The neurophysiological basis of excessive daytime sleepiness: suggestions of an altered state of consciousness.

Excessive daytime sleepiness (EDS) is characterized by difficulty staying awake during daytime, though additional features may be present. EDS is a significant problem for clinical and non-clinical populations, being associated with a range of negative outcomes that also represent a burden for society. Extreme EDS is associated with sleep disorders, most notably the central hypersomnias such as narcolepsy, Kleine-Levin syndrome, and idiopathic hypersomnia (IH). Although investigation of these conditions indicates that EDS results from diminished sleep quality, the underlying cause for this impairment remains uncertain. One possibility could be that previous research has been too narrow in scope with insufficient attention paid to non-sleep-related aspects. Here, we offer a broader perspective in which findings concerning the impact of EDS on cortical functioning are interpreted in relation to current understanding about the neural basis of consciousness. Alterations in the spatial distribution of cortical activity, in particular reduced connectivity of frontal cortex, suggest that EDS is associated with an altered state of consciousness.

Ultra-slow mechanical stimulation of olfactory epithelium modulates consciousness by slowing cerebral rhythms in humans.

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.

Combining electroencephalographic activity and instantaneous heart rate for assessing brain-heart dynamics during visual emotional elicitation in healthy subjects.

Emotion perception, occurring in brain areas such as the prefrontal cortex and amygdala, involves autonomic responses affecting cardiovascular dynamics. However, how such brain-heart dynamics is further modulated by emotional valence (pleasantness/unpleasantness), also considering different arousing levels (the intensity of the emotional stimuli), is still unknown. To this extent, we combined electroencephalographic (EEG) dynamics and instantaneous heart rate estimates to study emotional processing in healthy subjects. Twenty-two healthy volunteers were elicited through affective pictures gathered from the International Affective Picture System. The experimental protocol foresaw 110 pictures, each of which lasted 10 s, associated to 25 different combinations of arousal and valence levels, including neutral elicitations. EEG data were processed using short-time Fourier transforms to obtain time-varying maps of cortical activation, whereas the associated instantaneous cardiovascular dynamics was estimated in the time and frequency domains through inhomogeneous point-process models. Brain-heart linear and nonlinear coupling was estimated through the maximal information coefficient (MIC). Considering EEG oscillations in theθband (4-8 Hz), MIC highlighted significant arousal-dependent changes between positive and negative stimuli, especially occurring at intermediate arousing levels through the prefrontal cortex interplay. Moreover, high arousing elicitations seem to mitigate changes in brain-heart dynamics in response to pleasant/unpleasant visual elicitation.

Brain-heart linear and nonlinear dynamics during visual emotional elicitation in healthy subjects.

This study investigates brain-heart dynamics during visual emotional elicitation in healthy subjects through linear and nonlinear coupling measures of EEG spectrogram and instantaneous heart rate estimates. To this extent, affective pictures including different combinations of arousal and valence levels, gathered from the International Affective Picture System, were administered to twenty-two healthy subjects. Time-varying maps of cortical activation were obtained through EEG spectral analysis, whereas the associated instantaneous heartbeat dynamics was estimated using inhomogeneous point-process linear models. Brain-Heart linear and nonlinear coupling was estimated through the Maximal Information Coefficient (MIC), considering EEG time-varying spectra and point-process estimates defined in the time and frequency domains. As a proof of concept, we here show preliminary results considering EEG oscillations in the θ band (4-8 Hz). This band, indeed, is known in the literature to be involved in emotional processes. MIC highlighted significant arousal-dependent changes, mediated by the prefrontal cortex interplay especially occurring at intermediate arousing levels. Furthermore, lower and higher arousing elicitations were associated to not significant brain-heart coupling changes in response to pleasant/unpleasant elicitations.

Brain connectivity is altered by extreme physical exercise during non-REM sleep and wakefulness: indications from EEG and fMRI studies.

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.

A Classification method for eye movements direction during REM sleep trained on wake electro-oculographic recordings.

Rapid eye movements (REMs) are a peculiar and intriguing aspect of REM sleep, even if their physiological function still remains unclear. During this work, a new automatic tool was developed, aimed at a complete description of REMs activity during the night, both in terms of their timing of occurrence that in term of their directional properties. A classification stage of each singular movement detected during the night according to its main direction, was in fact added to our procedure of REMs detection and ocular artifact removal. A supervised classifier was constructed, using as training and validation set EOG data recorded during voluntary saccades of five healthy volunteers. Different classification methods were tested and compared. The further information about REMs directional characteristic provided by the procedure would represent a valuable tool for a deeper investigation into REMs physiological origin and functional meaning.

Metacognitive beliefs relate specifically to sleep quality in primary insomnia: a pilot study.

OBJECTIVE: To identify whether metacognitive aspects are a specific mental pattern of primary insomnia (PI) or an aspecific correlate of sleep alterations. METHODS: Sleep quality (Pittsburgh Sleep Quality Index: PSQI), anxiety (Self-rating Anxiety State: SAS), depression (Beck Depression Inventory: BDI) and metacognition (Metacognitions Questionnaire - Insomnia: MCQ-I) were evaluated in 24 PI patients, 13 snorers and 17 healthy controls. Rank-transformed PSQI, BDI, SAS and MCQ-I scores were submitted to one-way analysis of variance with group as a between-factor. PSQI was submitted to three-way analysis of covariance (ANCOVA) with MCQ-I, BDI or SAS as covariate and group as a between-factor. Post-hoc analyses were conducted using pairwise comparisons with Sidak correction. RESULTS: As expected, PSQI scores significantly differentiated the three groups, one from another: PI had highest scores followed by snorers and healthy controls. PI subjects had MCQ-I scores significantly higher than those of snorers and healthy controls; no difference between the latter groups was found. The ANCOVA on PSQI with MCQ-I as a covariate abolished the difference in sleep quality between PI and snorers, whereas covarying for BDI or SAS left the differences in sleep quality between the groups unchanged. CONCLUSION: These preliminary results lead to two main conclusions: (i) metacognitive aspects are more prominent in PI when compared to snorers and healthy controls; (ii) MCQI shows higher sensitivity in defining PI patients, with respect to PSQI. If these findings are confirmed and expanded by further studies, the development of a specific metacognitive model of primary insomnia may be warranted.

Minimal changes of thyroid axis activity influence brain functions in young females affected by subclinical hypothyroidism.

There is evidence of an association between thyroid hormones (TH) alterations and mental dysfunctions related to procedural and working memory functions, but the physiological link between these domains is still under debate, also for the presence of age as a confounding factor. Thus, we investigated the TH tuning of cerebral functions in young females affected by the borderline condition of subclinical hypothyroidism (SH) and in euthyroid females of the same age. The experiment consisted in the characterization of the affective state and cognitive abilities of the subjects by means of specific neuropsychological questionnaires, and of brain activity (EEG) in resting state and during the passive viewing of emotional video-clips. We found that SH had i) increased anxiety for Physical Danger; ii) better scores for both Mental Control and no-working-memory-related functions; iii) association between anxiety for Physical Danger and fT4 levels. Thus, in young adults, SH increases inward attention and paradoxically improves some cognitive functions. In addition, self-assessed questionnaires showed that SH had a greater susceptibility to unpleasant emotional stimulation. As for EEG data, SH compared to controls showed: i) reduction of alpha activity and of gamma left lateralization in resting state; ii) increased, and lateralized to the right, beta2 activity during stimulations. Both results indicated that SH have higher levels of arousal and greater susceptibility to negative emotion than controls. In conclusion, our study indicates that minimal changes in TH levels produce subtle but well-defined mental changes, thus encouraging further studies for the prediction of pathology evolution.

Cardiovascular changes during SCUBA diving: an underwater Doppler echocardiographic study.

AIM: Body immersion induces blood redistribution (from peripheral to intrathoracic vessels) and is a powerful autonomic stimulus (activating both parasympathetic and sympathetic systems). For these reasons, concerns have been raised about the safety of diving for subjects with previous heart disease. The aim of this study was to evaluate cardiovascular changes occurring during recreational SCUBA diving, as assessed by underwater Doppler echocardiography. METHODS: Eighteen healthy experienced divers underwent a 2D Doppler echocardiography basally, during two 15' steps of still SCUBA diving at different depths (10 m followed by 5 m) and shortly after the end of immersion. RESULTS: During dive, left ventricular (LV) diastolic volume and early left ventricular filling significantly increased (5 m vs. basal: P < 0.05 and P < 0.01, respectively), while both deceleration time of the early filling rate and late diastolic filling velocity significantly decreased (5 m and 10 m dive vs. basal: P < 0.01). LV volume increase and diastolic filling changes persisted at postdive evaluation, where a significant decrease in heart rate was also observed (P < 0.01 as compared to basal, 5-m and 10-m dive). CONCLUSION: This study documents that shallow-depth SCUBA diving induces LV enlargement and diastolic dysfunction. Direct underwater evaluation by Doppler echocardiography could be an appropriate tool for unmasking subjects at risk for underwater-related accidents.

Objective selection of EEG late potentials through residual dependence estimation of independent components.

This paper presents a novel method to objectively select electroencephalographic (EEG) cortical sources estimated by independent component analysis (ICA) in event-related potential (ERP) studies. A proximity measure based on mutual information is employed to estimate residual dependences of the components that are then hierarchically clustered based on these residual dependences. Next, the properties of each group of components are evaluated at each level of the hierarchical tree by two indices that aim to assess both cluster tightness and physiological reliability through a template matching process. These two indices are combined in three different approaches to bring to light the hierarchical structure of the cluster organizations. Our method is tested on a set of experiments with the purpose of enhancing late positive ERPs elicited by emotional picture stimuli. Results suggest that the best way to look for physiologically plausible late positive potential (LPP) sources is to explore in depth the tightness of those clusters that, taken together, best resemble the template. According to our results, after brain sources clustering, LPPs are always identified more accurately than from ensemble-averaged raw data. Since the late components of an ERP involve the same associative areas, regardless of the modality of stimulation or specific tasks administered, the proposed method can be simply adapted to other ERP studies, and extended from psychophysiological studies to pathological or sport training evaluation support.

Residual dependency estimation of independent components applied to EEG event related potentials associated with emotional processing.

Independent component analysis can be employed as an exploratory method in electroencephalographic (EEG) data analysis. However, the assumption of statistical independence among the estimated components is not always fulfilled by ICA-based numerical methods. Furthermore it may happen that one physiological source can be split in two or more components. As a consequence, the estimated components must be further investigated to assess the existence of reciprocal similarities. In this work a method for finding residual dependency subsets of component is proposed. Firstly a hierarchical clustering stage is carried out to classify ICA results. Then the hierarchical tree is investigated at each level by two indices to evaluate the tightness of all clusters. At the same time clustered scalp projections are compared with a template, which is shaped by applying ensemble ICA to a training dataset. Results are shown on EEG data acquired in event-related brain potentials (ERPs) studies for emotional pictures processing. In this kind of experiment ERPs are measured whilst unpleasant and neutral images are shown to a subject. The clustering procedure and the performance indices succeeded in isolating compact groups of components. These components, taken together, reflect the brain's biopotentials related to emotional processing at different cortical areas.

A minimal model for the respiratory sinus arrhythmia.

The cardiac and respiratory rhythms in humans are known to be coupled by several mechanisms. In particular, the first rhythm is deeply modulated by the second. In this report we propose a simple operational model for heart rate variability which, taking such modulation into account, reproduces the main features of some experimental sequences of RR intervals recorded from healthy subjects in the resting condition. Also, peer analysis of the model performance allows us to answer the question whether the observed behaviour should be ascribed to phase synchronisation of the heart beating to the respiratory rhythm. Lastly, the changes of the model activity brought about by changing its relevant parameters are analysed and discussed.

Heart rate variability in subjects with different hypnotic susceptibility receiving nociceptive stimulation and suggestions of analgesia.

The aim of the present study was to investigate the possible hypnotizability-related modulation of heart activity during nociceptive stimulation (pressor pain) and during nociceptive stimulation associated with the suggestion of analgesia in not hypnotized healthy individuals with a high (Highs) and a low (Lows) hypnotic susceptibility. ECG and respirogram were recorded. Standard time and frequency domain indexes were evaluated, together with the sd1 and sd2 values of the Poincaré plot over the RR series. Results showed self reports of analgesia in Highs and a significant increase of the respiratory frequency during stimulation in both groups. Very few significant differences between groups and among conditions were detected for mean RR and heart rate variability (HRV) through spectral analysis. and through the Poincaré indexes evaluation. On the contrary, a promising approach seems to be the study of the correlations among standard and Poincaré variables. In particular, different changes in (or even lost of) correlations were enlightened in Highs and Lows, suggesting a different modulation of RR in the two groups, probably due to the very low frequency components of HRV. Different roles of sympathetic and parasympathetic activities during stimulation can be suggested.

Head-down bed rest reduces the breathing rate short-term variability in subjects with orthostatic intolerance.

Orthostatic intolerance is the most serious symptom of cardiovascular deconditioning induced by microgravity. We have showed that in symptomatic subjects the baroreflex control of sinus node is affected by short term simulated microgravity. At present the influence of the respiration on the cardiovascular system in this condition is not clear. The aim of the present study was to examine the behaviour of the Breathing Rate (BR) in 5 Non-Symptomatic (NS) and 3 Symptomatic (S) subjects before and after 4 hours of head-down bed rest (HD).