1. Relationships between the timing of respiration and deglutition were studied in thirty awake healthy subjects at rest. Deglutition was monitored by submental electromyography, pharyngeal manometry and videofluoroscopy. Respiration was recorded by measurement of oronasal airflow and chest wall movement. Three types of deglutition were studied: injected bolus swallows, spontaneous swallows, and visually cued swallows of boluses previously placed in the mouth. 2. The effect of each swallow on respiratory rhythm was characterized by measurement of cophase, defined as the interval between the onset of deglutitive submental EMG activity to the onset of subsequent rescheduled inspirations. Cophase was determined for swallows initiated at different phases of the respiratory cycle. In all subjects deglutition caused phase resetting of respiratory rhythm. Cophase was largest for swallows initiated near the inspiratory-expiratory (I-E) transition and smallest for swallows initiated near the expiratory-inspiratory (E-I) transition. The pattern of respiratory resetting by deglutition was topologically classified as type 0. This pattern was shown for swallows induced by bolus injection or visual cue, and for spontaneous swallows. 3. The incidence of spontaneous deglutition was influenced by the position of the swallow in the respiratory cycle. Few spontaneous swallows were initiated near the E-I transition whereas most occurred from late inspiration to mid-expiration. 4. Deglutition caused an abrupt decrease in airflow leading to an interval of apnoea, followed by a period of expiration. The duration of deglutition apnoea for spontaneous swallows was shorter than that for 5 ml bolus swallows, and was unaffected by the respiratory phase of swallow initiation. The period of expiration after swallowing was longest for swallows initiated at the I-E transition, and shortest for E-I swallows. 5. The intervals between bolus injection and the onset of deglutition apnoea, and the timing of swallowing events, were not significantly altered by the phase in the respiratory cycle at which swallowing was exhibited. 6. To quantify the relationship between bolus flow and respiration, we determined the latencies between cessation of inspiratory airflow and arrival of the bolus at the larynx (a.), and between laryngeal bolus departure and resumption of inspiratory airflow (a). Both values were dependent upon the respiratory phase of swallowing. The lowest values for a and a were found for early-inspiratory and late-expiratory swallows, respectively. 7. We conclude that swallowing causes respiratory phase resetting with a pattern that is characteristic of the strong perturbations of an attractor-cycle oscillator. The threshold for initiation of swallowing in awake subjects is influenced by, but not strongly coupled to, the phase of respiration. We propose that respiratory timing, in addition to anatomical barriers within the upper airway, influences the vulnerability for aspiration during deglutition. Swallows initiated near the E-I transiti...

During swallowing, the airway is protected from aspiration of ingested material by brief closure of the larynx and cessation of breathing. Mechanoreceptors innervated by the internal branch of the superior laryngeal nerve (ISLN) are activated by swallowing, and connect to central neurones that generate swallowing, laryngeal closure and respiratory rhythm. This study was designed to evaluate the hypothesis that the ISLN afferent signal is necessary for normal deglutition and airway protection in humans. In 21 healthy adults, we recorded submental electromyograms, videofluoroscopic images of the upper airway, oronasal airflow and respiratory inductance plethysmography. In six subjects we also recorded pressures in the hypopharynx and upper oesophagus. We analysed swallows that followed a brief infusion (4–5 ml) of liquid barium onto the tongue, or a sip (1–18 ml) from a cup. In 16 subjects, the ISLN was anaesthetised by transcutaneous injection of bupivacaine into the paraglottic compartment. Saline injections using the identical procedure were performed in six subjects. Endoscopy was used to evaluate upper airway anatomy, to confirm ISLN anaesthesia, and to visualise vocal cord movement and laryngeal closure. Comparisons of swallowing and breathing were made within subjects (anaesthetic or saline injection vs. control, i.e. no injection) and between subjects (anaesthetic injection vs. saline injection). In the non‐anaesthetised condition (saline injection, 174 swallows in six subjects; no injection, 522 swallows in 20 subjects), laryngeal penetration during swallowing was rare (1.4 %) and tracheal aspiration was never observed. During ISLN anaesthesia (16 subjects, 396 swallows), all subjects experienced effortful swallowing and an illusory globus sensation in the throat, and 15 subjects exhibited penetration of fluid into the larynx during swallowing. The incidence of laryngeal penetration in the anaesthetised condition was 43 % (P < 0.01, compared with either saline or no injection) and of these penetrations, 56 % led to tracheal aspiration (without adverse effects). We further analysed the swallow cycle to evaluate the mechanism(s) by which fluid entered the larynx. Laryngeal penetration was not caused by premature spillage of oral fluid into the hypopharynx, delayed clearance of fluid from the hypopharynx, or excessive hypopharyngeal pressure generated by swallowing. Furthermore, there was no impairment in the ability of swallowing to halt respiratory airflow during the period of pharyngeal bolus flow. Rather, our observations suggest that loss of airway protection was due to incomplete closure of the larynx during the pharyngeal phase of swallowing. In contrast to the insufficient closure during swallowing, laryngeal closure was robust during voluntary challenges with the Valsalva, Müller and cough manoeuvres under ISLN anaesthesia. We suggest that an afferent signal arising from the ISLN receptor field is necessary for normal deglutition, especially for providing feedback to central neural circuits that faci...

Neuronal oscillators can function as bistable toggle switches, flipping between quiescence and rhythmic firing in response to an input stimulus. In theory, such switching should be sensitive to small noisy inputs if the bistable states are in close proximity, which we test here using a perfused squid axon preparation. We find that small noisy stimulus currents induce a multitude of paths between two nearby stable states: repetitive firing and quiescence. The pattern of on-off switching of the pacemaker depends on the intensity, spectral properties, and phase angle of stimulus current fluctuations. Analysis by spike-triggered averaging of the stimulus currents near the transitions reveals that sinusoidal stimuli timed antiphase or in phase with repetitive firing correlates with switching of the pacemaker off or on, respectively. Our results reveal a distinct form of bistability in which noise can either silence pacemaker activity, trigger repetitive firing, or induce sporadic burst patterns similar to those recorded in a variety of normal and pathological neurons.

Breathing patterns in preterm infants consist of highly variable interbreath intervals (IBIs) that might originate from nonlinear properties of the respiratory oscillator and its input-output responses to peripheral and central signals. Here, we explore a property of nonlinear control, the potential for large improvement in the stability of breathing using low-level exogenous stochastic stimulation. Stimulation was administered to 10 preterm infants (postconceptional age: mean 33.3 wk, SD 1.7) using a mattress with embedded actuators that delivered small stochastic displacements (0.021 mm root mean square, 0.090 mm maximum, 30-60 Hz); this stimulus was subthreshold for causing arousal from sleep to wakefulness or other detectable changes in the behavioral state evaluated with polysomnography. We used a test-retest protocol with multiple 10-min intervals of stimulation, each paired with 10-min intervals of no stimulation. Stimulation induced an approximately 50% reduction (P = 0.003) in the variance of IBIs and an approximately 50% reduction (P = 0.002) in the incidence of IBIs > 5 s. The improved stability of eupneic breathing was associated with an approximately 65% reduction (P = 0.04) in the duration of O(2) desaturation. Our findings suggest that nonlinear properties of the immature respiratory control system can be harnessed using afferent stimuli to stabilize eupneic breathing, thereby potentially reducing the incidence of apnea and hypoxia.