Kareken, D.A. et al. Olfactory system activation from sniffing: effects in piriform and orbitofrontal cortex. NeuroImage 22, 456-465

Department of Neurology, Neuropsychology Section (RI 1773), Indiana University School of Medicine, Indianapolis, IN 46202, USA.
NeuroImage (Impact Factor: 6.36). 06/2004; 22(1):456-65. DOI: 10.1016/j.neuroimage.2004.01.008
Source: PubMed


Neuroimaging studies suggest that piriform cortex is activated at least in part by sniffing. We used H(2)(15)O positron emission tomography (PET) to study 15 healthy volunteers while they participated in four conditions, two of which were sniffing odorants and odorless air. The remaining two conditions involved a constant, very low flow of either odorized or odorless air during velopharyngeal closure (VPC), a technique that prevents subject-induced airflow through the nasal passages. Contrary to expectation, sniffing under odorless conditions did not induce significant piriform and surrounding cortical (PC+) activity when compared to odorless VPC, even at a liberal statistical threshold. However, a small correlation emerged in PC+ between the difference signal of [odorless sniffing - odorless VPC] and peak rate of nasal pressure change. PC+ activity was, however, strongly evoked by odorant exposure during sniffing and VPC, with neither technique showing greater activation. Activity in orbitofrontal (olfactory association) cortex was absent during odorant stimulation (OS) with VPC, but present during odorant sniffing. Sniffing may therefore play an important role in facilitating the higher-order analysis of odors. A right orbitofrontal region was also activated with odorless sniffing, which suggests a possible orbitofrontal role in guided olfactory exploration.

Download full-text


Available from: Eric Claus,
  • Source
    • "However, the sensitivity of the olfactory system is enormous, and for some chemicals such as skatole/3-methylindole, as few as 10 molecules might be sufficient to trigger an action potential at the receptor level and the subsequent detection of the odor by the central nervous system (Hatt 2000). This sensitivity is partly achieved by actively sniffing the odorants and increasing the airflow of the dorsal medial airflow pathway (Kareken et al. 2004; Sobel et al. 2000). As pointed out previously, for the majority of volatile chemicals the olfactory system is more sensitive than trigeminal chemoreception (Shusterman 2001). "
    [Show abstract] [Hide abstract]
    ABSTRACT: There is a need of guidance on how local irritancy data should be incorporated into risk assessment procedures, particularly with respect to the derivation of occupational exposure limits (OELs). Therefore, a board of experts from German committees in charge of the derivation of OELs discussed the major challenges of this particular end point for regulatory toxicology. As a result, this overview deals with the question of integrating results of local toxicity at the eyes and the upper respiratory tract (URT). Part 1 describes the morphology and physiology of the relevant target sites, i.e., the outer eye, nasal cavity, and larynx/pharynx in humans. Special emphasis is placed on sensory innervation, species differences between humans and rodents, and possible effects of obnoxious odor in humans. Based on this physiological basis, Part 2 describes a conceptual model for the causation of adverse health effects at these targets that is composed of two pathways. The first, "sensory irritation" pathway is initiated by the interaction of local irritants with receptors of the nervous system (e.g., trigeminal nerve endings) and a downstream cascade of reflexes and defense mechanisms (e.g., eyeblinks, coughing). While the first stages of this pathway are thought to be completely reversible, high or prolonged exposure can lead to neurogenic inflammation and subsequently tissue damage. The second, "tissue irritation" pathway starts with the interaction of the local irritant with the epithelial cell layers of the eyes and the URT. Adaptive changes are the first response on that pathway followed by inflammation and irreversible damages. Regardless of these initial steps, at high concentrations and prolonged exposures, the two pathways converge to the adverse effect of morphologically and biochemically ascertainable changes. Experimental exposure studies with human volunteers provide the empirical basis for effects along the sensory irritation pathway and thus, "sensory NOAEChuman" can be derived. In contrast, inhalation studies with rodents investigate the second pathway that yields an "irritative NOAECanimal." Usually the data for both pathways is not available and extrapolation across species is necessary. Part 3 comprises an empirical approach for the derivation of a default factor for interspecies differences. Therefore, from those substances under discussion in German scientific and regulatory bodies, 19 substances were identified known to be human irritants with available human and animal data. The evaluation started with three substances: ethyl acrylate, formaldehyde, and methyl methacrylate. For these substances, appropriate chronic animal and a controlled human exposure studies were available. The comparison of the sensory NOAEChuman with the irritative NOAECanimal (chronic) resulted in an interspecies extrapolation factor (iEF) of 3 for extrapolating animal data concerning local sensory irritating effects. The adequacy of this iEF was confirmed by its application to additional substances with lower data density (acetaldehyde, ammonia, n-butyl acetate, hydrogen sulfide, and 2-ethylhexanol). Thus, extrapolating from animal studies, an iEF of 3 should be applied for local sensory irritants without reliable human data, unless individual data argue for a substance-specific approach.
    Archives of Toxicology 10/2014; 88(10):1855-1879. DOI:10.1007/s00204-014-1346-z · 5.98 Impact Factor
  • Source
    • "A review of the literature since the original work of Zatorre in 199210 to now, shows that many functional and structural imaging techniques were applied to study the olfactory system using a number of different olfactory tasks. Thus, due to the heterogeneity of methods used across the studies the interpretation and comparison of results from these experiments is often difficult4567891011121314151617. Furthermore, many results support the idea that the neural correlates of odor processing are strongly task dependent, involving a distributed network of structures - even outside olfactory core regions - determined by the nature of the context and of the olfactory and sensory task17. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A wide network of interconnected areas was previously found in neuroimaging studies involving normal as well as pathological subjects; however literature seems to suffer from a lack of investigation in glucose metabolism behaviour under olfactory condition. Thus, the present work describe for the first time a pure olfactory related brain response of metabolism by using (18)F-fluorodeoxyglucose-Positron Emission Tomography/Computer Tomography in eleven resting subjects undergoing a neutral and a pure olfactory condition. By contrasting these experimental phases, it was possible to depict a re-organization pattern of default mode network structures in a relatively ecological environment. Moreover, by correlating such pattern with a battery of validated olfactory and neuropsychological tests, our work allowed in showing peculiar correlation data that could cluster the subjects sample in a certain range of normality. We believe the present study could integrate the current knowledge in olfactory research and could be a start-up for future contributions.
    Scientific Reports 06/2014; 4:5146. DOI:10.1038/srep05146 · 5.58 Impact Factor
  • Source
    • "Our data also showed significant correlations between OFC volume and both odor discrimination and overall olfactory function. The human OFC has been reported to play a guide role in olfactory exploration [31], and to be partially involved in decision making [32,33]. When the OFC is surgically removed, both monkeys and humans show strikingly decreased odor discrimination ability [34,35]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The piriform cortex and cortical amygdala (PCA) and the orbitofrontal cortex (OFC) are considered olfactory-related brain regions. This study aims to elucidate the normal volumes of PCA and OFC of each age groups (20.0-70.0 year old), and whether the volumes of PCA and OFC decline with increasing age and diminishing olfactory function. One hundred and eleven healthy right-handed participants (54 males, 57 females), age 20.0 to 70.0 years were recruited to join this study after excluding all the major causes of olfactory dysfunction. Volumetric measurements of PCA and OFC were performed using consecutive 1-mm thick coronal slices of high-resolution 3-D MRIs. A validated olfactory function test (Sniffin' Sticks) assessed olfactory function, which measured odor threshold (THD), odor discrimination (DIS), and odor identification (ID) as well as their sum score (TDI). The volume of OFC decreased with age and significantly correlated with age-related declines in olfactory function. The volume of OFC showed significant age-group differences, particularly after 40 years old (p < 0.001), while olfactory function decreased significantly after 60 years old (p < 0.001). Similar age-related volumetric changes were not found for PCA (p = 0.772). Additionally, there was significant correlation between OFC and DIS on the Right Side (p = 0.028) and between OFC and TDI on both sides (p < 0.05). There was no similar correlation for PCA. Aging can have a great impact on the volume of OFC and olfactory function while it has much smaller effect on the volume of PCA. The result could be useful to establish normal volumes of PCA and OFC of each age group to assess neurological disorders that affect olfactory function.
    PLoS ONE 09/2013; 8(9):e74526. DOI:10.1371/journal.pone.0074526 · 3.23 Impact Factor
Show more