Big data in sleep medicine: prospects and pitfalls in phenotyping

Clinical polysomnography (PSG) databases are a rich resource in the era of “big data” analytics. We explore the uses and potential pitfalls of clinical data mining of PSG using statistical principles and analysis of clinical data from our sleep center. We performed retrospective analysis of self-reported and objective PSG data from adults who underwent overnight PSG (diagnostic tests, n=1835). Self-reported symptoms overlapped markedly between the two most common categories, insomnia and sleep apnea, with the majority reporting symptoms of both disorders. Standard clinical metrics routinely reported on objective data were analyzed for basic properties (missing values, distributions), pairwise correlations, and descriptive phenotyping. Of 41 continuous variables, including clinical and PSG derived, none passed testing for normality. Objective findings of sleep apnea and periodic limb movements were common, with 51% having an apnea–hypopnea index (AHI) >5 per hour and 25% having a leg movement index >15 per hour. Different visualization methods are shown for common variables to explore population distributions. Phenotyping methods based on clinical databases are discussed for sleep architecture, sleep apnea, and insomnia. Inferential pitfalls are discussed using the current dataset and case examples from the literature. The increasing availability of clinical databases for large-scale analytics holds important promise in sleep medicine, especially as it becomes increasingly important to demonstrate the utility of clinical testing methods in management of sleep disorders. Awareness of the strengths, as well as caution regarding the limitations, will maximize the productive use of big data analytics in sleep medicine

Instantaneous monitoring of sleep fragmentation by point process heart rate variability and respiratory dynamics

We present a novel, automatic point-process approach that is able to provide continuous, instantaneous estimates of heart rate variability (HRV) and respiratory sinus arrhythmia (RSA) in long duration data recordings such as those during an entire night of sleep. We analyze subjects with and without sleep apnea who underwent diagnostic polysomnography. The proposed algorithm is able to quantify multi-scale high time resolution autonomic signatures of sleep fragmentation, such as arousals and stage transitions, throughout an entire night. Results demonstrate the ability of our methods to track fast dynamic transitions from sleep to wake and between REM sleep and other sleep stages, providing resolution details not available in sleep scoring summaries. An automatic threshold-based procedure is further able to detect brief arousals, with the instantaneous indices characterizing specific arousal dynamic signatures

Advances in point process modeling: feature selection, goodness-of-fit and novel applications

The research contained in this thesis extends multivariate marked point process modeling methods for neuroscience, generalizes goodness-of-fit techniques for the class of marked point processes, and introduces the use of a general history-dependent point process model to the domain of sleep apnea. Our first project involves further development of a modeling tool for spiking data from neural populations using the theory of marked point processes. This marked point process model uses features of spike waveforms as marks in order to estimate a state variable of interest. We examine the informational content of geometric features as well as principal components of the waveforms at hippocampal place cell activity by comparing decoding accuracies of a rat's position along a track. We determined that there was additional information available beyond that contained in traditional geometric features used for decoding in practice. The expanded use of this marked point process model in neuroscience necessitates corresponding goodness-of-fit protocols for the marked case. In our second project, we develop a generalized time-rescaling method for marked point processes that produces uniformly distributed spikes under a proper model. Once rescaled, the ground process then behaves as a Poisson process and can be analyzed using traditional point process goodness-of-fit methods. We demonstrate the method's ability to detect quality and manner of fit through both simulation and real neural data analysis. In the final project, we introduce history-dependent point process modeling as a superior method for characterizing severe sleep apnea over the current clinical standard known as the apnea-hypopnea index (AHI). We analyze model fits using combinations of both clinical covariates and event observations themselves through functions of history. Ultimately, apnea onset times were consistently estimated with significantly higher accuracy when history was incorporated alongside sleep stage. We present this method to the clinical audience as a means to gain detailed information on patterns of apnea and to provide more customized diagnoses and treatment prescriptions. These separate yet complementary projects extend existing point process modeling methods and further demonstrate their value in the neurosciences, sleep sciences, and beyond