The human brain representation of odor identification

Odor identification (OI) tests are increasingly used clinically as biomarkers for Alzheimer's disease and schizophrenia. The aim of this study was to directly compare the neuronal correlates to identified odors vs. nonidentified odors. Seventeen females with normal olfactory function underwent a functional magnetic resonance imaging (fMRI) experiment with postscanning assessment of spontaneous uncued OI. An event-related analysis was performed to compare within-subject activity to spontaneously identified vs. nonidentified odors at the whole brain level, and in anatomic and functional regions of interest (ROIs) in the medial temporal lobe (MTL). Parameter estimate values and blood oxygenated level-dependent (BOLD) signal curves for correctly identified and nonidentified odors were derived from functional ROIs in hippocampus, entorhinal, piriform, and orbitofrontal cortices. Number of activated voxels and max parameter estimate values were obtained from anatomic ROIs in the hippocampus and the entorhinal cortex. At the whole brain level the correct OI gave rise to increased activity in the left entorhinal cortex and secondary olfactory structures, including the orbitofrontal cortex. Increased activation was also observed in fusiform, primary visual, and auditory cortices, inferior frontal plus inferior temporal gyri. The anatomic MTL ROI analysis showed increased activation in the left entorhinal cortex, right hippocampus, and posterior parahippocampal gyri in correct OI. In the entorhinal cortex and hippocampus the BOLD signal increased specifically in response to identified odors and decreased for nonidentified odors. In orbitofrontal and piriform cortices both identified and nonidentified odors gave rise to an increased BOLD signal, but the response to identified odors was significantly greater than that for nonidentified odors. These results support a specific role for entorhinal cortex and hippocampus in OI, whereas piriform and orbitofrontal cortices are active in both smelling and OI. Moreover, episodic as well as semantic memory systems appeared to support OI.     

Respiratory responses to olfactory stimuli in Parkinson's disease

There are many reports of olfactory impairment in patients with Parkinson's disease (PD) and the impairment can be observed before the appearance of typical PD symptom. Accordingly, olfactory screening tests may predict disease onset and indicates a need for early treatment before classic signs of the disease. Olfaction is dependent on inspiration, and activation of olfactory limbic areas are synchronized with the natural breathing cycle in animals and humans. Subconscious changes in respiratory pattern occur in response to odor stimulation. The use of olfactory stimuli to investigate respiratory pattern could be used to assess olfactory perception and serve as an index for olfactory limbic activation. In this study, we tested olfactory acuity in normal subjects and in patients with PD and recorded V(O2) and respiratory variables during pleasant and unpleasant odor presentation. All subjects were able to detect the odorants; however patients with PD were assigned to one of two groups, group that could recognize odors or the group with impaired odor recognition. Respiratory response toward unpleasant and pleasant odor recognition were weak in PD groups who could recognize odors than normal subject as well as emotional response to odor stimuli. PD group with impaired odor recognition showed no respiratory response toward odor stimuli. PD may experience difficulty in feeling positive emotions toward pleasant odors prior to the unpleasant odor because respiratory responses to pleasant odors may also be related to higher processes including intentional control of breathing pattern as a result of olfactory cortex processing and perceptions or emotions.     

Olfaction and the "data" memory system in rats

A set of studies was conducted to characterize the memory system involved in successive olfactory discrimination learning in rats. Two odors emanated from different arms of a radial maze; one of the arms contained a water reward. After training on four or five pairs of odors (20 trials per day), rats learned to discriminate the members of a new pair in 5-10 trials. Experiments in which either member of the pair was compared with a novel cue indicated that the rats learn both positive and negative odors, rather than simply ignoring the negative cue. The memories for the odors were apparently persistent, and no evidence for retroactive interference from subsequent training was obtained. Training on 30 pairs did not result in any slowing of subsequent learning, which suggest that the capacity of the memory system for odors is substantial. In a second group of experiments, we tested whether rats distinguish between odors by identifying unshared subcomponents or instead treat odors in a gestalt (i.e., unitary) fashion. Animals trained on three component odors with two in common did not recognize the elements that were unshared when these were presented by themselves. Even when one of the two shared components was combined with the differentiating component into a cue (i.e., two thirds of the original three-component odor), the new cue was treated as a novel odor. However, inclusion of a previously learned simple odor in a complex odor did affect the learning of that odor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Olfactory thresholds are associated with degree of dementia in Alzheimer's disease

Recent neuroanatomical studies have noted that regions of the olfactory pathways contain high levels of neuritic plaques and neurofibrillary tangles, pathological hallmarks of Alzheimer's disease; and that the olfactory epithelium, the most peripheral level of the system, exhibits anatomical and biochemical changes in Alzheimer's disease. The present experiments investigated thresholds for olfactory and taste stimuli in patients with Probable Alzheimer's disease. Olfactory thresholds of Alzheimer's patients were significantly elevated relative to controls and were significantly correlated with scores on dementia scales. Taste thresholds of Alzheimer's patients were within normal limits and unrelated to scores on dementia scales. These results suggest that increased olfactory thresholds in patients with Alzheimer's disease reflect the effects of the disease process and, thus, may aid in the diagnosis and in the understanding of Alzheimer's disease.     

Field potential response changes in the rabbit olfactory bulb accompany behavioral habituation during the repeated presentation of unreinforced odors

Summary Experiments were performed on waking rabbits to investigate the changes in both sniffing behavior and local field potential responses in the olfactory bulb during repeated exposure to unreinforced odors. Six rabbits were each implanted with 2 pairs of electrodes for differential recording of the bulbar extracellular field potential. Each animal was given 3 sequential sessions to each of 2 separate odors on 6 consecutive days, while monitoring the bulbar field potential activity and sniffing behavior. Behavioral sniffing responses exhibited rapid within-session decrement in amplitude and long term decrement across sessions. The within-session decrement showed spontaneous recovery between sessions. Both decremental changes in sniffing behavior were accompanied by changes in the bulbar field potential responses. The responses to novel odors were characterized by a reduction in amplitude of high frequency activity (40–80 Hz) and a corresponding increase in amplitude of low frequency activity (15–25 Hz). The high frequency component of the responses showed an initial increase in frequency to a novel odor on the first 3 presentations followed by a rapid decrease in frequency on subsequent trials in the first session which stabilized thereafter. No change in frequency or relative amplitude was observed for the low frequency component. The absolute difference between the odor evoked activity and the preceeding control activity measured on each trial showed a significant decrement across sessions with no evidence for spontaneous recovery. The results demonstrate that olfactory bulb responses to novel unreinforced odors show both rapid and long-term changes which parallel changes in sniffing behavior. These changes, which have been predicted by a theoretical model of the olfactory bulb (Freeman 1979a, b), are postulated to reduce the spatial specificity of the response pattern to unreinforced odors.     

Down's syndrome in middle age. Topographical distribution and immunoreactivity of brain lesions in an autopsied patient

A 45-year-old patient with Down's syndrome was autopsied. The brain, weighing 800 g, was small in size, and serial sections revealed generalized gyral atrophy and ventricular dilatation. In the gray matter, there was diffuse neuronal degeneration characterized by numerous neurofibrillary tangles (NFTs), senile plaques and frequent amyloid angiopathy. Histochemical and electron microscopical analyses of these lesions showed no qualitative difference from those in Alzheimer's disease. A topographical study of NFTs showed that they were numerous in the limbic system and cerebral neocortex. Various numbers of NFTs were seen in the olfactory bulb, thalamus, medial geniculate body, innominate substance, putamen, caudate, pallidum, central gray, reticular formation, certain midline nuclei of the brainstem, substantia nigra, red nucleus and dorsal vagal nucleus. This distribution pattern was not different qualitatively from that in Alzheimer's disease, and such a similarity was especially evident in the olfactory bulb, where many tufted and mitral cells as well as anterior olfactory nucleus cells showed NFTs. These common features of brain pathology in Down's syndrome and Alzheimer's disease may be due to a specific gene defect in both diseases.     

Perseveration of attention to conspecific odors and novel objects in castrated gerbils

Castrated male and female gerbils were tested for odor preference and for attention to conspecific odors and a novel object. Castrated gerbils housed with sham-operates preferred home odors, discriminated between two groups of male gerbils by olfactory cues, and perseverated in attention to odors of male gerbils and to a novel object. Similar perseveration to male conspecific odors was shown in gerbils given injections of L-DOPA (30 mg/kg). Combined treatment (castration and L-DOPA) resulted in additive effects on perseveration. This research challenges two general hypotheses of gonadal hormone function. The first, that changes in odor preference after castration are due to a loss in testicular androgen, is insufficient, because (1) female as well as male gerbils showed similar perseveration to odors, (2) there was a significant correlation between LH and duration of investigation of male conspecific odors, and (3) L-DOPA, the dopamine precurser, also caused perseveration to conspecific odors. The second, that gonadal hormones are responsible for persistence of attention, cannot be broadly generalized, because castration with resultant elevation of LH and regression of ventral glands resulted in perseveration of attention in male and female gerbils.     

Down's Syndrome in Middle Age

A 45 year old patient with Down's syndrome was autopsied. The brain, weighing 800 g, was small in size, and serial sections revealed generalized gyral atrophy and ventricular dilatation. In the gray matter, there was diffuse neuronal degeneration characterized by numerous neurofibrillary tangles (NFTs), senile plaques and frequent amyloid angiopathy. Histochemical and electron microscopical analyses of these lesions showed no qualitative difference from those in Alzheimer's disease. A topographical study of NFTs showed that they were numerous in the limbic system and cerebral neocortex. Various numbers of NFTs were seen in the olfactory bulb, thalamus, medial geniculate body, innominate substance, putamen, caudate, pallidum, central gray, reticular formation, certain midline nuclei of the brainstem, substantia nigra, red nucleus and dorsal vagal nucleus. This distribution pattern was not different qualitatively from that in Alzheimer's disease, and such a similarity was especially evident in the olfactory bulb, where many tufted and mitral cells as well as anterior olfactory nucleus cells showed NFTs. These common features of brain pathology in Down's syndrome and Alzheimer's disease may be due to a specific gene defect in both diseases. Acta Pathol Jpn 40: 735 743, 1990.     

Differences in naming accuracy of odors presented to the left and right nostrils

Two interlinked areas of debate within psychology are the existence of hemispheric specialization for olfactory processing and whether odors are processed primarily as perceptual codes or as a set of semantic features. This study compared accuracy in naming and judgments of familiarity by right handed subjects to common odors that were presented to the left or right nostrils. There was significantly better production of the correct name of the odor after left side presentation, than after right. Familiarity ratings were identical.     

Enrichment to odors improves olfactory discrimination in adult rats

The authors tested how prior odor enrichment affects the spontaneous discrimination of both preexposed and novel odors. Experimental rats were exposed to single odors or to pairs of similar or dissimilar odors for 1-hr periods twice daily over 20 days. Spontaneous discriminations between pairs of similar odors were tested before and after the odor exposure period using an olfactory habituation task. The authors found that (a) experimental rats did not spontaneously discriminate similar odor pairs before the exposure period, whereas they spontaneously discriminated them after the enrichment period, and (b) the improvement of performance was not selective for the odors used during enrichment. These results show that odor experience changes perception in the manner predicted based on other groups' electrophysiological experiments.     

The neuropsychology of olfaction in Alzheimer's disease

Roberts' proposal of a nasal route of entry for an Alzheimer's disease pathogen leads to a prediction of olfactory dysfunction in Alzheimer's patients. Recent studies suggesting the presence of olfactory deficits are reviewed. Special attention is given to problems in examining olfactory function in demented patients.     

Intrinsically bursting olfactory receptor neurons

Rhythmically bursting neurons are fundamental to neuronal network function but typically are not considered in the context of primary sensory signaling. We now report intrinsically bursting lobster primary olfactory receptor neurons that respond to odors with a phase-dependent burst of action potentials. Rhythmic odor input as might be generated by sniffing entrains the intrinsic bursting rhythm in a concentration-dependent manner and presumably synchronizes the ensemble of bursting cells. We suggest such intrinsically bursting olfactory receptor cells provide a novel way for encoding odor information.     

A role for the hamster's flank gland in heterosexual communication

It is commonly assumed that the male hamsters' flank glands subserve an agonistic role with other males as the intended recipients of the olfactory message. Because of little evidence to support such a relationship, two studies investigated whether females might selectively respond to male flank odors. In a free choice situation females spent more time in proximity with glandular rubbings obtained from intact males than those obtained from castrates or a clean control. Moreover, these sexually receptive females remained longer near odors from familiar as opposed to novel males. The second experiment demonstrated that receptive females spent more time in proximity with flank odors of dominant males as opposed to their subordinate partners or to a clean control. Females can use flank gland odors to discriminate among males as a function of their hormonal state, familiarity and dominance. If this occurs in the wild, such odors could provide cues which would facilitate intersexual selection.     

Volatile female odors activate the accessory olfactory system of male mice without physical contact

We previously reported that male mice are more attracted to volatile odors from intact female mice than from ovariectomized female mice. In the present study, we investigated male attraction to volatile odors from soiled bedding collected from the cages of estrous or ovariectomized female mice. There was no difference in the total time spent sniffing volatile odors from estrous and ovariectomized female mice, suggesting that female mice emit volatile odors which are not excreted into bedding. To test this possibility, we investigated c-Fos expression in the mitral cell layer and granule cell layer of the accessory olfactory bulb 60 min after exposure of male mice to volatile odors without physical contact. Volatile odors from an estrous female mouse significantly increased the total number of c-Fos positive cells in each of the rostral and caudal granule cell layer, but not in the mitral cell layer. After exposure to volatile odors from estrous bedding, the total number of c-Fos positive cells did not increase. Volatile odors from a male mouse did not increase the total number of c-Fos positive cells. Volatile odors from an ovariectomized female mouse increased c-Fos expression only in the caudal granule cell layer. These results suggest that female mice emit specific volatile odors which are not excreted into bedding, and that the volatile odors activate the accessory olfactory system of male mice without physical contact. To characterize the female-specific volatile odors, we conducted habituation-dishabituation tests. Whereas sham-operated male mice discriminated between volatile odors of estrous and ovariectomized female mice, vomeronasal organ-removed male mice did not. These results suggest that male mice discriminated whether or not female mice were ovariectomized, by volatile odors via the accessory olfactory system, and that the female-specific volatile odors are involved in reproduction.     

Effects of fluprazine hydrochloride on conspecific odor preferences in rats

The effect of Fluprazine Hydrochloride (DU 27716) on preference for conspecific male, estrous female and food odors was examined in male rats utilizing a two-compartment choice apparatus. Treatment with 8.0 mg/kg Fluprazine enhanced the preference of males for male odors but had no effect on preference for either estrous female or food odors. The drug-induced enhancement of male odor preference is consistent with the suggestion that Fluprazine interferes in some way with the processing of olfactory stimuli which normally precede offensive attack. The failure of the drug to alter the preference of males for estrous female odors suggests that the increased sniffing of estrous females noted during social testing may be secondary to other sources of conspecific stimulation or may reflect a highly transitory effect on olfactory processes. These results suggest that the suppressive effects of Fluprazine on intermale aggression and copulation are mediated by somewhat distinct mechanisms.     

Stability of preference for odors after short-term exposure in young spiny mice

The stability of olfactory preferences for artificial odors was studied in young spiny mouse pups (Acomys cahirinus). Subjects aged between 2 and 20 days were exposed to the odor of either cinnamon or cumin for 1.5 hr. The durability of preferences for the familiar versus novel odor was subsequently monitored in a three-choice preference test. The results suggest the existence of a sensitive phase for learning odor characteristics, through simple exposure, between Days 2 and 18 of the pups' postnatal life. The sensitive phase proved not be an “on-off” process, but the strongest effect of exposure to odors took place at about Days 4 and 6. However, the duration of preference for exposed odors was dependent on later experience with the odors during retests. The results point to an unusual plasticity in rapid learning of odors through simple exposure in precocial young spiny mice. © 1993 Johan Wiley & Sons, Inc.     

Odor signatures and kin recognition

The basis of olfactory signatures mediating human kin recognition was investigated in two experiments. The odors of mothers and offspring were correctly matched (by subjects unfamiliar with the stimulus individuals) at a greater than chance frequency. In contrast, subjects were not able reliably to match the odors of husbands and wives. These data support the hypotheses that characteristic individuals odors are genetically mediated and that kin recognition should be facilitated by the similarity of such familiar odors among close relatives.     

Effects of odor familiarity on the development of systematic exploration in the spiny mouse, Acomys cahirinus

Developmental changes in patterns of exploration by infant spiny mice, Acomys cahirinus are described. These were investigated using an unbaited radial maze and under three odor conditions; that is, animals were tested in the presence of either familiar (own) odors, unfamiliar conspecific odors, or no odors (washed floor). Two hypotheses were tested. The first was based on the results of a pilot study, and was that adult animals would explore the radial maze in a systematic and predictable fashion tending to move from one arm to the next sequentially. It was hypothesized that infants would adopt this sequential strategy only gradually, as they matured. The second hypothesis was that such patterns of exploration would depend upon the olfactory environment; the presence of familiar odors might facilitate systematic patterns of exploration in very young Acomys. The results showed that both adults and juveniles were less likely to move sequentially when tested with no conspecific odor present; sequential patterns of movement were most likely in the presence of unfamiliar odor, however. The only significant change with age in infants was found for animals tested with unfamiliar odors; these animals showed a dramatic increase in sequential behavior between 3 and 7 days of age. Two additional experiments are reported, which investigated the preferences of infant Acomys for unfamiliar conspecific odors, and it was found that very young (about 3 days) animals exhibit a preference for odors derived from unfamiliar conspecific litters, even when tested in the physical presence of their own parents. The results are discussed with reference to the use of olfactory information as directional cues for animals exploring the radial maze.     

Differential effects of lesions of the vomeronasal and olfactory nerves on garter snake (Thamnophis sirtalis) responses to airborne chemical stimuli

The roles of the main (MOS) and accessory (AOS) olfactory systems of garter snakes in response to airborne chemicals were investigated. Preoperatively, all snakes responded to airborne odors with increased tongue-flick rate and duration. Postoperatively, sham-operated snakes responded to airborne odors with increased tongue-flick rates, but snakes with main olfactory nerve cuts failed to respond to the odors, and snakes with vomeronasal nerve cuts responded to nonprey odors only. Preoperatively, exposure to earthworm odor produced more frequent and shorter duration tongue-flicks during locomotion compared with exposure to water. Postoperatively, only sham-lesioned snakes exhibited differential responding to earthworm odors. This study demonstrates that the MOS is critical for the initiation of tongue-flick behavior in response to airborne odors and that discrimination of odors with biological significance requires a functional AOS.     

Emotional reactivity to odors: Olfactory sensitivity and the span of emotional evaluation separate the genders

Numerous studies report gender differences in emotional reactivity in health and disease and the perception of odors is closely linked to the limbic system. In order to investigate gender differences in the emotional perception of odors we extended the Sniffin’ Stick Test with analogue rating scales for hedonic (pleasantness/unpleasantness) and intensity estimates. We matched 172 healthy subjects (86 females and 86 males) on age in order to balance the study population for three age strata (A: 19–39 years, B: 40–59, C: 60 years and above). Overall odors in our statistical analysis demonstrated significant gender differences for the absolute hedonic estimates but not for the relative hedonic and not for the intensity estimates. These findings demonstrate that women evaluate the pleasantness of perceived odors in a more extreme manner than men without significant differences in hedonic polarity (pleasantness/unpleasantness). Thus, we report a singular significant effect of gender on the dimension valence (hedonic estimation) independent from the dimension intensity. Our findings are in accordance with gender differences in facial reactivity to auditory stimuli and differences in the evaluation of emotional pictures. Investigating olfactory sensitivity females detected n-butanol and discriminated the 16 odors of the test significantly better than males. These results indicate that females possess higher olfactory sensitivity.