Olfactory Performance Can Be Influenced by the Presentation Order, Background Noise, and Positive Concurrent Feedback.

Sniffin' Sticks have become a popular procedure to measure overall olfactory functionality with 3 subtest: phenyl ethyl alcohol threshold test (T), discrimination (D), and identification (I). However, several procedural components specified by the original paper have not been tested nor has the impact of deviations been measured. The aim of the present work was to measure olfactory performance under modified testing procedures. First, the reverse order of subtests (IDT) was compared with more standard practices (TDI). Next, the possible impact of background noise and positive concurrent feedback were assessed. A total of 120 individuals participated in the study where the 3 conditional experiments, each involving 40 participants, were completed. Testing procedures that reversed the presentation order of subtests (I->D->T) scored a significantly lower overall TDI score than standard testing order with the threshold subtest being the most influenced. Additionally, nonverbal background noise lowered overall olfactory performance while concurrent feedback modulated threshold performance. These results emphasize the importance of testing parameters where olfactory perception and tasks may be modulated by adaptation and attentional distraction, respectively. This study helped furthermore to demonstrate that the investigated 3 deviations from the standard procedure revealed a significant impact on the performance outcome in olfactory assessment using the Sniffin' Sticks.

Characteristics of chemosensory disorders--results from a survey.

This survey was undertaken to investigate the nature of chemosensory dysfunction in relation to the underlying cause, severity, and course of the disease and to elucidate their clinical significance. A total of 269 patients (116 men and 149 women) with chemosensory disorders participated in the survey. Approximately 89 % had olfactory loss, either alone or in combination with taste loss and 2 % had gustatory loss alone; 7.4 % had chemosensory distortions. Dysosmia was significantly higher in those on more than four medicines per day (p < 0.02). Most patients (51.6 %) reported sudden onset of symptoms. Self-reported etiologies included: flu/infection (39.4 %), medication intake (13 %), sinusitis (12 %), operation (10.7 %), head-trauma (9.3 %), and not-specified (12.7 %). The most frequent complaint was diminished pleasure from eating followed by a decrease in general quality of life (QoL). Patients with gradual onset of symptoms or long-standing disease complained the least (p < 0.005). Of all etiologies, patients with SND complained the most (p < 0.04). Overall, 18.6 % ate more and 7.3 % ate less, 7.5 % changed their food preferences, and 19 % reported weight gain and 15.8 % weight loss. Haptic feedback was considered more important than visual appeal and acoustic feedback of food. Older patients however valued visual appeal more. When asked directly, 63 % reported having experienced household-mishaps, 58.1 % problems with social communication, 56.8 % reported having changed their sexual behavior and 35.9 % suffered depression. 60.4 % did not cope well with the changes in their lives. Women reported more problems than men, particularly relating to interpersonal communication (64.5 vs. 57.6 %) and mood (47.9 vs. 40.9 %). Women also had more frequent spontaneous recollections of smells (p < 0.02). Chemosensory disorders have a significant impact on QoL. Reduced pleasure from eating is the predominant complaint of patients seeking medical attention. The steeper the onset of symptoms, the worse the ability to cope with changes in daily life. Older patients value the visual appeal, whereas younger patients value the haptic feedback of foods.

Human olfactory lateralization requires trigeminal activation.

Rats are able to lateralize odors. This ability involves specialized neurons in the orbitofrontal cortex which are able to process the left, right and bilateral presentation of stimuli. However, it is not clear whether this function is preserved in humans. Humans are in general not able to differentiate whether a selective olfactory stimulant has been applied to the left or right nostril; however exceptions have been reported. Following a screening of 152 individuals with an olfactory lateralization test, we identified 19 who could lateralize odors above chance level. 15 of these "lateralizers" underwent olfactory fMRI scanning in a block design and were compared to 15 controls matched for age and sex distribution. As a result, both groups showed comparable activation of olfactory eloquent brain areas. However, subjects with lateralization ability had a significantly enhanced activation of cerebral trigeminal processing areas (somatosensory cortex, intraparietal sulcus). In contrast to controls, lateralizers furthermore exhibited no suppression in the area of the trigeminal principal sensory nucleus. An exploratory study with an olfactory change detection paradigm furthermore showed that lateralizers oriented faster towards changes in the olfactory environment. Taken together, our study suggests that the trigeminal system is activated to a higher degree by the odorous stimuli in the group of "lateralizers". We conclude that humans are not able to lateralize odors based on the olfactory input alone, but vary in the degree to which the trigeminal system is recruited.

A salty-congruent odor enhances saltiness: functional magnetic resonance imaging study.

Excessive intake of dietary salt (sodium chloride) may increase the risk of chronic diseases. Accordingly, various strategies to reduce salt intake have been conducted. This study aimed to investigate whether a salty-congruent odor can enhance saltiness on the basis of psychophysical (Experiment 1) and neuroanatomical levels (Experiment 2). In Experiment 1, after receiving one of six stimulus conditions: three odor conditions (odorless air, congruent, or incongruent odor) by two concentrations (low or high) of either salty or sweet taste solution, participants were asked to rate taste intensity and pleasantness. In Experiment 2, participants received the same stimuli during the functional magnetic resonance imaging scan. In Experiment 1, compared with an incongruent odor and/or odorless air, a congruent odor enhanced not only taste intensity but also either pleasantness of sweetness or unpleasantness of saltiness. In Experiment 2, a salty-congruent combination of odor and taste produced significantly higher neuronal activations in brain regions associated with odor-taste integration (e.g., insula, frontal operculum, anterior cingulate cortex, and orbitofrontal cortex) than an incongruent combination and/or odorless air with taste solution. In addition, the congruent odor-induced saltiness enhancement was more pronounced in the low-concentrated tastant than in the high-concentrated one. In conclusion, this study demonstrates the congruent odor-induced saltiness enhancement on the basis of psychophysical and neuroanatomical results. These findings support an alternative strategy to reduce excessive salt intake by adding salty-congruent aroma to sodium reduced food. However, there are open questions regarding the salty-congruent odor-induced taste unpleasantness.

Short or long runs: An exploratory study of odor-induced fMRI design.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) is a non-invasive neuroimaging technique widely used in olfactory research. During a typical fMRI olfactory block-design, one functional "run" refers to a combination of multiple blocks with continuous brain image acquisition. The current study investigated the length of functional runs on odor-induced brain response signals (blood oxygen level dependent [BLOD]) within the primary and key secondary olfactory areas. METHODS: Twenty-five female adults (age range 19 to 30 years, mean age 25 years) underwent a block-design fMRI measurement with odor stimulation. Twelve participants received the odor stimuli within a short run paradigm (six blocks in each 4-minute run, eight runs in total), and 13 participants received the odor stimulation with a long-run paradigm (12 blocks in each 8-minute run, four runs in total). For each paradigm, two odors (peach and rose) were alternatingly presented between runs. Participants rated odor intensity and pleasantness at the end of each run. Ratings and fMRI data were analyzed for different subsections and compared between groups. RESULTS: There was a higher level of brain activation in the insula and orbitofrontal cortex during the short-run paradigm as compared to the long-run paradigm. However, there was no difference for odor intensity or pleasantness ratings. CONCLUSION: The current study suggested the employment of short runs with multiple repetitions for odor stimulation during fMRI research. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:1110-1115, 2020.

Olfactory change detection.

The human olfactory system is characterized by poor temporal and spatial resolution. When determining changes in the environment, humans rather rely on visual than on olfactory information. Against this background, we developed a test in order to investigate the human capacity to detect changes in the olfactory environment and to determine potential modulators of olfactory change detection. Participants consecutively received four odors (2 odor qualities in 2 concentrations each) which were presented via a computer-controlled olfactometer. The participants' task was to react as soon as they perceived a change of the odor. For control purpose, the same paradigm was also presented with visual instead of olfactory stimuli. A total of 83 healthy participants (aged 18-34 years, 50 women) were included; all of them were screened for attention, olfactory function, chemical sensitivity and the subjective importance of the sense of smell. While visual changes were detected above chance by all participants, olfactory changes were reliably detected by only 24% of the participants. Those were characterized by high subjective importance of olfaction and low chemical sensitivity. Across all participants, changes of olfactory quality were detected more frequently than changes of olfactory concentration. These results suggest that olfaction is imprecise in guiding environmental change detection and may help to explain why humans typically rate the importance of vision higher than the importance of olfaction.

The influence of olfactory loss on dietary behaviors.

OBJECTIVES: To assess dietary behavior and possible changes in food selection in patients with smell loss. PATIENTS AND METHODS: A total of 176 patients (114 women and 62 men) age 17 to 86 years were classified into three diagnostic groups (normosmia, n = 12; hyposmia, n = 75; functional anosmia, n = 89) according to their olfactory test scores obtained with "Sniffin' Sticks." Group differences in food intake and dietary behaviors were investigated with a specifically designed questionnaire providing a dietary alterations score (DAS). RESULTS: Numerous dietary changes were reported, e.g., 29% of all patients reported that they eat less since the onset of olfactory dysfunction, 39% use more spices with their food, 47% go out to eat at restaurants less frequently, 37% eat less sweets, and 48% drink less sweet beverages. Subjects with weight gain or weight loss scored higher on the DAS scale than subjects who did not report changes in weight. Similarly, DAS scale changes were more pronounced in subjects with a gradual onset of olfactory loss compared to subjects with a sudden loss of olfaction. Finally, a change of taste preferences toward savory and salty foods was observed across all patients enrolled in the present study. CONCLUSIONS: Patients with olfactory loss report alterations of dietary behaviors. Numerous factors appear to impact the results of olfactory loss in terms of changes in diet.

Impaired brain response to odors in patients with varied severity of olfactory loss after traumatic brain injury.

Traumatic brain injury (TBI) as a major public health problem may lead to olfactory dysfunction. However, little is known about brain responses to odors in TBI olfactory loss patients. Nineteen healthy controls and forty TBI olfactory dysfunctional patients (19 with hyposmia and 21 with anosmia) underwent a functional magnetic resonance imaging scan when two odors (peach and coffee) were presented intranasally using a computerized olfactometer. Olfactory performance was measured using the "Sniffin' Sticks" test. TBI patients with hyposmia or anosmia showed decreased odor-induced brain activations in the primary olfactory area and insular cortex as compared to healthy controls (FWE-corrected peak p < 0.05). In addition, negative correlations were found between the time since injury (in month) and odor-induced brain responses in the right primary olfactory area for patients with hyposmia. Similar correlations were seen in the insula and orbitofrontal cortex for patients with anosmia. In conclusion, results from the current study are evidences for the impairment of central nervous processing of odor perception at all levels of the olfactory system among TBI patients with olfactory loss. In addition, the duration after the initial injury may have an impact on the severity of olfactory dysfunction.

Alterations of Brain Gray Matter Density and Olfactory Bulb Volume in Patients with Olfactory Loss after Traumatic Brain Injury.

Olfactory loss and traumatic brain injury (TBI) both lead to anatomical brain alterations in humans. Little research has been done on the structural brain changes for TBI patients with olfactory loss. Using voxel-based morphometry, the gray matter (GM) density was examined for 22 TBI patients with hyposmia, 24 TBI patients with anosmia, and 22 age-matched controls. Olfactory bulb (OB) volumes were measured by manual segmentation of acquired T2-weighted coronal slices using a standardized protocol. Brain lesions in the olfactory-relevant areas also were examined for TBI patients. Results showed that patients with anosmia have more frequent lesions in the OB, orbitofrontal cortex (OFC), and the temporal lobe pole, compared with patients with hyposmia. GM density in the primary olfactory area was decreased in both groups of patients. In addition, compared with controls, patients with anosmia showed GM density reduction in several secondary olfactory eloquent regions, including the gyrus rectus, medial OFC, anterior cingulate cortex, insula, and cerebellum. However, patients with hyposmia showed a lesser degree of GM reduction, compared with healthy controls. Smaller OB volumes were found for patients with olfactory loss, compared with controls. TBI patients with anosmia had the smallest OB volumes, which were caused by the lesions for OB. In addition, post-TBI duration was negatively correlated with GM density in the secondary olfactory areas in patients with hyposmia, but was positively correlated with GM density in the frontal and temporal gyrus in patients with anosmia. The GM density and OB volume reduction among TBI patients with olfactory loss was largely dependent on the location and severity of brain lesions in olfactory-relevant regions. Longer post-TBI duration had an impact on brain GM density changes, which indicate a decreased olfactory function in patients with hyposmia and possible compensatory mechanisms in patients with anosmia.

Different Neural Processing of Umami and Salty Taste Determined by Umami Identification Ability Independent of Repeated Umami Exposure.

There is a large inter-individual variation for umami taste perception. However the neural mechanism for this variability is not well understood. This study investigated brain responses to umami and salty taste among individuals with different umami identification abilities and the effect of repeated oral umami exposure on umami identification and neural processing of taste perceptions. Fifteen participants with high umami identification ability ("High Tasters, HT) and fifteen with low umami identification ability ("Low Tasters", LT) underwent three weeks of controlled exposure to umami taste (umami training). Prior to and after the training, participants underwent fMRI scans during which the umami taste solution and a control taste (salty) solution were delivered to their mouth using a gustometer. Taste intensity and pleasantness were rated after each scan. Umami taste identification was assessed before and after the umami training using "Taste Strips" test. Neuroimaging results showed different central processing of umami and salty taste based on umami identification ability, in which the umami LT had stronger activation in the thalamus and hippocampus while the umami HT showed stronger activation in the primary gustatory cortex. In addition, umami identification was significantly improved after umami training for LT. However, it was not reflected in changes in neural activation. The current study shows that attention and association/memory related brain structures play a significant role in the perception of umami taste; and with reference to the results of repeated umami exposure, the presence of very subtle changes regarding the neural processing.

Lateralized differences in olfactory function.

BACKGROUND: Birhinal testing of odor identification will not allow the detection of unilateral olfactory loss. The aim of the presented study was to evaluate side differences of odor identification in large groups of healthy subjects and in patients with nasal symptoms. PARTICIPANTS AND METHOD: Self-assessment of olfactory function and evaluation of olfactory function by means of a validated test were performed in 479 healthy subjects, in 765 patients with chronic rhinosinusitis (CRS), and in 53 patients with a tumor. A 12-item odor identification test ("Sniffin' Sticks") was used to evaluate olfactory function separately for each nostril. RESULTS: Fifteen percent of the healthy subjects demonstrated side differences in the identification of at least 3 out of 12 odors. Healthy elderly subjects showed larger side differences in identification of odor than younger ones; a general difference between odor identification with the right or left nostril was not found. Both CRS patients and patients with a tumor had larger side differences than healthy subjects. Only 20% of the patients with a tumor complained about impaired olfactory sensitivity, but more than 75% of them showed deficits in olfactory tests. CONCLUSION: Side differences of odor identification of 25% or greater should give reason for further investigation. Future studies are needed to investigate whether side differences in healthy subjects are a predicator of a higher risk for general olfactory loss.

Bimodal odor processing with a trigeminal component at sub- and suprathreshold levels.

Odors are typically bimodal in nature, interacting with the olfactory and trigeminal systems. The trigeminal component may be noticed (e.g. menthol) or perceptually ignored, leading to different neural substrates being recruited during odor encoding. Therefore, the current study was designed to explore the perceptual and central-nervous activations in response to pleasant bimodal odors using functional magnetic resonance imaging (fMRI). In this study, healthy subjects were exposed to odorants alone (unimodal) or with a "cooling" trigeminal component (bimodal) at sub- and suprathreshold concentrations with a portable olfactometer in a 3T fMRI scanner. Within the scanner, subjects reported all odorants as pleasant and intensity increasing with trigeminal concentration. Many of the regions of interest [orbital frontal cortex (OFC), insula, thalamus, cerebellum, postcentral gyrus and cingulate cortex] were activated during bimodal odor conditions when contrasted with unimodal, and interestingly, most of these activations were seen prior to trigeminal perception (e.g. at a sub-threshold level). This includes large bilateral activations within the OFC, insula, cerebellum and parts of the cingulate cortex. Additionally, activation of the thalamus was seen early in the stages of bimodal odor encoding suggesting its role of mediating attention toward the presence of two stimuli. Lastly, intensity encoding during bimodal processing shows overlap of previously demonstrated simple trigeminal encoding areas (medial cingulate cortex) and the more complex olfactory encoding areas (bilateral insula, superior temporal gyrus, OFC, and cerebellum), but not the amygdala.

Food-Related Odors Activate Dopaminergic Brain Areas.

Food-associated cues of different sensory categories have often been shown to be a potent elicitor of cerebral activity in brain reward circuits. Smells influence and modify the hedonic qualities of eating experience, and in contrast to smells not associated with food, perception of food-associated odors may activate dopaminergic brain areas. In this study, we aimed to verify previous findings related to the rewarding value of food-associated odors by means of an fMRI design involving carefully preselected odors of edible and non-edible substances. We compared activations generated by three food and three non-food odorants matching in terms of intensity, pleasantness and trigeminal qualities. We observed that for our mixed sample of 30 hungry and satiated participants, food odors generated significantly higher activation in the anterior cingulate cortex (right and left), insula (right), and putamen (right) than non-food odors. Among hungry subjects, regardless of the odor type, we found significant activation in the ventral tegmental area in response to olfactory stimulation. As our stimuli were matched in terms of various perceptual qualities, this result suggests that edibility of an odor source indeed generates specific activation in dopaminergic brain areas.

The Rewarding Effect of Pictures with Positive Emotional Connotation upon Perception and Processing of Pleasant Odors-An FMRI Study.

This fMRI study was designed to investigate the effect of cross-modal conditioning in 28 female volunteers. Subjects underwent initial fMRI block design scanning during which three pleasant olfactory stimuli were presented and had to be rated with respect to intensity and pleasantness. This was followed by an odor identification task spread out over 3 days: the experimental group was rewarded for successful trials (correct odor identification) with emotionally salient photos, whilst the control group only received randomly displayed, emotionally neutral, pictures. In the final scanning session, the odors were again presented, and subjects rated pleasantness and intensity. Both pleasantness ratings and fMRI data showed effects of the rewarding procedure. Activation in nucleus accumbens and the orbitofrontal cortex confirmed the hypothesis that learnt association of odors with visual stimuli of emotionally positive valence not only increases pleasantness of the olfactory stimuli but is also reflected in the activation of brain structures relevant for hedonic and reward processing. To our knowledge, this is the first paper to report successful cross-modal conditioning of olfactory stimuli with visual clues.

Cultural Adaptation of the Portuguese Version of the "Sniffin' Sticks" Smell Test: Reliability, Validity, and Normative Data.

The cross-cultural adaptation and validation of the Sniffin`Sticks test for the Portuguese population is described. Over 270 people participated in four experiments. In Experiment 1, 67 participants rated the familiarity of presented odors and seven descriptors of the original test were adapted to a Portuguese context. In Experiment 2, the Portuguese version of Sniffin`Sticks test was administered to 203 healthy participants. Older age, male gender and active smoking status were confirmed as confounding factors. The third experiment showed the validity of the Portuguese version of Sniffin`Sticks test in discriminating healthy controls from patients with olfactory dysfunction. In Experiment 4, the test-retest reliability for both the composite score (r71 = 0.86) and the identification test (r71 = 0.62) was established (p<0.001). Normative data for the Portuguese version of Sniffin`Sticks test is provided, showing good validity and reliability and effectively distinguishing patients from healthy controls with high sensitivity and specificity. The Portuguese version of Sniffin`Sticks test identification test is a clinically suitable screening tool in routine outpatient Portuguese settings.

Peripheral adaptive filtering in human olfaction? Three studies on prevalence and effects of olfactory training in specific anosmia in more than 1600 participants.

Selective processing of environmental stimuli improves processing capacity and allows adaptive modulation of behavior. The thalamus provides an effective filter of central sensory information processing. As olfactory projections, however, largely bypass the thalamus, other filter mechanisms must consequently have evolved for the sense of smell. We investigated whether specific anosmia - the inability to perceive a specific odor whereas detection of other substances is unaffected - represents an effective peripheral filter of olfactory information processing. In contrast to previous studies, we showed in a sample of 1600 normosmic subjects, that specific anosmia is by no means a rare phenomenon. Instead, while the affected odor is highly individual, the general probability of occurrence of specific anosmia is close to 1. In addition, 25 subjects performed daily olfactory training sessions with enhanced exposure to their particular "missing" smells for the duration of three months. This resulted in a significant improvement of sensitivity towards the respective specific odors. We propose specific anosmia to occur as a rule, rather than an exception, in the sense of smell. The lack of perception of certain odors may constitute a flexible peripheral filter mechanism, which can be altered by exposure.

Post-apoplectic reorganization of cortical areas processing passive movement and tactile stimulation--a neuromagnetic case study.

Magnetoencephalography (MEG) was used in a patient with right centro-parietal stroke to investigate the cortical processing of tactile pneumatic stimulation and passive movement of the impaired left and unaffected right-hand index finger. Source localization of somatosensory evoked magnetic fields (SEF) recorded 2 weeks after infarction demonstrated a spatial displacement of the contralateral SI generators in the affected hemisphere. The distance between SI sources activated by either stimulation technique was noticeably enlarged in comparison to the left hemisphere and to previous data from 12 healthy subjects. Follow-up MEG after 6 months revealed a closer spatial arrangement of the two modality-specific SEF generators and a diminution of the interhemispheric asymmetry of proprioception-related SI sources. The topographical alterations were accompanied by clear clinical improvement of both joint position sense and tactile sensation. The occurrence of ipsilateral SI activity following passive movement of only the impaired index finger might suggest a disinhibition of subthreshold, transcallosal excitatory pathways.

Olfaction as a marker for depression in humans.

BACKGROUND: Animal studies show a strong link between the loss of olfactory function and depressive behavior. We analyzed, whether olfactory function is a marker for depression in humans. If so, reduced olfactory function can be expected in depression that improves to level of normality after successful antidepressive treatment. METHODS: Twenty-seven female in-patients with depression were compared to 28 healthy age-matched women at the beginning and at the end of antidepressive therapy or at two visits, respectively. Olfactory function was assessed comprehensively including threshold, discrimination and identification testing, chemosensory event related potentials and olfactory functional magnetic resonance imaging. RESULTS: At the beginning of psychotherapy the patients exhibited reduced olfactory discrimination, prolonged latencies of the event-related potential and reduced activation in secondary olfactory structures (thalamus, insula, and left middle orbitofrontal). After therapy, patients improved significantly in all of the parameters and consequently the differences between control group and patients vanished. LIMITATIONS AND CONCLUSION: We conclude that olfaction is a marker for depression. However, the results are limited to a relatively selective sample of depressed women.