Eugene N. Bruce

Sample entropy tracks changes in electroencephalogram power spectrum with sleep state and aging.

Abstract: The regularity of electroencephalogram signals was compared between middle-aged (47.2 ± 2.0 years) and elderly (78.4 ± 3.8 years) female subjects in wake, nonrapid eye movement stages 2 and 3 (S-2, S-3), and rapid eye movement sleep. Signals from C3A2 leads of healthy subjects, acquired from polysomnograms obtained from the Sleep Heart Health Study, were analyzed using both sample entropy (SaEn) and power spectral analysis (delta, theta, alpha, and beta frequency band powers). SaEn changed systematically and significantly (P < 0.001) with sleep state in both age groups, following the relationships wake > rapid eye movement > S-2 > S-3. SaEn was found to be negatively correlated with delta power and positively correlated with beta power. Small changes in SaEn seem to reflect changes in spectral content rather than changes in regularity of the signal. A better predictor of SaEn than the frequency band powers was the logarithm of the power ratio (alpha + beta)/(delta + theta). Thus, SaEn seems to reflect the balance between sleep-promoting and alertness-promoting mechanisms. SaEn of the elderly was larger than that of middle-aged subjects in S-2 (P = 0.029) and rapid eye movement (P = 0.001), suggesting that cortical state is shifted toward alertness in elderly subjects in these sleep states compared with the middle-aged subjects.

Action of nicotine on the respiratory activity of the diaphragm and genioglossus muscles and the nerves that innervate them

Nicotine is known to alter respiration by stimulating peripheral chemoreceptors and receptors within the brain. In this study the sites of action and the effects of nicotine on hypoglossal nerve activity were compared to its effects on phrenic activity in paralyzed, vagotomized and chloralose-anesthetized cats. Since anesthesia is known to affect respiratory responses, we also compared the effects of intravenous nicotine given to conscious unsedated cats on genioglossus and diaphragm electrical activity. In eight conscious animals intravenous doses of nicotine ranging between 10 ng and 200 micrograms increased genioglossus activity significantly more than diaphragm activity. Studies in 26 anesthetized animals included injection of nicotine, intravenously, in the lateral ventricles, and application of nicotine to the ventrolateral surface of the medulla (the putative site of the central chemoreceptors) before and after section of the carotid sinus nerves. With all these interventions, changes in hypoglossal nerve activity were significantly greater than changes in phrenic nerve activity. The responses to nicotine could be blocked by application of hexamethonium to the ventrolateral medullary surface or by cooling the same area. The results indicate that: nicotine increases hypoglossal nerve activity by both its peripheral and central effects; nicotine has differential effects on different respiratory muscles and nerves; and the central action of nicotine may be mediated largely through receptors located near the ventral medullary surface.

Cardiorespiratory responses to glutamatergic antagonists in the caudal ventrolateral medulla of rats.

The role of caudal ventrolateral medullary (CVLM) depressor neurons in influencing arterial pressure and ventilation as well as the baroreflex control of arterial pressure was investigated, and the part played by excitatory N-methyl-D-aspartate (NMDA) and non-NMDA receptors in mediating the responses was determined. In urethane-anesthetized, spontaneously breathing rats unilateral microinjections into the caudal depressor area of the broad-band glutamatergic antagonist kynurenic acid (KYN, 5 nmol or 1.58 nmol), or NMDA antagonist 2-amino-5-phosphonovaleric acid (2-APV, 2.7 nmol), or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 0.257 nmol) caused a respiratory arrest within 4 min and the animals had to be artificially ventilated. Respiratory frequency increased on injecting KYN and CNQX while it did not change significantly with 2-APV. Apnea resulted from progressive decrease in tidal volume. During the apnea ventilation with 5% CO2 did not revive breathing. Mean arterial pressure (MAP) increased significantly with KYN and 2-APV injections but not with CNQX. The baroreflex decrease of MAP, elicited by left or right aortic depressor nerve stimulation, was significantly reduced or abolished after bilateral microinjections of all 3 antagonists. Ventilation as well as the baroreflex usually recovered after 1-1.5 h. Microinjections of the same doses of antagonists into the facial nucleus, as well as application of KYN (25 nmol) to the ventral medullary surface above the hypoglossal rootlets, had no significant effect. The results support previous findings that the CVLM neurons of the rat inhibit sympathetic neurons providing the vasomotor tone, and that an intact CVLM is obligatory for mediating the baroreflex decrease of arterial pressure. The results also indicate that: (1) the CVLM is essential for sustaining ventilation in the rat; (2) only NMDA receptors are involved in maintaining baseline blood pressure while both NMDA and non-NMDA receptors mediate the baroreceptor depressor reflex; and (3) both NMDA and non-NMDA receptor activation is necessary to sustain ventilation.

High-frequency oscillations in human respiratory electromyograms during voluntary breathing

Electromyograms (EMGs) from respiratory muscles were obtained from human subjects during voluntarily controlled breathing. In 10 studies on 6 subjects EMGs were recorded from the right and left lower ventrolateral surface of the rib cage while the subject emphasized the use of his diaphragm for breathing. Simultaneous samples of the 2 EMG signals of 256-ms duration were obtained once per inspiration (in either the first of second half of inspiration) from each of 30 consecutive breaths using a laboratory minicomputer. Individual power spectra for the 2 EMG signals, and the squared coherence spectrum between them, were calculated. From the coherence spectrum common high-frequency oscillations could be identified within two frequency ranges: 70-100 Hz and 20-50 Hz. Peaks at similar frequencies were identified in both early-inspiratory and late-inspiratory EMG signals. Similar experiments were done on 3 subjects from whom an esophageal diaphragm EMG was obtained as well. The coherence spectrum between the esophageal EMG and the right rib cage surface EMG again demonstrated the presence of common high-frequency oscillations in the same frequency ranges as above. Evidence of these oscillations was not usually apparent in the power spectra. When ECG signal components were allowed to contaminate some of the EMG data samples, the coherence spectrum could be altered considerably, leading to inappropriate conclusions regarding the presence or absence of high-frequency oscillations. It is hypothesized that these high-frequency oscillations are similar to those described in nerve recordings from previous studies on anesthetized and decerebrate cats and dogs and a mechanism for their expression in EMG signals is proposed. The coherence spectrum is a very sensitive method for detecting related signal components in two signals. That high-frequency oscillations can be detected using the less sensitive techniques of autocorrelation and power spectral analysis in some animal preparations may reflect an enhancement of these oscillations in those preparations.

Heart rate variability during sympatho-excitatory challenges: Comparison between spontaneous and metronomic breathing

Respiration influences heart rate variability, leading to the suggestion that respiration should be controlled to assess autonomic function by using heart rate variability. Clearly, control of respiration is advantageous or even essential in several experimental circumstances. However, control of respiration, by itself, produces a small, but significant, increase in mean heart rate and a decrease in respiratory synchronous variation in heart rate. We tested whether, in some experimental situations, it may be possible to arrive at similar interpretation about autonomic function with and without using control of respiratory rate. heart rate spectral powers from nine subjects were compared between spontaneous and metronomic breathing during two sympatho-excitatory stresses, lower body negative pressure (LBNP) and head up tilt (HUT). The normalized spectral powers in supine and HUT during spontaneous breathing were: 0.43 and 0.75 in very low (VLF) and 0.28 and 0.09 in high frequency (HF) regions. The powers during metronomic breathing were: 0.36 and 0.82 (VLF) and 0.36 and 0.09 (HF). The powers in supine and LBNP during spontaneous breathing were: 0.43 and 0.81 (VLF) and 0.28 and 0.06 (HF). The powers during metronomic breathing were: 0.36 and 0.80 (VLF) and 0.36 and 0.07 (HF). All p values were <0.05. Therefore, changes in heart rate spectral powers during HUT and LBNP were similar during metronomic breathing and spontaneous breathing. These results suggest that in experimental designs such as in our study, using metronomic breathing may not provide any additional insight into autonomic function than that can be obtained during spontaneous breathing.

Responses of hypoglossal and phrenic nerves to decreased respiratory drive in cats

Agents which depress respiration, such as alcohol, seem to increase the occurrence of obstructive apneas during sleep. It has been proposed that upper airway obstruction can result from an imbalance in the activity (or forces) produced by the upper airway muscles versus the chest wall muscles so that upper airway passages might be blocked when a disproportionate decrease in upper airway muscle activity occurs. This study examines the hypothesis that depression of respiration affects the activity of the hypoglossal nerve (the motor nerve to the tongue) more than the activity of the phrenic nerve (the motor nerve to the diaphragm). In addition, we examined the role of the putative central chemoreceptor area on the ventrolateral medullary surface (VMS) in maintaining phrenic and hypoglossal discharge. In chloralose-anesthetized, artificially ventilated, paralyzed cats, three methods of reducing respiratory drive were studied: hyperoxic hypocapnia (produced by mechanical hyperventilation), the application to the intermediate area of the ventral medullary surface of the respiratory depressant GABA and its agonist muscimol, and cooling the same area of the VMS (using a water-cooled thermode). All these interventions decreased hypoglossal nerve activity more than phrenic nerve activity (range of p values: p less than 0.001 to p less than 0.01). Moreover, the reduction in hypoglossal activity was greater with GABA and muscimol than with the other two maneuvers; this was statistically significant for both GABA versus VMS cooling (p less than 0.02) and muscimol versus VMS cooling (p less than 0.01). These results show that respiratory depression can differentially affect hypoglossal and phrenic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of Respiratory Muscles Activity by Means of Cross Mutual Information Function at Different Levels of Ventilatory Effort

Analysis of respiratory muscles activity is an effective technique for the study of pulmonary diseases such as obstructive sleep apnea syndrome (OSAS). Respiratory diseases, especially those associated with changes in the mechanical properties of the respiratory apparatus, are often associated with disruptions of the normally highly coordinated contractions of respiratory muscles. Due to the complexity of the respiratory control, the assessment of OSAS related dysfunctions by linear methods are not sufficient. Therefore, the objective of this study was the detection of diagnostically relevant nonlinear complex respiratory mechanisms. Two aims of this work were: 1) to assess coordination of respiratory muscles contractions through evaluation of interactions between respiratory signals and myographic signals through nonlinear analysis by means of cross mutual information function (CMIF); 2) to differentiate between functioning of respiratory muscles in patients with OSAS and in normal subjects. Electromyographic (EMG) and mechanomyographic (MMG) signals were recorded from three respiratory muscles: genioglossus, sternomastoid and diaphragm. Inspiratory pressure and flow were also acquired. All signals were measured in eight patients with OSAS and eight healthy subjects during an increased respiratory effort while awake. Several variables were defined and calculated from CMIF in order to describe correlation between signals. The results indicate different nonlinear couplings of respiratory muscles in both populations. This effect is progressively more evident at higher levels of respiratory effort.

CO2 control of the respiratory system: Plant dynamics and stability analysis

A stability analysis of respiratory chemical control is developed using a mathematical model of CO2 mass transport dynamics. Starting with a 3-compartment model of CO2 stores that distinguishes alveolar, muscle, and other tissue, model reduction techniques are applied to obtain a first-order representation of the respiratory plant. This model contains an effective tissue volume for CO2, whose derived value is much smaller than previously predicted. To investigate oscillatory instabilities, a controller which incorporates only peripheral chemoreceptor responses was added to the first-order plant model. An explicit stability index (SI) is obtained analytically from a linearized version of this model. SI varies directly with the controller gain and circulation delay time and inversely with the effective tissue volume and inspired CO2 concentration. Numerical simulations using the first-order nonlinear model show that SI is a good predictor of system stability. According to the linearized model, the system is stable for SI<1; from the nonlinear model, the system is stable for SI<1.1. For typical normal adults, the SI value is well within the stable region.

Bilaterally synchronized oscillations in human diaphragm and intercostal EMGs during spontaneous breathing

Bilaterally synchronized high-frequency oscillations have been found in recordings of human diaphragm and intercostal EMGs during spontaneous breathing (SB). Correlated frequencies (28-52 and/or 68-88 Hz) in the left and right diaphragm EMGs during SB: (1) are at similar values, but not as broad-band, as those found during voluntary breathing maneuvers; (2) often occur at the same values as correlated frequencies found in left and right intercostal EMGs; and (3) fluctuate with time.

Biphasic Response of Respiratory Frequency to Hypercapnea in Preterm Infants

ABSTRACT: The time course of the transient ventilatory response to a sudden change in Inspired gas from room air to 4% CO2 in air was examined in 11 healthy preterm neonates. Changes in minute ventilation (V1), tidal volume (VT), and respiratory frequency (f) were determined over 4 to 5 min of CO2 inhalation during both quiet (QS) and active sleep (AS) in each infant. In both states there was a brisk increase of mean V1 in response to 4% CO2, while mean VT increased more slowly and mean f only increased transiently at 1 to 2 min. Exponential curve fitting to the change in Vi and VT for each infant accounted for 64 ± 20% of the variance in Vi during QS as compared to 30 ± 18% during AS (p<0.003). In only six infants did exponential curves fitted to the changes in V1 and VT during QS reach 90% of their steady state values within 4 to 5 min of CO2 exposure. Their time to reach 90% of steady state was always shorter for V1 than VT (p<0.01). Frequency showed a biphasic response with a transient rise at 1 to 2 min (p<0.05) and return to control levels at steady state. These data indicate that not all preterm infants reach a new level of steady state ventilation within 4 to 5 min of 4% CO2 inhalation. Furthermore, many infants exhibit a biphasic response of f over time which causes V1 to reach steady state prior to VT.