Effect of aging on bolus kinematics during the pharyngeal phase of swallowing

Swallowing difficulty is a common complaint in the elderly and, although there are data for the biomechanics of liquid swallows, little is known about solid bolus motion, or kinematics, in the elderly. The aims of this study were as follows: 1) to characterize and compare solid and liquid bolus kinematics in the elderly and compare the findings with those in young subjects and 2) to correlate bolus kinematics and dynamics. Concurrent manometric-fluoroscopic techniques were used to study eight young and eight elderly subjects. The subjects performed four swallows each of 0.2-cm-diameter solid barium pellets and 5 ml of liquid barium during sagittal fluoroscopy and six-channel pharyngoesophageal manometry. Images were digitized for analysis of kinematic properties such as velocity and acceleration. Dynamic pressures were recorded and coordinated with kinematic events. Image analysis showed that velocity varied as the pellet passed through the hypopharynx, pharynx, and upper esophageal sphincter. In young subjects, pellet kinematics were characterized by two zones of pellet acceleration: one over the tongue base and another as the pellet passed through the upper esophageal sphincter. Although the elderly showed a similar zone of acceleration over the base of the tongue, the second zone of pellet acceleration was not seen. Decreasing pressure gradients immediately distal to the position of the solid pellet and liquid bolus characterized dynamics for all subjects. This decreasing pressure gradient was significantly larger in elderly than in young subjects. Bolus kinematics and dynamics were significantly altered among elderly compared with young subjects. Among these differences were the absence of hypopharyngeal bolus acceleration and a significant increase in the trans-sphincteric pressure gradient in the elderly.     

Changes in pharyngeal corticobulbar excitability and swallowing behavior after oral stimulation

Faucial pillar (FP) stimulation is commonly used in swallowing rehabilitation, yet its physiological basis remains uncertain. We investigated the effects of intraoral FP stimulation on human corticobulbar excitability and swallowing behavior, to explore the possibility of a central mechanism for functional change. In 10 healthy subjects, corticobulbar projections to pharynx were investigated with transcranial magnetic stimulation, via intraluminal electrodes, before and up to 1 h after 10 min of electrical FP stimulation with three frequencies (0.2, 1, and 5 Hz) or sham and peripheral (median nerve) stimulation. In a second study, swallowing behavior was assessed with videofluoroscopy before and after FP stimulation. FP stimulation at 5 Hz inhibited the corticobulbar projection (-14 +/- 6%, P < 0.02) and lengthened swallow response time (+114 +/- 24%, P = 0.02). By comparison, FP stimulation at 0.2 Hz facilitated this projection (+60 +/- 28%, P < 0.04), without enhancing swallowing behavior. Neither 1-Hz, sham, nor median nerve stimulation altered excitability. Thus changes in corticobulbar excitability to FP stimulation are frequency dependent with implications for the treatment for neurogenic swallowing dysfunction.     

Lung volume effects on pharyngeal swallowing physiology.

The experiment was a prospective, repeated-measures design intended to determine how the variation of lung volume affects specific measures of swallowing physiology. Swallows were recorded in 28 healthy subjects, who ranged in age from 21 to 40 yr (mean age of 29 yr), by using simultaneous videofluoroscopy, bipolar intramuscular electromyography, and respiratory inductance plethysmography. Each subject swallowed three standardized pudding-like consistency boluses at three randomized lung volumes: total lung capacity, functional residual capacity, and residual volume. The results showed that pharyngeal activity duration of deglutition for swallows produced at residual volume was significantly longer than those occurring at total lung capacity or at functional residual capacity. No significant differences were found for bolus transit time or intramuscular electromyography of the superior constrictor. The results of this experiment lend support to the hypothesis that the respiratory system may have a regulatory function related to swallowing and that positive subglottic air pressure may be important for swallowing integrity. Eventually, new treatment paradigms for oropharyngeal dysphagia that are based on respiratory physiology may be developed.     

The influence of chemical gustatory stimuli and oral anaesthesia on healthy human pharyngeal swallowing

This study explored the effects of taste and oral anaesthesia on human sequential swallowing. Subjects were healthy adults (n = 42, mean age 28 years, 21 females), investigated by means of a water swallow test. Taste stimuli comprised quinine, glucose, citrus and saline solutions compared with neutral water. Oral anaesthesia comprised topical lidocaine at doses of 10, 20 and 40 mg and compared with placebo. Data were collected on swallowing speed (volume per second), inter-swallow interval and swallowing capacity (volume per swallow). Compared with water, glucose, citrus and saline reduced swallowing speed (10.94 +/- 0.89 versus 9.56 +/- 0.79, 9.33 +/- 1.19, 9.37 +/- 0.92 ml/s respectively, P < 0.05). Inter-swallow interval was increased only by quinine and saline (1.47 +/- 1.11 versus 2.13 +/- 0.34 and 1.92 +/- 0.31 s, P < 0.04). Swallowing capacity was only marginally increased by quinine (P = 0.0759). Compared with the placebo, only 40 mg of lidocaine altered swallowing, immediately reducing the swallowing speed (7.89 +/- 2.34 versus 10.11 +/- 3.26 ml/s, P < 0.05) and increasing inter-swallow interval (1.67 +/- 0.38 versus 1.45 +/- 0.29 s, P < 0.01) without affecting capacity. By 15 min all measures except sensory thresholds had returned to baseline values. Thus, swallowing function is highly influenced by chemosensory input, providing insight into how oral sensation regulates pharyngeal swallowing.     

Laryngeal activity during upright vs. supine swallowing.

Previous investigations of human pharyngeal muscle activation patterns during swallowing found a relatively invariant muscle activation onset sequence in the upright position. However, different gravitational forces influence a liquid bolus when supine and could modify the central timing control of laryngeal airway protection during swallowing. The purpose of this study was to determine whether laryngeal muscle onset timing during swallowing differed between the supine and upright positions. Nine subjects performed six swallowing trials with a 2-ml water bolus in each position. Simultaneous electromyographic recordings were obtained from the submental complex (SMC) and the right and left thyroarytenoid (TA) muscles. Regardless of body position, the timing, amplitude, and duration of the TA muscles did not vary relative to the SMC. Therefore, the sequence of TA muscle activation relative to the SMC during swallowing appeared unaffected by gravitational influences.     

NMDA receptors in sensory information processing.

During the past year electrophysiological studies, particularly in the visual and somatosensory systems, have begun to uncover the specific roles played by NMDA receptors in the processing of sensory information. Many of the features of NMDA-receptor-mediated sensory responses reflect known properties of the receptor.     

Cortical swallowing processing in early subacute stroke

Background  

Dysphagia is a major complication in hemispheric as well as brainstem stroke patients causing aspiration pneumonia and increased mortality. Little is known about the recovery from dysphagia after stroke. The aim of the present study was to determine the different patterns of cortical swallowing processing in patients with hemispheric and brainstem stroke with and without dysphagia in the early subacute phase.     

The density of microflora in the oral and pharyngeal cavities.

A method for quantitative assessment of the microbial density on the mucous membranes in the oral and pharyngeal cavities is described. The results of the assessment are in agreement with the theoretical assumption based on the existence of a natural electrostatic filter. The highest density of microbes is on the tonsils where the positive pole of the filter is situated, so that a synergism between the defensive immunological role of the tonsils and the bioelectric potential pattern is obvious. The microbial densities in the oral cavity are more or less interdependent whereas the findings on the pharynx rear wall are isolated being probably perturbed by repeated swallowing.     

Temporal coordination of pharyngeal and laryngeal dynamics with breathing during swallowing: single liquid swallows.

The critical integration of timing and patterning between respiratory and swallowing events was studied with simultaneous videofluoroscopic and respiratory recording during single liquid swallows. Respiratory phase patterns and the onsets and durations of 12 predetermined swallowing events and associated respiratory activities were studied. Results showed four highly repeatable, temporally oriented sequences (clusters) of swallowing and related respiratory events. Two respiratory phase patterns were identified without statistically significant differences in frequency of occurrence between age, gender, or race. These findings will aid in the identification of normal and abnormal patterns of breathing and swallowing in patients with dysphagia.     

Bayesian inverse kinematics vs. least-squares inverse kinematics in estimates of planar postures and rotations in the absence of soft tissue artifact

A variety of inverse kinematics (IK) algorithms exist for estimating postures and displacements from a set of noisy marker positions, typically aiming to minimize IK errors by distributing errors amongst all markers in a least-squares (LS) sense. This paper describes how Bayesian inference can contrastingly be used to maximize the probability that a given stochastic kinematic model would produce the observed marker positions. We developed Bayesian IK for two planar IK applications: (1) kinematic chain posture estimates using an explicit forward kinematics model, and (2) rigid body rotation estimates using implicit kinematic modeling through marker displacements. We then tested and compared Bayesian IK results to LS results in Monte Carlo simulations in which random marker error was introduced using Gaussian noise amplitudes ranging uniformly between 0.2 mm and 2.0 mm. Results showed that Bayesian IK was more accurate than LS-IK in over 92% of simulations, with the exception of one center-of-rotation coordinate planar rotation, for which Bayesian IK was more accurate in only 68% of simulations. Moreover, while LS errors increased with marker noise, Bayesian errors were comparatively unaffected by noise amplitude. Nevertheless, whereas the LS solutions required average computational durations of less than 0.5 s, average Bayesian IK durations ranged from 11.6 s for planar rotation to over 2000 s for kinematic chain postures. These results suggest that Bayesian IK can yield order-of-magnitude IK improvements for simple planar IK, but also that its computational demands may make it impractical for some applications.     

Central regulation of the pharyngeal and upper esophageal reflexes during swallowing in the Japanese eel

We investigated the regulation of the pharyngeal and upper esophageal reflexes during swallowing in eel. By retrograde tracing from the muscles, the motoneurons of the upper esophageal sphincter (UES) were located caudally within the mid-region of the glossopharyngeal-vagal motor complex (mGVC). In contrast, the motoneurons innervating the pharyngeal wall were localized medially within mGVC. Sensory pharyngeal fibers in the vagal nerve terminated in the caudal region of the viscerosensory column (cVSC). Using the isolated brain, we recorded 51 spontaneously active neurons within mGVC. These neurons could be divided into rhythmically (n = 8) and continuously (n = 43) firing units. The rhythmically firing neurons seemed to be restricted medially, whereas the continuously firing neurons were found caudally within mGVC. The rhythmically firing neurons were activated by the stimulation of the cVSC. In contrast, the stimulation of the cVSC inhibited firing of most, but not all the continuously firing neurons. The inhibitory effect was blocked by prazosin in 17 out of 38 neurons. Yohimbine also blocked the cVSC-induced inhibition in five of prazosin-sensitive neurons. We suggest that the neurons in cVSC inhibit the continuously firing motoneurons to relax the UES and stimulate the rhythmically firing neurons to constrict the pharynx simultaneously.     

Patterns of esophageal inhibition during swallowing,pharyngeal stimulation,and transient LES relaxation. Lower esophageal sphincter

Lower esophageal sphincter (LES) relaxation and esophageal body inhibition co-occur during esophageal peristalsis but not necessarily during pharyngeal stimulation or transient LES relaxation (tLESR). This study examined these relationships and the impact on reflux. Nine young volunteers were studied. An artificial high-pressure zone (HPZ) was established, and pH was recorded 8 and 5 cm proximal to the LES. Pharyngeal stimulation was by water injection and gastric distension with liquid or gas. Peristalsis, pharyngeal stimulation, and spontaneous events were recorded. Swallowing relaxed the LES in 100% of trials (the HPZ in 80%) and caused no reflux. Pharyngeal stimulation relaxed the LES in two-thirds of trials, had no effect on the HPZ, and caused no reflux. Gastric distension was associated with 117 tLESRs, 48% with acid reflux, and 32% with gas reflux; there was no effect on the HPZ. We conclude that LES relaxation is a necessary but not sufficient condition for reflux. LES relaxation and esophageal body inhibition are independent events that may be concurrent (swallowing) or dissociated (tLESR).     

Assessment of intraluminal impedance for the detection of pharyngeal bolus flow during swallowing in healthy adults

Intraluminal impedance, a nonradiological method for assessing bolus flow within the gut, may be suitable for investigating pharyngeal disorders. This study evaluated an impedance technique for the detection of pharyngeal bolus flow during swallowing. Patterns of pharyngoesophageal pressure and impedance were simultaneously recorded with videofluoroscopy in 10 healthy volunteers during swallowing of liquid, semisolid, and solid boluses. The timing of bolus head and tail passage recorded by fluoroscopy was correlated with the timing of impedance drop and recovery at each recording site. Bolus swallowing produced a drop in impedance from baseline followed by a recovery to at least 50% of baseline. The timing of the pharyngeal and esophageal impedance drop correlated with the timing of the arrival of the bolus head. In the pharynx, the timing of impedance recovery was delayed relative to the timing of clearance of the bolus tail. In contrast, in the upper esophageal sphincter (UES) and proximal esophagus, the timing of impedance recovery correlated well with the timing of clearance of the bolus tail. Impedance-based estimates of pharyngoesophageal bolus clearance time correlated with true pharyngoesophageal bolus clearance time. Patterns of intraluminal impedance recorded in the pharynx during bolus swallowing are therefore more complex than those in the esophagus. During swallowing, mucosal contact between the tongue base and posterior pharyngeal wall prolongs the duration of pharyngeal impedance drop, leading to overestimation of bolus tail timing. Therefore, we conclude that intraluminal impedance measurement does not accurately reflect the bolus transit in the pharynx but does accurately reflect bolus transit across the UES and below.     

Tbx1 expression in pharyngeal epithelia is necessary for pharyngeal arch artery development

During embryonic life, the initially paired pharyngeal arch arteries (PAAs) follow a precisely orchestrated program of persistence and regression that leads to the formation of the mature aortic arch and great vessels. When this program fails, specific cardiovascular defects arise that may be life threatening or mild, according to the identity of the affected artery. Fourth PAA-derived cardiovascular defects occur commonly in DiGeorge syndrome and velocardiofacial syndrome (22q11DS), and in Tbx1(+/-) mice that model the 22q11DS cardiovascular phenotype. Tbx1 is expressed in pharyngeal mesoderm, endoderm and ectoderm, and, in addition, we show that it is expressed in precursors of the endothelial cells that line the PAAs, thus expanding the number of tissues in which Tbx1 is potentially required for fourth PAA development. In this study, we have used cell fate mapping and tissue-specific gene deletion, driven by six different Cre lines, to explore Tbx1 gene-dosage requirements in the embryonic pharynx for fourth PAA development. Through this approach, we have resolved the spatial requirements for Tbx1 in this process, and we show pharyngeal epithelia to be a critical tissue. We also thereby demonstrate conclusively that the role of Tbx1 in fourth PAA development is cell non-autonomous.     

Role of physical bolus properties as sensory inputs in the trigger of swallowing

Background

Swallowing is triggered when a food bolus being prepared by mastication has reached a defined state. However, although this view is consensual and well supported, the physical properties of the swallowable bolus have been under-researched. We tested the hypothesis that measuring bolus physical changes during the masticatory sequence to deglutition would reveal the bolus properties potentially involved in swallowing initiation.

Methods

Twenty normo-dentate young adults were instructed to chew portions of cereal and spit out the boluses at different times in the masticatory sequence. The mechanical properties of the collected boluses were measured by a texture profile analysis test currently used in food science. The median particle size of the boluses was evaluated by sieving. In a simultaneous sensory study, twenty-five other subjects expressed their perception of bolus texture dominating at any mastication time.

Findings

Several physical changes appeared in the food bolus as it was formed during mastication: (1) in rheological terms, bolus hardness rapidly decreased as the masticatory sequence progressed, (2) by contrast, adhesiveness, springiness and cohesiveness regularly increased until the time of swallowing, (3) median particle size, indicating the bolus particle size distribution, decreased mostly during the first third of the masticatory sequence, (4) except for hardness, the rheological changes still appeared in the boluses collected just before swallowing, and (5) physical changes occurred, with sensory stickiness being described by the subjects as a dominant perception of the bolus at the end of mastication.

Conclusions

Although these physical and sensory changes progressed in the course of mastication, those observed just before swallowing seem to be involved in swallowing initiation. They can be considered as strong candidates for sensory inputs from the bolus that are probably crucially involved in the triggering of swallowing, since they appeared in boluses prepared in various mastication strategies by different subjects.     

Respiration during feeding on solid food: alterations in breathing during mastication, pharyngeal bolus aggregation, and swallowing.

During feeding, solid food is chewed and propelled to the oropharynx, where the bolus gradually aggregates while the larynx remains open and breathing continues. The aggregated bolus in the valleculae is exposed to respiratory airflow, yet aspiration is rare in healthy individuals. The mechanism for preventing aspiration during bolus aggregation is unclear. One possibility is that alterations in the pattern of respiration during feeding could help prevent inhalation of food from the pharynx. We hypothesized that respiration was inhibited during bolus aggregation in the valleculae. Videofluorography was performed on 10 healthy volunteers eating solid foods with barium. Respiration was monitored concurrently with plethysmography and nasal air pressure. The timing of events during mastication, food transport, pharyngeal bolus aggregation, and swallowing were measured in relation to respiration. Respiratory cycle duration decreased during chewing (P < 0.001) but increased with swallowing (P < 0.001). During 66 recordings of vallecular bolus aggregation, there was inspiration in 8%, expiration in 41%, a pause in breathing in 17%, and multiple phases (including inspiration) in 35%. Out of 98 swallows, 47% started in the expiratory phase and 50% started during a pause in breathing, irrespective of bolus aggregation in the valleculae. Plethysmography was better than nasal manometry for determining the end of active expiration during feeding and swallowing with solid food. The hypothesis is rejected in that respiration was not inhibited during bolus aggregation. These findings suggest that airflow through the pharynx does not have a role in preventing aspiration during bolus aggregation in the oropharynx.     

Two distinct modulatory effects on calcium channels in adult rat sensory neurons.

D-ala2-D-leu5-enkephalin (100 to 1000 nM) reduces HVA Ca2+ currents of approximately 60% in 92% of the adult rat sensory neurons tested. In 80% of the cells sensitive to enkephalin, the reduction in Ca2+ current amplitude was associated with a prolongation of the current activation that was relieved by means of conditioning pulses in a potential range only about 10 mV positive to the current activation range in control conditions. The time course of the current activation was fitted to a single exponential in control, (tau = 2.23 msec +/- 0.14 n = 38) and double exponential with enkephalin, (tau 1 = 2.18 msec +/- 0.25 and tau 2 = 9.6 msec +/- 1, test pulse to -10 mV, 22 degrees C). A strong conditioning depolarizing prepulse speeded up the activation time course, completely eliminating the slow, voltage-sensitive exponential component, but it was only partial effective in restoring the current amplitude to control values. The voltage-independent inhibitory component that was not relieved could be recovered only by washing out enkephalin. In the remaining 20% of the cells affected, enkephalin decreased Ca2+ current amplitude without prolongation of Ca2+ channel activation. In these cases the conditioning voltage pulse was not effective in relieving the inhibition that persisted also at strong positive test potentials, on the outward currents. The voltage-dependent inhibition occurred slowly after enkephalin superfusion (tau congruent to 12 sec), whereas the voltage-independent one developed about ten times more rapidly. Dopamine (100 microM) could also induce both voltage-dependent and independent modulations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adaptation in sexuals vs. asexuals: clonal interference and the Fisher-Muller model

Fisher and Muller's theory that recombination speeds adaptation by eliminating competition among beneficial mutations has proved a popular explanation for the advantage of sex. Recent theoretical studies have attempted to quantify the speed of adaptation under the Fisher-Muller model, partly in an attempt to understand the role of "clonal interference" in microbial experimental evolution. We reexamine adaptation in sexuals vs. asexuals, using a model of DNA sequence evolution. In this model, a modest number of sites can mutate to beneficial alleles and the fitness effects of these mutations are unequal. We study (1) transition probabilities to different beneficial mutations; (2) waiting times to the first and the last substitutions of beneficial mutations; and (3) trajectories of mean fitness through time. We find that some of these statistics are surprisingly similar between sexuals and asexuals. These results highlight the importance of the choice of substitution model in assessing the Fisher-Muller advantage of sex.