Numerical modeling of turbulent and laminar airflow and odorant transport during sniffing in the human and rat nose

Human sniffing behavior usually involves bouts of short, high flow rate inhalation (>300 ml/s through each nostril) with mostly turbulent airflow. This has often been characterized as a factor enabling higher amounts of odorant to deposit onto olfactory mucosa than for laminar airflow and thereby aid in olfactory detection. Using computational fluid dynamics human nasal cavity models, however, we found essentially no difference in predicted olfactory odorant flux (g/cm2 s) for turbulent versus laminar flow for total nasal flow rates between 300 and 1000 ml/s and for odorants of quite different mucosal solubility. This lack of difference was shown to be due to the much higher resistance to lateral odorant mass transport in the mucosal nasal airway wall than in the air phase. The simulation also revealed that the increase in airflow rate during sniffing can increase odorant uptake flux to the nasal/olfactory mucosa but lower the cumulative total uptake in the olfactory region when the inspired air/odorant volume was held fixed, which is consistent with the observation that sniff duration may be more important than sniff strength for optimizing olfactory detection. In contrast, in rats, sniffing involves high-frequency bouts of both inhalation and exhalation with laminar airflow. In rat nose odorant uptake simulations, it was observed that odorant deposition was highly dependent on solubility and correlated with the locations of different types of receptors.     

Hemispheric lateralization in the processing of odor pleasantness versus odor names

It is well established that for most people linguistic processing is primarily a left hemisphere activity, whereas recent evidence has shown that basic odor perception is more lateralized to the right hemisphere. Importantly, under certain conditions, emotional responding also shows right hemisphere laterality. Hedonic (pleasantness) assessments constitute basic level emotional responses. Given that olfaction is predominantly ipsilateral in function, it was hypothesized that odor pleasantness evaluations may be accentuated by right nostril perception and that odor naming would be superior with left nostril perception. To test this prediction we presented eight familiar neutral-mildly pleasant odors for subjects to sniff through the left and right nostrils. Subjects smelled each odor twice (once through each nostril) at two different sessions, separated by 1 week. At each session subjects provided pleasantness, arousal and naming responses to each odorant. Results revealed that odors were rated as more pleasant when sniffed through the right nostril and named more correctly when sniffed through the left. No effects for arousal were obtained. These findings are consistent with previously demonstrated neural laterality in the processing of olfaction, emotion and language, and suggest that a local and functional convergence may exist between olfaction and emotional processing.     

Experimental and numerical determination of odorant solubility in nasal and olfactory mucosa

Odorant deposition in the nasal and olfactory mucosas is dependent on a number of factors including local air/odorant flow distribution patterns, odorant mucosal solubility and odorant diffusive transport in the mucosa. Although many of these factors are difficult to measure, mucosal solubility in the bullfrog mucus has been experimentally determined for a few odorants. In the present study an experimental procedure was combined with computational fluid dynamic (CFD) techniques to further describe some of the factors that govern odorant mucosal deposition. The fraction of odorant absorbed by the nasal mucosa (eta) was experimentally determined for a number of odorants by measuring the concentration drop between odorant 'blown' into one nostril and that exiting the contralateral nostril while the subject performed a velopharyngeal closure. Odorant concentrations were measured with a photoionization detector. Odorants were delivered to the nostrils at flow rates of 3.33 and 10 l/min. The velopharyngeal closure nasal air/odorant flows were then simulated using CFD techniques in a 3-D anatomically accurate human nose modeland the mucosal odorant uptake was numerically calculated. The comparison between the numerical simulations and the experimental results lead to an estimation of the human mucosal odorant solubility and the mucosal effective diffusive transport resistance. The results of the study suggest that the increase in diffusive resistance of the mucosal layer over that of a thin layer of water seemed to be general and non-odorant-specific; however, the mucosa solubility was odorant specific and usually followed the trend that odorants with lower water solubility were more soluble in the mucosa than would be predicted from water solubility alone. The ability of this approach to model odorant movement in the nasal cavity was evaluated by comparison of the model output with known values of odorant mucosa solubility.     

Distortion of olfactory perception: diagnosis and treatment

Clinically, olfaction can fail in any of three ways: (i) decreased sensitivity (hyposmia, anosmia) and two types of distortion (dysosmia); (ii) distorted quality of an odorant stimulation (troposmia); (iii) perceived odor when no odorant is present (phantosmia, hallucination). The distortions are usually much more upsetting to a person's quality of life than a simple loss. An ipsilatersal loss of olfactory sensitivity is often identified in the nostril with any type of olfactory distortion. The pathophysiology of a stimulated distortion (troposmia) is likely a decreased number of functioning olfactory primary neurons so that an incomplete characterization of the odorant is made. In phantosmia, two possible causations include an abnormal signal or inhibition from the primary olfactory neurons or peripheral olfactory or trigeminal signals that "trigger" a central process. The clinician's goal is to carefully define the problem (e.g. taste versus smell, real versus perceived, one versus two nostrils), to perform the appropriate examination and testing and to provide therapy if possible. Treatment includes assurance with no active therapy (because many of these will naturally resolve), topical medications, systemic medications, anesthesia to parts of the nose and, rarely, referral for surgical excision of olfactory neurons. Endoscopic transnasal operations have the advantage of treating phantosmia and sometimes allowing a return of olfactory ability after the operation.     

Brain mechanisms for extracting spatial information from smell

Forty years ago, von Békésy demonstrated that the spatial source of an odorant is determined by comparing input across nostrils, but it is unknown how this comparison is effected in the brain. To address this, we delivered odorants to the left or right of the nose, and contrasted olfactory left versus right localization with olfactory identification during brain imaging. We found nostril-specific responses in primary olfactory cortex that were predictive of the accuracy of left versus right localization, thus providing a neural substrate for the behavior described by von Békésy. Additionally, left versus right localization preferentially engaged a portion of the superior temporal gyrus previously implicated in visual and auditory localization, suggesting that localization information extracted from smell was then processed in a convergent brain system for spatial representation of multisensory inputs.     

Olfaction and sensory asymmetry

Eighty years ago it was demonstrated that odours presented tothe left side of the nose are much better perceived than odourspresented to the right side. This finding could not be corroboratedin our experiment. Some possible explanations are offered toaccount for the different results. It also turned out that olfactorysensitivity when smelling with both nostrils open is hardlyhigher than with one nostril open. It was furthermore suggestedthat differences between the two sides of the nose might playa role in studies where verbal and emotional processes are involved,as in olfactory recognition, memory and preference.     

A Computational Study of the Hydrodynamics in the Nasal Region of a Hammerhead Shark (Sphyrna tudes): Implications for Olfaction

The hammerhead shark possesses a unique head morphology that is thought to facilitate enhanced olfactory performance. The olfactory chambers, located at the distal ends of the cephalofoil, contain numerous lamellae that increase the surface area for olfaction. Functionally, for the shark to detect chemical stimuli, water-borne odors must reach the olfactory sensory epithelium that lines these lamellae. Thus, odorant transport from the aquatic environment to the sensory epithelium is the first critical step in olfaction. Here we investigate the hydrodynamics of olfaction in Sphyrna tudes based on an anatomically-accurate reconstruction of the head and olfactory chamber from high-resolution micro-CT and MRI scans of a cadaver specimen. Computational fluid dynamics simulations of water flow in the reconstructed model reveal the external and internal hydrodynamics of olfaction during swimming. Computed external flow patterns elucidate the occurrence of flow phenomena that result in high and low pressures at the incurrent and excurrent nostrils, respectively, which induces flow through the olfactory chamber. The major (prenarial) nasal groove along the cephalofoil is shown to facilitate sampling of a large spatial extent (i.e., an extended hydrodynamic “reach”) by directing oncoming flow towards the incurrent nostril. Further, both the major and minor nasal grooves redirect some flow away from the incurrent nostril, thereby limiting the amount of fluid that enters the olfactory chamber. Internal hydrodynamic flow patterns are also revealed, where we show that flow rates within the sensory channels between olfactory lamellae are passively regulated by the apical gap, which functions as a partial bypass for flow in the olfactory chamber. Consequently, the hammerhead shark appears to utilize external (major and minor nasal grooves) and internal (apical gap) flow regulation mechanisms to limit water flow between the olfactory lamellae, thus protecting these delicate structures from otherwise high flow rates incurred by sampling a larger area.     

Comparison between monorhinal and birhinal olfactory stimulations in bilateral electrodermal recordings

The study of olfactory lateralization in human subjects has given rise to many publications, but the findings have often been contradictory. Most research used either birhinal or monorhinal stimulations, but rarely a comparison between these two types of olfactory input. The aim of this study was to investigate variations in psychophysiological measurements and test each side of the nose and binasal performances. This work used bilateral electrodermal recordings and compared the skin conductance responses (SCRs) for a pleasant odorant (isoamyl acetate) and an unpleasant odorant (triethylamine) in a suprathreshold concentration on 30 dextral subjects (16 females and 14 males). First, the results reported no differences between the two nostrils but differences in electrodermal activity (EDA) in relation to the odorant: 1) higher amplitude in response to unpleasant versus pleasant odorant; 2) no differences between monorhinal and birhinal stimulations for the unpleasant odour but higher amplitude in response to birhinal versus monorhinal for the pleasant odour. Second, the results showed constant bilateral differences in EDA recordings and are discussed in terms of hemispheric asymmetry activation.     

脊椎动物中的一种解剖学新模型——黄鳝外周嗅觉系统

除单鼻型的圆口类外, 脊椎动物的左、右两侧嗅觉器官和嗅神经皆互为独立地分布于头前端, 而且它们的前鼻孔(外鼻孔)、嗅腔、嗅觉副囊腔(部分鱼具嗅觉副囊)与后鼻孔(或内鼻孔)也都互为相通, 且多呈开放状态。它们还通常具有一个体积相对较大且较稳定的嗅腔, 而嗅上皮则多位于嗅腔的一侧。此外, 鱼类的嗅囊与鼻窝之间通常也无明显间隙。然而, 运用常规的解剖学方法发现, 黄鳝(Monopterus albus)外周嗅觉系统(嗅觉器官和嗅神经)在解剖结构上已发生如下重大变化: (1)虽然具有前、后鼻孔, 但两者互不相通, 而嗅腔仅靠前鼻孔通至外界; (2)两侧嗅囊的末端及两侧嗅神经的前段均分别发生了合并。此外, 在该鱼上还发现:(1)嗅囊为一柔软而扁塌的长管囊结构, 其唯一的开口(即位于前鼻孔球上的前鼻孔)却常呈关闭状, 故此时该嗅腔实际上是一个体积被压扁到最小且暂时被封闭的空间; (2)嗅囊纵向地贴附于长鼻窝的内侧壁上, 它仅占鼻窝的一小部分空间, 故鼻窝显得相对很宽敞; (3)嗅觉副囊不与嗅腔相通, 而与鼻窝共同经后鼻孔通至外界; (4)两侧嗅囊的末端相向地穿越鼻窝内侧壁, 进入筛骨与额骨之间的“筛-额横管”, 在那里发生嗅囊合并;(5)嗅囊壁周缘几乎都内衬着嗅上皮, 且具数个褶窝(说明该嗅囊有扩张的可能)。因此, 黄鳝的这套解剖学特征不同于包括鱼类在内的所有脊椎动物的外周嗅觉系统。研究所发现的黄鳝这套形态学特征不仅为脊椎动物外周嗅觉系统的研究提供了一个独特的解剖学新模型, 同时也为动物进化研究提供了一个有关前、后鼻孔互不相通的进化特例。此外, 研究还依据上述发现提出嗅囊扩张-压缩假说以解释气味媒质进出于黄鳝这种特殊嗅腔的动力学机制。       

Psychophysical and behavioral characteristics of olfactory adaptation

Sensory adaptation allows organisms to reach behavioral equilibrium with the ambient environment and respond primarily to changes in stimulation. Given its functional significance, it is not surprising that adaptation in the olfactory system exhibits many of the same characteristics as adaptation in other sensory systems, including vision. Repeated or prolonged exposure to an odorant typically leads to stimulus-specific decreases in olfactory sensitivity to that odorant, but sensitivity recovers over time in the absence of further exposure. Psychophysical analysis shows that olfactory adaptation results in elevations in odor thresholds and in reduced responsiveness to suprathreshold stimulation. Further, the magnitude of the decrease and the time course of adaptation and recovery are dependent on the concentration of the odor and on the duration of exposure. It is generally agreed that olfactory adaptation can occur at multiple levels in the olfactory system and can involve both peripheral (receptor level) and more central (post-receptor) components. Evidence for peripheral and central involvement comes from studies showing that monorhinal stimulation results in adaptation in both the ipsilateral and contralateral nostril, although the degree of adaptation in the ipsilateral nostril is more profound and recovery is slower. Additional evidence for central involvement comes from studies that have found relatively small decreases in peripheral response following repeated stimulation despite substantial reductions in perceived intensity. Most psychophysical studies of adaptation, however, have not differentiated the peripheral and central processes. Although relatively few in number, studies of the parametric features of olfactory adaptation in both vertebrate (e.g. rat) and invertebrate (e.g. Drosophila, Caenorhabditis elegans) animal models appear to replicate the findings in psychophysical studies of adult humans. Despite the broad overall similarity of olfactory adaptation to adaptation in other sensory systems, olfactory adaptation exhibits some unique features. Adaptation in olfaction has been shown to be very long-lasting in some cases and may be modulated by the contribution of pre-neural events and physico-chemical properties of the odorant molecules that govern diffusion to receptor sites and post-receptor clearance.     

Odor Detection in Manduca sexta Is Optimized when Odor Stimuli Are Pulsed at a Frequency Matching the Wing Beat during Flight

Sensory systems sample the external world actively, within the context of self-motion induced disturbances. Mammals sample olfactory cues within the context of respiratory cycles and have adapted to process olfactory information within the time frame of a single sniff cycle. In plume tracking insects, it remains unknown whether olfactory processing is adapted to wing beating, which causes similar physical effects as sniffing. To explore this we first characterized the physical properties of our odor delivery system using hotwire anemometry and photo ionization detection, which confirmed that odor stimuli were temporally structured. Electroantennograms confirmed that pulse trains were tracked physiologically. Next, we quantified odor detection in moths in a series of psychophysical experiments to determine whether pulsing odor affected acuity. Moths were first conditioned to respond to a target odorant using Pavlovian olfactory conditioning. At 24 and 48 h after conditioning, moths were tested with a dilution series of the conditioned odor. On separate days odor was presented either continuously or as 20 Hz pulse trains to simulate wing beating effects. We varied pulse train duty cycle, olfactometer outflow velocity, pulsing method, and odor. Results of these studies, established that detection was enhanced when odors were pulsed. Higher velocity and briefer pulses also enhanced detection. Post hoc analysis indicated enhanced detection was the result of a significantly lower behavioral response to blank stimuli when presented as pulse trains. Since blank responses are a measure of false positive responses, this suggests that the olfactory system makes fewer errors (i.e. is more reliable) when odors are experienced as pulse trains. We therefore postulate that the olfactory system of Manduca sexta may have evolved mechanisms to enhance odor detection during flight, where the effects of wing beating represent the norm. This system may even exploit temporal structure in a manner similar to sniffing.     

Functional morphology of the nasal region of a hammerhead shark

We describe several novel morphological features in the nasal region of the hammerhead shark Sphyrna tudes. Unlike the open, rounded incurrent nostril of non-hammerhead shark species, the incurrent nostril of S. tudes is a thin keyhole-like aperture. We discovered a groove running anterior and parallel to the incurrent nostril. This groove, dubbed the minor nasal groove to distinguish it from the larger, previously described, (major) nasal groove, is common to all eight hammerhead species. Using life-sized plastic models generated at 200 μm resolution from an X-ray scan, we also investigated flow in the nasal region. Even modest oncoming flow speeds stimulate extensive, but not complete, circulation within the model olfactory chamber, with flow passing through the two main olfactory channels. Flow crossed from one channel to another via a gap in the olfactory array, sometimes guided by the interlamellar channels. Major and minor nasal grooves, as well as directing flow into the olfactory chamber, can, in conjunction with the nasal bridge separating incurrent and excurrent nostrils, limit flow passing into the olfactory chamber, possibly to protect the delicate nasal structures. This is the first simulation of internal flow within the olfactory chamber of a shark.     

Dual signal transduction mediated by a single type of olfactory receptor expressed in a heterologous system

Controversy exists over the relationship between the cAMP and IP3 pathways in vertebrate olfactory signal transduction, as this process is known to occur by either of the two pathways. Recent studies have shown that a single olfactory neuron responds to both cAMP- and IP3-producing odorants, suggesting the existence of an olfactory receptor protein that can recognize both ligands. In this study we found that the rat olfactory receptor I7, stably expressed in HEK-293 cells, triggers the cAMP pathway upon stimulation by a specific odorant (octanal) at concentrations lower than 10(-4) M; however, the receptor triggers both pathways at higher concentrations. This indicates that a single olfactory receptor, stimulated by a single pathway-inducing odorant, can evoke both pathways at high odorant concentrations. Using this heterologous system, both the dose-dependent response and receptor I7 specificity were analyzed. The dose-dependent Ca2+ response curve, which also includes the release of Ca2+ ions from internal stores at high odorant concentrations, was not monotonous, but had a local maximum and minimum with 10(-10) and 10(-7) M octanal, respectively, and reached a plateau at 10(-2) M octanal. The specificity of the I7 receptor was lower when exposed to higher concentrations of odorants.     

Functional MRI of the Olfactory System in Conscious Dogs

We depend upon the olfactory abilities of dogs for critical tasks such as detecting bombs, landmines, other hazardous chemicals and illicit substances. Hence, a mechanistic understanding of the olfactory system in dogs is of great scientific interest. Previous studies explored this aspect at the cellular and behavior levels; however, the cognitive-level neural substrates linking them have never been explored. This is critical given the fact that behavior is driven by filtered sensory representations in higher order cognitive areas rather than the raw odor maps of the olfactory bulb. Since sedated dogs cannot sniff, we investigated this using functional magnetic resonance imaging of conscious dogs. We addressed the technical challenges of head motion using a two pronged strategy of behavioral training to keep dogs'' head as still as possible and a single camera optical head motion tracking system to account for residual jerky movements. We built a custom computer-controlled odorant delivery system which was synchronized with image acquisition, allowing the investigation of brain regions activated by odors. The olfactory bulb and piriform lobes were commonly activated in both awake and anesthetized dogs, while the frontal cortex was activated mainly in conscious dogs. Comparison of responses to low and high odor intensity showed differences in either the strength or spatial extent of activation in the olfactory bulb, piriform lobes, cerebellum, and frontal cortex. Our results demonstrate the viability of the proposed method for functional imaging of the olfactory system in conscious dogs. This could potentially open up a new field of research in detector dog technology.     

Cerebral activation to intranasal chemosensory trigeminal stimulation

Although numerous functional magnetic resonance imaging (FMRI) studies have been performed on the processing of olfactory information, the intranasal trigeminal system so far has not received much attention. In the present study, we sought to delineate the neural correlates of trigeminal stimulation using carbon dioxide (CO(2)) presented to the left or right nostril. Fifteen right-handed men underwent FMRI using single runs of 3 conditions (CO(2) in the right and the left nostrils and an olfactory stimulant-phenyl ethyl alcohol-in the right nostril). As expected, olfactory activations were located in the orbitofrontal cortex (OFC), amygdala, and rostral insula. For trigeminal stimulation, activations were found in "trigeminal" and "olfactory" regions including the pre- and postcentral gyrus, the cerebellum, the ventrolateral thalamus, the insula, the contralateral piriform cortex, and the OFC. Left compared with right side stimulations resulted in stronger cerebellar and brain stem activations; right versus left stimulation resulted in stronger activations of the superior temporal sulcus and OFC. These results suggest a trigeminal processing system that taps into similar cortical regions and yet is separate from that of the olfactory system. The overlapping pattern of cortical activation for trigeminal and olfactory stimuli is assumed to be due to the intimate connections in the processing of information from the 2 major intranasal chemosensory systems.     

Homing pigeons subjected to section of the anterior commissure can build up two olfactory maps in the deflector lofts

Summary Pigeons kept in two cages with screens which deflect the wind clockwise (CW) or counterclockwise (CCW) show corresponding deflections in their initial orientation. In order to determine the nature of this phenomenon, experimental birds were treated as follows: 1. The anterior commissure of the forebrain (AC), which mediates the interhemispheric transfer of olfactory input was sectioned; 2. After surgery, each experimental bird was kept alternately in a CW cage with its right nostril plugged, and in a CCW cage with its left nostril plugged; the two treatments were alternated every 3 days for 69 days before test releases began. In 23 out of 28 cases the experimentals showed CW deflections when released with the right nostril plugged and CCW deflections when released with the left nostril plugged. The controls were intact, and their nostrils were free in each phase of the experiment. They were subdivided into two groups: one group was kept in the CW cage when the experimentals were in the same cage, the other group in the CCW cage when the experimentals stayed there. In the remaining time each group was kept in a fenced loft. The behaviour of controls demonstrated that the time the experimentals had spent in each kind of deflector cage had been long enough to produce the corresponding deflections in initial orientation. Control experiments were then performed on pigeons with the AC sectioned (2 series) and on intact birds (1 series), both maintained in lofts which did not deflect the wind, and released with one nostril plugged. They did not show deflections similar to those of the experimentals. The present results allow to conclude that the deflector loft effect is olfactory in nature, and that the AC sectioned pigeons, alternately subjected to different treatments in deflector cages are able to acquire two different odour maps for navigation.Abbreviations AC anterior commissure of the forebrain sectioned - CCW counterclockwise - CW clockwise     

Thoracic pressure and nasal patency

Maximum nasal flow rate in the right and left nostrils was simultaneously determined during expiration with the help of two flowmeters in 10 healthy subjects in different postures and in two patients, one with Horner's syndrome and the other with facial palsy. It was found that pressure on the hemithorax from any surface (i.e., lateral, anterior, posterior, or superior) leads to reduced patency of the ipsilateral nostril but increased patency of the nostril on the opposite site. In the patient with Horner's syndrome, the nostril on the affected side remained blocked even on compression of the opposite hemithorax, and in the one with facial nerve palsy, the nostril on the affected side remained patent despite compression of the hemithorax on that side. The findings suggest that compression of hemithorax leads to changes in the congestion of the nasal mucosa that may be mediated through autonomic nerves.     

Organization of the Olfactory and Respiratory Skeleton in the Nose of the Gray Short-Tailed Opossum Monodelphis domestica

The internal nasal skeleton in Monodelphis domestica, the gray short-tailed opossum, primarily supports olfactory and respiratory epithelia, the vomeronasal organ, and the nasal gland. This scaffold is built by the median mesethmoid, and the paired vomer and ethmoid bones. The mesethmoid ossifies within the nasal septum cartilage. The bilateral ethmoid segregates respiratory and olfactory regions, and its geometry offers insight into the functional, developmental, and genomic organization of the nose. It forms through partial coalescence of separate elements known as turbinals, which in Monodelphis comprise the maxilloturbinal, nasoturbinal, five endoturbinals, and two ectoturbinals. Geometry of the ethmoid increases respiratory mucosal surface area by a factor of six and olfactory mucosal surface by nearly an order of magnitude. Respiratory epithelium warms and humidifies inspired air, recovers moisture as air is exhaled, and may help mediate brain temperature. In contrast, the olfactory skeleton functions as a series of small funnels that support growth of new olfactory neurons throughout life. Olfactory mucosa lines the mouth of each funnel, forming blind olfactory recesses known as the ethmoid cells, and neuronal axons are funneled from the epithelium through tiny olfactory foramina in the cribriform plate, into close proximity with target glomeruli in the olfactory bulb of the brain where each axon makes its first synapse. The skeleton may thus mediate topological correspondence between odorant receptor areas in the nose with particular glomeruli in the olfactory bulb, enabling growth throughout life of new olfactory neurons and proper targeting by their axons. The geometric arrangement of odorant receptors suggests that a measure of volatility may be a component in the peripheral olfactory code, and that corresponding glomeruli may function in temporal signal processing. Supporting visualizations for this study are available online at www.DigiMorph.org.     

Partition coefficient and comparative olfactometry

The air/water partition coefficients of many odorants can becalculated from available data on their vapor pressures andsolubilities at 25°. A gas-flow method is described forobtaining equilibrium concentration data to calculate the coefficientsof certain odorants for which theoretical or gas chromatographictechniques are not applicable. It is shown that the odor thresholdsobtained in airdilution olfactometry agree with those measuredby sniff tests on aqueous dilutions, when the air/water partitioncoefficient is taken into consideration. Similar calculationsinvolving the oil/water partition coefficient show close correspondencebetween thresholds measured in water or safflower oil dilution.A conversion factor was obtained for comparing squeeze-bottlepair tests with stoppered flask 2/5 tests in the measurementof olfactory threshold.