Restoring bottom-up communication in brain-heart interplay after trauma-focused psychotherapy in breast cancer patients with post-traumatic stress disorder.

BACKGROUND: The psychological impact of breast cancer (BC) is substantial, with a significant number of patients (up to 32 %) experiencing post-traumatic stress disorder (PTSD). Exploring the emotional aspects of PTSD through the functional brain-heart interplay (BHI) offers valuable insights into the condition. BHI examines the functional interactions between cortical and sympathovagal dynamics. This study aims to investigate changes in functional directional BHI after trauma-focused (TF) psychotherapy, specifically Eye Movement Desensitization and Reprocessing (EMDR), in comparison to treatment as usual (TAU) among BC patients with PTSD. To our knowledge, this study represents the first examination of such changes. METHODS: We enrolled thirty BC patients who met the criteria for a PTSD diagnosis, with fourteen receiving EMDR and fifteen receiving TAU over a two- to three-month period. We analyzed changes in the emotional response during a script-driven imagery setting. Quantification of the functional interplay between EEG and sympathovagal dynamics was achieved using the synthetic data generation model (SDG) on electroencephalographic (EEG) and heartbeat series. Our focus was on the difference in the BHI index extracted at baseline and post-treatment. RESULTS: We found statistically significant higher coupling in the heart-to-brain direction in patients treated with EMDR compared to controls. This suggests that the flow of information from the autonomic nervous system to the central nervous system is restored following EMDR-induced recovery from PTSD. Furthermore, we observed a significant correlation between improvements in PTSD symptoms and an increase in functional BHI after EMDR treatment. CONCLUSIONS: TF psychotherapy, particularly EMDR, appears to facilitate the restoration of the bottom-up flow of interoceptive information, which is dysfunctional in patients with PTSD. The application of BHI analysis to the study of PTSD not only aids in identifying biomarkers of the disorder but also enhances our understanding of the changes brought about by TF treatments.

Classifying subclinical depression using EEG spectral and connectivity measures.

Detecting depression on its early stages helps preventing the onset of severe depressive episodes. In this study, we propose an automatic classification pipeline to detect subclinical depression (i.e., dysphoria) through the electroencephalography (EEG) signal. To this aim, we recorded the EEG signals in resting condition from 26 female participants with dysphoria and 38 female controls. The EEG signals were processed to extract several spectral and functional connectivity features to feed a nonlinear Support Vector Machine (SVM) classifier embedded with a Recursive Feature Elimination (RFE) algorithm. Our recognition pipeline obtained a maximum classification accuracy of 83.91% in recognizing dysphoria patients with a combination of connectivity and spectral measures. Moreover, an accuracy of 76.11% was achieved with only the 4 most informative functional connections, suggesting a central role of cortical connectivity in the theta band for early depression recognition. The present study can facilitate the diagnosis of subclinical conditions of depression and may provide reliable indicators of depression for the clinical community.

Ex-vivo quantitative ultrasound assessment of cartilage degeneration.

Osteoarthritis is a common disease that implies joint degeneration and that strongly affects the quality of life. Conventional radiography remains currently the most used diagnostic method, even if it allows only an indirect assessment of the articular cartilage and employ the use of ionizing radiations. A non-invasive, continuous and reliable diagnosis is crucial to detect impairments and to improve the treatment outcomes.Quantitative ultrasound techniques have proved to be very useful in providing an objective diagnosis of several soft tissues. In this study, we propose quantitative ultrasound parameters, based on the analysis of radiofrequency data derived from both healthy and osteoarthritis-mimicking (through chemical degradation) ex-vivo cartilage samples. Using a transmission frequency typically employed in the clinical practice (7.5-15 MHz) with an external ultrasound probe, we found results in terms of reflection at the cartilage surface and sample thickness comparable to those reported in the literature by exploiting arthroscopic transducers at high frequency (from 20 to 55 MHz). Moreover, for the first time, we introduce an objective metric based on the phase entropy calculation, able to discriminate the healthy cartilage from the degenerated one.Clinical Relevance- This preliminary study proposes a novel and quantitative method to discriminate healthy from degenerated cartilage. The obtained results pave the way to the use of quantitative ultrasound in the diagnosis and monitoring of knee osteoarthritis.

A novel quantitative and reference-free ultrasound analysis to discriminate different concentrations of bone mineral content.

Bone fracture is a continuous process, during which bone mineral matrix evolves leading to an increase in hydroxyapatite and calcium carbonate content. Currently, no gold standard methods are available for a quantitative assessment of bone fracture healing. Moreover, the available tools do not provide information on bone composition. Whereby, there is a need for objective and non-invasive methods to monitor the evolution of bone mineral content. In general, ultrasound can guarantee a quantitative characterization of tissues. However, previous studies required measurements on reference samples. In this paper we propose a novel and reference-free parameter, based on the entropy of the phase signal calculated from the backscattered data in combination with amplitude information, to also consider absorption and scattering phenomena. The proposed metric was effective in discriminating different hydroxyapatite (from 10 to 50% w/v) and calcium carbonate (from 2 to 6% w/v) concentrations in bone-mimicking phantoms without the need for reference measurements, paving the way to their translational use for the diagnosis of tissue healing. To the best of our knowledge this is the first time that the phase entropy of the backscattered ultrasound signals is exploited for monitoring changes in the mineral content of bone-like materials.

Quantifying the lagged Poincaré plot geometry of ultrashort heart rate variability series: automatic recognition of odor hedonic tone.

The application of Poincaré plot analysis to characterize inter-beat interval dynamics has been successfully proposed in the scientific literature for the assessment of humans' physiological states and related aberrations. In this study, we proposed novel descriptors to trace the evolution of Poincaré plot shape over the lags. Their reliability in ultra-short cardiovascular series analysis was validated on synthetic inter-beat series generated through a physiologically plausible integral pulse frequency modulation model. Furthermore, we used the proposed approach for the investigation of the direct relationship between autonomic nervous system (ANS) dynamics and hedonic olfactory elicitation, in a group of 30 healthy subjects. Participants with a similar olfactory threshold were selected, and were asked to score 5-s stimuli in terms of arousal and valence levels according to the Russell's circumflex model of affect. Their ANS response was investigated in 35-s windows after the elicitation. Experimental results showed a gender-specific, high discriminant power of the proposed approach, discerning between pleasant and unpleasant odorants with an accuracy of 83.33% and 73.33% for men and for women, respectively. Graphical Abstract Olfaction plays a crucial role in our life and is strictly related to the Autonomic Nervous System (ANS) activity, which can be monitored studying Heart Rate Variability. We used the Lagged Poincare Plot approach to recognize gender-specific ANS response in 35-second windows after the elicitation through pleasant/unpleasant odorants.

Clinical relevance of colonization with antimicrobial-resistant bacteria (AMRB) and methicillin susceptible Staphylococcus aureus (MSSA) for mothers during pregnancy.

PURPOSE: The impact of colonization with antimicrobial-resistant bacteria (AMRB) and methicillin-sensitive Staphylococcus aureus (MSSA) of healthy pregnant women is not described in detail in Germany. In this study, we screened for MSSA and AMRB, especially for methicillin-resistant S. aureus (MRSA) as well as extended-spectrum beta-lactamase (ESBL)-producing E. coli. Potential risk factors for colonization with AMRB/MSSA and the potential effects of colonization with these on the obstetric population were investigated. METHODS: From October 2013 until December 2015 pregnant women were screened before birth for colonization with AMRB/MSSA from the mammillae, nose, perianal and vaginal area. Before birth, the expectant mother was administered a standardized interview questionnaire by a trained interviewer. Data from the hospital admission records were also included. RESULTS: Samples from 651 pregnant women were analyzed. Colonization with MSSA was detected in 14.3% (n = 93), AMRB in 3.5% [(n = 23); MRSA: n = 3/ESBL: n = 20]. Significantly more colonization of AMRB/MSSA could be detected in women who had previously given birth compared to women who were nulliparous (p < 0.05). MSSA colonization was significantly associated with self-reported respiratory diseases during pregnancy (p < 0.05), but AMRB/MSSA colonization was not statistically associated with other types of infection. CONCLUSION: Our results demonstrate a low overall rate of colonization with AMRB/MSSA, as well as a low percentage of colonized pregnant women who developed infections. Multiparous women are at higher risk for colonization with MSSA/MRSA or ESBL. Because the prevalence of AMRB/MSSA is low, this study suggests that general screening of pregnant women without risk factors is not recommended.

The central autonomic network at rest: Uncovering functional MRI correlates of time-varying autonomic outflow.

Peripheral measures of autonomic nervous system (ANS) activity at rest have been extensively employed as putative biomarkers of autonomic cardiac control. However, a comprehensive characterization of the brain-based central autonomic network (CAN) sustaining cardiovascular oscillations at rest is missing, limiting the interpretability of these ANS measures as biomarkers of cardiac control. We evaluated combined cardiac and fMRI data from 34 healthy subjects from the Human Connectome Project to detect brain areas functionally linked to cardiovagal modulation at rest. Specifically, we combined voxel-wise fMRI analysis with instantaneous heartbeat and spectral estimates obtained from inhomogeneous linear point-process models. We found exclusively negative associations between cardiac parasympathetic activity at rest and a widespread network including bilateral anterior insulae, right dorsal middle and left posterior insula, right parietal operculum, bilateral medial dorsal and ventrolateral posterior thalamic nuclei, anterior and posterior mid-cingulate cortex, medial frontal gyrus/pre-supplementary motor area. Conversely, we found only positive associations between instantaneous heart rate and brain activity in areas including frontopolar cortex, dorsomedial prefrontal cortex, anterior, middle and posterior cingulate cortices, superior frontal gyrus, and precuneus. Taken together, our data suggests a much wider involvement of diverse brain areas in the CAN at rest than previously thought, which could reflect a differential (both spatially and directionally) CAN activation according to the underlying task. Our insight into CAN activity at rest also allows the investigation of its impairment in clinical populations in which task-based fMRI is difficult to obtain (e.g., comatose patients or infants).

[Multidrug-resistant gram-negative rods in the intensive care unit : Epidemiology, prevention and treatment options]. / Multiresistente gramnegative Stäbchenbakterien auf der Intensivstation : Epidemiologie, Prävention und Therapieoptionen.

In Germany, multidrug-resistant gram-negative rods (MRGN) are classified in two groups, namely those with resistance against three (3MRGN) and those with resistance against four (4MRGN) of the following antibiotic groups: acylureidopenicillins, third or fourth generation cephalosporins, fluoroquinolones and carbapenemes. The rate of 3MRGN enterobacteria and 4MRGN Pseudomonas aeruginosa has significantly increased in German intensive care units from 2008-2014. In contrast, 4MRGN enterobacteria are still rare. The 3MRGN and 4MRGN phenotypes can be associated with different antimicrobial resistance mechanisms such as the production of extended-spectrum ß­lactamases (ESBL) or carbapenemases. The strategy for the prevention and control of MRGN in intensive care units includes basic hygiene measures as well as special measures such as contact isolation of patients. The treatment of MRGN infections should be carried out according to the antimicrobial susceptibility test results.

Cardiovascular assessment of supportive doctor-patient communication using multi-scale and multi-lag analysis of heartbeat dynamics.

Emphatic doctor-patient communication has been associated with improved psycho-physiological well-being involving cardiovascular and neuroendocrine responses. Nevertheless, a comprehensive assessment of heartbeat linear and nonlinear dynamics throughout the communication of a life-threatening disease has not been performed yet. To this extent, we studied linear heartbeat dynamics through the extraction of time-frequency domain measurements, as well as heartbeat nonlinear and complex dynamics through novel approaches to compute multi-scale and multi-lag series analyses: namely, the multi-scale distribution entropy and lagged Poincaré plot symbolic analysis. Heart rate variability series were recorded from 54 healthy female subjects who were blind to the aim of the experiment. Participants were randomly assigned into two groups: 27 subjects watched a video where an oncologist discloses the diagnosis of a cancer metastasis to a patient, whereas the remaining 27 watched the same video including four additional supportive comments by the clinician. Considering differences between the beginning and the end of each communication video, results from non-parametric Wilcoxon tests demonstrated that, at a group level, significant differences occurred in heartbeat linear and nonlinear dynamics, with lower complexity during nonsupportive communication. Furthermore, a support vector machine algorithm, validated using a leave-one-subject-out procedure, was able to discern the supportive experience at a single-subject level with an accuracy of 83.33% when nonlinear features were considered, dropping to 51.85% when using standard HRV features only. In conclusion, heartbeat nonlinear and complex dynamics can be a viable tool for the psycho-physiological evaluation of supportive doctor-patient communication. Graphical Abstract Scheme of the three main stages of the study: signal acquisition during doctor-patient communication, ECG signal processing and pattern recognition results.

The Complexity of Dreams: a Multiscale Entropy Study on Cardiovascular Variability Series.

Uncovering the physiological correlates of dreams is one of the most ambitious aim of multidisciplinary neuroscientific research. Here we investigated Autonomic Nervous System (ANS) dynamics associated with a dream recall, with a particular focus on the complexity assessment on cardiovascular control. We recorded electrocardiogram and arterial blood pressure signals from eight healthy subjects during rapid-eye-movement sleep before awakenings. Recordings were then split into two groups: the ones with a dream experience, and the ones without recall of dream experiences. The randomness of cardiovascular variability series was assessed through Sample Entropy metrics, which did not show any statistical difference between groups. On the other hand, a multiscale complexity analysis based on Distribution Entropy and Fuzzy Entropy revealed that a higher cardiovascular complexity is associated with a dreaming experience.

Heartbeat Dynamics Analysis under Cold-Pressure Test using Wavelet p-Leader Non-Gaussian Multiscale Expansions.

Multiscale and multifractal (MF) analyses have been proven an effective tool for the characterisation of heartbeat dynamics in physiological and pathological conditions. However, pre-processing methods for the unevenly sampled heartbeat interval series are known to affect the estimation of MF properties. In this study, we employ a recently proposed method based on wavelet p-leaders MF spectra to estimate MF properties from cardiovascular variability series, which are also pre-processed through an inhomogeneous point-process modelling. Particularly, we exploit a non-Gaussian multiscale expansion to study changes in heartbeat dynamics as a response to a sympathetic elicitation given by the cold-pressor test. By comparing MF estimates from raw heartbeat series and the point-process model, results suggest that the proposed modelling provides features statistically discerning between stress and resting condition at different time scales. These findings contribute to a comprehensive characterization of autonomic nervous system activity on cardiovascular control during cold-pressor elicitation.

Resting State Neural Correlates of Cardiac Sympathetic Dynamics in Healthy Subjects.

Recent advances in functional Magnetic Resonance Imaging (fMRI) research have uncovered the existence of the central autonomic network (CAN), which comprises brain regions whose activity correlates with autonomic nervous system dynamics. By exploiting the spectral paradigm of heartbeat dynamics, cortical and sub-cortical areas functionally linked to vagal activity have been identified. However, due to methodological limitations, functional neural correlates of cardiac sympathetic dynamics remain uncharacterized. To this extent, we exploit the high spatiotemporal resolution of fMRI data from the Human Connectome Project to study the CAN activity by correlating a recently proposed instantaneous characterization of sympathetic activity (the sympathetic activity index - SAI) from heartbeat dynamics. SAI estimates are embedded into the probabilistic modeling of inhomogeneous point-processes, and are derived from a combination of disentangling coefficients linked to the orthonormal Laguerre functions. By analyzing resting state recordings from 34 young healthy people, we obtain positive correlations between instantaneous SAI estimates and a number of brain regions including frontal pole, insular cortex, frontal and temporal gyri, lateral occipital cortex, paracingulate and cingulate gyri, precuneus and temporal fusiform cortices, as well as thalamus, caudate nucleus, putamen, brain-stem, hippocampus, amygdala, and nucleus accumbens. Our findings significantly extend current knowledge on the CAN, opening new avenues in the characterization of healthy and pathological states in humans.

Quantification of Different Regulatory Pathways Contributing to Heartbeat Dynamics during Multiple Stimuli: a Proof of the Concept.

The dynamical interplay between brain and heart is mediated by several feedback mechanisms including the central autonomic network and baroreflex loop at a peripheral level, also for a short-term regulation. State of the art focused on the characterization of each regulatory pathway through a single stressor elicitation. However, no studies targeted the actual quantification of different mediating routes leading to the generation of heartbeat dynamics, particularly in case of combined exogenous stimuli. In this study, we propose a new approach based on computational modeling to quantify the contribution of multiple concurrent stimuli in modulating cardiovascular dynamics. In this preliminary attempt, the model estimates the high-frequency power of heartbeat dynamics, and derives disentangling coefficients quantifying the effect of multiple elicitations. Model evaluation is performed on healthy rate variability (HRV) series from fourteen healthy subjects undergoing physical (tilt-table) and mental stressors (aritmetics), as well as their combined administration. Results indicate that, at a group-wise level, in base of concurrent physical and mental elicitations, the physical stressor contributes for the 85% of the resulting heartbeat dynamics. These findings are in agreement with the current knowledge on heartbeat regulatory systems, providing valuable perspectives on the quantification of underlying generative mechanisms of HRV.

Wavelet p-Leader Non-Gaussian Multiscale Expansions for EEG series: an Exploratory Study on Cold-Pressor Test.

Brain dynamics recorded through electroencephalography (EEG) have been proven to be the output of a nonstationary and nonlinear system. Thus, multifractality of EEG series has been exploited as a useful tool for a neurophysiological characterization in health and disease. However, the role of EEG multifractality under peripheral stress is unknown. In this study, we propose to make use of a novel tool, the recently defined non-Gaussian multiscale analysis, to investigate brain dynamics in the range of 4-8Hz following a cold-pressor test versus a resting state. The method builds on the wavelet p-leader multifractal spectrum to quantify different types of departure from Gaussian and linear properties, and is compared here to standard linear descriptive indices. Results suggest that the proposed non-Gaussian multiscale indices were able to detect expected changes over the somatosensory and premotor cortices, over regions different from those detected by linear analyses. They further indicate that preferred responses for the contralateral somatosensory cortex occur at scales 2.5s and 5s. These findings contribute to the characterization of the so-called central autonomic network, linking dynamical changes at a peripheral and a central nervous system levels.

A Multiclass Arousal Recognition using HRV Nonlinear Analysis and Affective Images.

This paper reports on a multiclass arousal recognition system based on autonomic nervous system linear and nonlinear dynamics during affective visual elicitation. We propose a new hybrid method based on Lagged Poincaré Plot (LPP) and symbolic analysis, hereinafter called LPPsymb. This tool uses symbolic analysis to evaluate the irregularity of the trends of Lagged Poincaré Plot (LPP) quantifiers over the lags, and is here applied to investigate complex Heart Rate Variability (HRV) changes during emotion stimuli. In the experimental protocol 22 healthy subjects were elicited through a passive visualization of affective images gathered from the international affective picture system. LPPsymb and standard HRV analysis (defined in time and frequency domains) were applied to HRV series of one minute length. Then, an ad-hoc pattern recognition algorithm based on quadratic discriminant classifier was implemented and validated through a leave-onesubject-out procedure. The best performance of the proposed classification algorithm for recognizing the four classes of arousal was obtained using nine features comprising heartbeat complex dynamics, achieving an accuracy of 71.59%.

A New Sympathovagal Balance Index from Electrodermal Activity and Instantaneous Vagal Dynamics: A Preliminary Cold Pressor Study.

Sympathovagal balance, an autonomic index resulting from the sympathetic and parasympathetic influences on cardiovascular control, has been extensively used in the research practice. The current assessment is based on analyzing Heart Rate Variability (HRV) series in the frequency domain by regarding the ratio between the low and high frequency components (LF/HF). Nevertheless, LF and HF powers are known to be both influenced by vagal activity which strongly bias the accuracy of this method. To this extent, in this study we combine time-varying estimates from electrodermal activity (EDA) and HRV to propose a novel index of sympathovagal balance. Particularly, sympathetic activity is estimated from the EDA power calculated within the 0.045-0.25Hz bandwidth $(EDA_{Symp})$, whereas parasympathetic dynamics is measured instantaneously through a point-process modeling framework devised for heartbeat dynamics $(HF_{pp})$. We test our new index $SV = EDA_{Symp/HF_{pp}}$ on data gathered from 22 healthy subjects (7 females and 15 males) undergoing a 3 minutes gold standard protocol for sympathetic elicitation as the cold-pressor test (CPT). Results show that the activation of the proposed sympathovagal tone is consistent with CPT elicitation and is associated with a significantly higher statistical discriminant power than the standard LF/HF ratio, also revealing different dynamics between female and male subjects.

A new Modelling Framework to Study Time-Varying Directional Brain-Heart Interactions: Preliminary Evaluations and Perspectives.

We propose a novel modelling framework to study non-stationary, directional brain-heart interplay in a time varying fashion. Considering electroencephalographic (EEG) signals and Heart Rate Variability (HRV) series as inputs, a new multivariate formulation is derived from proper coupling functions linking cortical electrical activity and heartbeat dynamics generation models. These neural-autonomic coupling rules are formalised according to the current knowledge on the central autonomic network and fully parametrised in adaptive coefficients quantifying the information outflow from-brain-to- heart as well as from-heart-to-brain. Such coefficients can be effectively estimated by solving the model inverse problem, and profitably exploited for a novel assessment of brain-heart interactions. Here we show preliminary experimental results gathered from 27 healthy volunteers undergoing significant sympatho-vagal perturbations through cold-pressor test and discuss prospective uses of this novel methodological frame- work. Specifically, we highlight how the directional brain-heart coupling significantly increases during prolonged baroreflex elicitation with specific time delays and throughout specific brain areas, especially including fronto-parietal regions and lateralisation mechanisms in the temporal cortices.

A novel Heart Rate Variability analysis using Lagged Poincaré plot: A study on hedonic visual elicitation.

This paper reports on a novel method for the analysis of Heart Rate Variability (HRV) through Lagged Poincaré Plot (LPP) theory. Specifically a hybrid method, LPPsymb, including LPP quantifiers and related symbolic dynamics was proposed. LPP has been applied to investigate the autonomic response to pleasant and unpleasant pictures extracted from the International Affective Picture System (IAPS). IAPS pictures are standardized in terms of level of arousal, i.e. the intensity of the evoked emotion, and valence, i.e. the level of pleasantness/unpleasantness, according to the Circumplex model of Affects (CMA). Twenty-two healthy subjects were enrolled in the experiment, which comprised four sessions with increasing arousal level. Within each session valence increased from positive to negative. An ad-hoc pattern recognition algorithm using a Leave-One-Subject-Out (LOSO) procedure based on a Quadratic Discriminant Classifier (QDC) was implemented. Our pattern recognition system was able to classify pleasant and unpleasant sessions with an accuracy of 71.59%. Therefore, we can suggest the use of the LPPsymb for emotion recognition.

Investigation of Lagged Poincaré Plot reliability in ultra-short synthetic and experimental Heart Rate Variability series.

This study reports on the reliability of Lagged Poincaré Plot (LPP) parameters calculated from ultra-short cardiovascular time series (from 30 to 180 seconds). ity (HRV) signals, whereas a few studies have studied nonlinear approaches. Particularly, methods derived from the phase-space theory, especially the ones employing multi-lag analyses, are usually considered to be inaccurate with a low number of samples. Here we propose a comprehensive study about LPP, using both synthetic and real RR series. Specifically, we considered 109 5-minutes HRV series: 60 synthetic series generated through the Integral Pulse Frequency Modulation (IPFM) model and 49 experimental series acquired from healthy subjects during resting-state. Three parameters have been extracted through the ellipse-fitting method, SD1, SD2 and S, using ten values of lag. All LPP parameters were estimated by averaging estimates gathered from segments of 30, 120 and 180 seconds, and compared with the once from 5-minute series. Results showed Spearman's correlation coefficients higher than 0.9 in both synthetic and real series. In conclusion, SD1 gave promising results in terms of percentage absolute error, when it was extracted from series with a duration less than three minutes.

Resting-state brain correlates of cardiovascular complexity.

While estimates of complex heartbeat dynamics have provided effective prognostic and diagnostic markers for a wide range of pathologies, brain correlates of complex cardiac measures in general and of complex sympatho-vagal dynamics in particular are still unknown. In this study we combine resting state functional Magnetic Resonance Imaging (fMRI) and physiological signal acquisition from 34 healthy subjects selected from the Human Connectome Project (HCP) repository with inhomogeneous point-process approximate and sample heartbeat entropy measures (ipApEn and ipSampEn) to investigate brain areas involved in complex cardiovascular control. Our results show that activity in the Temporal Gyrus, Frontal Orbital Cortex, Temporal Fusiform and Opercular cortices, Planum Temporale, and Paracingulate cortex are negatively correlated with ipApEn dynamics. Activity in the same cortical areas as well as in the Temporal Fusiform cortex are negatively correlated with ipSampEn dynamics. No significant positive correlations were found. These pioneering results suggest that cardiovascular complexity at rest is linked to a few specific cortical brain structures, including crucial areas connected with parasympathetic outflow. This corroborates the hypothesis of a multidimensional central network which controls nonlinear cardiac dynamics under a predominantly vagally-driven tone.