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Voluntary apnea showcases extreme human adaptability in trained individuals like professional free divers. We evaluated the psychological and physiological adaptation and the functional cerebral changes using electroencephalography (EEG) and functional Magnetic Resonance Imaging (fMRI) to 6.5 min of dry static apnea performed by a world champion free diver. Compared to resting state at baseline, breath holding was characterized by increased EEG power and functional connectivity in the alpha band, along with decreased delta band connectivity. fMRI connectivity was increased within the default mode network (DMN) and visual areas but decreased in pre- and postcentral cortices. While these changes occurred in regions overlapping with cerebral signatures of several meditation practices, they also display some unique features that suggest an altered somatosensory integration. As suggested by self-reports, these findings could reflect the ability of elite free divers to create a state of sensory dissociation when performing prolonged apnea.

The fragmented sleep, fragmented mind hypothesis has associated sleep disturbances and dissociative states in subjects with dissociative traits, as supported by neurophysiological theories of consciousness stating that altered states might result from an altered functional interaction among brain modules due to inefficient sleep processes.Irrespective of dissociative traits, it is conceivable that a labile sleep-wake cycle might fuel dissociative states such as derealization, depersonalization, and dissociative amnesia.To verify whether acute sleep loss can prompt dissociative states and to identify possible psychophysiological correlates, we evaluated dissociative experiences (by means of Phenomenology of Consciousness Inventory and Clinician Administered Dissociative State Scale) and resting state EEG features (band-wise spectral content and phase synchronization) after total sleep deprivation.After deprivation, participants reported increased perception of altered state of consciousness and dissociative experiences, and a decreased perception of cognitive control. Analyzing the psychophysiological correlates of dissociative states following deprivation, we observed the following results: the higher the prefrontal theta spectral content, the higher the depersonalization state and the lower the self-awareness; the higher the intensity of the dissociative experiences, the higher the synchronization increase in alpha, beta, and gamma bands; the higher the decrease of higher-order functions, the higher the synchronization in the aforementioned bands.Thus, acute sleep deprivation appears to fuel dissociative experiences by establishing a state of consciousness promoted by a higher large-scale synchronization at high frequencies.

In this study, Piarulli et al. conduct a thorough classification procedure for EEG data acquired from tinnitus patients and healthy controls. The authors develop two classifiers that can accurately distinguish tinnitus patients from healthy controls as well as tinnitus patients with low and high distress levels. There exist no objective markers for tinnitus or tinnitus disorders, which complicates diagnosis and treatments. The combination of EEG with sophisticated classification procedures may reveal biomarkers that can identify tinnitus and accurately differentiate different levels of distress experienced by patients. EEG recordings were obtained from 129 tinnitus patients and 142 healthy controls. Linear support vector machines were used to develop two classifiers: the first differentiated tinnitus patients from controls, while the second differentiated tinnitus patients with low and high distress levels. The classifier for healthy controls and tinnitus patients performed with an average accuracy of 96 and 94% for the training and test sets, respectively. For the distress classifier, these average accuracies were 89 and 84%. Minimal overlap was observed between the features of the two classifiers. EEG-derived features made it possible to accurately differentiate healthy controls and tinnitus patients as well as low and high distress tinnitus patients. The minimal overlap between the features of the two classifiers indicates that the source of distress in tinnitus, which could also be involved in distress related to other conditions, stems from different neuronal mechanisms compared to those causing the tinnitus pathology itself.

Background Spasticity management in severely brain-injured patients with disorders of consciousness (DOC) is a major challenge because it leads to complications and severe pain that can seriously affect quality of life. Objectives We aimed to determine the feasibility of a single session of transcranial direct current stimulations (tDCS) to reduce spasticity in chronic patients with DOC. Methods We enrolled 14 patients in this double-blind, sham-controlled randomized crossover pilot study. Two cathodes were placed over the left and right primary motor cortex and 2 anodes over the left and right prefrontal cortex. Hypertonia of the upper limbs and level of consciousness were assessed by the Modified Ashworth Scale (MAS) and the Coma Recovery Scale-Revised (CRS-R). Resting state electroencephalography was also performed. Results At the group level, spasticity was reduced in only finger flexors. Four responders (29%) showed reduced hypertonicity in at least 2 joints after active but not sham stimulation. We found no behavioural changes by the CRS-R total score. At the group level, connectivity values in beta2 were higher with active versus sham stimulation. Relative power in the theta band and connectivity in the beta band were higher for responders than non-responders after the active stimulation. Conclusion This pilot study highlights the potential benefit of using tDCS for reducing upper-limb hypertonia in patients with chronic DOC. Large-sample clinical trials are needed to optimize and validate the technique.

Nidrâ yoga is an ancient yogic practice capable of inducing altered states of consciousness characterized by deep relaxation, strong concentration, acute self-awareness, and joy. In modern contemplative neuroscience language, it is known by the name yoga nidra, and few studies have investigated its phenomenological and psychophysiological effects. Six healthy volunteers (four females aged 31–74) performed 12 yoga nidra sessions guided by an expert during a 6-day retreat. Each session consisted of 10 minutes in a resting state (baseline) followed by 2 hours of yoga nidra. Psychometric data regarding dissociative experiences (Clinician Administered Dissociative States Scale) and the state of consciousness (Phenomenology of Consciousness Inventory) were collected after baseline and yoga nidra, while high-density EEG was recorded during the entire session. During nidra sessions, no sleep hallmarks (i.e., K-complexes and sleep spindles) were detected by the EEG in any subject. Psychometric data we re analyzed using a Wilcoxon signed-rank test corrected with the false discovery rate approach for multiple comparisons. Compared to baseline, yoga nidra practice was related to: (1) increased dissociative effects (p = 0.022); (2) perception of being in an altered state of consciousness (p = 0.026); (3) alterations in perceived body image (p = 0.022); (4) increased “meaningfulness” attributed to the experience (p = 0.026); (5) reduced rational thinking (p = 0.029); and (6) reduced volitional thought control (p = 0.026). First-person experience is discussed in relation to descriptive EEG power spectral density analysis, which was performed in one subject because of severe EEG artifacts in the other recordings; that subject showed, compared to baseline: (1) early increase of alpha and beta power, followed by a progressive widespread reduction; (2) widespread early increase of theta power, followed by a progressive reduction; and (3) widespread increase of gamma power in the latest stages. The present preliminary results enrich the knowledge of yoga nidra, elucidating its phenomenology and suggesting some psychophysiological correlates that future studies may address.

Transcranial direct current stimulation (tDCS) applied over the prefrontal cortex has been shown to improve behavioral responsiveness in patients with disorders of consciousness following severe brain injury, especially those in minimally conscious state (MCS). However, one potential barrier of clinical response to tDCS is the timing of stimulation with regard to the fluctuations of vigilance that characterize this population. Indeed, a previous study showed that the vigilance of MCS patients has periodic average cycles of 70 min (range 57−80 min), potentially preventing them to be in an optimal neural state to benefit from tDCS when applied randomly. To tackle this issue, we propose a new protocol to optimize the application of tDCS by selectively stimulating at high and low vigilance states. Electroencephalography (EEG) real-time spectral entropy will be used as a marker of vigilance and to trigger tDCS, in a closed-loop fashion. We will conduct a randomized controlled crossover clinical trial on 16 patients in prolonged MCS who will undergo three EEG-tDCS sessions 5 days apart (1. tDCS applied at high vigilance; 2. tDCS applied at low vigilance; 3. tDCS applied at a random moment). Behavioral effects will be assessed using the Coma Recovery Scale-Revised at baseline and right after the stimulations. EEG will be recorded throughout the session and for 30 min after the end of the stimulation. This unique and novel approach will provide patients’ tailored treatment options, currently lacking in the field of disorders of consciousness.

We investigated changes of slow-wave activity and sleep slow oscillations in the night following procedural learning boosted by reinforcement learning, and how these changes correlate with behavioural output. In the Task session, participants had to reach a visual target adapting cursor's movements to compensate an angular deviation introduced experimentally, while in the Control session no deviation was applied. The task was repeated at 13:00 hours, 17:00 hours and 23:00 hours before sleep, and at 08:00 hours after sleep. The deviation angle was set at 15° (13:00 hours and 17:00 hours) and increased to 45° (reinforcement) at 23:00 hours and 08:00 hours. Both for Task and Control nights, high-density electroencephalogram sleep recordings were carried out (23:30-19:30 hours). The Task night as compared with the Control night showed increases of: (a) slow-wave activity (absolute power) over the whole scalp; (b) slow-wave activity (relative power) in left centro-parietal areas; (c) sleep slow oscillations rate in sensorimotor and premotor areas; (d) amplitude of pre-down and up states in premotor regions, left sensorimotor and right parietal regions; (e) sigma crowning the up state in right parietal regions. After Task night, we found an improvement of task performance showing correlations with sleep slow oscillations rate in right premotor, sensorimotor and parietal regions. These findings suggest a key role of sleep slow oscillations in procedural memories consolidation. The diverse components of sleep slow oscillations selectively reflect the network activations related to the reinforced learning of a procedural visuomotor task. Indeed, areas specifically involved in the task stand out as those with a significant association between sleep slow oscillations rate and overnight improvement in task performance.

Brain connectivity is associated to behavioral states (e.g. wake, sleep) and modified by physical activity although, to date, it is not clear which components (e.g. hypothalamus-pituitary-adrenal axis hormones, cytokines) associated to the exercise are involved. In this pilot study, we used extreme exercise (UltraTriathlon) as a model to investigate physical-activity-related changes of brain connectivity. We studied post-race brain synchronization during wakefulness and sleep as well as possible correlations between exercise-related cytokines/hormones and synchronization features. For wakefulness, global synchronization was evaluated by estimating from fMRI data (12 athletes) the brain global connectivity (GC). GC increased in several brain regions, mainly related to sensory-motor activity, emotional modulation and response to stress that may foster rapid exchange of information across regions, and reflect post-race internally-focused mental activity or disengagement from previous motor programs. No significant correlations between cytokines/hormones and GC were found. For sleep (8 athletes), synchronization was evaluated by estimating the local-(cortical) and global-related (thalamo- cortical) EEG features associated to the phenomenon of Sleep Slow Oscillations (SSO) of NREM sleep. Results showed that: power of fast rhythms in the baseline preceding the SSO increased in midline and parietal regions; amplitude and duration of SSOs increased, mainly in posterior areas; sigma modulation in the SSO up state decreased. In the post race, IL-10 positively correlated with fast rhythms baseline, SSO rate and positive slope; IL-1ra and cortisol inversely correlated with SSO duration; TNF-α and C-reactive protein positively correlated with fast rhythm modulation in the SSO up state. Sleep results suggest that: arousal during sleep, estimated by baseline fast rhythms, is increased; SSO may be sustained by cortical excitability, linked to anti-inflammatory markers (IL-10); thalamo-cortical entrainment, (sigma modulation), is impaired in athletes with higher inflammatory markers.

Temporal fluctuations of cognitively-mediated behaviors in minimally conscious state (MCS) have been linked to changes of awareness, but the time-pattern of these variations remains ill-described. We analyzed 4-h EEG recordings from 12 patients with disorders of consciousness (6 MCS and 6 vegetative state/unresponsive wakefulness syndrome, VS/UWS). Relative powers (delta, theta, alpha, beta1 and beta2 bands) and spectral entropy were estimated (Fz, Cz and Pz derivations). Spectral entropy time-courses were then analyzed. MCS patients had higher theta and alpha and lower delta power when compared to VS/UWS. They showed higher spectral entropy mean value and higher time variability. MCS patients were characterized by spectral entropy fluctuations with periodicities of 70 min (range 57-80 min). Notably, these periodicities closely resemble those described in awake healthy subjects, which were hypothesized to be related to fluctuation in vigilance/attention. No significant periodicity was observed for VS/UWS. The spectral entropy periodicity found in MCS patients could reflect the fluctuation of awareness responsible for the inconsistency of MCS manifestation of cognitively-mediated behaviors. The presence of a 70 min periodicity in spectral entropy could permit clinicians to better choose their time-window when performing a clinical assessment of consciousness. It could also permit to monitor fluctuations in cognitive performance (i.e., response to command) during complementary testing by passive or active electrophysiological or functional neuroimaging paradigms or in resting state conditions.

Purpose Working in oncology departments is a stressful and emotionally consuming experience and oncology professionals are particularly at risk for developing stress-related syndromes. Defense mechanisms (high-adaptive) and mindfulness dispositions are known as facilitators of well-being and adaptation. In this study we analysed the role of these unconscious and conscious strategies in protecting the oncology clinicians from stress-related symptoms. Method A convenience sample of 63 oncology professionals was assessed on defense style, mindfulness disposition, depression and anxiety symptoms using self-reported questionnaires. Demographic and professional information was included in data collection. Results Results did not show significance differences in demographic and professional characteristics among all studied variables. Mature defense style and mindfulness were highly and negatively correlated with depression and anxiety, while a positive association was found between immature defense style and both depression and anxiety symptoms. Hierarchical multiple regression analyses found defense styles and mindfulness as predictors of depression, whereas only immature defense style predicted anxiety. Conclusions The present study provides the first empirical evidence of the influence of unconscious defense mechanisms and conscious mindfulness dispositions in protecting oncology professionals from depression and anxiety symptoms. Defense mechanisms and mindfulness share several common-points and should be seen as complementary in enhancing physical and psychological well-being. Further studies are required for a deeper understanding of the impact of mindfulness and defenses in improving adaptation.

The coupling between respiration and neural activity within olfactory areas and hippocampus has recently been unambiguously demonstrated, its neurophysiological basis sustained by the well-assessed mechanical sensitivity of the olfactory epithelium. We herein hypothesize that this coupling reverberates to the whole brain, possibly modulating the subject’s behavior and state of consciousness. The olfactory epithelium of 12 healthy subjects was stimulated with periodical odorless air-delivery (frequency 0.05 Hz, 8 s on, 12 off). Cortical electrical activity (High Density-EEG) and perceived state of consciousness have been studied. The stimulation induced i) an enhancement of delta-theta EEG activity over the whole cortex mainly involving the Limbic System and Default Mode Network structures, ii) a reversal of the overall information flow directionality from wake-like postero-anterior to NREM sleep-like antero-posterior, iii) the perception of having experienced an Altered State of Consciousness. These findings could shed further light via a neurophenomenological approach on the links between respiration, cerebral activity and subjective experience, suggesting a plausible neurophysiological basis for interpreting altered states of consciousness induced by respiration-based meditative practices.

Background: Transcranial direct current stimulation (tDCS) was recently shown to promote recovery of voluntary signs of consciousness in some patients in minimally conscious state (MCS). However, it remains unclear why clinical improvement is only observed in a subgroup of patients. Objectives: In this retrospective study, we investigated the relationship between tDCS responsiveness and neuroimaging data from MCS patients. Methods: Structural Magnetic Resonance Imaging (MRI), Fluorodeoxyglucose Positron emission tomography (FDG-PET) and clinical electroencephalography (EEG) were acquired in 21 sub-acute and chronic MCS patients (8 tDCS responders) who subsequently (

Aims: We assessed the inter-relationship that exists between variations of different biochemical and hematological parameters following strenuous endurance exercise in Ironmen by using multiple factor analysis (MFA). MFA was used to estimate the associations among groups of parameters in order to identify concurrent changes in many different biochemical variables. Materials & methods: In total, 14 Ironman athletes were followed before and early after a race. MFA was applied to the parameters that showed a significant variation after the race, as we previously described in detail. Specifically, MFA standardizes data in each group and calculates the global axes (GAs), which are the linear combination of original parameters that maximize the global data variance. Results: MFA identified three global axes (GAs) as significant, explaining approximately 62% of the global data variance. The first GA contained NT-proBNP, IL-1ra, IL-6, IL-8 and the oxidative index. The second and third GAs included calcium, creatinine, potassium, uric acid, hemoglobin, hematocrit and glucose. Analysis of the first two GAs showed that changes in the oxidative index were associated with variations in IL-8 and NT-proBNP. Conclusion: Among all the variables considered, MFA evidenced a close relationship between variations in oxidative stress, IL-8 and NT-proBNP, which may have a meaning in the mechanisms related to the physiological response after strenuous acute exercise.

In this paper is presented an analysis of the phase lag index (PLI) in healthy controls and patients with disorders of consciousness aimed to find differences in connectivity of brain sources between these two states in different frequency bands. It was analyzed a total of 50 EEGs, 28 from healthy patients and 22 from patients with disorders of consciousness with two kind of montages, bipolar and mastoid referenced. The patients show a higher PLI in lower frequency bands with significative differences for interhemispheric distances between electrodes using a mastoid reference.

Objective: Studying the thalamic role in the cortical expression of the Sleep Slow Oscillation (SSO) in humans by comparing SSO features in a case of Fatal Familial Insomnia (FFI) and a group of controls. Methods: We characterize SSOs in a 51-year-old male with FFI carrying the D178N mutation and the methionine/methionine homozygosity at the polymorphic 129 codon of the PRNP gene and in eight gender and age-matched healthy controls. Polysomnographic (21 EEG electrodes, two consecutive nights) and volumetric- (Diffusion tensor imaging Magnetic Resonance Imaging DTI MRI) evaluations were carried out for the patient in the middle course of the disease (five months after the onset of insomnia; disease duration: 10 months). We measured a set of features describing each SSO event: the wave shape, the event-origin location, the number and the location of all waves belonging to the event, and the grouping of spindle activity as a function of the SSO phase. Results: We found that the FFI individual showed a marked reduction of SSO event rate and wave morphological alterations as well as a significant reduction in grouping spindle activity, especially in frontal areas. These alterations paralleled DTI changes in the thalamus and the cingulate cortex. Conclusions: This work gives a quantitative picture of spontaneous SSO activity during the NREM sleep of a FFI individual. The results suggest that a thalamic neurodegeneration specifically alters the cortical expression of the SSO. This characterization also provides indications about cortico-thalamic interplays in SSO activity in humans.

The surrounding world has a strong impact on the way we feel and perceive the events that happens in daily life. The power of environments to elicit emotions in humans has been widely studied in experimental psychology by using exposure to photographs or real situations. These researches do not reproduce the vividness of events in ordinary life and do not permit to control the situations that happen within. By reproducing a realistic scenario similar to daily life and by controlling the social narratives happening within, Virtual Reality (VR) is a powerful tool to investigate the effect of environments on humans’ feelings and emotions. In this study we have animated the emotional content of a realistic virtual scenario with a dynamic scene in order to introduce a novel approach to investigate the effect of environments in human feeling based on the Emotional Narrative Virtual Environment (ENVE) paradigm. A sample of 36 subjects experimented 3 ENVEs with a Fear, Disgust and Happy emotional content, made to live with a social narratives, in an immersive VR setup. Results showed the ability of ENVE to elicit specific emotional state in participants and corroborate the idea that the ENVE approach can be used in environmental psychology or to treat persons with mental disease.

Sleep Slow Oscillations (SSOs), paradigmatic EEG markers of cortical bistability (alternation between cellular downstates and upstates), and sleep spindles, paradigmatic EEG markers of thalamic rhythm, are two hallmarks of sleeping brain. Selective thalamic lesions are reportedly associated to reductions of spindle activity and its spectrum ~14 Hz (sigma), and to alterations of SSO features. This apparent, parallel behavior suggests that thalamo-cortical entrainment favors cortical bistability. Here we investigate temporally-causal associations between thalamic sigma activity and shape, topology, and dynamics of SSOs. We recorded sleep EEG and studied whether spatio-temporal variability of SSO amplitude, negative slope (synchronization in downstate falling) and detection rate are driven by cortical-sigma-activity expression (12–18 Hz), in 3 consecutive 1 s-EEG-epochs preceding each SSO event (Baselines). We analyzed: (i) spatial variability, comparing maps of baseline sigma power and of SSO features, averaged over the first sleep cycle; (ii) event-by-event shape variability, computing for each electrode correlations between baseline sigma power and amplitude/slope of related SSOs; (iii) event-by-event spreading variability, comparing baseline sigma power in electrodes showing an SSO event with the homologous ones, spared by the event. The scalp distribution of baseline sigma power mirrored those of SSO amplitude and slope; event-by-event variability in baseline sigma power was associated with that in SSO amplitude in fronto-central areas; within each SSO event, electrodes involved in cortical bistability presented higher baseline sigma activity than those free of SSO. In conclusion, spatio-temporal variability of thalamocortical entrainment, measured by background sigma activity, is a reliable estimate of the cortical proneness to bistability.

A series of ERP components, each provided with both a precise timing with respect to stimulation and a specific cortical localization, reflects the temporal succession of processing stages of music information. This makes the musical stimulus potentially usable to probe residual brain functions in non-communicating patients with disorders of consciousness. In an attempt to find a simple stimulation protocol that was suitable for use in a clinical setting, the purpose of this study was to verify whether a minimum-length musical stimulus, provided with a definite music-syntactic connotation, was still able to elicit musical ERPs in a group of eight healthy subjects. The stimulus was composed of the minimum number of chords necessary and sufficient to enable the subject to predict a plausible closure of the sequence (priming) and, at the same time, to provide him/her with the closing chord of the sequence (target), either congruous (probable closing) or not (improbable closing) to the tonal context. The subject's task was to discriminate and recognize the irregular targets. The components that were expected to be elicited, in this experimental situation, were ERAN, N5, P600/LPC. Conversely, in addition to these former components, we unexpectedly observed a N400-like component. To determine whether this component was a real N400, we submitted our data to a sLORETA analysis in order to identify its cortical generators. Irregular chords showed higher current densities with respect to regular ones on the right-sided medial and superior temporal gyri, superior and inferior parietal lobules, fusiform and parahippocampal gyri, and on the bilateral posterior cingulate cortex. In particular, the N400-like wave seems to share with the word-primed music-elicited N400 certain generators that are located in cortical areas BA 21/37 and BA 22. This suggests that even chord-primed chord targets can convey extra-musical meanings and that, consequently, they might be useful in assessing residual higher-order information-processing capabilities in non-communicating patients with disorders of consciousness.

We review current models of consciousness in the context of wakefulness and sleep. We show that recent results on Slow Wave Sleep, including our own works, naturally fit within consciousness models. In particular, Sleep Slow Oscillations, namely low-frequency (

Criticality reportedly describes brain dynamics. The main critical feature is the presence of scale-free neural avalanches, whose auto-organization is determined by a critical branching ratio of neural-excitation spreading. Other features, directly associated to second-order phase transitions, are: (i) scale-free-network topology of functional connectivity, stemming from suprathreshold pairwise correlations, superimposable, in waking brain activity, with that of ferromagnets at Curie temperature; (ii) temporal long-range memory associated to renewal intermittency driven by abrupt fluctuations in the order parameters, detectable in human brain via spatially distributed phase or amplitude changes in EEG activity. Herein we study intermittent events, extracted from 29 night EEG recordings, including presleep wakefulness and all phases of sleep, where different levels of mentation and consciousness are present. We show that while critical avalanching is unchanged, at least qualitatively, intermittency and functional connectivity, present during conscious phases (wakefulness and REM sleep), break down during both shallow and deep non-REM sleep. We provide a theory for fragmentation-induced intermittency breakdown and suggest that the main difference between conscious and unconscious states resides in the backwards causation, namely on the constraints that the emerging properties at large scale induce to the lower scales. In particular, while in conscious states this backwards causation induces a critical slowing down, preserving spatiotemporal correlations, in dreamless sleep we see a self-organized maintenance of moduli working in parallel. Critical avalanches are still present, and establish transient auto-organization, whose enhanced fluctuations are able to trigger sleep-protecting mechanisms that reinstate parallel activity. The plausible role of critical avalanches in dreamless sleep is to provide a rapid recovery of consciousness, if stimuli are highly arousing.

This scientific commentary refers to ‘Neural detection of complex sound sequences in the absence of consciousness’, by Tzovara et al. (doi:10.1093/brain/awv041). Event related potentials (ERPs), classically measured by EEG, are the electrophysiological brain responses to a stimulus. Somatosensory and auditory ERPs have been used as a non-invasive tool for assessing brain functions and predicting outcomes in disorders of consciousness and coma (for review see Bruno et al. , 2011). While early ERPs (such as the absence of cortical responses on somatosensory-evoked potentials) predict poor outcomes, cognitive ERPs may be indicative of recovery of consciousness after coma (Vanhaudenhuyse et al. , 2008). Auditory cognitive ERPs permit assessment of residual higher-order processing, such as echoic memory (e.g. using mismatch negativity potentials), acoustic and semantic discrimination (e.g. P3 or P300 evoked potentials), and incongruent language detection (e.g. N400 potentials). Classically, these ERP paradigms are based on the detection of a stimulus in violation of an auditory regularity, composed of two neural events, each characterized at the EEG level by a stereotypical morphology and latency: a mismatch negativity followed by a later complex named P300 further divided into an early (P300a) and a late component (P300b). The mismatch negativity is thought to reflect unconscious processing (Daltrozzo et al. , 2009), whereas the P300b has been linked to consciousness (Bekinschtein et al. , 2009). Neither of these ERP components are specific to auditory stimuli and both can be elicited by other sensory modalities. However, auditory cognitive ERPs have been used most extensively in the field of coma because they are easy to deliver and—in contrast to visual ERPs—can be easily acquired in eyes closed conditions. Given the …

Purpose We describe the case of a subject in a post-traumatic Minimally Conscious State (MCS) who retrieved full interaction with the environment after midazolam infusion. We studied EEG correlates of the "awakening reaction" in the different domains of frequency, time and cortical topography, along with the intrinsic connectivity within both the task-positive and the linguistic network. Methods EEG recorded before and after midazolam administration has been submitted to spectral power analysis, sLORETA analysis and intrinsic connectivity analysis within both functional networks. Results A critical change in the power spectrum profile was observed after midazolam: a) the power between 1 and 12 Hz decreased, reaching its maximum difference with respect to pre-infusion at about 7 Hz and b) the power between 12 and 30 Hz increased, with a maximum difference at about 15 Hz. At the same time, midazolam induced significant connectivity changes, especially for these two frequency bands, within both functional networks. Conclusions We advance some hypotheses about certain aspects of the recovery from the MCS both in terms of anatomo-functional correlations and functional brain systems and we make inferences about the role that some kind of 'catatonic' symptoms might play in determining and/or maintaining this peculiar clinical state.

Spaceflights "environment" negatively affects sleep and its functions. Among the different causes promoting sleep alterations, such as circadian rhythms disruption and microgravity, stress is of great interest also for earth-based sleep medicine. This study aims to evaluate the relationships between stress related to social/environmental confinement and sleep in six healthy volunteers involved in the simulation of human flight to Mars (MARS500). Volunteers were sealed in a spaceship simulator for 105 days and studied at 5 specific time-points of the simulation period. Sleep EEG, urinary cortisol (24 h preceding sleep EEG recording) and subjectively perceived stress levels were collected. Cognitive abilities and emotional state were evaluated before and after the simulation. Sleep EEG parameters in the time (latency, duration) and frequency (power and hemispheric lateralization) domains were evaluated. Neither cognitive and emotional functions alterations nor abnormal stress levels were found. Higher cortisol levels were associated to: (i) decrease of sleep duration, increase of arousals, and shortening of REM latency; (ii) reduction of delta power and enhancement of sigma and beta in NREM N3; and (iii) left lateralization of delta activity (NREM and REM) and right lateralization of beta activity (NREM). Stressful conditions, even with cortisol fluctuations in the normal range, alter sleep structure and sleep EEG spectral content, mirroring pathological conditions such as primary insomnia or insomnia associated to depression. Correlations between cortisol fluctuations and sleep changes suggest a covert risk for developing allostatic load, and thus the need to develop ad-hoc countermeasures for preventing sleep alterations in long lasting manned space missions.

During non-REM sleep the largest EEG response evoked by sensory stimulation is the K-complex (eKC), composed of an initial positive bump (P200) followed by a bistable cortical response: a giant negative deflection (N550) and a large positive one (P900), respectively reflecting down states and up states of < 1 Hz oscillations.Sensory-modality-independent topology of N550 and P900, with maximal detection rate on fronto-central areas, has been consistently reported, suggesting that sensory inputs arise to the cortex avoiding specific primary sensory areas. However, these studies neglected latencies of all KC components as a function of electrode sites.Our aim is to identify, component by component, which topological/dynamical properties of eKCs depend on stimulus modality and which are mainly related to local cortical properties. We measured temporal and morphological features of acoustic, tactile and visual eKCs to disentangle specific sensory excitatory activities from aspecific responses due to local proneness to bistability, measured by means of the N550 descending steepness (synchronization in falling into down state).While confirming the sensory-modality independence of N550 and P900 topology with maximal detection rate in fronto-central areas, four main original results emerge from this study: (i) the topology of P200 latency depends on the sensory modality with earliest waves in the stimulation-related primary sensory areas; (ii) P200 rapidly travels as a cortical excitation; (iii) P200-like excitations when KCs are not evoked are detected over the scalp with significantly smaller amplitudes in fronto-central areas, compared to eKC P200s; and (iv) N550 latency mirrors its mean local steepness which is a function of topological proneness to bistability.From these results we can describe the emergence N550/P900 complex as the interplay between a waxing P200 cortical travel and higher fronto-central proneness to bistability.In conclusion, eKCs exhibit a physiological dichotomy: P200 acts as a traveling cortical excitation whose function is to induce the bistable cortical response (N550/P900), which in turn is crucial for maintaining sleep and unconsciousness.

Introduction Metacognitive beliefs and associated actions seem to be a stigma of primary insomnia. Indeed mental activity of primary insomniacs during the night is mainly devoted to generate thought control strategies, including reappraisal, worry and thought suppression. These strategies, in turn, induce a vicious cycle, maintaining insomnia. Our aim is to identify whether metacognitive aspects are a specific mental pattern of primary insomnia or an aspecific correlate of sleep alterations. Materials and methods We have studied 24 primary insomniacs (test group), 24 snorers, complaining nocturnal awakenings without diagnosis of obstructive sleep apnea syndrome (control group), and 20 healthy controls (sham group). Quality of sleep was assessed by Pittsburgh Sleep Quality Index (PSQI), while metacognitive aspects by means of Metacognitions Questionnaire – Insomnia (MCQI). Total score of both indices were log-transformed and tested for normality (Lilliefors test). PSQI scores were normally distributed whereas for MCQI scores the null hypothesis was rejected. On this basis, PSQI was submitted to analysis of variance with group as a 3 level between factor (test, control and sham groups) while MCQI to Kruskal–Wallis test with group as a between factor. Parametric post hocs were conducted applying unpaired t-tests with Sidak correction whereas non-parametric ones through Mann–Whitney test with Sidak correction. Results For both tests a significant group effect (p Conclusion These preliminary results allowed us to draw two main conclusions: (i) metacognitive aspects selectively characterize mental activity of primary insomniacs; (ii) MCQI, with respect to PSQI, showed higher sensitivity in defining primary insomniacs. In conclusion, the promising psychometric properties of MCQI will help to develop a specific metacognitive model of primary insomnia. Acknowledgements Dr. A.Agrimi, Dr. D.Menicucci.

While several mental functions are characterized by parallel computation performed by moduli in the cortex, consciousness is sustained by a serial global integration: a single scene at a time takes place. Studies on complex systems show that macroscopic variables, integrating many components activities, undergo fluctuations with an intermittent serial structure when the system is in a state called ‘‘criticality’’, characterized by avalanches with inverse-power-law (scale-free) distribution densities of sizes and inter-event times. Criticality has been established in human brain dynamics during wakefulness. Here we review how the critical hypothesis is able to explain many recent studies on brain complex dynamics. We focus, in particular, on the global, serial, intermittent behavior that can be assessed via high-density electroencephalograms, studying transitions between metasta- ble states. Established as it is during wakefulness, it remained unsolved whether this global intermittent dynamics correlates with consciousness or with a non-task-driven default mode, also present in non-conscious states, like deep (NREM) sleep. Here we show that in NREM sleep seriality breaks down, and re-establishes during REM sleep (dreams), with unaltered spacial structure, in terms of complex branching of avalanches. We conjecture that this connectivity is exploited in NREM sleep by neural bistability, resetting and ‘‘par- allelizing’’ portions of the cortex. &nbsp

We discuss the critical brain hypothesis and its relationship with intermittent renewal processes displaying power-law decay in the distribution of waiting times between two consecutive renewal events. In particular, studies on complex systems in a “critical” condition show that macro- scopic variables, integrating the activities of many individual functional units, undergo fluctuations with an intermittent serial structure characterized by avalanches with inverse-power-law (scale-free) distribution densities of sizes and inter-event times. This condition, which is denoted as “fractal in- termittency”, was found in the electroencephalograms of subjects observed during a resting state wake condition. It remained unsolved whether fractal intermittency correlates with the stream of consciousness or with a non-task-driven default mode activity, also present in non-conscious states, like deep sleep. After reviewing a method of scaling analysis of intermittent systems based of event- driven random walks, we show that during deep sleep fractal intermittency breaks down, and re- establishes during REM (Rapid Eye Movement) sleep, with essentially the same anomalous scaling of the pre-sleep wake condition. From the comparison of the pre-sleep wake, deep sleep and REM conditions we argue that the scaling features of intermittent brain events are related to the level of consciousness and, consequently, could be exploited as a possible indicator of consciousness in clinical applications.

During NREM sleep cortical activity corresponding to EEG fast rhythms (FRs>10 Hz) is interrupted by fragments of neural stillness (down-states), responsible for the negative peak within sleep slow oscillation (SSO). Researchers still debate whether the down-states spontaneously occur or need an initial overshoot in fluctuating activity. Herein, we studied temporally-isolated SSO in healthy subjects in order to identify two distinct EEG markers defining a putative initial up-state: i) a significant positive deflection and ii) an associated FR increase, before the negative peak. We found a positive bump preceding the down-state, which is detectable already at the cortical SSO origin site, both during N2 and N3. This early positive deflection, concurrent with a broadband activation, is characterized by an increase of sigma activity (12-18 Hz) from N2 to N3, while an opposite trend was observed for sigma activity crowning the up-state following the negative peak. Also, we found: (i) FR activations during up-states up to high gamma frequencies; (ii) depressed sigma activity in after-spindle recovery phase; and (iii) tightly coordinated activities between distinct bands (12-36 Hz, ~70 Hz, ~85 Hz and 105-125 Hz). The correlation between different bands suggested a common mechanism for sigma and gamma, and the pre-down-state activation associated with the initial bump suggested an activity ignition for down-state, whose intensity is dependent on sleep stage. In conclusion, we hypothesize that FR accompanying SSO could mark i) sleep homeostatic processes, such as the regulation/stabilization of sleep, counterbalancing the detrimental effects of continuous inputs from peripheries, and ii) neural mechanisms favoring the storage of information acquired during wakefulness.