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Multiscale entropy (MSE) is a widely used metric for characterizing the nonlinear dynamics of physiological processes. Significant variability, however, exists in the methodological approaches to MSE which may ultimately impact results and their interpretations. Using publications focused on balance-related center of pressure (COP) dynamics, we highlight sources of methodological heterogeneity that can impact study findings. Seventeen studies were systematically identified that employed MSE for characterizing COP displacement dynamics. We identified five key methodological procedures that varied significantly between studies: (1) data length; (2) frequencies of the COP dynamics analyzed; (3) sampling rate; (4) point matching tolerance and sequence length; and (5) filtering of displacement changes from drifts, fidgets, and shifts. We discuss strengths and limitations of the various approaches employed and supply flowcharts to assist in the decision making process regarding each of these procedures. Our guidelines are intended to more broadly inform the design and analysis of future studies employing MSE for continuous time series, such as COP. [ABSTRACT FROM AUTHOR]

Abstract  Cardiovascular signals are largely analyzed using traditional time and frequency domain measures. However, such measures fail to account for important properties related to multiscale organization and non-equilibrium dynamics. The complementary role of conventional signal analysis methods and emerging multiscale techniques, is, therefore, an important frontier area of investigation. The key finding of this presentation is that two recently developed multiscale computational tools––multiscale entropy and multiscale time irreversibility––are able to extract information from cardiac interbeat interval time series not contained in traditional methods based on mean, variance or Fourier spectrum (two-point correlation) techniques. These new methods, with careful attention to their limitations, may be useful in diagnostics, risk stratification and detection of toxicity of cardiac drugs. [ABSTRACT FROM AUTHOR]

Background: In older adults, depression has been associated with increased fall risk, but the reasons for this link are not fully clear. Given parallels between major depression and Parkinson's disease, we hypothesized that major depression and related affective disorders would be associated with impairment in the ability to regulate the stride-to-stride fluctuations in gait cycle timing. Methods: We measured stride-to-stride fluctuations of patients with two forms of mood disorders, unipolar major depressive disorder (MDD) and bipolar disorder, and compared their gait to that of a healthy control group. The primary outcomes were two measures of gait unsteadiness that have been associated with fall risk: stride time variability and swing time variability. Results: Compared to the control group, the two patient groups tended to walk more slowly and with decreased swing time and increased stride time. However, none of these differences was statistically significant. Compared to the control group, swing time variability was significantly larger in the subjects with bipolar disorder (p < 0.0001) and in the subjects with MDD (p < 0.0004). Conclusions: Patients with MDD and patients with bipolar disorder display gait unsteadiness. This perturbation in gait may provide a mechanistic link connecting depression and falls. The present findings also suggest the possibility that measurement of variability of gait may provide a readily quantifiable objective approach to monitoring depression and related affective disorders. [ABSTRACT FROM AUTHOR]

The author comments on the study "Synchronization in human musical rhythms and mutually interacting complex systems," by H. Hennig. The author discusses the synchronization process by Hennig between two individuals playing musical rhythms together to examine the cross-correlation of tempo time series. Also mentioned is the application of artificial synchronized music in the biomedical area.

Previous studies of cerebral autoregulation mainly focused on the changes of blood flow in response to large perturbations in blood pressure introduced by interventions at time frequency <0.1Hz. This approach may not be feasible for patients with impaired Cerebral autoregulation or cardiovascular regulation. However, due to the noisy nature of physiological signals, assessment of dynamic autoregulation during steady state remains a challenge in clinical and diagnostic medicine. Here we propose a new technique to assess cerebral autoregulation dynamics from spontaneous peripheral blood pressure (BP) and cerebral blood flow velocity (BFV) oscillations under resting conditions. Adapting a newly developed technique_the multimodal pressure-flow (MMPF) analysis, we show that cerebral autoregulation in healthy subjects during supine baseline can be characterized by specific phase delays between dominant spontaneous cerebral BFV oscillations and subsequent BP oscillations over the frequency range (∼0.1 Hz to 0.4Hz) that is beyond the previously recognized effective region of cerebral autoregulation. In addition, phase shifts of spontaneous BFV and BP oscillations are significantly reduced in people with type 2 diabetes, indicating altered dynamics of BP-BFV relationship and, thus, impairment of vasoregulation. These findings indicate that cerebral autoregulatory processes can operate at shorter time scales (<10 sec) and control pressure-flow relationship during quasi-steady state at frequency > 0.1 Hz, and that type 2 diabetes alters short-term dynamics of cerebral vasoregulation. ADA-Funded Research [ABSTRACT FROM AUTHOR]

Cerebral autoregulation (CA) is an important vascular control mechanism responsible for relatively stable cerebral blood flow despite changes of systemic blood pressure (BP). Impaired CA may leave brain tissue unprotected against potentially harmful effects of BP fluctuations. It is generally accepted that CA is less effective or even inactive at frequencies >∼0.1 Hz. Without any physiological foundation, this concept is based on studies that quantified the coupling between BP and cerebral blood flow velocity (BFV) using transfer function analysis. This traditional analysis assumes stationary oscillations with constant amplitude and period, and may be unreliable or even invalid for analysis of nonstationary BP and BFV signals. In this study we propose a novel computational tool for CA assessment that is based on nonlinear dynamic theory without the assumption of stationary signals. Using this method, we studied BP and BFV recordings collected from 39 patients with chronic ischemic infarctions and 40 age-matched non-stroke subjects during baseline resting conditions. The active CA function in non-stroke subjects was associated with an advanced phase in BFV oscillations compared to BP oscillations at frequencies from ∼0.02 to 0.38 Hz. The phase shift was reduced in stroke patients even at >= 6 months after stroke, and the reduction was consistent at all tested frequencies and in both stroke and non-stroke hemispheres. These results provide strong evidence that CA may be active in a much wider frequency region than previously believed and that the altered multiscale CA in different vascular territories following stroke may have important clinical implications for post-stroke recovery. Moreover, the stroke effects on multiscale cerebral blood flow regulation could not be detected by transfer function analysis, suggesting that nonlinear approaches without the assumption of stationarity are more sensitive for the assessment of the coupling of nonstationary physiological signals. [ABSTRACT FROM AUTHOR]

Background: Seasonal depression has generated considerable clinical interest in recent years. Despite a common belief that people in higher latitudes are more vulnerable to low mood during the winter, it has never been demonstrated that human's moods are subject to seasonal change on a global scale. The aim of this study was to investigate large-scale seasonal patterns of depression using Internet search query data as a signature and proxy of human affect. Methodology/Principal Findings: Our study was based on a publicly available search engine database, Google Insights for Search, which provides time series data of weekly search trends from January 1, 2004 to June 30, 2009. We applied an empirical mode decomposition method to isolate seasonal components of health-related search trends of depression in 54 geographic areas worldwide. We identified a seasonal trend of depression that was opposite between the northern and southern hemispheres; this trend was significantly correlated with seasonal oscillations of temperature (USA: r =20.872, p,0.001; Australia: r =20.656, p<0.001). Based on analyses of search trends over 54 geological locations worldwide, we found that the degree of correlation between searching for depression and temperature was latitude-dependent (northern hemisphere: r =20.686; p<0.001; southern hemisphere: r = 0.871; p,0.0001). Conclusions/Significance: Our findings indicate that Internet searches for depression from people in higher latitudes are more vulnerable to seasonal change, whereas this phenomenon is obscured in tropical areas. This phenomenon exists universally across countries, regardless of language. This study provides novel, Internet-based evidence for the epidemiology of seasonal depression. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is an abnormal rhythm of the heart, which can increase heart-related complications. Paroxysmal AF episodes occur intermittently with varying duration. Human-based diagnosis of paroxysmal AF with a longer-term electrocardiogram recording is time-consuming. Here we present a fully automated ensemble model for AF episode detection based on RR-interval time series, applying a novel approach of information-based similarity analysis and ensemble scheme. By mapping RR-interval time series to binary symbolic sequences and comparing the rank-frequency patterns of m-bit words, the dissimilarity between AF and normal sinus rhythms (NSR) were quantified. To achieve high detection specificity and sensitivity, and low variance, a weighted variation of bagging with multiple AF and NSR templates was applied. By performing dissimilarity comparisons between unknown RR-interval time series and multiple templates, paroxysmal AF episodes were detected. Based on our results, optimal AF detection parameters are symbolic word length m = 9 and observation window n = 150, achieving 97.04% sensitivity, 97.96% specificity, and 97.78% overall accuracy. Sensitivity, specificity, and overall accuracy vary little despite changes in m and n parameters. This study provides quantitative information to enhance the categorization of AF and normal cardiac rhythms. [ABSTRACT FROM AUTHOR]

Healthy systems exhibit complex dynamics on the changing of information embedded in physiologic signals on multiple time scales that can be quantified by employing multiscale entropy (MSE) analysis. Here, we propose a measure of complexity, called entropy of entropy (EoE) analysis. The analysis combines the features of MSE and an alternate measure of information, called superinformation, useful for DNA sequences. In this work, we apply the hybrid analysis to the cardiac interbeat interval time series. We find that the EoE value is significantly higher for the healthy than the pathologic groups. Particularly, short time series of 70 heart beats is sufficient for EoE analysis with an accuracy of 81% and longer series of 500 beats results in an accuracy of 90%. In addition, the EoE versus Shannon entropy plot of heart rate time series exhibits an inverted U relationship with the maximal EoE value appearing in the middle of extreme order and disorder [ABSTRACT FROM AUTHOR]

The complex fluctuations in heart rate variability (HRV) reflect cardiac autonomic modulation and are an indicator of congestive heart failure (CHF). This paper proposes a novel nonlinear approach to HRV investigation, the multi dynamic trend analysis (MDTA) method, based on the empirical mode decomposition algorithm of the Hilbert-Huang transform combined with a variable-sized slidingwindow method. Electrocardiographic signal data obtained from the PhysioNet database were used. These data were from subjects with CHF (mean age=59.4±8.4), an age-matched elderly healthy control group (59.3±10.6), and a healthy young group (30.3±4.8); the HRVs of these subjects were processed using the MDTA method, time domain analysis, and frequency domain analysis. Among all HRV parameters, the MDTA absolute value slope (MDTS) and MDTA deviation (MDTD) exhibited the greatest area under the curve (AUC) of the receiver operating characteristics in distinguishing between the CHF group and the healthy controls (AUC=1.000) and between the healthy elderly subject group and the young subject group (AUC=0.834±0.067 for MDTS; 0.837±0.066 for MDTD). The CHF subjects presented with lower MDTA indices than those of the healthy elderly subject group. Furthermore, the healthy elderly subjects exhibited lower MDTA indices than those of the young controls. The MDTA method can adaptively and automatically identify the intrinsic fluctuation on variable temporal and spatial scales when investigating complex fluctuations in the cardiac autonomic regulation effects of aging and CHF. [ABSTRACT FROM AUTHOR]

Background: Genetic polymorphisms in the gene encoding the β-adrenergic receptors (β-AR) have a pivotal role in the functions of the autonomic nervous system. Using heart rate variability (HRV) as an indicator of autonomic function, we present a bottom-up genotype-phenotype analysis to investigate the association between β-AR gene polymorphisms and heart rate dynamics. Methods: A total of 221 healthy Han Chinese adults (59 males and 162 females, aged 33.6±10.8 years, range 19 to 63 years) were recruited and genotyped for three common β-AR polymorphisms: β1-AR Ser49Gly, β2-AR Arg16Gly and β2-AR Gln27Glu. Each subject underwent two hours of electrocardiogram monitoring at rest. We applied an information-based similarity (IBS) index to measure the pairwise dissimilarity of heart rate dynamics among study subjects. Results: With the aid of agglomerative hierarchical cluster analysis, we categorized subjects into major clusters, which were found to have significantly different distributions of β2-AR Arg16Gly genotype. Furthermore, the non-randomness index, a nonlinear HRV measure derived from the IBS method, was significantly lower in Arg16 homozygotes than in Gly16 carriers. The non-randomness index was negatively correlated with parasympathetic-related HRV variables and positively correlated with those HRV indices reflecting a sympathovagal shift toward sympathetic activity. Conclusions: We demonstrate a bottom-up categorization approach combining the IBS method and hierarchical cluster analysis to detect subgroups of subjects with HRV phenotypes associated with β-AR polymorphisms. Our results provide evidence that β2-AR polymorphisms are significantly associated with the acceleration/deceleration pattern of heart rate oscillation, reflecting the underlying mode of autonomic nervous system control. [ABSTRACT FROM AUTHOR]

Background: Patients frequently report that weather changes trigger headache or worsen existing headache symptoms. Recently, the method of empirical mode decomposition (EMD) has been used to delineate temporal relationships in certain diseases, and we applied this technique to identify intrinsic weather components associated with headache incidence data derived from a large-scale epidemiological survey of headache in the Greater Taipei area. Methodology/Principal Findings: The study sample consisted of 52 randomly selected headache patients. The weather time-series parameters were detrended by the EMD method into a set of embedded oscillatory components, i.e. intrinsic mode functions (IMFs). Multiple linear regression models with forward stepwise methods were used to analyze the temporal associations between weather and headaches. We found no associations between the raw time series of weather variables and headache incidence. For decomposed intrinsic weather IMFs, temperature, sunshine duration, humidity, pressure, and maximal wind speed were associated with headache incidence during the cold period, whereas only maximal wind speed was associated during the warm period. In analyses examining all significant weather variables, IMFs derived from temperature and sunshine duration data accounted for up to 33.3% of the variance in headache incidence during the cold period. The association of headache incidence and weather IMFs in the cold period coincided with the cold fronts. Conclusions/Significance: Using EMD analysis, we found a significant association between headache and intrinsic weather components, which was not detected by direct comparisons of raw weather data. Contributing weather parameters may vary in different geographic regions and different seasons. [ABSTRACT FROM AUTHOR]

Background: Cardiac extra-cellular matrix (ECM) fibrosis plays an important role in the pathophysiology of heart failure (HF). It may provide electrical heterogeneity and a substrate for arrhythmogenicity, which may cause sudden cardiac death (SCD). Methods: Twenty-one patients with manifestations of HF and a left ventricular ejection fraction (LVEF) ≤50% were enrolled. The median age was 62 years and median LVEF was 33%. Time- and frequency-domain analysis of heart rate variability (HRV) on 24 h ambulatory electrocardiography recording was assessed. Serum markers of ECM turnover including type I and III aminoterminal propeptide of procollagen (PINP and PIIINP), matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed. Results: The serum PIIINP concentration was correlated significantly with standard deviation of all normal to normal R-R intervals (SDNN) (r=-0.722, p=<0.001), percentage of adjacent NN interval differences >50 ms (pNN50) (r=-0.528, p=0.014), percentage of adjacent NN interval differences >20 ms (pNN20) (r=-0.545, p=0.002), very low frequency (VLF) (r=-0.490, p=0.024), low frequency (LF) (r=-0.491, p=0.024), and high frequency (HF) (r=-0.513, p=0.018). PINP, MMP-2, -9, TIMP-1 were not correlated with time- and frequency-domain analysis of HRV. Conclusions: PIIINP was significantly correlated with time- and frequency-domain analysis of HRV in HF patients. PIIINP is a potential serological marker to evaluate cardiac autonomic control and risk of SCD in HF patients. Clin Chem Lab Med 2010;48:1821-7. [ABSTRACT FROM AUTHOR]

Introduction: Enhanced characterization of sleep architecture, compared with routine polysomnographic metrics such as stage percentages and sleep efficiency, may improve the predictive phenotyping of fragmented sleep. One approach involves using stage transition analysis to characterize sleep continuity. Methods and Principal Findings: We analyzed hypnograms from Sleep Heart Health Study (SHHS) participants using the following stage designations: wake after sleep onset (WASO), non-rapid eye movement (NREM) sleep, and REM sleep. We show that individual patient hypnograms contain insufficient number of bouts to adequately describe the transition kinetics, necessitating pooling of data. We compared a control group of individuals free of medications, obstructive sleep apnea (OSA), medical co-morbidities, or sleepiness (n = 374) with mild (n = 496) or severe OSA (n = 338). WASO, REM sleep, and NREM sleep bout durations exhibited multi-exponential temporal dynamics. The presence of OSA accelerated the ''decay'' rate of NREM and REM sleep bouts, resulting in instability manifesting as shorter bouts and increased number of stage transitions. For WASO bouts, previously attributed to a power law process, a multi-exponential decay described the data well. Simulations demonstrated that a multi-exponential process can mimic a power law distribution. Conclusion and Significance: OSA alters sleep architecture dynamics by decreasing the temporal stability of NREM and REM sleep bouts. Multi-exponential fitting is superior to routine mono-exponential fitting, and may thus provide improved predictive metrics of sleep continuity. However, because a single night of sleep contains insufficient transitions to characterize these dynamics, extended monitoring of sleep, probably at home, would be necessary for individualized clinical application. [ABSTRACT FROM AUTHOR]

Background: Balance during quiet stance involves the complex interactions of multiple postural control systems, which may degrade with frailty. The complexity of center of pressure (COP) dynamics, as quantified using multiscale entropy (MSE), during quiet standing is lower in older adults, especially those with falls. We hypothesized that COP dynamics from frail elderly individuals demonstrate less complexity than those from nonfrail elderly controls; complexity decreases when performing a dual task; and postural complexity during quiet standing is independent of other conventional correlates of balance control, such as age and vision. [ABSTRACT FROM PUBLISHER]

Determining trend and implementing detrending operations are important steps in data analysis. Yet there is no precise definition of "trend" nor any logical algorithm for extracting it. As a result, various ad hoc extrinsic methods have been used to determine trend and to facilitate a detrending operation. In this article, a simple and logical definition of trend is given for any nonlinear and nonstationary time series as an intrinsically determined monotonic function within a certain temporal span (most often that of the data span), or a function in which there can be at most one extremum within that temporal span. Being intrinsic, the method to derive the trend has to be adaptive. This definition of trend also presumes the existence of a natural time scale. All these requirements suggest the Empirical Mode Decomposition (EMD) method as the logical choice of algorithm for extracting various trends from a data set. Once the trend is determined, the corresponding detrending operation can be implemented. With this definition of trend, the variability of the data on various time scales also can be derived naturally. Climate data are used to illustrate the determination of the intrinsic trend and natural variability. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the effects of stroke on regulation of cerebral blood flow in response to fluctuations in systemic blood pressure (BP). The autoregulatory dynamics are difficult to assess because of the nonstationarity and nonlinearity of the component signals. Methods: We studied 15 normotensive, 20 hypertensive and 15 minor stroke subjects (48.0 ± 1.3 years). BP and blood flow velocities (BFV) from middle cerebral arteries (MCA) were measured during the Valsalva maneuver (VM) using transcranial Doppler ultrasound. Results: A new technique, multimodal pressure-flow analysis (MMPF), was implemented to analyze these short, nonstationary signals. MMPF analysis decomposes complex BP and BFV signals into multiple empirical modes, representing their instantaneous frequency-amplitude modulation. The empirical mode corresponding to the VM BP profile was used to construct the continuous phase diagram and to identify the minimum and maximum values from the residual BP (BPR) and BFV (BFVR) signals. The BP-BFV phase shift was calculated as the difference between the phase corresponding to the BPR and BFVR minimum (maximum) values. BP-BFV phase shifts were significantly different between groups. In the normotensive group, the BFVR minimum and maximum preceded the BPR minimum and maximum, respectively, leading to large positive values of BP-BFV shifts. Conclusion: In the stroke and hypertensive groups, the resulting BP-BFV phase shift was significantly smaller compared to the normotensive group. A standard auto-regulation index did not differentiate the groups. The MMPF method enables evaluation of autoregulatory dynamics based on instantaneous BP-BFV phase analysis. Regulation of BP-BFV dynamics is altered with hypertension and after stroke, rendering blood flow dependent on blood pressure. [ABSTRACT FROM AUTHOR]

Studies whether fractal and complexity measures of heart rate (HR) behavior are altered in patients with stable angina pectoris. Altered correlation properties in PR interval dynamics of patients with stable angina; Better performance of short-term fractal scaling exponent in detecting abnormalities in HR behavior.