Oscillatory Biomedical Signals: Frontiers in Mathematical Models and Statistical Analysis

Herein we describe new frontiers in mathematical modeling and statistical analysis of oscillatory biomedical signals, motivated by our recent studies of network formation in the human brain during the early stages of life and studies forty years ago on cardiorespiratory patterns during sleep in infants and animal models. The frontiers involve new nonlinear-type time–frequency analysis of signals with multiple oscillatory components, and efficient particle filters for joint state and parameter estimators together with uncertainty quantification in hidden Markov models and empirical Bayes inference.

Interactive effects of maternal cigarette smoke, heat stress, hypoxia, and lipopolysaccharide on neonatal cardiorespiratory and cytokine responses

Maternal cigarette smoke (CS) exposure exhibits a strong epidemiological association with Sudden Infant Death Syndrome, but other environmental stressors, including infection, hyperthermia, and hypoxia, have also been postulated as important risk factors. This study examines whether maternal CS exposure causes maladaptations within homeostatic control networks by influencing the response to lipopolysaccharide, heat stress, and/or hypoxia in neonatal rats. Pregnant dams were exposed to CS or parallel sham treatments daily for the length of gestation. Offspring were studied at postnatal days 6–8 at ambient temperatures (Ta) of 33°C or 38°C. Within each group, rats were allocated to control, saline, or LPS (200 µg/kg) treatments. Cardiorespiratory patterns were examined using head-out plethysmography and ECG surface electrodes during normoxia and hypoxia (10% O2). Serum cytokine concentrations were quantified from samples taken at the end of each experiment. Our results suggest maternal CS exposure does not alter minute ventilation (V̇e) or heart rate (HR) response to infection or high temperature, but independently increases apnea frequency. CS also primes the inflammatory system to elicit a stronger cytokine response to bacterial insult. High Ta independently depresses V̇e but augments the hypoxia-induced increase in V̇e. Moreover, higher Ta increases HR during normoxia and hypoxia, and in the presence of an immune challenge, increases HR during normoxia, and reduces the increase normally associated with hypoxia. Thus, while most environmental risk factors increase the burden on the cardiorespiratory system in early life, hyperthermia and infection blunt the normal HR response to hypoxia, and gestational CS independently destabilizes breathing by increasing apneas.

Developmental changes in cardiorespiratory patterns of sleep-associated apnea in northern elephant seals

The development of heart rate and respiratory patterns related to sleep-associated apnea were studied in northern elephant seal (Mirounga angustirostris) pups and adult males. Heart rate patterns became more refined in conjunction with an age-related increase in apnea duration in pups. That is, older pups showed significant sinus arrhythmia, while breathing and apneic heart rate were both stable and similar in magnitude to the sinus arrhythmia minimum. By contrast, younger pups showed poor or nonexistent sinus arrhythmia and shorter apnea durations with a variable and/or high heart rate during apnea. Apnea duration was positively correlated with the development of sinus arrhythmia and negatively correlated with both eupneic and apneic heart rate. Adult males showed extremely well-developed patterns of sinus arrhythmia and, in all cases, the minimum heart rate during the sinus arrhythmia was lower than the average heart rate recorded during apnea. These results suggest that seal pups are not born with the cardiac control associated with voluntary long duration apnea, but that apnea tolerance increases with refined cardiorespiratory control.