Aspiration removal of orbitofrontal cortex disrupts cholinergic fibers of passage to anterior cingulate cortex in rhesus macaques.

The study of anthropoid nonhuman primates has provided valuable insights into frontal cortex function in humans, as these primates share similar frontal anatomical subdivisions (Murray et al. 2011). Causal manipulation studies have been instrumental in advancing our understanding of this area. One puzzling finding is that macaques with bilateral aspiration removals of orbitofrontal cortex (OFC) are impaired on tests of cognitive flexibility and emotion regulation, whereas those with bilateral excitotoxic lesions of OFC are not (Rudebeck et al. 2013). This discrepancy is attributed to the inadvertent disruption of fibers of passage by aspiration lesions but not by excitotoxic lesions. Which fibers of passage are responsible for the impairments observed? One candidate is cholinergic fibers originating in the nucleus basalis magnocellularis (NBM) and passing nearby or through OFC on their way to other frontal cortex regions (Kitt et al. 1987). To investigate this possibility, we performed unilateral aspiration lesions of OFC in three macaques, and then compared cholinergic innervation of the anterior cingulate cortex (ACC) between hemispheres. Histological assessment revealed diminished cholinergic innervation in the ACC of hemispheres with OFC lesions relative to intact hemispheres. This finding indicates that aspiration lesions of the OFC disrupt cholinergic fibers of passage, and suggests the possibility that loss of cholinergic inputs to ACC contributes to the impairments in cognitive flexibility and emotion regulation observed after aspiration but not excitotoxic lesions of OFC.

Autobiographical memory and daily schemas at work.

This exploratory study examines how daily schemas for work activities influence retrospective memory. Twelve subjects were asked to describe their 'typical day' at work, and to recall their work activities of yesterday and of the same day a week ago. The number of basic activities occurring in each description was counted, and the number of basic activities occurring in the typical day description was viewed as an index of the degree of elaboration of the schema. There were three major findings. First, people recalled fewer activities from last week than they did from yesterday, and those activities that were recalled from last week tended to be those that were in the daily schema. Second, there was a tendency for people with highly elaborated daily schemas to recall more activities from last week than people with poorly elaborated schemas. And third, there were more schematic references in the recalls from last week than in those from yesterday. Taken together, these findings indicate that there are strong schematic influences on the recall of activities from last week, but not on those from yesterday. The discussion points to a number of research issues, both applied and theoretical, which arise from this preliminary investigation of daily work schemas.

Persistence of enhanced aerosol deposition in the lung after recovery from carbachol-induced airway obstruction.

Time course recovery from induced airway obstruction by carbachol infusion (CI; 0.2 microgram.kg-1.min-1 for 40 min), carbachol aerosol (CA; 10 breaths of 2% solution), and histamine aerosol (HA; 25-50 breaths of 5% solution) challenge was investigated in conscious sheep (n = 6 each). Total lung aerosol deposition and airway caliber as assessed by pulmonary airflow resistance (RL) were measured every 20-30 min up to 4 h after the challenges. Aerosol deposition was measured by monitoring aerosol concentration continuously with a laser aerosol photometer while the sheep rebreathed 1.0-micron-diam inert oil droplets delivered by a 0.25-liter bag-in-box system driven by a respiratory pump at a breathing frequency of 30 breaths/min. Total accumulated deposition at the fifth breath (AD5) as percentage of the initial aerosol concentration was determined and used as an aerosol deposition index. Percent changes in AD5 from baseline were compared with corresponding changes in RL. Both RL and AD5 increased after Cl, CA, and HA: 192-477% for RL and 23-44% for AD5 (P less than 0.05). Mean RL return to baseline values 1 h after CI and HA and 2 h after CA. Mean AD5 returned to baseline at 1 h post-HA. In contrast, mean AD5 remained elevated for 2-4 h after CI and CA (P less than 0.05), and the increased AD5 could not be reversed by a bronchodilator aerosol. The persistence of enhanced aerosol deposition long after the return of RL to baseline suggests that complete recovery of airway conditions after CI and CA takes much longer than predicted by RL.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosol deposition in the lung with asymmetric airways obstruction: in vivo observation.

Both the total and regional aerosol deposition were measured in six adult sheep before and after an induction of asymmetric airway obstructions, either by local instillation of carbachol solution (CS, 0.1%) distal to the right main bronchus or inhalation challenge of the right lung with carbachol aerosol (CA, 10 breaths). Total lung deposition was determined by monitoring inert monodisperse aerosols [1.0 micron mass median aerodynamic diam (MMAD)] breath-by-breath, at the mouth, by means of a laser aerosol photometer. Cumulative aerosol deposition over the first five breaths as a percent of the initial aerosol concentration (AD5) was used as a deposition index. Regional deposition pattern was determined by scintigraphic images of sulfur-colloid aerosol (1.5 microns MMAD) tagged with 99mTc. Radioactivity counts in the right (R) and left lung (L) were expressed as a percent of the whole lung count. Half-lung AD5 was then determined by multiplying AD5 by fractional radioaerosol depositions in R or L. Pulmonary airflow resistance (RL mean +/- SE), as determined by an esophageal balloon technique, increased by 111 +/- 28 and 250 +/- 96% after CA and CS, respectively (P less than 0.05). AD5 also increased in all the sheep tested by 29 +/- 3 and 52 +/- 8%, respectively, after CA and CS (P less than 0.05). Radioaerosol deposition pattern was even at base line (R/L = 51:49) but shifted toward the unchallenged L after CS (R/L = 40:60). Deposition pattern after CA was variable: a shift toward L in three, no change in one, and a shift toward the R lung in two sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway responsiveness to inhaled and intravenous carbachol in sheep: effect of airway mucus.

Excessive airway mucus can alter both the mass and site of aerosol deposition, which, in turn, may affect airway responsiveness to inhaled materials. In six prone sheep, we therefore measured pulmonary airflow resistance (RL) and cumulative aerosol deposition during five standard breaths (AD5) at base line and 3 min after inhalation challenge with 2% carbachol in buffered saline (10 breaths, tidal volume = 500 ml) or after an intravenous loading dose of carbachol (3 micrograms/kg) followed by a constant infusion of 0.3 micrograms.kg-1.min-1 with and without instillation of 20 ml of a mucus simulant (MS) into the distal end of each of the main bronchi or 30 ml of MS into the right main bronchus only by means of a flexible fiber-optic bronchoscope. Before carbachol challenge, RL did not change with MS into either both lungs or one lung only. AD5 increased from 36 +/- 2% (SE) before to 42 +/- 2% after MS instillation into both lungs (P less than 0.05) but remained unchanged after MS into one lung. After carbachol inhalation, RL increased significantly by 154 +/- 20 before and 126 +/- 25% after MS into both lungs and 162 +/- 24 before and 178 +/- 31% after MS into one lung (P less than 0.05). When the percent increase in RL was normalized for total aerosol deposition (% delta RL/AD5), the normalized values were lower after MS (3.0 +/- 0.5) than before MS (4.4 +/- 0.3) into both lungs (P less than 0.05) but were not significantly different before and after MS into the right lung only.(ABSTRACT TRUNCATED AT 250 WORDS)

Oropharyngeal deposition and delivery aspects of metered-dose inhaler aerosols.

Oropharyngeal deposition and subsequent delivery of metered-dose inhaler (MDI) aerosols into the lung were measured with the actuator alone and with 4 different kinds of auxiliary devices; open-end straight tube, Aerochamber, Nebuhaler, and InspirEase. The total mass of dry aerosol discharged directly from the actuator, from the auxiliary devices, and through the oropharyngeal model was determined by collecting the aerosol on the absolute filter and weighing the filter. Aerosol depositions in the auxiliary devices and in the oropharynx as well as the amount of aerosol delivered past the oropharynx were determined as percentages of the total aerosol mass output from the actuator alone. Six different MDI aerosols, 3 bronchodilators, and 3 corticosteroids were used. With the actuator alone, oropharyngeal deposition ranged from 33 to 71% at an inspiratory flow rate of 0.33 L/s, depending on the type of MDI aerosols. Aerosol delivery into the lung was 29 to 67%. With the auxiliary devices, oropharyngeal deposition markedly decreased to the range below 6% regardless of the type of auxiliary device and aerosol. A major deposition (23 to 72%) occurred in the auxiliary devices except for Nebuhaler in which a much reduced deposition (8 to 18%) occurred. Aerosol delivery into the lung was in the range of 40 to 72% with the open-end tube, 26 to 62% with the Aerochamber, 34 to 60% with InspirEase, and 31 to 92% with Nebuhaler. Although a substantial increase in aerosol delivery (as much as 38%) was found with a large size Nebuhaler, the aerosol delivery with other smaller auxiliary devices used was comparable to those obtained without the auxiliary devices.

Criteria for mucus transport in the airways by two-phase gas-liquid flow mechanism.

The critical conditions for mucous layer transport in the respiratory airways by two-phase gas-liquid flow mechanism were investigated by using 0.5- and 1.0-cm-ID tube models. Several test liquids with rheological properties comparable to human sputum were supplied continuously into the vertically positioned tube models in such a way that the liquid could form a uniform layer while traveling upward through the tube with a continuous upward airflow. The critical airflow rate and critical liquid layer thickness required for the upward transport of the liquids were determined. The critical airflow rate was in the Reynolds number (Re) range of 142-1,132 in the 0.5-cm-ID tube model and 708-2,830 in the 1.0-cm-ID tube model depending on the types of liquids tested. In both models, the critical airflow rate was lower with viscoelastic liquids than with viscous oils. The critical liquid layer thickness ranged from 0.2 to 0.5 mm in the 0.5-cm-ID tube model and 0.8 to 1.4 mm in the 1.0-cm-ID tube model at Re of 2,800. These values decreased rapidly with increasing airflow rate. The critical thickness relative to the tube diameter ranged from 3 to 15% of the respective tube diameter and was lower by approximately 30-50% in the 0.5-cm-ID tube model than in the 1.0-cm-ID tube model over the entire Re range tested. The results indicate that the critical conditions for the mucus transport by two-phase gas-liquid flow mechanism are within the range that can be achieved in patients with bronchial hypersecretions during normal breathing.

Aerosol deposition in the airway model with excessive mucus secretions.

Aerosol deposition in the airways with excessive mucus secretions was investigated utilizing an in vitro airway model lined with various mucus simulants of differing rheological properties. The airway model was made with a straight glass tube (1.0 cm ID and 20 cm in length) and positioned vertically. The mucus simulants were supplied into the tube at a constant rate and made to move upward through the tube as a thin layer (0.6-1.7 mm) undergoing a random wave motion by means of upward airflow. Aerosols (3.0 and 5.0-micron diam) were passed through the mucus-lined tube at flow rates of 0.33-1.17 l/s, and the deposition of the aerosols in the tube was determined by sampling the aerosols at the inlet and the outlet of the tube on filters. During the sampling, pressure drop across the tube model was also measured. Deposition efficiency in the 20-cm-long mucus-lined tube ranged from 13 to 92% with 3.0-micron-diam particles and from 66 to 98% with 5.0-micron-diam particles. This deposition was 25-300 times higher than that in the dry tube. The deposition was higher with increasing viscosity of mucus but was lower with increasing elasticity of mucus. Pressure drop across the mucus-lined tube was much higher than that in the dry tube, and the increase was more prominent with mucous layers with higher viscosity but lower elasticity values. Therefore, aerosol deposition showed a good positive relationship with pressure drop. However, percent increase of aerosol deposition in the mucus-lined tube was 2-5 times higher than that of pressure drop.(ABSTRACT TRUNCATED AT 250 WORDS)