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Essential tremor: mild olfactory dysfunction in a cerebellar disorder.

Olfactory dysfunction has been reported to occur in patients with cerebellar disorders, including degenerative ataxias and essential tremor (ET). Previous studies have not considered the effects of mild cognitive deficits, which can occur in ET, and could explain the lower olfaction test scores in ET cases. We more than doubled our initial sample (37 ET cases and 37 controls) [Louis ED, Bromley SM, Jurewicz EC, Watner D. Olfactory dysfunction in essential tremor: a deficit unrelated to disease duration or severity. Neurology 2002;59:1631-3. ] and made adjustments for the mini mental status test score. The University of Pennsylvania Smell Identification Test score remained lower in 87 ET cases compared to 92 controls after adjustment for mini mental status test score and other potential confounders (p = 0.04). These findings: suggest that olfactory dysfunction in ET patients occurs independently of mild cognitive deficits and support recent work that the cerebellum may play a role in central olfactory processing.

Aged↗

Response to urinary volatiles and chemosensory function decline with age in a prosimian primate.

The age-related decline in olfaction is well documented in humans. However, no data are available to date on changes in olfactory sensitivity with age in nonhuman primates. In the male gray mouse lemur (Microcebus murinus), a prosimian primate, the sense of smell is of high relevance for the modulation of both behavioral and physiological functions. We first assessed the effect of aging on physiological responses to urinary cues by measuring reproductive function in adult and aged males exposed to urine odor of preoestrous females. We then evaluated the effect of aging on chemosensory function using a discrimination test in freely behaving animals. Our results indicate that whereas adult animals show a clear increase in testosterone levels when exposed to female urine odor, this effect is lacking in aged animals. In addition, chemosensory function shows a progressive decline with age. Using both physiological responses to urinary volatiles and spontaneous behavior, this study provides the first data set on the effect of aging on chemosensory responsiveness in a nonhuman primate.

Aging↗

Multidimensional scaling of ferrous sulfate and basic tastes.

The status of metallic sensations as a primary or basic taste category is controversial. Ferrous sulfate (FeSO4) has been suggested as a prototypical metallic chemosensory stimulus. At least part of the metallic sensation from FeSO4 arises from a metallic retronasal smell. The quality of this sensation was studied via multidimensional scaling (MDS) of taste similarities, with and without nasal closure to eliminate retronasal olfactory sensations. The metallic stimulus was embedded in a series containing classical "basic taste" stimuli, alum and monosodium glutamate. With olfaction available, the metallic stimulus plotted away from basic tastes and taste mixtures. Scaled ratings of sensory properties related to metallic taste (iron-nail, copper-penny-like, aftertaste) of FeSO4 decreased with nasal closure. Results are consistent with the idea that ferrous sulfate produces a distinctly different sensation from the traditional basic tastes, which includes both olfactory and oral sensations.

Adolescent↗

There's no place like home: cage odours and place preference in subordinate CD-1 male mice.

Prior studies using mice have shown that scent marks are an important source of information and can cause behavioural changes in other individuals. Studies have also shown that scent marks in the environment can affect the outcome of social interactions between mice. We used conditioned place preference tests to investigate whether CD-1 male mice (Mus musculus) are reinforced by olfactory cues from the home cage. Soiled bedding from the home cage was presented in the initially less preferred chamber of the apparatus to determine whether this association would reduce the unconditioned preference for one chamber over the other. We tested the effects of social rank and housing condition by comparing the performance of dyads that were polarised into dominant and subordinate relationships, both when paired and when separated, with mice that were isolated throughout. The development of conditioned place preference (CPP) supported by home cage odours was influenced by social rank but not by housing condition. Only subordinate mice showed CPP to home cage odours, and this effect was seen irrespective of whether they were housed with a dominant cage mate or alone. Neither dominant (paired or separated) nor isolated mice showed any change in their preference for the chamber associated with home cage odours. This suggests that the smell of home is a more powerful reinforcer for subordinate mice in that it can produce contextual conditioning to the environment in which it is experienced.

Analysis of Variance↗

Associations between olfactory identification and verbal memory in patients with schizophrenia, first-degree relatives, and non-psychiatric controls.

OBJECTIVE: Olfactory identification deficits and verbal memory impairments may represent trait markers for schizophrenia. The aims of this study were to: (1) assess olfactory identification in patients, first-degree relatives, and non-psychiatric controls, (2) determine differences in verbal memory functioning in these three groups, and (3) study correlations between olfactory identification and three specific verbal memory domains. METHOD: A total of 106 participants-41 patients with schizophrenia or related disorders, 27 relatives, and 38 controls-were assessed with the University of Pennsylvania Smell Identification Test (UPSIT) and the Wechsler Memory Scale-Third Edition. Linear mixed models, accounting for clustering within families and relevant covariates, were used to compare scores across groups and to examine associations between olfactory identification ability and the three verbal memory domains. RESULTS: A group effect was apparent for all four measures, and relatives scored midway between patients and controls on all three memory domains. UPSIT scores were significantly correlated with all three forms of verbal memory. Age, verbal working memory, and auditory recognition delayed memory were independently predictive of UPSIT scores. CONCLUSIONS: Impairments in olfactory identification and verbal memory appear to represent two correlated risk markers for schizophrenia, and frontal-temporal deficits likely account for both impairments.

Adult↗

Odortypes and MHC peptides: Complementary chemosignals of MHC haplotype?

The olfactory and immune systems must perform optimally in the task of recognizing thousands of molecules to ensure survival. A particularly intriguing link between these systems is that animals can smell differences in the major histocompatibility complex (MHC), a cluster of highly polymorphic genes found on human chromosome 6 and mouse chromosome 17. Two different sets of compounds found in urine have been postulated to convey information on MHC haplotype: volatile compounds (odortypes) and MHC peptides. Here we argue for complementary roles for these chemosignals.

Animals↗

Can memories kindle nonconvulsive behavioral seizures in humans? Case report exemplifying the "limbic psychotic trigger reaction".

We present three hypotheses-(1) the limbic psychotic trigger reaction (LPTR) is a form of nonconvulsive behavioral seizures (NCBS), (2) kindling may occur in the LPTR, and (3) kindling may occur with memory stimuli-and report a case that may exemplify a LPTR kindled by memory and triggered by light and smell. The LPTR has a primate model, in which NCBS are kindled by intermittent exposure to actual subthreshold stimuli. In humans, we propose that such triggering stimuli can be revived by memory alone. Thus, individualized stimuli can trigger partial limbic seizures or seizure-like bizarre episodes with a transient loss of frontal control functions. We present a case of paroxysmal episodes of out-of-character, bizarre, unplanned nonvoluntary acts that occurred with flat affect and without drive motivation (e.g., "fire setting"). Implicated is a transient state of limbic "paleo-consciousness" with preserved memory, autonomic arousal, and first-time brief psychosis (e.g., olfactory, visual hallucinations and depersonalization with olfactory attributes). As in kindled primates, LPTR patients do not show a consistent pattern of morphological brain abnormality; half have had an abnormal electroencephalogram, computed tomography scan, or magnetic resonance image at some time during their lives, and half (including the new patient) have had closed head injuries.

Adult↗

Olfactory regulation of maternal behavior in mammals.

In mammals, olfactory cues are extensively used in many aspects of maternal care to ensure the coordination of mother-infant interactions and consequently the normal development of the offspring. Outside the period of parturition and lactation, when the young are not a behavioral priority, olfactory cues play an inhibitory role on maternal responsiveness since in most mammalian species studied so far, nonpregnant females find the odor of young aversive. On the contrary at the time of parturition, a shift in the hedonic value of infantile odors occurs so that the young now become a very potent stimulus and this sensorial processing constitutes an important part of the maternal motivational system. Moreover, infants' odors provide a basis for individual recognition by their mothers and some species (ungulates) have developed highly specialized mechanisms for processing of the infant signals. Perception of the smell of the young also regulates various aspects of maternal behavior. Dodecyl propionate, a compound released by of pup's preputial glands, has been shown to influence anogenital licking behavior, a fundamental pattern of maternal behavior in rodents. While there is no functional specificity of either the main or the accessory olfactory systems in the development of maternal behavior amongst species, it appears that only the main olfactory system is implicated when individual odor discrimination of the young is required. Neural structures, such as the main olfactory bulb, undergo profound changes when exposed to offspring odors at parturition. These changes in synaptic circuitry contribute both to maternal responsiveness to these odors, to their memorization, and to effects of long-term maternal experience.

Animals↗

Emerging views on the distinct but related roles of the main and accessory olfactory systems in responsiveness to chemosensory signals in mice.

In rodents, the nasal cavity contains two separate chemosensory epithelia, the main olfactory epithelium, located in the posterior dorsal aspect of the nasal cavity, and the vomeronasal/accessory olfactory epithelium, located in a capsule in the anterior aspect of the ventral floor of the nasal cavity. Both the main and accessory olfactory systems play a role in detection of biologically relevant odors. The accessory olfactory system has been implicated in response to pheromones, while the main olfactory system is thought to be a general molecular analyzer capable of detecting subtle differences in molecular structure of volatile odorants. However, the role of the two systems in detection of biologically relevant chemical signals appears to be partially overlapping. Thus, while it is clear that the accessory olfactory system is responsive to putative pheromones, the main olfactory system can also respond to some pheromones. Conversely, while the main olfactory system can mediate recognition of differences in genetic makeup by smell, the vomeronasal organ (VNO) also appears to participate in recognition of chemosensory differences between genetically distinct individuals. The most salient feature of our review of the literature is that there are no general rules that allow classification of the accessory olfactory system as a pheromone detector and the main olfactory system as a detector of general odorants. Instead, each behavior must be considered within a specific behavioral context to determine the role of these two chemosensory systems. In each case, one system or the other (or both) participates in a specific behavioral or hormonal response.

Animals↗

Sexual incentive motivation, olfactory preference, and activation of the vomeronasal projection pathway by sexually relevant cues in non-copulating and naive male rats.

There are some apparently healthy male rats that fail to mate after repeated testing with receptive females. We have previously shown that these "non-copulator (NC)" males show no partner preference for a receptive female when given the opportunity to physically interact with a sexually receptive female or a sexually active male. We also demonstrated that although NC males prefer odors from estrous females to odors from anestrous females, this preference is significantly reduced in comparison to the preference displayed by copulating (C) males. The aim of the present study was to evaluate in NC males sexual incentive motivation, that is, the approach behavior of male rats to either a sexually receptive female or a sexually active male in a test where the subjects can smell, hear, and see the stimulus animal but prevents their physical interaction. In addition, we determined whether NC rats have alterations in their ability to detect odors from conspecifics or odors related to food. In the detection of odors from conspecifics, we determined if these NC males are sexually attracted toward odors from receptive females or sexually active males. For food-related odors, we quantified the time it took the subjects to locate a hidden a piece of apple. Finally, using the induction of Fos-immunoreactivity (Fos-IR) as an index of neuronal activation, we compared the response of the vomeronasal projection pathway (VN pathway) of C and NC male rats exposed to estrous bedding. Males without sexual experience (WSE) were included in all experiments to determine the importance of previous heterosexual experience in the different behavioral tests and in the activity of the VN pathway. In the sexual incentive motivation test, we found that C and WSE male rats have a clear preference for estrous females over sexually active males, whereas NC male rats showed no preference. In odor tests, our results showed that C males had a clear preference for odors from estrous females as opposed to odors from sexually active males. Although NC and WSE male rats showed a preference for estrous female odors, this preference was significantly reduced compared to that shown by C males. No differences were found between WSE, C, and NC males in the detection of stimuli associated with food-related odors. A significant increase in Fos-IR was observed in the mitral cell layer of the accessory olfactory bulb in all groups when exposed to estrous bedding. However, only the C male rats exposed to estrous female bedding showed an increase Fos-IR in all structures of the VN pathway. An increase in Fos-IR was observed in the medial preoptic area (MPOA) of WSE males exposed to estrous bedding. No increases in Fos-IR were detected along the VN pathway in NC male rats. We proposed that NC male rats do not display sexual behavior due to a reduced sexual motivation that could be caused by alterations in the neuronal activity of the VN pathway during the processing of estrous odors.

Animals↗

New evidence that the MHC influences odor perception in humans: a study with 58 Southern Brazilian students.

Increasing evidence suggests a correlation between mate choice, odor preference, and genetic similarity at the Major Histocompatibility Complex (MHC) in a variety of animals, including our species. The MHC is a highly polymorphic group of genes that play an important role in the immunological self/nonself recognition. Its products have been reported to take part on the variety of compounds and reactions that together build an individual's body odor. It has been suggested, therefore, that animals use body odor as a guide to identify possible mates as MHC-similar or MHC-dissimilar from their own genotype. Preference for a MHC-dissimilar partner enhances MHC heterozygosity of an individual's offspring. The possible adaptive advantages are clear: it is a mechanism of avoiding inbreeding and MHC-heterozygous offspring may have enhanced immunocompetence. The aim of this study was to search, in our species, new evidence on the correlation between specificities at HLA-A and HLA-B and assessments of pleasantness regarding specific body odors. HLA is the name for the human MHC. Four olfactory sessions were performed with 58 young Southern Brazilian students, in order to investigate whether assessments of pleasantness of body odors from individuals correlate to a person's HLA phenotype. Body odors were collected via sweat and urine from all participants. Women smelled and scored all male odor samples and men did the same with all female samples. We found a significant correlation only when female smellers evaluated male sweat odors.

Adolescent↗

Physiologic responses to sensory stimulation by food: nutritional implications.

The importance of sensory factors (both the sensory properties of foods and sensory abilities of consumers) in food selection is widely accepted. Less recognized and understood are the effects of sensory stimulation on physiologic processes. Mere exposure to the sight, smell, taste, and textural attributes of foods elicits myriad digestive, endocrinologic, thermogenic. cardiovascular, and renal responses. The responses are rapid (generally occurring within minutes of sensory stimulation), small (relative to the magnitude achieved when food is actually being metabolized), and transient (returning to near-baseline levels within minutes). Nevertheless, they have been hypothesized to prime the body to better absorb and use ingested nutrients. They are termed preabsorptive or cephalic phase responses. This review summarizes current knowledge of stimuli that trigger cephalic phase responses and selected response features (eg, magnitude and type of enzymes or hormones released). Mechanisms by which cephalic phase responses may influence nutrient absorption and use are proposed. Current knowledge of the behavioral and physiologic importance of cephalic phase responses is limited, thereby hampering development of dietary recommendations for preventive or therapeutic interventions. Further study of several identified promising areas of application and other easily proposed situations may provide a basis for expanded medical nutrition therapy.

Animals↗

Sex differences in olfactory identification and Wisconsin Card Sorting performance in schizophrenia: relationship to attention and verbal ability.

We investigated the hypothesis that different prefrontal brain systems (i.e., dorsal vs. ventral) and sex contribute differentially to cognitive deficit in schizophrenia. Performance was assessed among clinically stable, chronic schizophrenic outpatients and matched normal control subjects on olfactory identification [on the University of Pennsylvania Smell Identification Test (UPSIT)] and on executive functions [using the Wisconsin Card Sorting Test (WCST)]. Patients were impaired on both tests compared to controls, and male schizophrenics were impaired on the WCST compared to female schizophrenics. The pattern of results suggests that gender differences on the UPSIT are mildly accentuated in schizophrenia. The data support our previous study indicating that UPSIT performance is largely independent of the executive or attentional deficits typically associated with schizophrenia, with the exception of verbal ability. Further research with larger samples is required to test the hypothesis that there is a severely impaired subgroup of male patients with diffuse prefrontal dysfunctions.

Adolescent↗

Olfactory identification and psychosis.

BACKGROUND: Olfactory identification performance has been investigated in several psychiatric populations, with deficits most commonly reported in patients with schizophrenia. In this study, olfactory identification performance was investigated in a more homogenous group of treatment-refractory patients with schizophrenia (T-RS) and in two additional psychiatric groups who demonstrate some similarities to the patients with schizophrenia in terms of symptomotology and medication regime. METHODS: The olfactory identification performance of 16 T-RS patients was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) and compared to that of 16 normal control subjects and two other psychiatric patient groups: 19 affective disorder patients requiring maintenance antipsychotic medication and 20 affective disorder patients not receiving antipsychotic medication. RESULTS: The olfactory identification performance of T-RS patients was significantly lower than that of normal controls but not significantly different from either affective disorder group. The olfactory identification performance of affective disorder patients receiving antipsychotic medication was significantly lower than that of affective disorder patients not receiving antipsychotic medication. DISCUSSION: Results are discussed in the context of a possible link between psychotic symptomotology and olfactory identification performance.

Adult↗

Olfactory identification and apolipoprotein E epsilon 4 allele in mild cognitive impairment.

To investigate olfactory identification and apolipoprotein E epsilon 4 allele in patients with mild cognitive impairment (MCI), we used Cross-Cultural Smell Identification Test (CC-SIT) from University of Pennsylvania to assess olfactory identification performance and polymerase chain reaction (PCR) to detect apolipoprotein E epsilon 4 (ApoE epsilon 4) allele in 28 patients with MCI and the 30 age-matched control subjects in present study. The Mann-Whitney U test demonstrated that the MCI group performed significantly worse on CC-SIT than the normal aging group (P<0.01). For MCI patients olfaction scores correlated positively with CAMCOG-C (r=0.61, P<0.01), but not with age, gender or years of education. In normal subjects, the CC-SIT score showed no significant associations with age, gender, years of education, or CAMCOG-C. As the least common allele in Chinese, epsilon 4 was found in 13.3% of controls and in 35.8% of MCI in this study. ApoE epsilon 4 was significantly higher in MCI group than normal group (chi(2)=4.65, P<0.01). There was a significant effect of allele status on odor identification: subjects with epsilon 4 allele were not able to identify as many odors as the subjects without epsilon 4 allele (P<0.01). These results suggested that the decreased olfactory identification in MCI may be a marker for the early diagnosis of Alzheimer's disease, and ApoE genotype may be part of the basis of olfactory identification decline.

Age Factors↗

Hemispheric differences in odour recognition.

Two experiments were designed in order to study hemispheric differences in odour recognition in normal subject. In the first experiment subjects first smelled an odour and then a visual stimulus (a picture or a word related or unrelated to the odour) was flashed either to the left or to the right hemisphere for 150 milliseconds. Subjects had to press a key if the two stimuli (olfactory and visual) matched and another key if they did not. Reaction time analysis showed that the responses were faster when the second stimulus (either picture or word) was presented to the right hemisphere. In a second experiment the first stimulus was auditory rather than olfactory. Subjects were instructed to listen to names of odorants and then to respond to pictures or written names as in the first experiment. In this case a left hemisphere advantage emerged, presumably related to the priming of the left hemisphere by the auditorially presented verbal stimulus.

Analysis of Variance↗

Comparison of health of occupants and characteristics of houses among control homes and homes insulated with urea formaldehyde foam. I. Methodology.

The methodology of a study in which a comparison is made of the health and house characteristics of the occupants of 231 control homes and 571 houses containing urea formaldehyde foam insulation (UFFI) is described. All homes and occupants were examined on two occasions separated by an interval of 12 months, during which two-thirds of the UFFI houses performed remedial work. The occupants were examined using a health questionnaire and a series of objective tests including pulmonary function, nasal airway resistance, sense of smell, nasal surface cytology, and patch tests. The houses were assessed using a questionnaire and measurements of indoor formaldehyde and carbon dioxide levels. No obvious bias has been identified in this survey with respect to the representativeness of the population studied, the classification of the UFFI and control groups, and the input from both the respondents and observers. The symptom responses made by individuals within the same households were not correlated. Quality control assessment of the objective health tests and formaldehyde sampling and assays demonstrated that these procedures remained stable over the two phases of the study, with the exception of the expected decrease in the pulmonary flow rates over 1 year and a small unexpected increase in the forced vital capacity and the forced expiratory volume in 1 s.

Airway Resistance↗

Comparison of methyl anthranilate and denatonium benzoate as aversants for learning in chicks.

Methyl anthranilate (MeA) has been widely used as a taste aversant for domestic chicks in the one-trial passive avoidance learning (PAL) task. However, MeA has a strong smell that may be aversive to chicks. Therefore, odourless denatonium benzoate (DB) has been suggested as an alternative taste aversant in PAL. The present study was designed to compare the efficacy of MeA and DB as aversants in the one-trial PAL task. In this task, young chicks peck a visually conspicuous bead coated with a taste aversant and in a single trial learn to avoid a similar, but uncoated bead at subsequent presentation. In Experiment 1, chicks were trained using a silver-coloured bead coated with 100% MeA, 0.5% DB or distilled water. After 3 h, MeA-trained, but not DB-trained chicks, exhibited significantly higher avoidance of the test bead than water-trained chicks. In Experiment 2, three pre-training presentations of an uncoated red bead preceded training with the silver bead. MeA-trained chicks showed significantly higher avoidance of the test bead than water-trained chicks. The numbers of water- and DB-trained chicks that avoided pecking the test bead were low and not significantly different from each other. However, DB-trained chicks exhibited significantly longer latencies to peck the test bead than water-trained chicks, indicating that they had retained some memory of the task. Thus, 0.5% DB is a weaker aversant than MeA and it does not induce high levels of learning in the one-trial PAL task. However, DB may prove useful for investigating weakly reinforced learning.

Animals↗