Anosmic Group Research Articles

Validation of the local applicability of the 'TIB' Olfactory Test Device in the era of COVID-19.

ObjectiveTo evaluate the validity and test–retest reliability of the novel ‘TIB’ Olfactory Test Device (TIB) and to determine its normative values.MethodsThe study stratified the study subjects into normosmic, hyposmic and anosmic groups according to their olfactory function. The olfactory function of the subjects was evaluated using both the traditional Chinese version of the University of Pennsylvania of Smell Identification Test (UPSIT-TC) and the TIB. The normosmic group was used to retest with the UPSIT-TC and TIB at an inter-test interval of at least 7 days. The cut-off scores of TIB among the three different groups were determined by receiver operating characteristic curve analysis.ResultsThis study enrolled 180 subjects: 60 in each group. The mean scores of TIB were 44.1 for the normosmic group, 27.5 for the hyposmic group and 10.9 for the anosmic group. The TIB scores were significantly different across the three groups. There was a significant correlation between the first and second TIB tests (r = 0.506). The cut-off scores were 41 for normosmic subjects and 24 for hyposmic subjects.ConclusionThe validity and test–retest reliability results suggest that the TIB is an appropriate olfactory test for the Taiwanese population.

The impact of MR-guided attenuation correction (compared to CT-based AC) on the diagnosis of anosmia based on 99m-Tc Ethyl-Cysteinate-Dimer SPECT images

99m-Tc Ethyl-Cysteinate-Dimer SPECT and MR imaging play a significant role in diagnosing anosmia. In this study, two-tissue class and three-tissue class attenuation maps (2C-MR and 3CMR) obtained from MR images were compared with CT-based attenuation correction (CTAC). Afterward, the presence of hypo-perfusion in brain lobes was evaluated in SPECT images. The 2C-MRAC map was generated through segmentation of T1-W MR images into air and soft-tissue, while in the 3C-MRAC map, the cortical bone was also considered. For investigating MRAC approaches, the difference between activity concentration (ACC) values was estimated in 144 volumes of interest. Ten normal and fourteen anosmic patients were compared by calculating the average normalized count and standard uptake value ratio parameters in the brain lobes. The comparison between attenuation correction strategies represented that MRAC images resulted in underestimation of the ACC values which was more substantial in the cortical area rather than in central regions (maximum 9% vs. 6% for 2C-MR and maximum 5.5% vs. 3.5% for 3C-MR). Nevertheless, there was a strong correlation between the MRAC and CTAC methods with a correlation coefficient of 0.7 for both 2C-MR and 3C-MR. The statistical analysis between normal and affected groups indicated the hypoperfusion in the cortex of Lh_frontal, Rh and Lh_temporal lobes with p-values < 0.05. Using MRAC resulted in underestimation of activity concentration which was partly eliminated by considering the cortical bone in the 3C-MR attenuation map. Hypo-perfusion was perceived in Frontal and Temporal lobes in SPECT-MRAC images of the anosmic group.

Faster olfactory adaptation in patients with olfactory deficits: an analysis of results from odor threshold testing.

Patients with olfactory deficits often report rapid and lasting olfactory adaptation compared to the time when they had normal olfactory function. However, this phenomenon receives little scientific attention. This retrospective study aimed to compare the patterns of olfactory adaptation in normosmic controls and patients with olfactory impairment by analyzing the trajectory of turning points in odor threshold tests based on the staircase technique. 4120 subjects (1684 hyposmia, 1742 anosmia and 694 normosmic controls) were included in this study. Their odor threshold, odor discrimination and odor identification ability were assessed using the Sniffin’ Sticks. We analyzed the trajectory of turning points in the odor threshold test. Current results suggested that patients with hyposmia needed significantly more trials to reach the final threshold scores than controls and anosmic group, and controls needed more trials than anosmic group. The difference between the first turning point and final threshold scores in the anosmic group was significantly larger than in the hyposmia group and in controls. People with poor olfaction seem to adapt faster to olfactory stimuli. The trajectory of turning points in odor threshold test may serve as an indicator of olfactory adaptation and function of olfactory receptors. Olfactory adaptation may provide a new tool in the assessment of subtle olfactory loss.

Association between Olfactory Deficit and Motor and Cognitive Function in Parkinson's Disease.

ObjectiveTo investigate whether baseline olfactory dysfunction in Parkinson’s disease (PD) patients is associated with baseline and longitudinal motor and cognitive function.MethodsWe recruited 228 drug-naïve PD patients who were followed for a mean of 6 years. Patients underwent the Cross-Cultural Smell Identification Test (CCSIT), a neuropsychological test, and N-(3-[18F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane positron emission tomography within 6 months of the baseline evaluation. Olfactory dysfunction was categorized as normosmia (CCSIT score ≥ 9), hyposmia (CCSIT score 5–8), and anosmia (CCSIT score ≤ 4). During the follow-up period, we investigated changes in the levodopa-equivalent dose (LED) and the occurrence of wearing-off, levodopa-induced dyskinesia, and dementia.ResultsAmong the PD patients, 80.7% were hyposmic at the time of diagnosis, and 26.1% were anosmic. Baseline olfactory dysfunction was not associated with either initial parkinsonian motor symptoms or with the longitudinal LED increment and motor complications. Meanwhile, the anosmic group had lower baseline scores on the Korea version of the Boston Naming Test and Stroop color reading test than the normosmic and hyposmic groups. The anosmic group exhibited a higher rate of conversion to dementia than the normosmic [adjusted hazard ratio (HR) 3.99, 95% confidence interval (CI) 1.08–14.72] and hyposmic (adjusted HR 2.48, 95% CI 1.15–5.32) PD groups, regardless of baseline motor deficits and cognitive status.ConclusionBaseline olfactory dysfunction was not associated with motor deficits and complications, but it was associated with cognitive dysfunction and prognosis, suggesting that severe olfactory impairment may reflect early cortical involvement, probably in the frontotemporal region, and rapid spreading of Lewy body pathology.

Short inter-stimulus intervals can be used for olfactory electroencephalography in patients of varying olfactory function

Use of chemosensory event-related potentials (ERPs) is limited by relatively poor signal-to-noise ratios (SNRs). We hypothesized that by reducing the standard inter-stimulus interval (ISI), the increased number of trial repetitions possible may increase SNR. In order to further investigate this, we performed the largest study to date assessing chemosensory ERP using short and long ISIs in 101 participants of varying olfactory function. Using rose odor (phenylethylalcohol, PEA) as a relatively selective olfactory stimulant, we found no significant difference in the proportion of individuals in whom ERPs were recorded using short or long ISIs. This was true in normosmic, hyposmic and functionally anosmic individuals. We also demonstrated significantly increased SNR using short PEA-ISIs, in the normosmic and functionally anosmic groups. Comparing between groups of different olfactory function, hyposmic patients achieved faster onsets and greater amplitudes than normosmics under the PEA-10s protocol. This could be due to increased stimulus attendance, but requires confirmation with further research.

Spectrum of phenotype and genotype of congenital isolated hypogonadotropic hypogonadism in Asian Indians.

Congenital isolated hypogonadotropic hypogonadism (IHH) is caused due to defect in GnRH neuronal development, migration and action. Although genetic aetiology of IHH is increasingly being studied, Asian Indian data on phenotypic spectrum and genetic basis are scarce. To investigate the phenotypic and genotypic spectrum of IHH in Asian Indian subjects. A cohort of 135 IHH probands were characterized phenotypically for reproductive and nonreproductive features and screened for rare sequence variations (RSVs) in five genes KAL1, FGFR1, FGF8, GNRHR and KISS1R. Of 135 probands [56 normosmic IHH (nIHH) and 79 Kallmann syndrome (KS)], 20 were familial cases. KS group had more male dominance (M:F ratio of 8:1) as compared to nIHH group (M:F ratio of 1·5:1). Complete absence of puberty was more prevalent in KS probands (81% in KS vs 46% in nIHH). The prevalence of MRI abnormalities was more in anosmic group (92·8%) as compared to hyposmic (37·5%) and normosmic groups (15·4%). No particular nonreproductive phenotypic predominance was seen in any group. Genotyping revealed rare sequence variation (RSV) detection rate of 15·5% in five genes studied: (KAL1 - 4·4%, FGFR1 - 4·4%, GNRHR - 6·7%, oligogenicity - 1·5%). Prevalence of RSV was more common in familial cases (35%) as compared to sporadic (12·2%). GNRHR RSV p.C279Y (not reported in patients of ethnicities other than south Asians) was recurring in four unrelated patients. In our cohort, 60% were KS with majority of males and a severe reproductive phenotype as against nIHH. Contribution of the genetic burden for the five genes studied was 15·5%. RSV p.C279Y in GNRHR may have a founder effect originating from south Asia. This study provides a model for molecular and phenotypic representation of Asian Indian subjects with IHH.

Olfactory training induces changes in regional functional connectivity in patients with long-term smell loss.

Recently, olfactory training has been introduced as a promising treatment for patients with olfactory dysfunction. However, less is known about the neuronal basis and the influence on functional networks of this training. Thus, we aimed to investigate the neuroplasticity of chemosensory perception through an olfactory training program in patients with smell loss.The experimental setup included functional MRI (fMRI) experiments with three different types of chemosensory stimuli. Ten anosmic patients (7f, 3m) and 14 healthy controls (7f, 7m) underwent the same testing sessions. After a 12-week olfactory training period, seven patients (4f, 3m) were invited for follow-up testing using the same fMRI protocol. Functional networks were identified using independent component analysis and were further examined in detail using functional connectivity analysis.We found that anosmic patients and healthy controls initially use the same three networks to process chemosensory input: the olfactory; the somatosensory; and the integrative network. Those networks did not differ between the two groups in their spatial extent, but in their functional connectivity. After the olfactory training, the sensitivity to detect odors significantly increased in the anosmic group, which was also manifested in modifications of functional connections in all three investigated networks.The results of this study indicate that an olfactory training program can reorganize functional networks, although, initially, no differences in the spatial distribution of neural activation were observed.

Differences in anosmic and normosmic group in bimodal odorant perception: a functional- MRI study

So-called bimodal odorants are able to stimulate the intranasal trigeminal system at relatively low concentrations. Using them as stimuli, the current study focused on the interaction between the olfactory and trigeminal systems at a cerebral level. In the experiment, menthol was used at two concentrations, low and high, and these were delivered to two groups of subjects, a healthy control group and an anosmic group who were unable to perceive smells. A computer-controlled olfactometer based on principles of air-dilution was used to deliver the stimuli, while the brain functions were assessed by a functional magnetic resonance imaging (fMRI) technique. SPM5 was used for data analysis. The results showed that normosmic subjects exhibited activation in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC), prefrontal cortex (PFC), and cerebellum. Whilst anosmic subjects activated the same area inside the anterior cingulate; moreover a cluster of activation was found in the left parahippocampal gyrus. In controls, an effect of stimulus intensity was localized between the anterior cingulated, the medial frontal gyrus and the cerebellum; such areas could not be found in anosmic subjects. These results suggest that the olfactory system modifies trigeminally mediated information causing an evident effect in the differentiation between stimulus intensities.

Odor identification deficits identify Parkinson's disease patients with poor cognitive performance

Olfactory dysfunction is a prodromal and prevalent nonmotor symptom of Parkinson's disease. Unlike olfactory dysfunction in Alzheimer's disease, it is believed to be unrelated to cognitive impairment. However, recent research has implicated cholinergic denervation in Parkinson's disease hyposmia and linked it to verbal memory. This research hypothesized that severe odor identification deficits may identify patients with Parkinson's disease at risk for cognitive impairment. The current study tested this hypothesis by comparing 24 functionally anosmic, nondemented patients with Parkinson's disease and 39 nonanosmic, nondemented patients with Parkinson's disease with 29 healthy control participants on composite scores of memory, processing speed, executive function, and language. The functionally anosmic group had significantly poorer visual and verbal memory than the nonanosmic group, which was indistinguishable from the control group. Furthermore, the functionally anosmic group had reduced processing speed compared with the nonanosmic patients with Parkinson's disease, who, in turn, were outperformed by the control group. On the composite language score, the score of the functionally anosmic group was significantly reduced compared with that of the control group, whereas the nonanosmic group scored in the medium range. The 2 patient groups did not differ on executive functioning. These findings demonstrate co-occurrence between reduced cognitive function and olfactory deficits in functionally anosmic patients with Parkinson's disease and support the notion of more severe cognitive deficits in this group.

Clinical Significance of Olfactory Event‐Related Potentials Related to Orthonasal and Retronasal Olfactory Testing

The purpose of this study was to evaluate the likelihood of recording olfactory event-related potentials (OERPs) in patients with an olfactory dysfunction and to correlate the electrophysiological responses to orthonasal and retronasal olfactory testing. DESIGN/MATERIALS AND METHODS: This was a prospective study of 65 patients with different origins of their olfactory loss. Orthonasal olfactory function was assessed with the "Sniffin' Sticks" test (orthonasal score; maximal score 48) and retronasal olfactory function with odorized powders presented intraorally (retronasal score; maximal score 20). The OERPs were obtained after presentation of 2-phenyl ethyl alcohol, the selected olfactory stimulus. Causes of olfactory dysfunction included postinfectious olfactory loss (n = 15), head trauma (n = 26), nasal polyposis (n = 15), and mixed causes (idiopathic, toxic, drug induced) (n = 9). Based on orthonasal testing, 32 and 33 patients were diagnosed with anosmia and hyposmia, respectively. Twenty-two patients from the hyposmic group demonstrated reliable OERPs. No OERPs were recorded in the anosmic group. Prevalence of OERPs in a cohort of patients with olfactory dysfunction was 33.8% (22 of 65). Median score (expressed as the percentage of the maximal score that could be obtained theoretically) in which OERPs were recorded was 50% (24 of 48) with orthonasal testing and 80% (16 of 20) with retronasal testing. Patients with olfactory dysfunction usually demonstrate OERPs in one third of the cases. When olfactory dysfunction is in the range that separates normosmic subjects from anosmic patients, patients may have identifiable OERPs. Interpretation of both orthonasal and retronasal psychophysical olfactory testing should be supported by the recording of OERPs in a clinical setting.

The combined olfactory test in a Chinese population

To establish an olfactory test in the Hong Kong Chinese population. Prospective analysis of the results of a combined olfactory test (COT) for patients with olfactory dysfunction and for normal subjects attending a secondary and tertiary ear, nose and throat centre. Our COT was based on and modified from the Connecticut Chemosensory Research Centre test. It consisted of an odour identification test involving nine substances and a threshold test using a series of threefold dilutions of 1-butanol. From September 1998 to June 2002, 188 Hong Kong Chinese patients with olfactory dysfunction and subjects with normal olfaction were prospectively recruited. The subjects were categorized into normal, hyposmic and anosmic groups. The olfactory function of the main group of subjects (n = 153) was assessed with the COT by a blinded observer and also quantified with a visual analogue scale; the results were analysed to validate the discriminative ability of the COT. Another subgroup of subjects (n = 35) was tested with the COT twice with a two-week interval to evaluate test-retest reliability. There were 42 normal, 68 hyposmic and 43 anosmic subjects within the main group (total n = 153). The identification scores, threshold scores and combined olfactory scores were statistically significantly different between the anosmic, hyposmic and normal groups of subjects (p < 0.001). The combined olfactory score correlated with the visual analogue score and the correlation coefficient was 0.56 (p < 0.01). The mean time spent on each COT was 8.6 minutes (standard deviation = 3.4 minutes). The test-retest reliability of the COT was satisfactory, with a one-way model intraclass correlation coefficient of 0.87 (n = 35). The satisfactory discriminative ability and test-retest reliability of the COT have been demonstrated in this study. The COT is a feasible method for assessing sense of smell in the Hong Kong Chinese population.

Zinc sulphate-induced anosmia decreases the nerve fibre density in the anterior cerebral artery of the rat

Detailed quantitative studies have demonstrated a topographical heterogeneity of nerve fibre densities in the cerebral arteries at the base of the brain as well as local changes in ageing and Alzheimer's patients. In this study, we test the hypothesis that local patterns of innervation are influenced by changes in flow fluctuations. This was investigated by inducing chronic anosmia and monitoring the nerve fibre density in the basal cerebral arteries in the adult rat. The olfactory epithelium was examined after staining with hematoxylin and eosin and showed a marked reduction of thickness in the anosmic group compared to the control group. The olfactory bulb was histochemically stained for succinate dehydrogenase (SDH) activity and showed a reduced staining in the anosmic group compared to the controls. Whole mount preparations of the basal cerebral arteries were immunostained for the general neural marker protein gene product (PGP) 9.5. The nerve fibre densities of the vessel walls were quantified by image analysis and expressed as area percentage and intercept density. This analysis showed a significant reduction in area percentage for the first part of the anterior cerebral artery, as well as for the second part of the anterior cerebral artery, and a significant reduction in intercept density for the second part of the anterior cerebral artery in the anosmic group. We conclude that peripherally induced anosmia decreases nerve fibre density in the anterior cerebral artery that may be due to a decreased metabolic activity in the rhinencephalon and, as a consequence, a reduction of flow fluctuations in the blood vessels supplying this area occurs.

Olfaction and the navigational performance of homing pigeons on the Atlantic coast of Morocco

Young homing pigeons were transferred from Italy to a loft located on the Atlantic Coast of Morocco. This location is extraordinary because from early spring to the end of summer winds continually blow from the north‐northeast. The pigeons were given free‐flight experience from the loft before they were tested for their navigational ability. For the test releases, the pigeons were divided into a control and anosmic group. The orientation and homing performance of the anosmic birds were generally poor and similar to what has been observed in other geographic regions following anosmia. The navigational performance of the control birds varied according to the direction of displacement. From the north and east the birds performed well and outperformed the anosmic birds. From the south they performed poorly and similar to the anosmic birds. Although preliminary, the data from the control birds suggest that natural variation in the distribution of winds, and presumably the odours they carry, can influence the structure of the homing pigeon navigational map.

Metabolic contribution of CO2 to the "group effect".

Metabolic rates (VCO2) were determined in 22 mice. Subsequently 11 of the mice were placed into separate metabolic chambers. Each chamber was connected to one other metabolic chamber containing one mouse. The metabolic rates of the 11 "donor" and the 11 "'recipient" mice were measured. Afterwards the direction of airflow was reversed so that the previous donor became the recipient mouse and the previous recipient became the donor. Again VCO2 was measured. When the mice were donors, VCO2 = 2.75 +/- 1.0 ml CO2 . g-1 . h-1, whereas when recipients, VCO2 = 1.9 +/- 1.0 ml CO2 . g-1 . h-1 (P less than 0.01). Eleven of the mice were then made anosmic using an intranasal instillation of 5% ZnSO4. Anosmia was confirmed behaviorally. The metabolic rates of the anosmic and control mice were again determined when each was a donor and a recipient. VCO2 dropped from 3.1 to 1.8 ml CO2 . g-1 . h-1 from donor status to recipient status. Finally, VCO2 was determined when all 22 mice were exposed to 0.05% CO2 or 0.2% CO2 in air (the level of CO2 in the exhaust air of donor mice). VCO2 dropped from 3.0 +/- 0.38 on 0.05% CO2 to 1.7 +/- 1.01 on 1.01 ml CO2 . g-1 . h-1 on 0.2% CO2 in the anosmic group and from 2.9 +/- 0.29 to 1.91 +/- 0.51 ml CO2 . g-1 . h-1 in the control group when exposed to the same gases. These experiments suggest that the airborne factor emanating from the donor chambers was acting systematically and not via the olfactory system. This factor may be a low level of CO2.

Habituation of stimulus-elicited investigation in gerbils after olfactory bulbectomy

Normal gerbils habituate rapidly when presented with a novel object in the stimulus-elicited investigation paradigm. In this paradigm, gentled gerbils are given a series of one minute trials with a novel object in a small arena. They are then given a series of similar trials in which the odor of strange male gerbils is under one of five holes in the floor of the same arena. Gerbils with bilateral olfactory bulbectomies habituated more slowly to the object than normal gerbils or those anosmized peripherally by unilateral bulbectomy combined with stitching of the contralateral naris. In contrast, the two anosmic groups habituated at the same rate as normal gerbils when tested for investigation of five holes and odor although neither group of anosmic gerbils selectively localized the odor. In comparison to normal gerbils with no specific odor present, habituation was delayed for both experimental groups. In addition, both anosmic groups habituated normally on an activity score. Therefore, it was concluded that habituation can be affected differentially by the surgical conditions dependent on the task being measured. These data support the hypotheses (a) that the olfactory bulbs have a role in behaviors that are not dependent on olfactory information and (b) that habituation is not a single process mediated uniformly for all behaviors.

Sex-eliciting behavior of the female rat: Discrimination of receptivity by anosmic and intact males

Cue stimuli defining the receptive female rat may be arbitrarily dichotomized as olfactory and nonolfactory, the latter primarily relating to assorted precopulatory movements. Experiment 1 compared the ability of sexually experienced anosmic and intact males to discriminate an estrous female within a group of nonestrous females. Although anosmic males were handicapped during the initial minutes of exposure, both groups readily identified the receptive female. Experiment 2 compared anosmic and intact groups of males exposed to an haloperidol-treated, immobile, estrous female within a group of nonestrous females. Although intact males were fully capable of identifying and copulating with the motionless estrous female, anosmic males were obviously disadvantaged as revealed by their high incidence of copulatory attempts with nonreceptive females. The results emphasize a functional duality of olfactory and nonolfactory behaviors of the female as redundant arousal and directional systems for guiding male copulatory behaviors.

Social-olfactory experience and initiation of copulation in the virgin male rat

Two experiments examined the role of olfactory sensation for initiation of normal copulatory behavior of mature male rats. Experiment 1 compared copulatory performance of peripherally anosmic social isolates with that of intact isolate controls. The results revealed significantly lower mounting, intromission, and ejaculation frequencies of the anosmic group and suggested that nonolfactory cues attain significance via an associative-learning process. Experiment 2 compared three social isolate groups of mature males with varying sexual experience prior to anosmia. Four 1-hr tests were conducted at 5-day intervals. The results indicated comparable copulatory performance of the experienced groups and absence of copulation by the majority of the nonexperienced group. With a 12-day continuous exposure to intact females, all noncopulators eventually impregnated. The results are discussed with reference to the requirement of social experience for initiation of normal sexual performance in the male rat.

Compensatory ovulation in blinded rats and-or those from which the olfactory bulb had been removed.

Summary. Thirty-two prepubertal, female rats (Southern Farms) were allocated to intact control, bilateral optic enucleation (blinded), bilateral olfactory bulb removal (anosmic) and blinded\p=m-\anosmic groups. Olfactory bulbs were surgically removed between 27 and 29 days of age and eyes were removed at 30 days of age. One ovary was removed from each animal between 107 and 112 days of age on Day 2 (metoestrus) of the oestrous cycle. The number of eggs ovulated was determined by flushing the oviducts with normal saline solution. All rats completed one oestrous cycle and were killed at metoestrus of the following cycle. There was no difference in the number of ova shed between the four groups at the time of removal of the first ovary. One cycle later, compensatory ovulation was found at autopsy to have occurred in all animals. Controls ovulated 10\m=.\3\m=+-\0\m=.\5eggs; blinded, 9\m=.\6\m=+-\0\m=.\7;anosmic, 10\m=.\3\m=+-\0\m=.\3;and blinded\p=m-\anosmic,9\m=.\7\m=+-\0\m=.\8. Follicular development was quantitatively analysed in both intact and hemispayed blinded and/or anosmic rats. These data suggest that pituitary\p=m-\ovarian function as evaluated by the number of eggs ovulated is not affected by blinding and/or anosmia.