Shamim Nemati

A simplified method for determining phenotypic traits in patients with obstructive sleep apnea

We previously published a method for measuring several physiological traits causing obstructive sleep apnea (OSA). The method, however, had a relatively low success rate (76%) and required mathematical modeling, potentially limiting its application. This paper presents a substantial revision of that technique. To make the measurements, continuous positive airway pressure (CPAP) was manipulated during sleep to quantify 1) eupneic ventilatory demand, 2) the level of ventilation at which arousals begin to occur, 3) ventilation off CPAP (nasal pressure = 0 cmH(2)O) when the pharyngeal muscles are activated during sleep, and 4) ventilation off CPAP when the pharyngeal muscles are relatively passive. These traits could be determined in all 13 participants (100% success rate). There was substantial intersubject variability in the reduction in ventilation that individuals could tolerate before having arousals (difference between ventilations #1 and #2 ranged from 0.7 to 2.9 liters/min) and in the amount of ventilatory compensation that individuals could generate (difference between ventilations #3 and #4 ranged from -0.5 to 5.5 liters/min). Importantly, the measurements accurately reflected clinical metrics; the difference between ventilations #2 and #3, a measure of the gap that must be overcome to achieve stable breathing during sleep, correlated with the apnea-hypopnea index (r = 0.9, P < 0.001). An additional procedure was added to the technique to measure loop gain (sensitivity of the ventilatory control system), which allowed arousal threshold and upper airway gain (response of the upper airway to increasing ventilatory drive) to be quantified as well. Of note, the traits were generally repeatable when measured on a second night in 5 individuals. This technique is a relatively simple way of defining mechanisms underlying OSA and could potentially be used in a clinical setting to individualize therapy.

Quantifying the ventilatory control contribution to sleep apnoea using polysomnography.

Elevated loop gain, consequent to hypersensitive ventilatory control, is a primary nonanatomical cause of obstructive sleep apnoea (OSA) but it is not possible to quantify this in the clinic. Here we provide a novel method to estimate loop gain in OSA patients using routine clinical polysomnography alone. We use the concept that spontaneous ventilatory fluctuations due to apnoeas/hypopnoeas (disturbance) result in opposing changes in ventilatory drive (response) as determined by loop gain (response/disturbance). Fitting a simple ventilatory control model (including chemical and arousal contributions to ventilatory drive) to the ventilatory pattern of OSA reveals the underlying loop gain. Following mathematical-model validation, we critically tested our method in patients with OSA by comparison with a standard (continuous positive airway pressure (CPAP) drop method), and by assessing its ability to detect the known reduction in loop gain with oxygen and acetazolamide. Our method quantified loop gain from baseline polysomnography (correlation versus CPAP-estimated loop gain: n=28; r=0.63, p<0.001), detected the known reduction in loop gain with oxygen (n=11; mean±sem change in loop gain (ΔLG) −0.23±0.08, p=0.02) and acetazolamide (n=11; ΔLG −0.20±0.06, p=0.005), and predicted the OSA response to loop gain-lowering therapy. We validated a means to quantify the ventilatory control contribution to OSA pathogenesis using clinical polysomnography, enabling identification of likely responders to therapies targeting ventilatory control. Ventilatory instability can be measured by clinical polysomnography to guide nonanatomical sleep apnoea therapy http://ow.ly/AyXT3

Biomimetic Brain Machine Interfaces for the Control of Movement

Quite recently, it has become possible to use signals recorded simultaneously from large numbers of cortical neurons for real-time control. Such brain machine interfaces (BMIs) have allowed animal subjects and human patients to control the position of a computer cursor or robotic limb under the guidance of visual feedback. Although impressive, such approaches essentially ignore the dynamics of the musculoskeletal system, and they lack potentially critical somatosensory feedback. In this mini-symposium, we will initiate a discussion of systems that more nearly mimic the control of natural limb movement. The work that we will describe is based on fundamental observations of sensorimotor physiology that have inspired novel BMI approaches. We will focus on what we consider to be three of the most important new directions for BMI development related to the control of movement. (1) We will present alternative methods for building decoders, including structured, nonlinear models, the explicit incorporation of limb state information, and novel approaches to the development of decoders for paralyzed subjects unable to generate an output signal. (2) We will describe the real-time prediction of dynamical signals, including joint torque, force, and EMG, and the real-time control of physical plants with dynamics like that of the real limb. (3) We will discuss critical factors that must be considered to incorporate somatosensory feedback to the BMI user, including its potential benefits, the differing representations of sensation and perception across cortical areas, and the changes in the cortical representation of tactile events after spinal injury.

Data fusion for improved respiration rate estimation

We present an application of a modified Kalman-Filter (KF) framework for data fusion to the estimation of respiratory rate from multiple physiological sources which is robust to background noise. A novel index of the underlying signal quality of respiratory signals is presented and then used to modify the noise covariance matrix of the KF which discounts the effect of noisy data. The signal quality index, together with the KF innovation sequence, is also used to weight multiple independent estimates of the respiratory rate from independent KFs. The approach is evaluated both on a realistic artificial ECG model (with real additive noise) and on real data taken from 30 subjects with overnight polysomnograms, containing ECG, respiration, and peripheral tonometry waveforms from which respiration rates were estimated. Results indicate that our automated voting system can out-perform any individual respiration rate estimation technique at all levels of noise and respiration rates exhibited in our data. We also demonstrate that even the addition of a noisier extra signal leads to an improved estimate using our framework. Moreover, our simulations demonstrate that different ECG respiration extraction techniques have different error profiles with respect to the respiration rate, and therefore a respiration rate-related modification of any fusion algorithm may be appropriate.

Transfer Entropy Estimation and Directional Coupling Change Detection in Biomedical Time Series

BackgroundThe detection of change in magnitude of directional coupling between two non-linear time series is a common subject of interest in the biomedical domain, including studies involving the respiratory chemoreflex system. Although transfer entropy is a useful tool in this avenue, no study to date has investigated how different transfer entropy estimation methods perform in typical biomedical applications featuring small sample size and presence of outliers.MethodsWith respect to detection of increased coupling strength, we compared three transfer entropy estimation techniques using both simulated time series and respiratory recordings from lambs. The following estimation methods were analyzed: fixed-binning with ranking, kernel density estimation (KDE), and the Darbellay-Vajda (D-V) adaptive partitioning algorithm extended to three dimensions. In the simulated experiment, sample size was varied from 50 to 200, while coupling strength was increased. In order to introduce outliers, the heavy-tailed Laplace distribution was utilized. In the lamb experiment, the objective was to detect increased respiratory-related chemosensitivity to O2 and CO2 induced by a drug, domperidone. Specifically, the separate influence of end-tidal PO2 and PCO2 on minute ventilation (V˙E) before and after administration of domperidone was analyzed.ResultsIn the simulation, KDE detected increased coupling strength at the lowest SNR among the three methods. In the lamb experiment, D-V partitioning resulted in the statistically strongest increase in transfer entropy post-domperidone for PO2→V˙E. In addition, D-V partitioning was the only method that could detect an increase in transfer entropy for PCO2→V˙E, in agreement with experimental findings.ConclusionsTransfer entropy is capable of detecting directional coupling changes in non-linear biomedical time series analysis featuring a small number of observations and presence of outliers. The results of this study suggest that fixed-binning, even with ranking, is too primitive, and although there is no clear winner between KDE and D-V partitioning, the reader should note that KDE requires more computational time and extensive parameter selection than D-V partitioning. We hope this study provides a guideline for selection of an appropriate transfer entropy estimation method.

An artificial vector model for generating abnormal electrocardiographic rhythms.

We present generalizations of our previously published artificial models for generating multi-channel ECG to provide simulations of abnormal cardiac rhythms. Using a three-dimensional vectorcardiogram (VCG) formulation, we generate the normal cardiac dipole for a patient using a sum of Gaussian kernels, fitted to real VCG recordings. Abnormal beats are specified either as perturbations to the normal dipole or as new dipole trajectories. Switching between normal and abnormal beat types is achieved using a first-order Markov chain. Probability transitions can be learned from real data or modeled by coupling to heart rate and sympathovagal balance. Natural morphology changes from beat-to-beat are incorporated by varying the angular frequency of the dipole as a function of the inter-beat (RR) interval. The RR interval time series is generated using our previously described model whereby time- and frequency-domain heart rate (HR) and heart rate variability characteristics can be specified. QT-HR hysteresis is simulated by coupling the Gaussian kernels associated with the T-wave in the model with a nonlinear factor related to the local HR (determined from the last n RR intervals). Morphology changes due to respiration are simulated by introducing a rotation matrix couple to the respiratory frequency. We demonstrate an example of the use of this model by simulating HR-dependent T-wave alternans (TWA) with and without phase-switching due to ectopy. Application of our model also reveals previously unreported effects of common TWA estimation methods.

Respiration and heart rate complexity: effects of age and gender assessed by band-limited transfer entropy

Aging and disease are accompanied with a reduction of complex variability in the temporal patterns of heart rate. This reduction has been attributed to a break down of the underlying regulatory feedback mechanisms that maintain a homeodynamic state. Previous work has established the utility of entropy as an index of disorder, for quantification of changes in heart rate complexity. However, questions remain regarding the origin of heart rate complexity and the mechanisms involved in its reduction with aging and disease. In this work we use a newly developed technique based on the concept of band-limited transfer entropy to assess the aging-related changes in contribution of respiration and blood pressure to entropy of heart rate at different frequency bands. Noninvasive measurements of heart beat interval, respiration, and systolic blood pressure were recorded from 20 young (21-34 years) and 20 older (68-85 years) healthy adults. Band-limited transfer entropy analysis revealed a reduction in high-frequency contribution of respiration to heart rate complexity (p<0.001) with normal aging, particularly in men. These results have the potential for dissecting the relative contributions of respiration and blood pressure-related reflexes to heart rate complexity and their degeneration with normal aging.

An open-source standard T-Wave alternans detector for benchmarking

We describe an open source algorithm suite for T-Wave Alternans (TWA) detection and quantification. The software consists of Matlab implementations of the widely used Spectral Method and Modified Moving Average with libraries to read both WFDB and ASCII data under windows and Linux. The software suite can run in both batch mode and with a provided graphical user interface to aid waveform exploration. Our software suite was calibrated using an open source TWA model, described in a partner paper by Clifford and Sameni. For the PhysioNet/CinC Challenge 2008 we obtained a score of 0.881 for the Spectral Method and 0.400 for the MMA method. However, our objective was not to provide the best TWA detector, but rather a basis for detailed discussion of algorithms.

An artificial multi-channel model for generating abnormal electrocardiographic rhythms

We present generalizations of our previously published artificial models for generating multi-channel ECG so that the simulation of abnormal rhythms is possible. Using a three-dimensional vectorcardiogram (VCG) formulation, we generate the normal cardiac dipole for a patient using a sum of Gaussian kernels, fitted to real VCG recordings. Abnormal beats are then specified either as new dipoles, or as perturbations of the existing dipole. Switching between normal and abnormal beat types is achieved using a hidden Markov model (HMM). Probability transitions can be learned from real data or modeled by coupling to heart rate and sympathovagal balance. Natural morphology changes form beat-to-beat are incorporated as before from varying the angular frequency of the dipole as a function of the inter-beat (RR) interval. The RR interval time series is generated using our previously described model whereby time-and frequency-domain heart rate (HR) and heart rate variability (HRV) characteristics can be specified. QT-HR hysteresis is simulated by coupling the Gaussian kernels associated with the T-wave in the model with a nonlinear factor related to the local HR (determined from the last n RR intervals). Morphology changes due to respiration are simulated by coupling the RR interval to the angular frequency of the dipole. We demonstrate an example of the use of this model by simulating T-Wave Alternans (TWA). The magnitude of the TWA effect is modeled as a disturbance on the T-loop of the dipole with a magnitude that differs in each of the three VCG planes. The effect is then turned on or off using a HMM. The values of the transition matrix are determined by the local heart rate, such that when the HR ramps up towards 100 BPM, the probability of observing a TWA effect rapidly but smoothly increases. In this way, no dasiasuddenpsila switching from non-TWA to TWA is observed, and the natural tendency for TWA to be associated with a critical HR-related activation level is simulated. Finally, to generate multi-lead signals, the VCG is mapped to any set of clinical leads using a Dower-like transform derived from a least-squares optimization between known VCGs and known lead morphologies. ECGs with calibrated amounts of TWA were generated by this model and included in the PhysioNet/CinC Challenge 2008 data set.

Tornado Detection Using a Neuro–Fuzzy System to Integrate Shear and Spectral Signatures

Abstract Tornado vortices observed from Doppler radars are often associated with strong azimuthal shear and Doppler spectra that are wide and flattened. The current operational tornado detection algorithm (TDA) primarily searches for shear signatures that are larger than the predefined thresholds. In this work, a tornado detection procedure based on a fuzzy logic system is developed to integrate tornadic signatures in both the velocity and spectral domains. A novel feature of the system is that it is further enhanced by a neural network to refine the membership functions through a feedback training process. The hybrid approach herein, termed the neuro–fuzzy tornado detection algorithm (NFTDA), is initially verified using simulations and is subsequently tested on real data. The results demonstrate that NFTDA can detect tornadoes even when the shear signatures are degraded significantly so that they would create difficulties for typical vortex detection schemes. The performance of the NFTDA is assessed with...