 2mA peak to peak and a random frequency of 6-10Hz for 20 minutes. EEG data were filtered from 1Hz to 40Hz and were further divided into 2 seconds epochs. Visual inspection and independent component analysis (ICA) were used to remove eyeblinks and muscle artefacts. Bad channels were interpolated using spherical interpolation and data were re-referenced to the overall average of electrodes. A z-score normalization was, then, performed on each channel. Power of EEG signal was calculated for each standard frequency bands: Delta (0-4 Hz), Theta (4-8 Hz), Alpha (8-12 Hz) and Beta (12-25 Hz), and multitapers method was used to compute power spectral density [13]. Non-parametric corrected cluster permutation test [14] was performed to compare the significant difference of the power topographic maps before and after each session. Electrode clusters with p-value below 0.01 were considered as significant power changes. Results and Discussion: Considering EEG analysis, after anodal tDCS, the two tailed cluster permutation test showed significant increase in the power of Alpha and Beta bands in all electrodes and decrease in the power of Delta and Theta bands in frontal electrode clusters. Electrode clusters with significant power change (p<0.01) are shown in Fig.2 for each stimulation modality. After active tPCS, a significant power increase was observed only in Theta power. This was consistent with the frequency of pulses used for tPCS (i.e., 6-10Hz) as well as the peak frequency in the power spectral density of EEG signals of the patient (i.e., 6-10Hz) (Fig.3). TDCS, but not tPCS, resulted in a significant improvement in CRS-R total score. Indeed, after anodal tDCS, the patient’s CRS-R total score increased from 10 to 15 (defining the patient as a tDCS responder[6]). The patient’s diagnosis remained the same after tDCS (MCS+) but she showed systematic response to commands and objects’ localisation that were not observed before. On the other hand, before and after active tPCS, the CRS-R score remained at 14. In the sham condition, the CRS-R score decreased from 15 to 13 after the session. Increase of Alpha and Beta power and decrease of Theta and Delta power after anodal tDCS is consistent with the increase of consciousness level [15,16] and therefore, could underlie the behavioral outcome increase observed in CRS-R scores. However, increase of Theta power after active tPCS did not result in any improvement in the behavioural outcome of the patient. This could be related to the number of tPCS sessions or the frequency of stimulation. However, it could be relevant to mention that even if not behavioral changes were obsevred with the CRS-R, the patient’s caregivers and relatives noticed that she stayed awake for longer period of time during the day and had difficulties to sleep at night for two days after the tPCS session. Therefore, it may be hypothesized that the CRS-R was not sensitive enough, in her case, to capture behavioural changes following tPCS. Conclusion: In this first experimental clinical trial, the effect of active tDCS and tPCS on neurophysiological and behavioral outcomes were tested in one patient in MCS. The results showed that the anodal tDCS significantly increased alpha and beta EEG frequency bands and decreased delta and theta frequency bands which was paralleled by a clinical improvement observed with the CRS-R score. On the other hand, active tPCS had no significant behavioral effect on the CRS-R score but induced a significant increase in theta power as expected...