Wan-Hsin Hsieh

Suprachiasmatic neuron numbers and rest–activity circadian rhythms in older humans

The suprachiasmatic nucleus (SCN) of the hypothalamus, the master mammalian circadian pacemaker, synchronizes endogenous rhythms with the external day–night cycle. Older humans, particularly those with Alzheimer disease (AD), often have difficulty maintaining normal circadian rhythms compared to younger adults, but the basis of this change is unknown. We report that the circadian rhythm amplitude of motor activity in both AD subjects and age‐matched controls is correlated with the number of vasoactive intestinal peptide–expressing SCN neurons. AD was additionally associated with delayed circadian phase compared to cognitively healthy subjects, suggesting distinct pathologies and strategies for treating aging‐ and AD‐related circadian disturbances. Ann Neurol 2015;78:317–322

Prevalence, Characteristics, Mapping, and Catheter Ablation of Potential Rotors in Nonparoxysmal Atrial Fibrillation

Background— Identification of critical atrial substrates in patients with nonparoxysmal atrial fibrillation (AF) failing to respond to pulmonary vein isolation is important. This study investigated the signal characteristics, substrate nature, and ablation results of rotors during AF. Methods and Results— In total, 53 patients (age=55±8), 31 with persistent AF and 22 with long-lasting AF, underwent pulmonary vein isolation and substrate modification of complex fractionated atrial electrograms. Small-radius-reentrant rotors were identified from signal analyses of the dominant frequency and fractionation interval and nonlinear analyses (newly developed, beat-to-beat nonlinear measurement of the repetitiveness of the electrogram morphology >6 seconds). In 15% of the patients, activation maps demonstrated occurrences of rotor-like small-radius reentrant circuits (n=9; 1.1 per patient; cycle length=110±21 ms; diameter=11±6 mm) with fibrillation occurring outside these areas. Rotors were identified by conventional point-by-point mapping and signal analyses and were subsequently eradicated by catheter ablation in these patients. Persistent AF for <1 year, a smaller left atrial size, substrates with higher mean voltages and shorter total activation durations predicted a higher incidence of rotors (all P<0.05). In the multivariable model, areas of reentrant circuits exhibited a higher dominant frequency, kurtosis, and higher degree of a beat-to-beat electrogram similarity than areas without or outside the rotors (all P<0.05). Conclusions— Rotor-like re-entry with fibrillatory conduction was found in a limited number of patients with nonparoxysmal AF after pulmonary vein isolation. Those areas were characterized by rapid repetitive activity with a high degree of electrogram similarity.

Nonlinear Analysis of Fibrillatory Electrogram Similarity to Optimize the Detection of Complex Fractionated Electrograms During Persistent Atrial Fibrillation

Nonlinear Analysis of Atrial Fibrillation. Introduction: Currently, the identification of complex fractionated atrial electrograms (CFEs) in the substrate modification is mostly based on cycle length‐derived algorithms. The characteristics of the fibrillation electrogram morphology and their consistency over time are not clear. The aim of this study was to optimize the detection algorithm of crucial CFEs by using nonlinear measure electrogram similarity.

Detecting phase-amplitude coupling with high frequency resolution using adaptive decompositions.

BACKGROUND Phase-amplitude coupling (PAC)--the dependence of the amplitude of one rhythm on the phase of another, lower-frequency rhythm - has recently been used to illuminate cross-frequency coordination in neurophysiological activity. An essential step in measuring PAC is decomposing data to obtain rhythmic components of interest. Current methods of PAC assessment employ narrowband Fourier-based filters, which assume that biological rhythms are stationary, harmonic oscillations. However, biological signals frequently contain irregular and nonstationary features, which may contaminate rhythms of interest and complicate comodulogram interpretation, especially when frequency resolution is limited by short data segments. NEW METHOD To better account for nonstationarities while maintaining sharp frequency resolution in PAC measurement, even for short data segments, we introduce a new method of PAC assessment which utilizes adaptive and more generally broadband decomposition techniques - such as the empirical mode decomposition (EMD). To obtain high frequency resolution PAC measurements, our method distributes the PAC associated with pairs of broadband oscillations over frequency space according to the time-local frequencies of these oscillations. COMPARISON WITH EXISTING METHODS We compare our novel adaptive approach to a narrowband comodulogram approach on a variety of simulated signals of short duration, studying systematically how different types of nonstationarities affect these methods, as well as on EEG data. CONCLUSIONS Our results show: (1) narrowband filtering can lead to poor PAC frequency resolution, and inaccuracy and false negatives in PAC assessment; (2) our adaptive approach attains better PAC frequency resolution and is more resistant to nonstationarities and artifacts than traditional comodulograms.

Novel assessment of temporal variation in fractionated electrograms using histogram analysis of local fractionation interval in patients with persistent atrial fibrillation.

Background—The characteristics of atrial electrograms associated with atrial fibrillation (AF) termination are controversial. We investigated the electrogram characteristics that indicate procedural AF termination during continuous complex fractionated electrogram ablation. Methods and Results—Fifty-two consecutive patients with persistent AF (47 men; aged 54±9 years), who underwent electrogram-based catheter ablation in the left atrium and coronary sinus after pulmonary vein isolation, were enrolled. The intracardiac bipolar atrial electrogram recordings were characterized by (1) fractionation interval (FI) analysis (>6 seconds), (2) kurtosis (shape of the FI histogram), and (3) skewness (asymmetry of the FI histogram). Sites showing complex, fractionated electrograms (mean FI ⩽60 ms) were targeted, and AF was terminated in 20 patients (38%) after the pulmonary vein isolation. The conventional complex fractionated electrogram sites (mean ⩽120 ms) in patients with AF termination exhibited higher median kurtosis (2.69 [interquartile range, 2.03–3.46] versus 2.35 [interquartile range, 1.79–2.48]; P=0.024) and higher complex fractionated electrogram-mean interval (102.7±19.8 versus 87.7±15.0; P=0.008) than patients without AF termination. Furthermore, AF termination sites had higher median kurtosis than targeted sites without AF termination (5.13 [interquartile range, 3.51–6.47] versus 4.18 [interquartile range, 2.91–5.34]; P<0.01) in patients with procedural termination. In addition, patients with AF termination had a higher sinus rhythm maintenance rate after a single procedure than patients without AF termination (log-rank test, P=0.007). Conclusions—A kurtosis analysis using the FI histogram may be a useful tool in identifying the critical substrate for persistent AF and potential responders to catheter ablation.

Interactive Effects of Dorsomedial Hypothalamic Nucleus and Time-Restricted Feeding on Fractal Motor Activity Regulation.

One evolutionary adaptation in motor activity control of animals is the anticipation of food that drives foraging under natural conditions and is mimicked in laboratory with daily scheduled food availability. Food anticipation is characterized by increased activity a few hours before the feeding period. Here we report that 2-h food availability during the normal inactive phase of rats not only increases activity levels before the feeding period but also alters the temporal organization of motor activity fluctuations over a wide range of time scales from minutes up to 24 h. We demonstrate this multiscale alteration by assessing fractal patterns in motor activity fluctuations—similar fluctuation structure at different time scales—that are robust in intact animals with ad libitum food access but are disrupted under food restriction. In addition, we show that fractal activity patterns in rats with ad libitum food access are also perturbed by lesion of the dorsomedial hypothalamic (DMH)—a neural node that is involved in food anticipatory behavior. Instead of further disrupting fractal regulation, food restriction restores the disrupted fractal patterns in these animals after the DMH lesion despite the persistence of the 24-h rhythms. This compensatory effect of food restriction is more clearly pronounced in the same animals after the additional lesion of the suprachiasmatic nucleus (SCN)—the central master clock in the circadian system that generates and orchestrates circadian rhythms in behavior and physiological functions in synchrony with day-night cycles. Moreover, all observed influences of food restriction persist even when data during the food anticipatory and feeding period are excluded. These results indicate that food restriction impacts dynamics of motor activity at different time scales across the entire circadian/daily cycle, which is likely caused by the competition between the food-induced time cue and the light-entrained circadian rhythm of the SCN. The differential impacts of food restriction on fractal activity control in intact and DMH-lesioned animals suggest that the DMH plays a crucial role in integrating these different time cues to the circadian network for multiscale regulation of motor activity.

The Use of Signal Analyses of Ventricular Tachycardia Electrograms to Predict the Response of Antitachycardia Pacing in Patients with Implantable Cardioverter‐Defibrillators

Antitachycardia pacing (ATP), a quick, painless, and effective therapy available in implantable cardioverter‐defibrillators (ICDs), can terminate most, but not all, sustained ventricular tachycardias (VTs). This study investigated the possible ventricular electrogram (EGM) factors for predicting the effectiveness of ATP therapy from ICD recordings.

Probing the Fractal Pattern of Heartbeats in Drosophila Pupae by Visible Optical Recording System.

Judiciously tuning heart rates is critical for regular cardiovascular function. The fractal pattern of heartbeats — a multiscale regulation in instantaneous fluctuations — is well known for vertebrates. The most primitive heart system of the Drosophila provides a useful model to understand the evolutional origin of such a fractal pattern as well as the alterations of fractal pattern during diseased statuses. We developed a non-invasive visible optical heart rate recording system especially suitable for long-term recording by using principal component analysis (PCA) instead of fluorescence recording system to avoid the confounding effect from intense light irradiation. To deplete intracellular Ca2+ levels, the expression of sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) was tissue-specifically knocked down. The SERCA group shows longer heart beat intervals (Mean ± SD: 1009.7 ± 151.6 ms) as compared to the control group (545.5 ± 45.4 ms, p < 0.001). The multiscale correlation of SERCA group (scaling exponent: 0.77 ± 0.07), on the other hand, is weaker than that of the control Drosophila (scaling exponent: 0.85 ± 0.03) (p = 0.016).