An integrated approach based on advanced CTG parameters and Doppler measurements for late growth restriction management.

BACKGROUND: The clinical diagnosis of late Fetal Growth Restriction (FGR) involves the integration of Doppler ultrasound data and Fetal Heart Rate (FHR) monitoring through computer assisted computerized cardiotocography (cCTG). The aim of the study was to evaluate the diagnostic power of combined Doppler and cCTG parameters by contrasting late FGR -and healthy controls. METHODS: The study was conducted from January 2018 to May 2020. Only pregnant women who had the last Doppler measurement obtained within 1 week before delivery and cCTG performed within 24 h before delivery were included in the study. Two hundred forty-nine pregnant women fulfilling the inclusion criteria were enrolled in the study; 95 were confirmed as late FGR and 154 were included in the control group. RESULTS: Among the extracted cCTG parameters, Delta Index, Short Term Variability (STV), Long Term Variability (LTV), Acceleration and Deceleration Phase Rectified Slope (APRS, DPRS) values were lower in the late FGR participants compared to the control group. In the FGR cohort, Delta, STV, APRS, and DPRS were found different when stratifying by MCA_PI (MCA_PI <5th centile or > 5th centile). STV and DPRS were the only parameters to be found different when stratifying by (UA_PI >95th centile or UA_PI <95th centile). Additionally, we measured the predictive power of cCTG parameters toward the identification of associated Doppler measures using figures of merit extracted from ROC curves. The AUC of ROC curves were accurate for STV (0,70), Delta (0,68), APRS (0,65) and DPRS (0,71) when UA_PI values were > 95th centile while, the accuracy attributable to the prediction of MCA_PI was 0.76, 0.77, 0.73, and 0.76 for STV, Delta, APRS, and DPRS, respectively. An association of UA_PI>95th centile and MCA_PI<5th centile with higher risk for NICU admission, was observed, while CPR < 5th centile resulted not associated with any perinatal outcome. Values of STV, Delta, APRS, DPRS were significantly lower for FGR neonates admitted to NICU, compared with the uncomplicated FGR cohort. CONCLUSIONS: The results of this study show the contribution of advanced cCTG parameters and fetal Doppler to the identification of late FGR and the association of those parameters with the risk for NICU admission. TRIAL REGISTRATION: Retrospectively registered.

Impact of nuchal cord on antenatal and intrapartum foetal heart rate surveillance and perinatal outcome.

Analysing antepartum and intrapartum computerised cardiotocographic (cCTG) parameters in physiological term pregnancies with nuchal (NC) or body cord (BC), in order to correlate them with labour events and neonatal outcome. We enrolled 808 pregnant women, composed of 264 with 'one NC', 121 with 'multiple NCs', 39 with BC and 384 with 'no NC', were monitored from the 37th week of gestation before labour, while 49 pregnant women with 'one or more NCs' and 47 with 'no NCs' were analysed during labour. No differences in maternal characteristics, foetal pH at birth and 5-min Apgar score were observed. The birth weight was significantly lower in the 'multiple NCs' group, while 1-minute Apgar score was lower in the BC group than the other groups, respectively. No relevant differences in cCTG parameters were observed, except for LTI, Delta and number of variable decelerations in antepartum period and only variable deceleration in intrapartum period.Impact statementWhat is already known on this subject? Ultrasound cannot predict which foetuses with NCs are likely to have problem during labour. The question arose if single or multiple NC could affects FHR monitoring prior and during labour.What do the results of this study add? Computerised cardiotocography (cCTG) is a standardised method developed to reduce inter- and intra-observer variability and the poor reproducibility of visual analysis. Few studies have investigated the influence of NCs on FHR variability and, to our knowledge, no one has evaluated its linear and nonlinear characteristics in antepartum and intrapartum period using a computerised analysis system. No differences in maternal characteristics, foetal pH at birth and 5-min Apgar score were observed. Birth weight was significantly lower in the 'multiple NCs' group, while 1-min Apgar score was lower in the BC group than the other groups, respectively. Foetuses with 'one or more NCs' evidenced a larger number of prolonged second stage and meconium-stained liquor cases, while the operative vaginal delivery and emergency caesarean section rates were unchanged. No relevant differences in cCTG parameters were observed, except for LTI, Delta and number of variable decelerations in antepartum period and only variable deceleration in intrapartum period.What are the implications of these findings for clinical practice and/or further research? cCTG monitoring results confirmed their usefulness for assessing the state of good oxygenation for all foetuses investigated.

Ethnic analogies and differences in fetal heart rate variability signal: A retrospective study.

AIM: We aimed to analyze computerized cardiotocographic (cCTG) parameters (including fetal heart rate baseline, short-term variability, Delta, long-term irregularity [LTI], interval index [II], low frequency [LF], movement frequency [MF], high frequency [HF], and approximate entropy [ApEn]) in physiological term pregnancies in order to correlate them with ethnic differences. The clinical meaning of numerical parameters may explain physiological or paraphysiological phenomena that occur in fetuses of different ethnic origins. METHODS: A total of 696 pregnant women, including 384 from Europe, 246 from sub-Saharan Africa, 45 from South-East Asia, and 21 from South America, were monitored from the 37th to the 41st week of gestation. Statistical analysis was performed with the analysis of variance test, Pearson correlation test and receiver-operator curves (P < 0.05). RESULTS: Our results showed statistically significant differences (P < 0.05) between white and black women for Delta, LTI, LF, MF, HF, and ApEn; between white and Asian women for Delta, LTI, MF, and the LF/(HF + MF) ratio; and between white and Latina women for Delta, LTI, and ApEn. In particular, Delta and LTI performed better in the white group than in the black, Asian, and Latina groups. Instead, LF, MF, HF, and ApEn performed better in the black than in the white group. CONCLUSION: Our results confirmed the integrity and normal functionality of both central and autonomic nervous system components for all fetuses investigated. Therefore, CTG monitoring should include both linear and nonlinear components of fetal heart rate variability in order to avoid misinterpretations of the CTG trace among ethnic groups.

Telemedicine to Improve Access to Specialist Care in Fetal Heart Rate Monitoring: Analysis of 17 Years of TOCOMAT Network Clinical Activity.

BACKGROUND: The objective of this article is to provide an overview of the clinical experience of our telemedicine network (TOCOMAT) for fetal well-being assessment through computerized Cardiotocography (cCTG), analyzing cultural, socioeconomic, and environmental conditions of pregnant women and its economic sustainability over time. MATERIALS AND METHODS: We used the central data store, including all cCTG records collected in Campania region (Italy) during 17 years of activity. The Operations Center acquires the traces recorded in the Remote Units and simultaneously performs a complex fetal heart rate analysis. An Internet or phone conference calling is available to discuss the information transmitted. Finally, the report is send back to the Remote Units. RESULTS: The number of cCTG traces performed was constantly increasing, despite the progressive reduction in the number of peripheral units involved. Pregnant women in Remote Unit group were younger and overweight and showed a higher incidence of diabetes and fetal defects than Operations Center ones. Moreover, a high rate of African migrant women and low socioeconomic and cultural standards were found in Remote Unit group. The cost analysis showed an economic advantage both in the reduction of inappropriate admissions and in the improvement of admission indicators (hospital stay days) for pregnant women. DISCUSSION: The global economic recession has had a significant impact on the Italian regional healthcare system and socioeconomic deprivation. CONCLUSIONS: Telemedicine could avoid unnecessary referral to Level III centers (Hospital) in Campania region, where the average population density is very high, allowing equal access to ultra-specialist assessment irrespective of the geographical location of the pregnant woman with medium to high risk, as well as rationalizing the costs for maternal and fetal care.

Computerised analysis of antepartum foetal heart parameters: New reference ranges.

We selected 4012 cCTG records (one trace for each patient) performed in healthy pregnancies from 30th to 42nd gestational week using foetal heart rate (FHR), short-term variability (STV), long-term irregularity (LTI), Delta, approximate entropy (ApEn), spectral components as low frequency (LF), median frequency (MF), high frequency (HF) and LF/(HF + MF) ratio were analysed. Reference nomograms were created and sensitivity and specificity for the prediction of foetal compromise were calculated which were 90% and 89%, respectively. Changes of cCTG parameters according to gestational week were evaluated: FHR (r = -.65) and LF (r = -.87) showed a statistically significant reduction (p < .05) with gestational age. STV (r = .59), LTI (r = .69), Delta (r = .67), and MF (r = .88) showed a statistically significant increase (p < .05) with gestational age. In contrast, for ApEn (r = -.098), HF (r = .14) and LF/(HF + MF) ratio (r = -.47) a non-statistically significant change was found (p > .05). The identification of reference ranges for cCTG indexes in according to gestational age could provide a more objective examination of cCTG trace.

A deep learning mixed-data type approach for the classification of FHR signals.

The Cardiotocography (CTG) is a widely diffused monitoring practice, used in Ob-Gyn Clinic to assess the fetal well-being through the analysis of the Fetal Heart Rate (FHR) and the Uterine contraction signals. Due to the complex dynamics regulating the Fetal Heart Rate, a reliable visual interpretation of the signal is almost impossible and results in significant subjective inter and intra-observer variability. Also, the introduction of few parameters obtained from computer analysis did not solve the problem of a robust antenatal diagnosis. Hence, during the last decade, computer aided diagnosis systems, based on artificial intelligence (AI) machine learning techniques have been developed to assist medical decisions. The present work proposes a hybrid approach based on a neural architecture that receives heterogeneous data in input (a set of quantitative parameters and images) for classifying healthy and pathological fetuses. The quantitative regressors, which are known to represent different aspects of the correct development of the fetus, and thus are related to the fetal healthy status, are combined with features implicitly extracted from various representations of the FHR signal (images), in order to improve the classification performance. This is achieved by setting a neural model with two connected branches, consisting respectively of a Multi-Layer Perceptron (MLP) and a Convolutional Neural Network (CNN). The neural architecture was trained on a huge and balanced set of clinical data (14.000 CTG tracings, 7000 healthy and 7000 pathological) recorded during ambulatory non stress tests at the University Hospital Federico II, Napoli, Italy. After hyperparameters tuning and training, the neural network proposed has reached an overall accuracy of 80.1%, which is a promising result, as it has been obtained on a huge dataset.

Placental dysfunction in uncomplicated and complicated intrauterine growth restriction by preeclampsia and neonatal outcome.

OBJECTIVES: To investigate the use of computerized cardiotocography (cCTG) parameters in Intrauterine Growth Restriction (IUGR) pregnancies for the prediction of 1) complication with preeclampsia; 2) placental histological abnormalities, and 3) neonatal outcomes. . STUDY DESIGN: A single-center observational retrospective case-control study was performed by reviewing medical records, cCTG databases and pathological reports of women with singleton pregnancy and IUGR uncomplicated (controls) and complicated by preeclampsia (cases). Primary endpoint was the association between cCTG parameters and preeclampsia in IUGR. Secondary endpoints were the association between cCTG parameters and 1) placental abnormalities, and 2) neonatal outcomes. The one-way ANOVA test was used to compare cCTG parameters in cases and controls. t-test was applied to compare neonatal outcomes and placental abnormalities in both groups. The Spearman Test value Correlation coefficients between the cCTG parameters and neonatal outcome in the two groups. A p value < .05 was considered significant for all analyses. RESULTS: Among all cCTG parameters, a significant association with preeclampsia in IUGR was found for Fetal Heart Rate (FHR, p = .008), Delta (p = .018), Short Term Variability (STV, p = .021), Long Term Variability (LTV, p = .028), Acceleration Phase Rectified Slope (APRS, p = .018) and Deceleration Phase Rectified Slope (DPRS, p = .038). Of all placental histologic abnormalities, only vascular alterations at least moderate were significantly associated with increased FHR (p = .02). About neonatal outcomes, all cCTG parameters were significantly associated with birth weight, Apgar index at 1 and 5 min, pH and pCO2. FHR, LTI, Delta, Approximate Entropy (ApEn) and LF were significantly associated with pO2; LTI, Interval Index (II) and ApEn with base excess. Among controls, Delta, ApEn, Low Frequency (LF) and High Frequency (HF) were significantly associated with pCO2, while among cases, STV and Delta were significantly associated with pH; STV, LTI, Delta, ApEn, LF and HF with pCO2; STV, LTI, Delta and ApEn with pO2; HF with base excess; FHR and LF with lactates. CONCLUSIONS: cCTG parameters may be useful to detect complication with preeclampsia in IUGR pregnancies. Regarding placental status, cCTG parameters may detect overall circulation alterations, but not specific histological abnormalities. Lastly, all cCTG parameters may predict neonatal outcomes, helping to tailor the patients' management.

Effects of dialysate glucose concentration on heart rate variability in chronic hemodialysis patients: results of a prospective randomized trial.

BACKGROUND: Chronic hemodialysis (HD) patients suffer from an appallingly high cardiovascular mortality. During HD, patients are exposed to dialysate glucose, which may alter blood glucose levels and thus exert effects on the autonomic nervous system. Heart rate variability (HRV) is an established indicator of autonomic nervous system activity and a predictor of cardiovascular outcomes. This study investigated the effects of two commonly used dialysate glucose concentrations [100 mg/dl (HD100), and 200 mg/dl (HD200)] on HRV in chronic HD patients. METHODS: In this prospective, randomized, controlled, single-masked, cross-over trial, subjects were randomized to receive HD100 or HD200 for a period of 3 weeks followed by a cross-over to the respective other dialysate (www.clinicaltrials.gov #NCT00618033). Blood glucose and insulin levels were measured before and after HD. Intradialytic Holter electrocardiograms were recorded and HRV time domain, frequency domain and complexity parameters analyzed. RESULTS: Twenty-three HD patients (age 56 ± 12 years, 11 male, 14 black, 11 with diabetes) were studied. Diabetic subjects showed significantly higher serum glucose levels with HD200 as compared to HD100 (HD100: 146 ± 48 mg/dl; HD200: 192 ± 57 mg/dl; p < 0.01); this hyperglycemia was accompanied by an increase of the high-frequency band of HRV (p = 0.019), a reflection of increased parasympathetic activity. HRV did not change in nondiabetic subjects. CONCLUSION: In diabetic subjects, the use of HD200 increased vagal tone. Given the importance of sympathetic activation to counteract intradialytic hypotension, our findings support the use of HD100 in diabetic HD patients.

Intrapartum cardiotocography with and without computer analysis: a systematic review and meta-analysis of randomized controlled trials.

Objective: To evaluate whether intrapartum cardiotocography with computer analysis decreases the incidence of newborn metabolic acidosis or obstetric intervention when compared with visual analysis through a systematic review with meta-analysis of randomized controlled trials.Methods: The research was conducted using Medline, Embase, Web of Science, Scopus, ClinicalTrial.gov, Ovid and Cochrane Library as electronic databases from the inception of each database to May 2018. Selection criteria included randomized trial evaluating women with cephalic presentation at term or late preterm term during labor who were randomized to electronic fetal heart rate monitoring with either computer analysis (i.e. intervention group) or standard visual analysis (i.e. control group). Trials evaluating antenatal fetal heart rate monitoring in women not in labor were excluded. The primary outcome was incidence of newborn metabolic acidosis, defined as pH less than 7.05 and base deficit greater than 12 mmol/L. Secondary outcomes were mode of delivery, admission to neonatal intensive care unit, hypoxic-ischemic encephalopathy, and perinatal death. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI).Results: Three randomized controlled trials (RCTs), including 54,492 participants, which met inclusion criteria for this meta-analysis, were analyzed. All the included trials enrolled women with cephalic presentation at term or late preterm. Women were randomized in the active first stage of labor and all of them received continuous cardiotocography (CTG) from randomization until delivery. Women who received continuous CTG during labor with computerized analysis had similar risk of newborn metabolic acidosis. No between group differences were found in the secondary outcomes.Conclusions: Compared with visual analysis, use of computer analysis of fetal monitoring signals during labor did not significantly reduce the rate of metabolic acidosis or obstetric intervention.

Multifractality and heart rate variability.

In this paper, we participate to the discussion set forth by the editor of Chaos for the controversy, "Is the normal heart rate chaotic?" Our objective was to debate the question, "Is there some more appropriate term to characterize the heart rate variability (HRV) fluctuations?" We focused on the approximately 24 h RR series prepared for this topic and tried to verify with two different techniques, generalized structure functions and wavelet transform modulus maxima, if they might be described as being multifractal. For normal and congestive heart failure subjects, the h(q) exponents showed to be decreasing for increasing q with both methods, as it should be for multifractal signals. We then built 40 surrogate series to further verify such hypothesis. For most of the series (approximately 75%-80% of cases) multifractality stood the test of the surrogate data employed. On the other hand, series coming from patients in atrial fibrillation showed a small, if any, degree of multifractality. The population analyzed is too small for definite conclusions, but the study supports the use of multifractal series to model HRV. Also it suggests that the regulatory action of autonomous nervous system might play a role in the observed multifractality.

A blind method for the estimation of the Hurst exponent in time series: theory and application.

Nowadays many methods for the estimation of self-similarity (Hurst coefficient, H) in time series are available. Most of them, even if very effective, need some a priori information to be applied. We analyzed the eight most used methods for H estimation (working both in time and in frequency). We tested these methods on data generated with four kinds of time series models (fBm and fGn generated iteratively with Feder algorithm, 1f(alpha), and the fractional autoregressive integrated moving-average) in the range 0.1

Nonlinear indices of heart rate variability in chronic heart failure patients: redundancy and comparative clinical value.

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.

Assessing nonlinear properties of heart rate variability from short-term recordings: are these measurements reliable?

Several parameters assessing nonlinear properties of heart rate variability (HRV) from short-term (<10 min) laboratory recordings have been proposed so far, but their reliability is unknown. In this study, we addressed this issue analysing a comprehensive set of these indices. In 42 healthy subjects (mean age (min-max): 38 (26-56) years, 21 men) we recorded 5 min of supine ECG in two consecutive days. From RR intervals we computed 11 nonlinear HRV indices, representative of symbolic dynamics, entropy, fractality, predictability, empirical mode decomposition and Poincaré plot families. Absolute reliability was assessed by the 95% limits of random variation and relative reliability was assessed computing the intraclass correlation coefficient (ICC). We found marked differences in the reliability of short-term nonlinear indices of HRV. In the majority of indices, changes in test-retest measurements ranged between about -30% and +50%, indicating good absolute reliability while in the others the change was <-60% and >140%. Relative reliability was substantial (0.6 < ICC < 0.8) in half of the indices, moderate in one and poor in the remaining. Compared to classical linear indices, nonlinear HRV parameters seem more suitable for individual test-retest evaluations but, due to a reduced ICC, they need increased sample size in comparative studies involving two groups of subjects.

HRV scaling exponent identifies postinfarction patients who might benefit from prophylactic treatment with amiodarone.

Analysing the Holter recordings collected at baseline during the European Myocardial Infarction Amiodarone Trial (EMIAT), we evaluate the possibility of using alpha, the slope of the power spectrum of heart rate variability signals (HRV) in the vicinity of f = 0, for postinfarction risk stratification. We found no relevant difference in the values of alpha for the placebo population. On the contrary, in the amiodarone arm, the distinction in the survival rates of those with high or low alpha-values was highly significant. Moreover, high risk patients with respect to alpha (higher values) did not seem to benefit from amiodarone. The results suggest that alpha might convey physiologic information that is different than what is expressed by other HRV characteristics, such as the triangular index. When combining high risk patients in term of triangular index (<20) and low risk patients with respect to alpha (

Clinical correlates of non-linear indices of heart rate variability in chronic heart failure patients.

We assessed the clinical correlates of a comprehensive set of non-linear heart rate variability (HRV) indices computed from 24-h Holter recordings for 200 stable chronic heart failure (CHF) patients [median age (lower quartile, upper quartile) 54 (47, 58) years, LVEF 23% (19%, 28%)]. A total of 19 non-linear indices belonging to six major families, namely symbolic dynamics, entropy, empirical mode decomposition, fractality-multifractality, unpredictability and Poincaré plots, were considered. Most indices showed a significant association with ejection fraction and with the severity of symptoms, while only two (one each from the fractality and Poincaré plot families) showed an association with aetiology. Only one symbolic dynamics variable was associated with the presence of non-sustained ventricular tachycardia and two symbolic dynamics variables were associated with the rate of ventricular ectopic events. Our results demonstrate the existence of selective links between non-linear indexes of HRV and the clinical status and functional impairment of CHF patients. This indicates that further studies should be designed to investigate the physiopathological mechanisms involved in such links.

Evaluation of the Acceleration and Deceleration Phase-Rectified Slope to Detect and Improve IUGR Clinical Management.

OBJECTIVE: This study used a new method called Acceleration (or Deceleration) Phase-Rectified Slope, APRS (or DPRS) to analyze computerized Cardiotocographic (cCTG) traces in intrauterine growth restriction (IUGR), in order to calculate acceleration- and deceleration-related fluctuations of the fetal heart rate, and to enhance the prediction of neonatal outcome. METHOD: Cardiotocograms from a population of 59 healthy and 61 IUGR fetuses from the 30th gestation week matched for gestational age were included. APRS and DPRS analysis was compared to the standard linear and nonlinear cCTG parameters. Statistical analysis was performed through the t-test, ANOVA test, Pearson correlation test and receiver operator characteristic (ROC) curves (p < 0, 05). RESULTS: APRS and DPRS showed high performance to discriminate between Healthy and IUGR fetuses, according to gestational week. A linear correlation with the fetal pH at birth was found in IUGR. The area under the ROC curve was 0.865 for APRS and 0.900 for DPRS before the 34th gestation week. CONCLUSIONS: APRS and DPRS could be useful in the identification and management of IUGR fetuses and in the prediction of the neonatal outcome, especially before the 34th week of gestation.

Biomedical signal processing and modeling in cardiovascular systems.

This article revisits the subject of short-term heart-rate and arterial-pressure variability from the perspective of model structures that can be useful in defining signal processing algorithms. We draw a general scheme of the oscillation sources and interactions that contribute to cardiovascular control mechanisms and highlight the elements that were considered in different modeling works. The origin, superposition, and interaction of respiratory high-frequency (HF) and vasomotor low-frequency (LF) rhythms is presented as the integration of supraspinal and spinal circuits, vasomotor activity, and pressure control loops. We analyze in detail the necessity of considering all relevant interactions for the algorithms designed to estimate the baroreflex sensitivity. We also pinpoint the components of cardiorespiratory coupling in relation to the analysis of data from the acoustic quantification of the left ventricular volume. Finally, we analyze the tendency to produce complex behaviors even in extremely simplified systems involving interactions between oscillatory mechanisms.

Blood pressure variability and cardiovascular autonomic control during hemodialysis in peripheral vascular disease patients.

Hemodialysis (HD) patients with peripheral vascular disease (PVD) are at higher risk of mortality. The main objectives of this work were to investigate the hypothesis of an association between the PVD and an altered control system on peripheral resistance in response to volume depletion induced by HD treatment; and to investigate whether HD induced increase of pulse pressure (PP) is associated with PVD. Continuous blood pressure (BP) was recorded during HD treatment at the beginning and at the end of HD. The overhydration condition was evaluated by means of whole body bioimpedance spectroscopy, measured before each HD treatment. BP variability, heart rate variability and baroreflex sensitivity were then analyzed. Patients affected by PVD reported a prevalence of peripheral local control as shown by higher values of very low frequency in diastolic blood pressure (DBP) variability and a reduced cardiac baroreflex with respect to patients not affected by this pathology. HD treatment induced a significant increase of PP and LF% in DBP series in PVD patients only. Our results suggested that differences in BP variability and PP changes could be related not only to an underlying vascular disease, but also to an alteration in autonomic control.

The estimation of long-term memory characteristics in MEA neuronal culture recordings.

The nonlinear analysis of multichannel MEA recordings from neuronal networks is becoming a central topic in Neuroengineering. Up-to-date these kind of analyses required complex ad hoc methods. In this paper we introduce a new approach that allows the analysis of the whole-neuronal-network-activity with well-established nonlinear signal processing methods. In particular, we show here the estimation of long-term-memory behaviors through the Periodogram method in the bursting activity of cortical neuron cultures during development. Moreover, we show how this method is able to highlight structural activity changes of the network.

How do TTX and AP5 affect the post-recovery neuronal network activity synchronization?

A lot of methods were created in last decade for the spatio-temporal analysis of multi-electrode array (MEA) neuronal data sets. The greater part of these methods does not consider the network as a whole but performs an analysis channel by channel. In this paper we illustrate how a very simple approach that considers the total network activity, is able to show interesting neuronal network features. In particular we perform two different analyses: a connectivity examination studying networks at different days in vitro and an analysis of the long period effects of the administration of two common neuro-active drugs, i.e. TTX and AP5. Our analysis is performed considering burst topology, i.e. cataloguing network bursts as Global (if they involve more than the 25% of the MEA channels) or Local (if less that 25%). This division allows, in the first analysis, to understand the network connectivity (increasing from div 1 to 6) and decreasing till reaching a plateau (from div 6 to 10). The second analysis highlights a substantial difference between the long period effects of TTX and AP5. While TTX induces a massive Global activity explosion, sign of a prolonged inhibitory synapse depression, AP5 shows only a modest Local activity increase, mark of the low effect of NMDA receptors on a mature neuronal network without inputs.