Intranasal localizability of odorants: influence of stimulus volume.

When an odorant is presented to one side of the nose and air to the other, the ability to localize which side received the odorant depends upon trigeminal nerve stimulation. It has been shown that performance on this lateralization task increases as stimulus concentration increases. In this study, we determined the influences of stimulus volume and sex on the ability to localize each of 8 odorants presented at neat concentrations: anethole, geraniol, limonene, linalool, menthol, methyl salicylate, phenyl ethanol, and vanillin. At a low stimulus volume (11 mL), only menthol was localized at an above-chance level. At a high stimulus volume (21 mL), above-chance localization occurred for all odorants except vanillin. Women were significantly better than men in localizing menthol. Stimuli rated as most intense were those that were most readily localized. The detection performance measures, as well as rated intensity values, significantly correlated with earlier findings of the trigeminal detectability of odorants presented to anosmic and normosmic subjects. This study suggests that differences in stimulus volume may explain some discrepant findings within the trigeminal chemosensory literature and supports the concept that vanillin may be a "relatively pure" olfactory stimulus.

Olfaction in dentistry.

Practitioners of oral medicine frequently encounter patients with complaints of taste disturbance. While some such complaints represent pathological processes specific to the gustatory system, per se, this is rarely the case. Unless taste-bud mediated qualities such as sweet, sour, bitter, salty, umami, chalky, or metallic are involved, 'taste' dysfunction inevitably reflects damage to the sense of smell. Such 'taste' sensations as chicken, chocolate, coffee, raspberry, steak sauce, pizza, and hamburger are dependent upon stimulation of the olfactory receptors via the nasopharynx during deglutition. In this paper, we briefly review the anatomy, physiology, and pathophysiology of the olfactory system, along with means for clinically assessing its function. The prevalence, etiology, and nature of olfactory disorders commonly encountered in the dental clinic are addressed, along with approaches to therapy and patient management.

[99mTc]TRODAT-1 SPECT imaging correlates with odor identification in early Parkinson disease.

BACKGROUND: In vivo imaging of the dopamine transporter with [99mTc]TRODAT-1 (TRODAT) and olfactory testing have both been proposed as potential biomarkers in Parkinson disease (PD). OBJECTIVE: To evaluate the relationship between TRODAT SPECT imaging, odor identification skills, and motor function in patients with early PD. METHODS: Twenty-four patients with a clinical diagnosis of early-stage PD (mean Hoehn & Yahr stage = 1.4) underwent TRODAT imaging, Unified PD Rating Scale (UPDRS) ratings of motor function, and administration of the University of Pennsylvania Smell Identification Test (UPSIT). Brain images were obtained using a standardized processing protocol and specific uptake ratios for striatal regions of interest were calculated. Partial correlations between the imaging indices, disease duration, UPSIT scores, and UPDRS motor scores were then calculated. RESULTS: UPSIT scores were correlated with TRODAT uptake in the striatum as a whole (r = 0.66, p = 0.001). The putamen showed the strongest correlation with the UPSIT (r = 0.74; p < 0.001). The correlation between dopamine transporter density in the caudate and UPSIT was moderate (r = 0.36, p = 0.11), but was not significant. CONCLUSIONS: Olfactory function is highly correlated with dopamine transporter imaging abnormalities in early Parkinson disease (PD). Further studies are warranted to determine whether changes over time in these two measures are also correlated in early PD.

Olfactory dysfunction in degenerative ataxias.

Several lines of evidence suggest that the cerebellum may play a role in higher-order olfactory processing. In this study, we administered the University of Pennsylvania Smell Identification Test (UPSIT), a standardised test of olfactory function, to patients with ataxias primarily due to cerebellar pathology (spinocerebellar ataxias and related disorders) and to patients with Friedreich ataxia, an ataxia associated mainly with loss of afferent cerebellar pathways. UPSIT scores were slightly lower in both patient groups than in the control subjects, but no differences were noted between the scores of the Friedreich and the other ataxia patients. Within the Friedreich ataxia group, the smell test scores did not correlate with the number of pathologic GAA repeats (a marker of genetic severity), disease duration, or categorical ambulatory ability. UPSIT scores did not correlate with disease duration, although they correlated marginally with ambulatory status in the patients with cerebellar pathology. This study suggests that olfactory dysfunction may be a subtle clinical component of degenerative ataxias, in concordance with the hypothesis that the cerebellum or its afferents plays some role in central olfactory processing.

Olfactory dysfunction in schizophrenia and temporal lobe epilepsy.

BACKGROUND: Schizophrenia and mesial temporal lobe epilepsy (TLE) represent two common brain disorders that share dysfunction of temporo-limbic neural substrates. OBJECTIVE: We evaluated whether patients with schizophrenia exhibited olfactory performance more similar to right or left temporal lobe epilepsy patients. METHODS: Odor identification ability and detection threshold sensitivity were measured in 40 patients with schizophrenia, 14 patients with right- and 18 patients with left-temporal lobe epilepsy (TLE) patients, and 25 healthy controls. Odor identification was assessed with the University of Pennsylvania Smell Identification Test (UPSIT) and odor detection threshold sensitivity with a single-staircase procedure using the stimulant phenyl ethyl alcohol (PEA). RESULTS: Relative to controls, only patients with schizophrenia and right TLE exhibited significant impairment in UPSIT performance. Left TLE patients and controls performed comparably on the UPSIT. Detection threshold sensitivity to PEA did not differ significantly among the four groups. CONCLUSIONS: These data suggest a greater reliance of olfactory processing on right hemisphere structures and are also consistent with recent neuroimaging studies that have implicated aberrant processing of olfactory information in right hemispheric brain regions in schizophrenia.

NaCl thresholds: relationship to anterior tongue locus, area of stimulation, and number of fungiform papillae.

NaCl detection thresholds were determined for 12.5- and 50-mm(2) lingual areas at four anterior tongue locations in eight subjects using a device that allowed for accurate temporal and spatial presentation of tastants to small regions of the anterior tongue. The locations, all on the right side of the tongue, were the tongue tip, an area 1.7 cm posterior to the tongue tip, and regions 1.7 and 3.4 cm posterior to the tip along the tongue's lateral margin. Stimulus duration was 0.75 s. Thresholds were established using a two-alternative forced-choice single-staircase procedure, and the number of fungiform papillae at each stimulation site was counted with the aid of videomicroscopy. NaCl thresholds were lower for the 50-mm(2) than the 12.5-mm(2) stimulation area at all target sites, and were directly related to papillary number among and within the stimulated regions. For a given number of papillae, thresholds were lower within the 12.5-mm(2) than within the 50-mm(2) stimulation region, likely reflecting taste bud density and activation of common afferent pathways. The tongue tip was more sensitive than any other tongue region, and the lateral margins were seemingly more sensitive than the lingual centrum. Large individual differences in taste sensitivity and tongue papilla numbers were noted, and some subjects were insensitive to the highest tastant concentrations at the nontip loci. This study empirically demonstrates that NaCl detection sensitivity varies across discrete regions of the anterior tongue and is related to the relative number and density of fungiform papillae.

Olfaction and its alteration by nasal obstruction, rhinitis, and rhinosinusitis.

The sense of smell has been largely ignored by otorhinolaryngologists, even though 1) its medical stewardship falls within their specialty's purview, 2) olfactory dysfunction is not uncommon in the general population, and 3) disorders of olfaction have significant quality of life, nutritional, and safety consequences. This report provides a succinct overview of the major intranasal neural systems present in humans (namely, cranial nerves O, I, and V, and the nonfunctional accessory [vomeronasal] organ system), along with a summary of notable findings resulting from the application of modern olfactory tests to patient populations, emphasizing diseases of the nose. Such tests have led to the discovery of significant influences of age, gender, smoking, toxic exposure, and genetics on the ability to smell. Within the field of otorhinolaryngology, they have revealed that 1) surgical and medical interventions in patients with rhinosinusitis do not, on average, lead to complete recovery of olfactory function, despite common beliefs to the contrary, and 2) associations are generally lacking between measures of airway patency and olfactory function in such cases. These findings have thrown into question the dogma that olfactory loss in rhinosinusitis is attributable primarily to blockage of airflow to the receptors and have led to histopathological studies demonstrating significant olfactory epithelial compromise in sinonasal syndromes.

Olfactory-evoked regional cerebral blood flow in Alzheimer's disease.

Olfaction is impaired in Alzheimer's disease (AD). It was hypothesized that AD would reduce olfactory-evoked perfusion in mesial temporal olfactory (piriform) cortex, where neuropathology begins. Seven AD patients and 8 elderly controls (ECs) underwent olfactory threshold and identification tests and olfactory stimulation during positron emission tomography. Odor identification was impaired in AD, but threshold was not. Olfactory stimulation in ECs activated right and left piriform areas and right anterior ventral temporal cortex. AD patients had less activation in right piriform and anterior ventral temporal cortex but not in the left piriform area. Although orbital cortex did not activate in ECs, there was a significant between-groups difference in this area. Right piriform activation correlated with odor identification. Impaired odor identification likely reflects sensory cortex dysfunction rather than cognitive impairment. Given olfactory bulb projections to the mesial temporal lobe, olfactory stimulation during functional imaging might detect early dysfunction in this region.

Olfaction.

The main and accessory olfactory systems have received considerable attention on the part of scientists and clinicians during the last decade, largely because of (a) quantum advances in understanding their genetically expressed receptor mechanisms, (b) evidence that their receptor cells undergo neurogenesis and both programmed and induced cell death, and (c) important technical and practical developments in psychophysical measurement. The latter developments have led to the proliferation of standardized olfactory testing in laboratories and clinics, and to the discovery that smell loss is among the first signs of a number of neurodegenerative diseases, including Alzheimer's disease and idiopathic Parkinson's disease. Recent controversial claims that humans possess a functioning vomeronasal system responsive to "pheromones" has added further interest in intranasal chemoreception. This review focuses on recent progress made in understanding olfactory function, emphasizing transduction, measurement, and clinical findings.

A re-examination of the rate of vocational dysfunction among patients with anosmia and mild to moderate closed head injury.

This study sought to verify two earlier reports that up to 93% of patients with closed head injury (CHI) and anosmia are vocationally dysfunctional due to executive impairments associated with orbitofrontal damage. Participants were 11 men and 4 women identified from a pool of 60 potential subjects referred for evaluation of trauma-related chemosensory dysfunction at the University of Pennsylvania Smell and Taste Center from 1988 to 1994. These 15 subjects met four criteria: (i) willingness to complete a brief semi-structured interview concerning their pre- and post-CHI work history; (ii) age <60 years; (iii) evidence of mild to moderate CHI; and (iv) scores on the University of Pennsylvania Smell Identification Test indicative of anosmia or severe microsmia and non-malingering. In contrast to the earlier reports, only 7% of the subjects were vocationally dysfunctional. This study calls into question previous reports suggesting that anosmia is a reliable predictor of post-CHI vocational outcome.

Olfaction - Quantification and management.

Patients with olfactory disorders are often referred to the otolaryngologist for assessment and treatment. Karely, however, is the otolaryngologist prepared to provide such services. In a previous paper in this journal, we described the basic anatomy and physiology of the olfactory system. Additionally, we listed a standardized nomenclature for classifying olfactory disturbances, and reviewed means for clinically assessing such disorders. In this paper, we provide a more detailed protocol for evaluating patients with loss of smell, incorporating sensory, imaging, and medical approaches employed at the Smell and laste Center of the University of Pennsylvania, USA. Examples of common syndromes encountered in everyday practice are deicribed.

Reduced olfactory bulb volume in patients with schizophrenia.

OBJECTIVE: The authors' goal in this study was to compare the size of olfactory bulbs of patients with schizophrenia and those of healthy subjects. METHOD: Magnetic resonance imaging scans of olfactory bulbs were obtained from 26 patients with schizophrenia and 22 healthy comparison subjects. A reliable region of interest procedure was used to measure olfactory bulb volume. RESULTS: Patients exhibited 23% smaller bilateral bulb volume than comparison subjects, independent of acute clinical, demographic, or treatment measures. Bulb volume correlated with odor detection sensitivity in healthy subjects but not in patients with schizophrenia. CONCLUSIONS: Patients with schizophrenia exhibit structural olfactory deficits as well as functional olfactory deficits. The olfactory system may be a model system in which to study the neurobiology of the disorder.

Effects of a pressure surround on the regional taste detection threshold for sodium chloride.

The question as to whether tactile stimulation alters proximal taste function in humans has never been answered, despite the suggestion of anatomical and physiological associations between somatosensory and gustatory function in a number of species. In this study, we established NaCl detection thresholds for a 25 mm2 anterior tongue region on four test occasions in each of 12 men and 12 women. Testing was performed using the Regional Automated Taste Testing System (RATTS), a device that allows for accurate temporal and spatial presentation of tastants to the lingual surface. On each test occasion, a different negative pressure (vacuum suction) was applied around the stimulus presentation field of the glass stimulation device (i.e. 40, 50, 60 and 70 mmHg). The order of presentation of the vacua was systematically counterbalanced among subjects across sessions using 4 x 4 Latin square sequences. Neither the vacua nor their order of presentation meaningfully altered the taste threshold values, even though the higher vacua produced persistent discernible discomfort in most subjects. On average, taste thresholds tended to be marginally lower in women than in men. These data indicate that static vacuum-induced tactile stimulation around a discrete anterior taste field has no meaningful influence on NaCl detection threshold sensitivity.

A light and electron microscopic study of taurine-like immunoreactivity in the main olfactory bulb of frogs.

The distribution of taurine in the frog olfactory bulb was studied using light and electron microscopic immunohistochemical techniques. At the light microscopic level, taurine-like immunoreactivity (taurine-LI) was found in (i) fibers coursing from the olfactory nerve layer to the glomerular layer, (ii) cell bodies and processes primarily located in the caudal part of the granule cell layer (GCL), and (iii) puncta outlining unstained somata of mitral cells and cells in the GCL. In consecutive sections processed for taurine or GABA, numerous cells of the caudal GCL displayed taurine-LI and GABA-like immunoreactivity (GABA-LI). A bimodal distribution of the cross-sectional cell area for GABA-LI cells implied their morphological diversity, and the peak for larger GABA-LI cells coincided with the maximum for taurine-LI cells. At the electron microscopic level, single immunogold labeling showed that GABA-LI, but not taurine-LI, is present in granule cells, whereas both taurine-LI and GABA-LI were localized in a 'non-granule' type of cell. The double labeling procedure demonstrated coexistence of taurine-LI and GABA-LI in neurons of a 'non-granule' type. These cells had some ultrastructural features typical of short axon cells in the GCL of the mammalian olfactory bulb and were tentatively considered as short axon-like cells. Results suggest that, in the frog olfactory bulb, taurine is contained in primary olfactory afferents and short axon-like cells of the GCL co-localizing GABA and taurine.

Chronic dexamethasone treatment potentiates insult to olfactory receptor cells produced by 3-methylindole.

The effect of chronic dexamethasone treatment on damage to olfactory receptor cells produced by 3-methylindole (3-MI) was examined. Twelve rats were injected, every other day, with dexamethasone (1.5 mg/kg, i.p.), and 12 rats with saline alone. Injections began 1 week before and continued, in different rats, from 1 to 4 weeks after a single intraperitoneal administration of 150 mg/kg 3-MI. One, two, three, and four weeks after exposure to 3-MI, different groups of rats, three specimens per each treatment condition, received bilateral application of horseradish peroxidase to the olfactory mucosa and were subsequently sacrificed. Anterograde labeling of primary afferents, i.e., an inverse correlate of the degree of cellular damage, was quantitatively determined by measuring the mean optical density (MOD) of staining in sections of the olfactory bulb. In saline-injected rats, the MOD values were 27.0, 46.6, 87.1, and 104.7 for one, two, three, and four post-3-MI weeks, respectively. The corresponding values in the dexamethasone-treated rats were 15.7, 29.7, 87.5, and 110.5. The MOD values of the dexamethasone-injected rats were significantly lower than those of the saline-injected rats for post-3-MI weeks 1 and 2, indicative of stronger damage to olfactory receptor cells in the rats treated with the glucocorticoid. The data suggest that dexamethasone potentiates the 3-MI olfactotoxicity during the first 2 weeks after insult. This effect, at least partly, may be due to the inducing action of dexamethasone on the cytochrome P450 responsible for metabolic bioactivation of 3-MI.

An automated regional taste-testing system.

A fully programmable and portable automated regional taste-testing system is described. This system utilizes a glass stimulator held to the surface of the tongue by a mild vacuum. Temporally and spatially discrete trains of stimuli, delivered from a bank of glass reservoirs through microprocessor-controlled Teflon solenoid valves and both glass and Tygon tubing, can be delivered to the lingual surface at millisecond durations. Rinses between stimuli are similarly programmed. The stimulus delivery is monitored at the surface of the tongue, using a capacitance sensor to alert the subject of stimulus delivery. An example of the application of this system is shown, in which we demonstrate that the detection threshold for NaCl is inversely related to stimulus duration by a power function.

Olfactory dysfunction in multiple sclerosis: relation to longitudinal changes in plaque numbers in central olfactory structures.

Scores on the University of Pennsylvania Smell Identification Test (UPSIT), as well as the numbers of MRI-determined plaques within the inferior frontal and temporal lobes, were obtained on three or four separate occasions in each of five MS patients over an 18- to 20-month period. A close association was observed, longitudinally, between the remission and exacerbation of plaque numbers and UPSIT scores, with more plaques reflecting lower UPSIT scores. These observations further support the hypothesis that olfactory loss in MS is associated with fluctuations in plaque numbers in central olfactory brain regions.

Olfactory dysfunction in schizophrenia: a qualitative and quantitative review.

Olfactory dysfunction in patients with schizophrenia has been a topic of increasing interest, with deficits in odor identification, detection threshold sensitivity, discrimination, and memory being reported. Despite increasing knowledge, controversy has existed about possible differential deficits among olfactory tests as well as the influences of gender, smoking, and medication status on olfactory measures. To help elucidate some of this controversy, we conducted a qualitative and quantitative (meta-analytic) review of the English language literature on olfaction in schizophrenia. Moderator variables such as gender, medication status, and smoking history were also examined. Results indicated that substantial olfactory deficits, across all domains, are observed in patients with schizophrenia. No differential deficits were observed across domains of odor identification, detection threshold sensitivity, discrimination, and memory. The influences of gender, medication status, and smoking on effect sizes were not significant across studies. This supports the hypothesis of primary dysfunction in the olfactory system that is regulated by brain regions where structural and functional abnormalities have also been reported in neuroimaging studies.

Posttraumatic smell loss: relationship of psychophysical tests and volumes of the olfactory bulbs and tracts and the temporal lobes.

RATIONALE AND OBJECTIVES: The purpose of this study was to define the primary sites of injury in patients with posttraumatic anosmia and hyposmia with magnetic resonance (MR) imaging and to determine if these sites correlated with the results of psychophysical olfactory tests. MATERIALS AND METHODS: Thirty-six patients with subjective loss in olfaction after head trauma underwent volumetric MR studies of the olfactory bulbs and tracts and temporal lobes. Pearson correlations were computed between olfactory bulb and tract and temporal lobe volumes and the patients' scores on tests of odor identification (including the University of Pennsylvania Smell Identification Test [UPSIT]), detection, and memory. Analysis of variance was used to compare volumes of the control subjects and the posttraumatic patients. RESULTS: The olfactory bulbs and tracts (32 [89%] of 36 patients), the subfrontal lobes (22 [61%] of 36 patients), and the temporal lobes (11 [31%] of 36 patients) showed the highest incidence of posttraumatic encephalomalacia. Left olfactory bulb and tract volumes showed a statistically significant correlation with left and total UPSIT scores. A statistically significant difference (P < .001) was found in the right and left olfactory bulb and tract volumes between anosmic and hyposmic patients and between posttraumatic patients and control subjects. CONCLUSION: Olfactory bulb and tract damage may correlate with deficits in odor identification. Olfactory bulb and tract and frontal lobe encephalomalacia coexist in many patients.