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Biomedical subjects

J A Daubenspeck

Publications and source records attributed to J A Daubenspeck.

At least 19 recordsLinked to original sources

Modulation of breathing using imperceptible unloading.

We investigated the role of V(T) and V(T)/T(I) modulation of breathing in awake human subjects. We applied a PRBS of volume (incrementing ramp) or flow (decrementing wave) assist at levels below the perceptual threshold in order to stimulate respiratory feedback. We modeled the PRBS data with linear difference equations to obtain impulse-response profiles of V(T), V(T)/T(I), T(I) and factorial(P(MUS)). We limited cortical responses to our stimuli by applying sub-threshold levels of assist, and we limited humoral effects (O2 and CO2) by augmenting mechanical respiratory output intermittently and by small amounts. We found that flow or volume assist elicited similar significant increases in V(T) and V(T)/T(I). During flow assist there was a significant decrease in factorial(P(MUS)) and T(I) was reduced, albeit not significantly; however, volume assist did not modify T(I) or factorial(P(MUS)). The earlier onset of flow assist, relative to volume assist, may explain the difference between the responses. We conclude that vagally mediated inspiratory flow receptors in the chest wall or lungs may modulate breathing on a breath by breath basis when small, imperceptible increases in airflow occur early during inspiration. Furthermore, lung volume feedback during imperceptible unloading (occurring at the end of inspiration) was less effective. Finally, pseudorandom unloading with imperceptible stimuli provides a useful tool to study reflex regulation of ventilation in awake subjects without confounding cortical influences.

Adult↗

Midlatency respiratory-related somatosensory activity and perception of oral pressure pulses in normal humans.

A direct relationship exists within subjects between midlatency features (<100 ms poststimulus) of respiratory-related evoked potentials and the perceived magnitude of applied oral pressure pulse stimuli. We evaluated perception in 18 normal subjects using cross-modality matching of applied pressure pulses via grip force and estimated mechanoafferent activity in these subjects by computing the global field power (GFP) from respiratory-related evoked potentials recorded over the right side of the scalp. We compared across subjects 1) the predicted magnitude production for a standard pressure pulse and 2) the slope (beta) and 3) the intercept (INT) of the Stevens power law to the summed GFP over 20-100 ms poststimulus. Both the magnitude production for a standard pressure pulse and the beta showed an inverse relationship with the summed GFP over 20-100 ms poststimulus, although there was no relationship between INT and the summed GFP. This may partially reflect characteristics of the mechanosensors and surely includes aspects of cognitive judgment, because we found and corrected for a high correlation between, respectively, beta (and INT) for pressure pulses and beta (and INT) for estimation of line lengths, a nonrespiratory modality. The relatively shallow, even inverse GFP-to-perception relationship suggests that, despite marked differences in the magnitude of afferent traffic, normal subjects seem to perceive things similarly.

Algorithms↗

Identification of respiratory vagal feedback in awake normal subjects using pseudorandom unloading.

Evidence of the Hering-Breuer reflex has been found in humans during anesthesia and sleep but not during wakefulness. Cortical influences, present during wakefulness, may mask the effects of this reflex in awake humans. We hypothesized that, if lung volume were increased in awake subjects unaware of the stimulus, vagal feedback would modulate breathing on a breath-to-breath basis. To test this hypothesis, we employed proportional assist ventilation in a pseudorandom sequence to unload the respiratory system above and below the perceptual threshold in 17 normal subjects. Tidal volume, integrated respiratory muscle pressure per breath, and inspiratory time were recorded. Both sub- and suprathreshold stimulation evoked a significant increase in tidal volume and inspiratory flow rate, but a significant decrease in inspiratory time was present only during the application of a subthreshold stimulus. We conclude that vagal feedback modulates respiratory timing on a breath-by-breath basis in awake humans, as long as there is no awareness of the stimulus.

Adult↗

Acute hypoxia activates human 8-12 Hz physiological tremor.

Hypoxia causes arousal. Therefore, we hypothesized that hypoxia activates the human somatomotor system and should augment tremor. We determined the effects of hypoxia, PET(O2) = 45+/-2.2 mm Hg, hypocapnia, and the hypocapnic-hypoxic interaction on finger tremor during elastic loading. A total of 12 healthy male volunteers were studied during five conditions: eupnea, hypocapnic hypoxia, eucapnic hypoxia, hypocapnic normoxia, and eucapnic normoxia. Acceleration power spectra were computed to quantify 8-12 Hz tremor. Hypoxia significantly augmented 8-12 Hz physiological tremor (P=0.002). Furthermore, six subjects (50%) exhibited significantly more tremor during hypocapnic hypoxia (hH) than during eucapnic hypoxia (eH). We conclude that acute hypoxia augments 8-12 Hz physiological tremor, and hypocapnia further augments this tremor in some subjects. As such, hypoxic tremor is activated physiological tremor, and entrainment of spinal alpha-motoneuron activity may be the final common pathway.

Acute Disease↗

Respiratory related evoked responses to graduated pressure pulses using wavelet transform methods.

In this study, the respiratory related evoked responses (RREPs) from ten normal subjects in response to brief varying pressure pulses at -6, - 10 and - 17 cm H2O with a duration of 200 ms were recorded to investigate how midlatency cortical evoked potentials measured on the scalp are affected in response to pressure pulses of varying magnitude at the mouth. Wavelet decomposition was performed for eight frequency scales in time for the RREPs. The RREPs at each wavelet scale were enhanced by eliminating the wavelet coefficients due to the artifacts and noise. After denoising, the third (125-250 Hz), fourth (62.5-125 Hz), fifth (31.25-62.5 Hz) and sixth (15.62-31.25 Hz) wavelet scales were quantified using the global field power estimates which serve to reduce the contamination by facial electromyogram responses evoked by the pressure stimulus. Our results show that the estimates of the global field power (GFP) at the third, fourth and fifth wavelet scales between 25 and 100 ms poststimulus were significantly increased when the pressure pulse was increased from -6 to -17cm H2O. On average, the total GFP from all scales, summed over the period 30-90 ms poststimulus, doubled from baseline with the -6 cm H2O stimulus, and increased linearly by 40% between -6 and -17 H2O. This supports the use of the GFP as an index of respiratory mechanoreceptor input to the central nervous system.

Biomedical Engineering↗

Global field power helps separate respiratory-related evoked potentials from EMG contamination.

Respiratory-related evoked potentials (RREPs) were stimulated by brief (200-ms) oral pressure pulses (-10 cmH(2)O) applied at the onset of inspiration in 12 subjects. Scalp potentials were measured at 30 sites on a rectangular grid that encompassed the right side of the scalp overlying the somatosensory cortex (SSC). Concurrent and significant masseter EMG (mEMG) activity was evoked by the pressure pulse, and we found correlational evidence for contamination of the RREP by the mEMG. The global field power (GFP) was used to provide a robust, reference-independent measure of SSC activation that provided partial insulation from mEMG contamination. The mean GFP from all subjects, reflective of afferent information from respiratory mechanoreceptors, showed a latency to onset of significant afferent SSC activity of approximately 25 ms. Scalp GFP activity during control experiments (absence of applied pressure) was significant and may reflect ongoing afferent activity from inspiration.

Adolescent↗

Contribution of supraglottal mechanoreceptor afferents to respiratory-related evoked potentials in humans.

We used the global field power (GFP) to estimate the magnitude and timing of activation of the somatosensory cortex by respiratory mechanoreceptor afferents in normal humans in response to brief, negative oral pressure pulses applied at the onset of inspiration. We compared responses before (test) and after insertion of a laryngeal mask airway (LMA) that prevented supraglottal airway receptors from sensing the applied stimulus. Evoked potential responses without supraglottic stimulation were smaller, with delayed or missing features, than those with all receptors stimulated. Supraglottic receptors contribute about one-half of the GFP summed over the 100 ms poststimulus, and subglottal receptors, including those in the larynx, provide a GFP response approximately 38% above baseline. The most obvious difference between test and LMA responses occurred at 55 ms on average, when the LMA GFP lacked activation features seen in the test condition. We conclude that mechanoreceptors above the larynx are responsible for a major portion of the midlatency afferent information arriving at the somatosensory cortex in response to applied pressure pulses.

Adult↗

Vagal feedback in the entrainment of respiration to mechanical ventilation in sleeping humans.

We studied the capacity of four "normal" and six lung transplant subjects to entrain neural respiratory activity to mechanical ventilation. Two transplant subjects were studied during wakefulness and demonstrated entrainment indistinguishable from that of normal awake subjects. We studied four normal subjects and four lung transplant subjects during non-rapid eye movement (NREM) sleep. Normal subjects entrained to mechanical ventilation over a range of ventilator frequencies that were within +/-3-5 breaths of the spontaneous respiratory rate of each subject. After lung transplantation, during which the vagi were cut, subjects did demonstrate entrainment during NREM sleep; however, entrainment only occurred at ventilator frequencies at or above each subject's spontaneous respiratory rate, and entrainment was less effective. We conclude that there is no absolute requirement for vagal feedback to induce entrainment in subjects, which is in striking contrast to anesthetized animals in which vagotomy uniformly abolishes entrainment. On the other hand, vagal feedback clearly enhances the fidelity of entrainment and extends the range of mechanical frequencies over which entrainment can occur.

Adult↗

Investigating the contamination of electroencephalograms by facial muscle electromyographic activity using matching pursuit.

It has been widely recognized and previously reported that electrical fields from facial muscle electromyographic (EMG) activity can contaminate the electroencephalogram (EEG), even when closely spaced, bipolar electrode configurations are used (personal observations). We suspected that EEG signals evoked in response to pressure changes in the upper airway may include EMG contamination subsequent to muscle reflexes triggered by the stimuli. We evaluated the potential contamination of the background EEG by voluntary activation of a facial muscle by obtaining simultaneous recordings in human subjects of the EEG (from Cz-C4) and masseter muscle EMG (from a bipolar surface electrode pair) before (quiet) and after voluntary tensing (VTen). Matching pursuit analysis permitted identification of different time-frequency patterns for each signal during the quiet period because the EMG signal has mostly atoms above 30 Hz compared to the EEG signal. However, the EEG showed periods of low-frequency activity unmatched in the EMG TF pattern below 30 Hz. During the tensing, most of the atoms of both the EEG and EMG shifted to the higher frequency regions above 100 Hz, making the separation difficult. These results further suggest that the matching pursuit method may not separate the background EEG from phasic EMG signals, both of which are nonstationary in nature.

Artifacts↗

Effect of perception of mechanical loading on human respiratory pattern regulation.

We applied external flow resistive (R) and elastic (E) mechanical loads over the entire respiratory cycle to five normal subjects by using a pseudorandom loading protocol. Loads ranged in magnitude from imperceptible (R0/E0) through just perceptible (R1/E1) to large (R2/E2) and resulted in respiratory pattern responses that were due to reflex responses alone (R0/E0) or to a combination of reflex responses and behavioral reactions to the perception of impeded breathing (R1/E1 and R2/E2). Pattern regulation dynamics were estimated from the computed impulse responses of tidal volume and inspiratory and expiratory durations. We anticipated that emergence of behavioral contributions would be marked by increased variability in response strategies and by increased nonlinearity in the observed responses. Regarding the immediate pattern response to loading, there was a tendency for increased qualitative variation across subjects as the load size increased, but the within-subject variability (coefficient of variation) was unaffected. We found no evidence for increased nonlinearity as loads became perceptible. The emergence of behavioral control in some instances seemed to be marked by reduction of complexity of the impulse response to one dominated by the zeroth-order lag, leading to dynamically simpler responses compared to control.

Adult↗

Early and late respiratory-related cortical potentials evoked by pressure pulse stimuli in humans.

Although respiratory-related cortical evoked potentials (CEPs) have been obtained in humans, early-latency responses have been obtained only with direct electrical stimulation of respiratory afferents. We have recorded both early and late cortical activity in response to a relatively novel stimulus consisting of a 300-ms negative pressure pulse applied to the mouth near the start of selected inspirations, when mouth pressure attained a predetermined threshold. This stimulus caused highly reproducible and rapid changes in mouth pressure and was effective in eliciting CEPs to a wide range of applied pressures. Using pulses of approximately -2 to -25 cmH2O, we obtained an early positive component with a mean latency of approximately 20 ms and a subsequent negative component at approximately 30 ms in normal subjects. Peak-to-peak amplitude varied directly, and component latencies inversely, as a function of pulse magnitude. Using -5- to -10-cmH2O stimuli, we also measured a later positive-negative-positive response with mean component latencies of 96.7 +/- 15.1, 147 +/- 14.8, and 237.6 +/- 23.5 ms, respectively. The early-latency activity was resistant to manipulations of stimulus predictability, whereas the later waves were attenuated or disappeared when load presentation was made completely predictable. We validated our method by eliminating the possibility of tactile stimulation of the lips and teeth as the origin of the evoked responses. We propose that early-latency activity derives from precortical structures and may provide a window on the functioning of respiratory afferents in normal subjects and in patients with respiratory disease.

Adult↗

Immediate diaphragmatic electromyogram responses to imperceptible mechanical loads in conscious humans.

We used an esophageal electrode to measure the amplitude and neural inspiratory and expiratory (N TE) timing responses of crural diaphragmatic electrical activity in response to flow-resistive (R) and elastic (E) loads at or below the threshold for conscious detection, applied pseudorandomly to the oral airway of eight normal subjects. We observed a rapid first-breath neural reflex that modified respiratory timing such that N TE lengthened significantly in response to R loads in six of eight subjects and shortened in response to E loading in six of seven subjects. The prolongation of N TE with R loading resulted primarily from lengthening the portion of N TE during which phasic activity in the diaphragm is absent (TE NDIA), whereas E loading shortened N TE mainly by reducing TE NDIA. Most subjects responded to both types of loading by decreasing mean tonic diaphragmatic activity, the average level of muscle activity that exists when no phasic changes are occurring, as well as its variability. The observed timing responses are consistent in direction with optimally adaptive pattern regulation, whereas the modulation of tonic activity may be useful in neural regulation of end-expiratory lung volume.

Adult↗

Time course of laryngeal aperture response to expiratory resistance loading in humans.

Expiratory laryngeal restriction in normal humans is augmented immediately following expiratory flow resistance loading applied to the mouth. The time course of this increased narrowing reflects the dynamics of the physiological stimuli that govern laryngeal control during expiration. Lung volume, expiratory airflow and upper airway pressure are possible factors influencing the larynx, and a comparison of their dynamics with those observed for laryngeal narrowing during control and loaded expirations ought to indicate the possible contribution of each source. We examined the dynamics of lung volume, airflow and laryngeal aperture subsequent to single breath applications of small flow resistance loads (2 and 5 cm H2O.L-1.sec) in 3 subjects using video image analysis techniques to define accurately the laryngeal aperture variation with time. The earliest deviation of the loaded expired volume time course from the control trajectory lagged the earliest occurrence of a significant increase in laryngeal narrowing with the larger load. Augmented laryngeal narrowing occurred simultaneously with deviation of the expired flow from the control trajectory. The responses to the smaller load were noisier, but were consistent with the hypothesis that information other than lung volume modulates the early laryngeal response to these loads, and receptors responding to the rate of change of lung volume (airflow) and/or upper airway pressure may be involved.

Adult↗

Selective reflex activation of the genioglossus in humans.

In anesthetized or decerebrate animals, negative pressure applied to the upper airway selectively activates the hypoglossal nerve compared with the phrenic nerve. Conversely, positive pressure reduces hypoglossal nerve activity out of proportion to any change in the phrenic neurogram. We have tested the hypothesis that analogous pressure changes applied to awake humans would selectively inhibit or activate genioglossal electromyographic (EMGge) activity relative to diaphragmatic electromyographic activity (EMGdi). We studied seven normal subjects in a head-out body plethysmograph. Pressure at the mouth was either atmospheric, +10 cmH2O, or -10 cmH2O, and lung volume was held constant by applying an identical pressure to the body surface. Thus the transmural pressure distorting the respiratory system was applied only to the upper airway. Subjects breathed CO2-enriched (2-3%) room air to stimulate phasic respiratory EMGge activity. We found that -10 cmH2O pressure applied selectively to the upper airway resulted in a 49% enhancement of peak-integrated EMGge activity, but EMGdi activity remained at control levels. Positive pressure did not result in any changes in EMGge or EMGdi activity. Neither pressure resulted in significant changes in the magnitude or pattern of ventilation. We conclude that reflex mechanisms maintaining upper airway patency are demonstrable in awake humans and probably have an important role in moment-to-moment modulation of upper airway muscle activity in normal awake humans.

Adolescent↗

Targeted inspiratory muscle training improves respiratory muscle function and reduces dyspnea in patients with chronic obstructive pulmonary disease.

STUDY OBJECTIVE: To examine the effects of targeted inspiratory muscle training on respiratory muscle function, clinical ratings of dyspnea, and perception of resistive loads in symptomatic patients with chronic obstructive pulmonary disease. DESIGN: Randomized, placebo-controlled trial with an 8-week treatment period. SETTING: Outpatient pulmonary clinic and pulmonary function laboratory. PARTICIPANTS: We studied 19 patients with moderate to severe chronic obstructive pulmonary disease, assigning 10 patients to an experimental group and 9 to a control group. INTERVENTIONS: Patients in both groups trained for 15 minutes twice each day using a device that provided breath-to-breath visual feedback of training intensity. Patients in the experimental group trained at six increasing levels of inspiratory resistance, whereas the patients in the control group trained at a constant, nominal level of resistance. MEASUREMENTS AND RESULTS: Although there was no statistically discernible difference in the effects of targeted muscle training on the mean difference in maximal inspiratory pressures between the two groups (9.83 cm H2O; 95% CI, -7.37 to 27.03), patients in the experimental group did show a significant increase in inspiratory muscle strength (15.03 cm H2O; P = 0.01). Experimental subjects also had decreased dyspnea after 8 weeks of training compared with control subjects (P = 0.003). Improvements in physiologic values and in dyspnea ratings were correlated. The perception of added resistive loads was not affected by inspiratory muscle training. CONCLUSIONS: Targeted inspiratory muscle training may enhance respiratory muscle function and reduce dyspnea in symptomatic patients with moderate to severe chronic obstructive pulmonary disease.

Aged↗

Human breathing pattern responses to loading with increased background impedance.

We determined the influence of the background level of mechanical impedance on the respiratory responses to very small mechanical loads, at or below the threshold for conscious perception. We used a pseudorandom load application technique to estimate the immediate pattern responses from the zeroth lag of the cross correlation between the load application sequence and the respiratory pattern components of tidal volume (VT), inspiratory and expiratory time (TI and TE), and the instantaneous respiratory frequency (f), minute ventilation (VI), and mean inspiratory flow (VT/TI). Elevation of the background resistance served to reduce the TI and TE responses to small perturbations in resistance from those in the control background state, which resulted in generally smaller perturbations of f, VI, and VT/TI. Elevation of the background elastance, however, served to initiate a TI reduction not seen in the control state but did not appreciably affect the rest of the pattern responses to the load perturbations. Thus the neural reflexes involved in breath-by-breath pattern regulation are modulated by the background level of the respiratory impedance, as well as by the type and size of the load perturbation.

Adult↗

Diaphragmatic electromyography using a multiple electrode array.

We have developed a new technique for diaphragmatic electromyography using an array of seven sequential electrode pairs at 1.0-cm spacing on an esophageal catheter. This array provides information about the spatial distribution of the electrical field generated by the diaphragm and reveals a sharply peaked variation of electrical potential with distance along the esophagus. The rectified and integrated information from each of the seven pairs is summed to give an approximation to the total electrical activity over the span of the array, providing a signal that is relatively insensitive to the position of the array over approximately 4 cm of catheter movement and removes the requirement for balloon stabilization of the catheter. With our array, we have confirmed the artifact in the evoked compound muscle action potential that seems to be related to diaphragmatic shape as reported by others who used supramaximal phrenic nerve stimulation, but the magnitude of this artifact (compared with the functional residual capacity level) was modest near functional residual capacity, averaging 12 +/- 14% (SD) for lung volumes 1.0 l above and -4 +/- 15% for lung volumes 1.0 l below functional residual capacity along the rib cage-abdomen relaxation line.

Action Potentials↗