The olfactory striae: A historical perspective on the inconsistent anatomy of the bulbar projections.

Central olfactory pathways (i.e., projection axons of the mitral and tufted cells), and especially olfactory striae, lack common terminology. This is due to their high degree of intra- and interindividual variability, which has been studied in detail over the past century by Beccari, Mutel, Klass, Erhart, and more recently, by Duque Parra et al. These variations led to some confusion about their number and anatomical arrangement. Recent advances in fiber tractography have enabled the precise in vivo visualization of human olfactory striae and the study of their projections. However, these studies require their algorithms to be set up according to the presumed anatomy of the analyzed fibers. A more precise definition of the olfactory striae is therefore needed, not only to allow a better analysis of the results but also to ensure the quality of the data obtained. By studying the various published works on the central olfactory pathways from the first systematic description by Soemmerring to the present, I have traced the different discussions on the olfactory tracts and summarized them here. This review adopts a systematic approach by addressing each stria individually and tracing the historical background of what was known about it in the past, compared to the current knowledge. The chronological and organized approach used provides a better understanding of the anatomy of these essential structures of the olfactory system.

Mapping the Microstructure and Striae of the Human Olfactory Tract with Diffusion MRI.

The human sense of smell plays an important role in appetite and food intake, detecting environmental threats, social interactions, and memory processing. However, little is known about the neural circuity supporting its function. The olfactory tracts project from the olfactory bulb along the base of the frontal cortex, branching into several striae to meet diverse cortical regions. Historically, using diffusion magnetic resonance imaging (dMRI) to reconstruct the human olfactory tracts has been prevented by susceptibility and motion artifacts. Here, we used a dMRI method with readout segmentation of long variable echo-trains (RESOLVE) to minimize image distortions and characterize the human olfactory tracts in vivo We collected high-resolution dMRI data from 25 healthy human participants (12 male and 13 female) and performed probabilistic tractography using constrained spherical deconvolution (CSD). At the individual subject level, we identified the lateral, medial, and intermediate striae with their respective cortical connections to the piriform cortex and amygdala (AMY), olfactory tubercle (OT), and anterior olfactory nucleus (AON). We combined individual results across subjects to create a normalized, probabilistic atlas of the olfactory tracts. We then investigated the relationship between olfactory perceptual scores and measures of white matter integrity, including mean diffusivity (MD). Importantly, we found that olfactory tract MD negatively correlated with odor discrimination performance. In summary, our results provide a detailed characterization of the connectivity of the human olfactory tracts and demonstrate an association between their structural integrity and olfactory perceptual function.SIGNIFICANCE STATEMENT This study provides the first detailed in vivo description of the cortical connectivity of the three olfactory tract striae in the human brain, using diffusion magnetic resonance imaging (dMRI). Additionally, we show that tract microstructure correlates with performance on an odor discrimination task, suggesting a link between the structural integrity of the olfactory tracts and odor perception. Lastly, we generated a normalized probabilistic atlas of the olfactory tracts that may be used in future research to study its integrity in health and disease.

A comparative neuroimaging perspective of olfaction and higher-order olfactory processing: on health and disease.

Olfactory dysfunction is often the earliest indicator of disease in a range of neurological and psychiatric disorders. One tempting working hypothesis is that pathological changes in the peripheral olfactory system where the body is exposed to many adverse environmental stressors may have a causal role for the brain alteration. Whether and how the peripheral pathology spreads to more central brain regions may be effectively studied in rodent models, and there is successful precedence in experimental models for Parkinson's disease. It is of interest to study whether a similar mechanism may underlie the pathology of psychiatric illnesses, such as schizophrenia. However, direct comparison between rodent models and humans includes challenges under light of comparative neuroanatomy and experimental methodologies used in these two distinct species. We believe that neuroimaging modality that has been the main methodology of human brain studies may be a useful viewpoint to address and fill the knowledge gap between rodents and humans in this scientific question. Accordingly, in the present review article, we focus on brain imaging studies associated with olfaction in healthy humans and patients with neurological and psychiatric disorders, and if available those in rodents. We organize this review article at three levels: 1) olfactory bulb (OB) and peripheral structures of the olfactory system, 2) primary olfactory cortical and subcortical regions, and 3) associated higher-order cortical regions. This research area is still underdeveloped, and we acknowledge that further validation with independent cohorts may be needed for many studies presented here, in particular those with human subjects. Nevertheless, whether and how peripheral olfactory disturbance impacts brain function is becoming even a hotter topic in the ongoing COVID-19 pandemic, given the risk of long-term changes of mental status associated with olfactory infection of SARS-CoV-2. Together, in this review article, we introduce this underdeveloped but important research area focusing on its implications in neurological and psychiatric disorders, with several pioneered publications.

Effects of Brain Size on Adult Neurogenesis in Shrews.

Shrews are small animals found in many different habitats. Like other mammals, adult neurogenesis occurs in the subventricular zone of the lateral ventricle (SVZ) and the dentate gyrus (DG) of the hippocampal formation. We asked whether the number of new generated cells in shrews depends on their brain size. We examined Crocidura russula and Neomys fodiens, weighing 10-22 g, and Crocidura olivieri and Suncus murinus that weigh three times more. We found that the density of proliferated cells in the SVZ was approximately at the same level in all species. These cells migrated from the SVZ through the rostral migratory stream to the olfactory bulb (OB). In this pathway, a low level of neurogenesis occurred in C. olivieri compared to three other species of shrews. In the DG, the rate of adult neurogenesis was regulated differently. Specifically, the lowest density of newly generated neurons was observed in C. russula, which had a substantial number of new neurons in the OB compared with C. olivieri. We suggest that the number of newly generated neurons in an adult shrew's brain is independent of the brain size, and molecular mechanisms of neurogenesis appeared to be different in two neurogenic structures.

SPARK-X: non-parametric modeling enables scalable and robust detection of spatial expression patterns for large spatial transcriptomic studies.

Spatial transcriptomic studies are becoming increasingly common and large, posing important statistical and computational challenges for many analytic tasks. Here, we present SPARK-X, a non-parametric method for rapid and effective detection of spatially expressed genes in large spatial transcriptomic studies. SPARK-X not only produces effective type I error control and high power but also brings orders of magnitude computational savings. We apply SPARK-X to analyze three large datasets, one of which is only analyzable by SPARK-X. In these data, SPARK-X identifies many spatially expressed genes including those that are spatially expressed within the same cell type, revealing new biological insights.

Ontogeny of the brain of Microglanis garavelloi Shibatta and Benine 2005 (Teleostei: Siluriformes: Pseudopimelodidae).

The gross brain morphology and the peripheral olfactory organ of Microglanis garavelloi are described throughout development, and the relationship of these organs to the general behaviour of the species is discussed. During the development, the main brain subdivisions undergo a series of morphological changes keeping a relatively constant volume increase. However, we observed different growth rates in the brains of males and females when these were compared. During the maturation process, a series of hormonal events result in the development of some secondary sexual traits in the brain of male specimens, like faster growth rate of brain areas linked to motor control, olfactory and visual responses. The number of olfactory-organ lamellae increases continuously in both males and females, during their maturation period. These results suggest that changes may be caused by cognitive demands that this species is exposed to throughout its lifespan. The gross morphological arrangement of the central nervous system indicates shared patterns with other members of the family Pseudopimelodidae.

A novel technique for olfactory bulb measurements.

BACKGROUND: To introduce new ways to calculate OB volumes, checking their validity and comparing them to already established technique i.e. OB volumetric based on manual segmentation of OB boundaries. METHODS: Two approaches were used to calculate OB volumes (1) Manual Segmentation using planimetric manual contouring; (2) Box-frame method, calculating the parameters based on a box placed around the OB. RESULTS: We calculated OB volumes using both techniques and found comparable outcomes. High inter-observer reliability was found for volumes calculated by both observers. For manual segmentation, Cronbach's alpha (α) was 0.91 and 0.93 for right and left OB volume, respectively, whereas for the box-frame method α was 0.94 and 0.90 for right and left OB, respectively. CONCLUSIONS: The simple box-frame method of OB volume calculation appears reliable. Its results are comparable to an established technique.

Unexplained repeated pregnancy loss is associated with altered perceptual and brain responses to men's body-odor.

Mammalian olfaction and reproduction are tightly linked, a link less explored in humans. Here, we asked whether human unexplained repeated pregnancy loss (uRPL) is associated with altered olfaction, and particularly altered olfactory responses to body-odor. We found that whereas most women with uRPL could identify the body-odor of their spouse, most control women could not. Moreover, women with uRPL rated the perceptual attributes of men's body-odor differently from controls. These pronounced differences were accompanied by an only modest albeit significant advantage in ordinary, non-body-odor-related olfaction in uRPL. Next, using structural and functional brain imaging, we found that in comparison to controls, most women with uRPL had smaller olfactory bulbs, yet increased hypothalamic response in association with men's body-odor. These findings combine to suggest altered olfactory perceptual and brain responses in women experiencing uRPL, particularly in relation to men's body-odor. Whether this link has any causal aspects to it remains to be explored.

The brain of the African wild dog. II. The olfactory system.

Employing a range of neuroanatomical stains, we detail the organization of the main and accessory olfactory systems of the African wild dog. The organization of both these systems follows that typically observed in mammals, but variations of interest were noted. Within the main olfactory bulb, the size of the glomeruli, at approximately 350 µm in diameter, are on the larger end of the range observed across mammals. In addition, we estimate that approximately 3,500 glomeruli are present in each main olfactory bulb. This larger main olfactory bulb glomerular size and number of glomeruli indicates that enhanced peripheral processing of a broad range of odorants is occurring in the main olfactory bulb of the African wild dog. Within the accessory olfactory bulb, the glomeruli did not appear distinct, rather forming a homogenous syncytia-like arrangement as seen in the domestic dog. In addition, the laminar organization of the deeper layers of the accessory olfactory bulb was indistinct, perhaps as a consequence of the altered architecture of the glomeruli. This arrangement of glomeruli indicates that rather than parcellating the processing of semiochemicals peripherally, these odorants may be processed in a more nuanced and combinatorial manner in the periphery, allowing for more rapid and precise behavioral responses as required in the highly social group structure observed in the African wild dog. While having a similar organization to that of other mammals, the olfactory system of the African wild dog has certain features that appear to correlate to their environmental niche.

Evaluation of olfactory bulbus volume and olfactory sulcus depth by 3 T MR.

OBJECTIVE: The aim of this study was to evaluate olfactory bulbus volume (OBV) and olfactory sulcus depth (OSD) according to age and sex with 3 T MRI in a healthy Turkish population. MATERIALS AND METHODS: In the current study, 200 patients who had cranial MRI were retrospectively evaluated. They were divided into the following groups to examine the effects of age: group 1: 18-30 years old; group 2: 31-40 years old; group 3: 41-50 years old; group 4: 51-60 years old; and group 5: >60 years old. OBV and OSD measurements were performed on coronal T2-weighted brain MR images. The mean right and left olfactory bulb volume and sulcus depths were used for evaluation. RESULTS: The mean age was 46.5 ± 18.1 (range 18-86) years. The mean OBV value of both sides was 91.17 ± 7.8 mm 3 in all patients. The mean OSD value of both sides was 8.62 ± 0.84 mm in all patients. There was no statistically significant difference in OBV and OSD between sexes (P < 0.236; P < 0.482). Group 5 (>60 years old) was found to have significantly lower OBV and OSD values than the other groups (all P < 0.001). CONCLUSION: The normal values of OBV and OSD should be established according to age to determine decreased OBV and OSD values.

Olfactory Dysfunction in the COVID-19 Outbreak.

The first cases of coronavirus 2019 disease (COVID-19) occurred in Wuhan, China, and the disease rapidly become a public health emergency of international proportions. COVID-19 can cause mild-to-severe acute respiratory syndrome (SARS) and is caused by the SARS-CoV-2 coronavirus. The clinical manifestations of COVID-19 include fever, dry cough, fatigue, sputum production, shortness of breath, sore throat, and headache. We performed this narrative review to analyze the current literature on postviral olfactory dysfunction related to the SARSCoV- 2 pandemic. Since the initial anecdotal reports from China, increasingly frequent international reports on COVID-19 indicate that 5% to 85% of affected patients lose their sense of smell, thus highlighting the very heterogeneous nature of the literature in this area. Therefore, we advise home isolation measures and/or social distancing, as well as tests to detect SARS-CoV-2 when possible, in patients with sudden and severe loss of smell who cannot be promptly evaluated.

Comparative growth in the olfactory system of the developing chick with considerations for evolutionary studies.

Despite the long-held assumption that olfaction plays a relatively minor role in the behavioral ecology of birds, crown-group avians exhibit marked phylogenetic variation in the size and form of the olfactory apparatus. As part of a larger effort to better understand the role of olfaction and olfactory tissues in the evolution and development of the avian skull, we present the first quantitative analysis of ontogenetic scaling between olfactory features [olfactory bulbs (OBs) and olfactory turbinates] and neighboring structures (cerebrum, total brain, respiratory turbinates) based on the model organism Gallus gallus. The OB develops under the predictions of a concerted evolutionary model with rapid early growth that is quickly overcome by the longer, sustained growth of the larger cerebrum. A similar pattern is found in the nasal cavity where the morphologically simple (non-scrolled) olfactory turbinates appear and mature early, with extended growth characterizing the larger and scrolled respiratory turbinates. Pairwise regressions largely recover allometric relationships among the examined structures, with a notable exception being the isometric trajectory of the OB and olfactory turbinate. Their parallel growth suggests a unique regulatory pathway that is likely driven by the morphogenesis of the olfactory nerve, which serves as a structural bridge between the two features. Still, isometry was not necessarily expected given that the olfactory epithelium covers more than just the turbinate. These data illuminate a number of evolutionary hypotheses that, moving forward, should inform tradeoffs and constraints between the olfactory and neighboring systems in the avian head.

The trade-off between the olfactory bulb and eyeball volume in precocious puberty.

Background The olfactory bulb (OB) and eyeball size change depending on age and puberty. There is a well-established trade-off between sensory structures of the brain such as the eye and the olfactory bulb that depend on environmental circumstances in the evolutionary history of animals. The aim of this study was to developmentally investigate the potential reciprocal changes between OB and eyeball volumes (EV) in girls with precocious puberty (PP). Methods A total of 148 girls aged between 5 and 8 years (63 PP, 85 healthy) were included in the study. Exclusion criteria: Cases of anosmia/hyposmia, neurodegenerative disorder, refractive errors and trauma. The pituitary height (PH), EV and OB volumes were measured on segmentation of a magnetic resonance image (MRI) slice using manual countering. The corrected measurements by body surface were used in all statistical analyses. Results In girls with PP, the means of the OB volume and PH were larger (71.11 ± 20.64 mL) and higher (4.62 ± 1.18 mm), respectively, while the mean of EVs was smaller (11.24 ± 2.62 cm3) (p = 0.000). Cut-off values were 62.27 mL, 10.7 cm3 and 4.71 mm for OB volume, EV and PH, respectively. While negative correlations were found between OB volume-EV and EV-PH (r63 = -0.224, p = 0.001 and r63 = -0.116, p = 0.001, respectively), OB volume was positively correlated with PH (r63 = 0.578, p = 0.001). Conclusions The present study demonstrates that girls with PP have significantly larger OB volume, but smaller EV, and there is negative correlation between the two structures. These results indicate that there is trade-off between anatomical dimensions of OB and eyeball in favor of OB in PP girls.

Can social behaviour drive accessory olfactory bulb asymmetries? Sister species of caviomorph rodents as a case in point.

In mammals, the accessory olfactory or vomeronasal system exhibits a wide variety of anatomical arrangements. In caviomorph rodents, the accessory olfactory bulb (AOB) exhibits a dichotomic conformation, in which two subdomains, the anterior (aAOB) and the posterior (pAOB), can be readily distinguished. Interestingly, different species of this group exhibit bias of different sign between the AOB subdomains (aAOB larger than pAOB or vice versa). Such species-specific biases have been related with contrasting differences in the habitat of the different species (e.g. arid vs. humid environments). Aiming to deepen these observations, we performed a morphometric comparison of the AOB subdomains between two sister species of octodontid rodents, Octodon lunatus and Octodon degus. These species are interesting for comparative purposes, as they inhabit similar landscapes but exhibit contrasting social habits. Previous reports have shown that O. degus, a highly social species, exhibits a greatly asymmetric AOB, in which the aAOB has twice the size of the pAOB and features more and larger glomeruli in its glomerular layer (GL). We found that the same as in O. degus, the far less social O. lunatus also exhibits a bias, albeit less pronounced, to a larger aAOB. In both species, this bias was also evident for the mitral/tufted cells number. But unlike in O. degus, in O. lunatus this bias was not present at the GL. In comparison with O. degus, in O. lunatus the aAOB GL was significantly reduced in volume, while the pAOB GL displayed a similar volume. We conclude that these sister species exhibit a very sharp difference in the anatomical conformation of the AOB, namely, the relative size of the GL of the aAOB subdomain, which is larger in O. degus than in O. lunatus. We discuss these results in the context of the differences in the lifestyle of these species, highlighting the differences in social behaviour as a possible factor driving to distinct AOB morphometries.

On a remarkable sexual dimorphic trait in the Characiformes related to the olfactory organ and description of a new miniature species of Tyttobrycon Géry (Characiformes: Characidae).

Among the order Characiformes, secondary sexual dimorphism is commonly associated to the occurrence of bony hooks on fins, shape and length of the dorsal and anal fins, and sexual dichromatism. The analysis of a new miniature Characidae species of the genus Tyttobrycon, described herein, yielded to the discovery of a sexually dimorphic trait related to nostril aperture and number of olfactory lamellae. In this type of dimorphism, mature males present larger nostril aperture and higher number of olfactory lamella than females. A dimorphic olfactory organ is for the first time recorded and described for a member of the Characiformes. Gross morphology and development of brain and peripheral olfactory organ of Tyttobrycon sp. n. are described and compared to other species of Characidae. It is hypothesized that such dimorphic trait is related to male-male detection during cohort competition in small characids. The new species of Tyttobrycon is diagnosed from its congeners by the number of branched anal-fin rays (19-21) and the absence of a caudal-peduncle blotch. It occurs in a small tributary of Rio Madeira basin, near to the limit between Brazil and Bolivia, Acre State, Brazil.

Anatomy of the olfactory system.

Of the principal sensory systems (vision, olfaction, taste, hearing, and balance), olfaction is one of the oldest. This ubiquitous system has both peripheral and central subdivisions. The peripheral subdivision is comprised of the olfactory epithelium and nerve fascicles, whereas the central subdivision is made up of the olfactory bulb and its central connections. Humans lack the "accessory olfactory system" of many other mammals, exhibiting only a nonfunctioning vestige of its peripheral element, the vomeronasal organ. Compared to most mammals, major elements of the human olfactory system are reduced; for example, humans have fewer turbinates than many mammals, and their olfactory epithelia are found only on one or two of these structures and their adjacent surfaces. Nonetheless, humans retain a full complement of functional cellular elements including a regenerating population of olfactory sensory neurons. These neurons extend long ciliary processes into the mucus that form a mat of cilia on which the odorant receptors are located. The olfactory sensory neurons send their axons directly to synapse within the olfactory bulb. Mitral and tufted cells then relay impulses from the bulb to other brain regions. This chapter describes the general anatomy and microanatomy of the olfactory system.

Diseases of the nasal cavity.

Despite garnering minimal attention from the medical community overall, olfaction is indisputably critical in the manner in which we as humans interact with our surrounding environment. As the initial anatomical structure in the olfactory pathway, the nasal airway plays a crucial role in the transmission and perception of olfactory stimuli. The goal of this chapter is to provide a comprehensive overview of olfactory disturbances as it pertains to the sinonasal airway. This comprises an in-depth discussion of clinically relevant nasal olfactory anatomy and physiology, classification systems of olfactory disturbance, as well as the various etiologies and pathophysiologic mechanisms giving rise to this important disease entity. A systematic clinical approach to the diagnosis and clinical workup of olfactory disturbances is also provided in addition to an extensive review of the medical and surgical therapeutic modalities currently available.

Anatomy of the olfactory mucosa.

The classic notion that humans are microsmatic animals was born from comparative anatomy studies showing the reduction in the size of both the olfactory bulbs and the limbic brain relative to the whole brain. However, the human olfactory system contains a number of neurons comparable to that of most other mammals, and humans have exquisite olfactory abilities. Major advances in molecular and genetic research have resulted in the identification of extremely large gene families that express receptors for sensing odors. Such advances have led to a renaissance of studies focused on both human and nonhuman aspects of olfactory physiology and function. Evidence that olfactory dysfunction is among the earliest signs of a number of neurodegenerative and neuropsychiatric disorders has led to considerable interest in the use of olfactory epithelial biopsies for potentially identifying such disorders. Moreover, the unique features of the olfactory ensheathing cells have made the olfactory mucosa a promising and unexpected source of cells for treating spinal cord injuries and other neural injuries in which cell guidance is critical. The olfactory system of humans and other primates differs in many ways from that of other species. In this chapter we provide an overview of the anatomy of not only the human olfactory mucosa but of mucosae from a range of mammals from which more detailed information is available. Basic information regarding the general organization of the olfactory mucosa, including its receptor cells and the large number of other cell types critical for their maintenance and function, is provided. Cross-species comparisons are made when appropriate. The polemic issue of the human vomeronasal organ in both the adult and fetus is discussed, along with recent findings regarding olfactory subsystems within the nose of a number of mammals (e.g., the septal organ and Grüneberg ganglion).

Central olfactory structures.

Axons from the olfactory bulb (OB) project to multiple central structures of the brain, many of which, in turn, send axons back into the OB and/or to one another. These secondary sensory regions underlie many aspects of odor representation, valence, and learning, as well as serving some nonolfactory functions, though many details remain unclear. We here describe the connectivity and essential structural and functional properties of these postbulbar olfactory regions in the mammalian brain.