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Functional magnetic resonance imaging (fMRI) is used to study brain functional connectivity (FC) after filtering the physiological noise (PN). Herein, we employ: adaptive filtering for removing nonstationary PN; random variables (RV) coefficient for FC analysis. Comparisons with standard techniques were performed by quantifying PN filtering and FC in neural vs. non-neural regions. As a result, adaptive filtering plus RV coefficient showed a greater suppression of PN and higher connectivity in neural regions, representing a novel effective approach to analyze fMRI data.

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.

Rapid eye movements (REMs) are a prominent feature of REM sleep, and their distribution and time density over the night represent important physiological and clinical parameters. At the same time, REMs produce substantial distortions on the electroencephalographic (EEG) signals, which strongly affect the significance of normal REM sleep quantitative study. In this work a new procedure for a complete and automated analysis of REM sleep is proposed, which includes both a REMs detection algorithm and an ocular artifact removal system. The two steps, based respectively on Wavelet Transform and adaptive filtering, are fully integrated and their performance is evaluated using REM simulated signals. Thanks to the integration with the detection algorithm, the proposed artifact removal system shows an enhanced accuracy in the recovering of the true EEG signal, compared to a system based on the adaptive filtering only. Finally the artifact removal system is applied to physiological data and an estimation of the actual distortion induced by REMs on EEG signals is supplied.

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., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Many electroencephalographic (EEG) studies on the cortical dynamics induced by unpleasant picture viewing demonstrated the modulation of event-related potentials (ERPs) components as a function of valence and the increase of gamma band responses to emotional stimuli; while only a few studies investigated phase synchronization phenomena such as inter-trial or between regions phase locking of gamma responses to emotional stimulation. The aim of this study was to provide a complete description of the cortical dynamics induced by unpleasant and neutral pictures viewing, from the ERP averages to gamma rhythm modulation, and its phase synchronization. Gamma rhythm modulation was estimated by the event-related synchronization (ERS) approach, and phase synchrony between trials and between cortical regions was studied by extending the phase-locking statistics (PLS) approach. Consistent with previous literature, an increase in P300 and late positive potential and an increase in gamma activity during viewing of unpleasant pictures as compared to neutral ones were found. No inter-trial synchronization was evoked by the stimuli, whereas widespread phase locking between sites was identified. In particular, differences in gamma synchronization between unpleasant and neutral stimuli were found. Specifically, at early (0-250 ms) lags from stimulus onset, in the 38-45 Hz gamma interval, stronger inter-site synchronizations for the unpleasant stimuli, even though quite widespread across the scalp, mainly involved the interhemispheric synchronization between temporal and frontal regions. In contrast, in the 30-37 Hz gamma interval, stronger synchronizations for the responses to neutral trials were found in the 500-750 time interval, mainly involving the temporo-parietal regions. These findings suggest that the full elaboration of unpleasant stimuli requires a tight interhemispheric communication between temporal and frontal regions that is realized by means of phase synchronization at about 40 Hz. In addition, in contrast with the idea of a broadband modulation of high-frequency activity by cognitive/emotional stimuli, the present findings i.e. stronger BRS responses to either emotional or neutral trials at specific frequency and time range, indicate that specific intervals of gamma activity could be each primarily involved in a specific aspect of stimulus processing., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The mental control of ventilation with all associated phenomena, from relaxation to modulation of emotions, from cardiovascular to metabolic adaptations, constitutes a psychophysiological condition characterizing voluntary breath-holding (BH). BH induces several autonomic responses, involving both autonomic cardiovascular and cutaneous pathways, whose characterization is the main aim of this study. Electrocardiogram and skin conductance (SC) recordings were collected from 14 elite divers during three conditions: free breathing (FB), normoxic phase of BH (NPBH) and hypoxic phase of BH (HPBH). Thus, we compared a set of features describing signal dynamics between the three experimental conditions: from heart rate variability (HRV) features (in time and frequency-domains and by using nonlinear methods) to rate and shape of spontaneous SC responses (SCRs). The main result of the study rises by applying a Factor Analysis to the subset of features significantly changed in the two BH phases. Indeed, the Factor Analysis allowed to uncover the structure of latent factors which modeled the autonomic response: a factor describing the autonomic balance (AB), one the information increase rate (IIR), and a latter the central nervous system driver (CNSD). The BH did not disrupt the FB factorial structure, and only few features moved among factors. Factor Analysis indicates that during BH (1) only the SC described the emotional output, (2) the sympathetic tone on heart did not change, (3) the dynamics of interbeats intervals showed an increase of long-range correlation that anticipates the HPBH, followed by a drop to a random behavior. In conclusion, data show that the autonomic control on heart rate and SC are differentially modulated during BH, which could be related to a more pronounced effect on emotional control induced by the mental training to BH.

Independent component analysis and blind source separation methods are steadily gaining popularity for separating individual brain and non-brain source signals mixed by volume conduction in electroencephalographic data. Despite the advancements on these techniques, determining the number of embedded sources and their reliability are still open issues. In particular to date no method takes into account trial-to-trial variability in order to provide a reliability measure of independent components extracted in Event Related Potentials (ERPs) studies. In this work we present ErpICASSO, a new method which modifies a data-driven approach named ICASSO for the analysis of trials (epochs). In addition to ICASSO the method enables the user to estimate the number of embedded sources, and provides a quality index of each extracted ERP component by combining trial-to-trial bootstrapping and CCA projection. We applied ErpICASSO on ERPs recorded from 14 subjects presented with unpleasant and neutral pictures. We separated potentials putatively related to different systems and identified the four primary ERP independent sources. Standing on the confidence interval estimated by ErpICASSO, we were able to compare the components between neutral and unpleasant conditions. ErpICASSO yielded encouraging results, thus providing the scientific community with a useful tool for ICA signal processing whenever dealing with trials recorded in different conditions.

Aim: To examine the links between quality of sleep and the severity of intestinal symptoms in irritable bowel syndrome (IBS)., Methods: One hundred and forty-two outpatients (110 female, 32 male) who met the Rome III criteria for IBS with no psychiatric comorbidity were consecutively enrolled in this study. Data on age, body mass index (BMI), and a set of life-habit variables were recorded, and IBS symptoms and sleep quality were evaluated using the questionnaires IBS Symptom Severity Score (IBS-SSS) and Pittsburgh Sleep Quality Index (PSQI). The association between severity of IBS and sleep disturbances was evaluated by comparing the global IBS-SSS and PSQI score (Pearson's correlation and Fisher's exact test) and then analyzing the individual items of the IBS-SSS and PSQI questionnaires by a unitary bowel-sleep model based on item response theory (IRT)., Results: IBS-SSS ranged from mild to severe (120-470). The global PSQI score ranged from 1 to 17 (median 5), and 60 patients were found to be poor sleepers (PSQI > 5). The correlation between the global IBS-SSS and PSQI score indicated a weak association (r = 0.2 and 95% CI: -0.03 to 0.35, P < 0.05), which becomes stronger using our unitary model. Indeed, the IBS and sleep disturbances severities, estimated as latent variables, resulted significantly high intra-subject correlation (posterior mean of r = 0.45 and 95% CI: 0.17 to 0.70, P < 0.05). Moreover, the correlations between patient features (age, sex, BMI, daily coffee and alcohol intake) and IBS and sleep disturbances were also analyzed through our unitary model. Age was a significant regressor, with patients ≤ 50 years old showing more severe bowel disturbances (posterior mean = -0.38, P < 0.05) and less severe sleep disturbances (posterior mean = 0.49, P < 0.05) than older patients. Higher daily coffee intake was correlated with a lower severity of bowel disturbances (posterior mean = -0.31, P < 0.05). Sex (female) and daily alcohol intake (modest) were correlated with less severe sleep disturbances., Conclusion: The unitary bowel-sleep model based on IRT revealed a strong positive correlation between the severity of IBS symptoms and sleep disturbances.

Whether prolonged strenuous exercise performed by athletes at sea level can produce interstitial pulmonary edema is under debate. Chest sonography allows to estimate extravascular lung water, creating ultrasound lung comet-tail (ULC) artifacts. The aim of the study was to determine whether pulmonary water content increases in Ironmen (n = 31) during race at sea level and its correlation with cardiopulmonary function and systemic proinflammatory and cardiac biohumoral markers. A multiple factor analysis approach was used to determine the relations between systemic modifications and ULCs by assessing correlations among variables and groups of variables showing significant pre-post changes. All athletes were asymptomatic for cough and dyspnea at rest and after the race. Immediately after the race, a score of more than five comet tail artifacts, the threshold for a significant detection, was present in 23 athletes (74%; 16.3 ± 11.2; P < 0.01 ULC after the race vs. rest) but decreased 12 h after the end of the race (13 athletes; 42%; 6.3 ± 8.0; P < 0.01 vs. soon after the race). Multiple factor analysis showed significant correlations between ULCs and cardiac-related variables and NH(2)-terminal pro-brain natriuretic peptide. Healthy athletes developed subclinical increase in pulmonary water content immediately after an Ironman race at sea level, as shown by the increased number of ULCs related to cardiac changes occurring during exercise. Hemodynamic changes are one of several potential factors contributing to the mechanisms of ULCs.

Resting-state EEG signals undergo rapid transition processes (RTPs) that glue otherwise stationary epochs. We study the fractal properties of RTPs in space and time, supporting the hypothesis that the brain works at a critical state. We discuss how the global intermittent dynamics of collective excitations is linked to mentation, namely non-constrained non-task-oriented mental activity.

We propose a model for the passage between metastable states of mind dynamics. As changing points we use the rapid transition processes simultaneously detectable in EEG signals related to different cortical areas. Our model consists of a non-Poissonian intermittent process, which signals that the brain is in a condition of complexity, upon which a Poisson process is superimposed. We provide an analytical solution for the waiting-time distribution for the model, which is well obeyed by physiological data. Although the role of the Poisson process remains unexplained, the model is able to reproduce many behaviors reported in literature, although they seem contradictory.

Purpose: To study by ultrasounds cardiac morphology and function early after breath-hold diving in deep water in elite athletes., Methods: Fifteen healthy male divers (age 28 +/- 3 years) were studied using Doppler-echocardiography, immediately before (basal condition, BC) and two minutes after breath-hold diving (40 meters, acute post-apnea condition, APAC). Each subject performed a series of three consecutive breath-hold dives (20-30 and 40 m depth)., Results: End-diastolic left ventricular (LV) diameter (EDD) and end-diastolic LV volume (EDV) increased significantly (p < 0.01). Stroke volume (SV), cardiac index (CI), septal and posterior systolic wall-thickening (SWT) also significantly increased after diving (p < 0.01). No wall motion abnormalities were detected, and wall motion score index was unchanged between BC and APAC. Doppler mitral E wave increased significantly (p < 0.01), whereas the A wave was unchanged. Systemic vascular resistance (SVR) decreased significantly after diving (p < 0.05). In the factor analysis, filtering out the absolute values smaller than 0.7 in the loading matrix, it resulted that factor I consists of EDV, posterior SWT, SV and CI, factor II of diastolic blood pressure, waves A and E and factor III of heart rate and SVR., Conclusions: Systo-diastolic functions were improved in the early period after deep breath-hold diving due to favorable changes in loading conditions relative to pre-diving, namely the recruitment of left ventricular preload reserve and the reduction in afterload.

We study the electroencephalogram (EEG) of 30 closed-eye awake subjects with a technique of analysis recently proposed to detect punctual events signaling rapid transitions between different metastable states. After single-EEG-channel event detection, we study global properties of events simultaneously occurring among two or more electrodes termed coincidences. We convert the coincidences into a diffusion process with three distinct rules that can yield the same mu only in the case where the coincidences are driven by a renewal process. We establish that the time interval between two consecutive renewal events driving the coincidences has a waiting-time distribution with inverse power-law index mu approximately 2 corresponding to ideal 1/f noise. We argue that this discovery, shared by all subjects of our study, supports the conviction that 1/f noise is an optimal communication channel for complex networks as in art or language and may therefore be the channel through which the brain influences complex processes and is influenced by them.

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.

Prolonged breath hold (BH) represents a valid model for studying the cardiac adaptation to acute hypoxemia in humans. Cardiac magnetic resonance (CMR) allows a three-dimensional, high-resolution, noninvasive, and nonionizing anatomical and functional evaluation of the heart. The aim of the study was to assess the adaptation of the cardiovascular system to prolonged BH in air. Ten male volunteer diving athletes (age 30 +/- 6 yr) were studied during maximal BH duration with CMR. Four epochs were studied: I, rest; II and III, intermediate BH; and IV, peak BH. Oxygen saturation (So(2)), heart rate (HR), blood pressure (BP), systemic vascular resistance (VR), end-diastolic (EDV) and end-systolic volumes (ESV), stroke volume (SV), cardiac output (CO), ejection fraction (EF), maximal elastance index (EL), systolic wall thickening (SWT), and end-systolic wall stress (ESWS) of the left ventricle (LV) were measured in all four BH epochs. Average BH duration was 3.7 +/- 0.3 min. So(2) was reduced (I: 97 +/- 0.2%, range 96-98%, vs. IV: 84 +/- 2.0%, range 76-92%; P < 0.00001). BP, EDV, ESV, SV, CO, and ESWS linearly increased from epochs I to IV, whereas EF, EL, and SWT showed an opposite behavior, decreasing from resting to epoch IV (all trends are P < 0.01). During prolonged BH in air, a marked enlargement of the LV chamber occurs in healthy diving athletes. This response to acute hypoxemia allows SV,CO, and arterial pressure to be maintained despite the severe reduction in LV contractile function.

The oscillatory pattern of pial arterioles, i.e. vasomotion, has been described since early 1980s, but the impact of neural activation on such oscillations has never been formally examined. Sciatic nerve stimulation, a well characterized model for studying neurovascular coupling (NVC), leads to a neural activity-related increase of pial arteriolar diameter in the contralateral hindlimb somatosensory cortex. Exploiting such an experimental model, the aim of the present study was to explore vasomotion and its changes during NVC with a novel analytical approach. Indeed, to characterize oscillations, we evaluated the total spectral power in the range 0.02-2.00 Hz and subdivided this frequency interval into seven 50% overlapping frequency bands. Results indicated that only arterioles overlying the stimulated hindlimb cortex showed a significant increase of total power, unlike arterioles overlaying the whisker barrel cortex, used as control for the vascular response specificity. The total power increase was sustained mainly by marked increments in the low frequency range, with two peaks at 0.03 and 0.08 Hz, and by a wide increase in the high frequency range (0.60-2.00 Hz) in the averaged spectrum. These activity-related spectral changes suggest: (i) that it is possible to assess the vascular responses by using total power; (ii) the existence of at least three distinct mechanisms involved in the control of NVC, two with a feedback frequency loop in the low frequency range and another one in the high range; (iii) a potential involvement of vasomotion in NVC. Moreover, these findings highlight the oscillatory nature of the mechanisms controlling NVC.

Aims: We aimed to assess the mutual interrelationships and to compare the prognostic value of a comprehensive set of nonlinear indices of heart rate variability (HRV) in a population of chronic heart failure (CHF) patients., Methods and Results: Twenty nonlinear HRV indices, representative of symbolic dynamics, entropy, fractality-multifractality, predictability, empirical mode decomposition, and Poincaré plot families, were computed from 24-hour Holter recordings in 200 stable CHF patients in sinus rhythm (median age [interquartile range]: 54 [47-58] years, LVEF: 23 [19-28]%, NYHA class II-III: 88%). End point for survival analysis (Cox model) was cardiac death or urgent transplantation. Homogeneous variables were grouped by cluster analysis, and in each cluster redundant variables were discarded. A prognostic model including only known clinical and functional risk factors was built and the ability of each selected HRV variable to add prognostic information to this model assessed. Bootstrap resampling was used to test the models stability. Four nonlinear variables showed a correlation >0.90 with classical linear ones and were discarded. Correlations >0.80 were found between several nonlinear variables. Twelve clusters were obtained and from each cluster a candidate predictor was selected. Only two variables (from empirical mode decomposition and symbolic dynamics families) added prognostic information to the clinical model., Conclusion: This exploratory study provides evidence that, despite some redundancies in the informative content of nonlinear indices and strong differences in their prognostic power, quantification of nonlinear properties of HRV provides independent information in risk stratification of CHF patients.

The cognitive characteristics of highly hypnotizable subjects (Highs) allow them to easily modify their cognitive and autonomic state. Under hypnosis, Highs receiving cognitive, fear-like stimulation exhibit the cardiovascular changes typical of fear/stress, but also show an EEG pattern indicating a balance between fear-induced arousal and hypnotic relaxation. Indeed, hypnosis is effective in the attenuation of both emotional experience and behaviour (emotional numbing). The aim of the present experiment was to investigate the possible different role of relaxation and suggestion in hypnotic emotional numbing. Tonic skin conductance, respirogram, heart rate, systolic and diastolic blood pressure were recorded in 3 groups of hypnotized subjects: Group 1 received a fearful guided imagery associated with threat suggestions (Threat) followed by the same fearful suggestion associated with numbing instructions (relaxation and "No-Threat"); Group 2 received the same instructions in the opposite order of presentation; Group 3 received the fearful suggestion with threat instructions twice. The numbing suggestion reduced fear-related emotional experience and autonomic responses; if No-Threat preceded Threat, the heart rate, heart rate variability and blood pressure were also reduced during Threat, in spite of self reports of high negative emotion. Thus, 1) the subjective experience and the autonomic response to fear can be dissociated; 2) the efficacy of numbing suggestion is extended to a subsequent Threat stimulation; 3) habituation does not contribute to the numbing effect. The results indicate that the specific numbing suggestion is the main factor in hypnotic modulation of the experience of fear.

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.

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.

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).