Valentin A. Schriever

Preventing olfactory deterioration: olfactory training may be of help in older people.

Although it is plausible that ChEIs may result in peripheral cholinergic adverse events, this large population-based study found no significant association between ChEI use and upper GI bleeding in elderly adults. Lack of a significant association between ChEIs and upper GI bleeding may be because adverse GI events resulting from ChEIs are typically transient and decrease with continued use of the drugs. This study has potential limitations. First, use of administrative databases precludes the ability to capture clinically important information such as disease severity and GI pathology. Second, given the small proportion of the subjects who received rivastigmine or galantamine, the effect of individual ChEIs on upper GI bleeding could not be meaningfully compared with that of the nonuser cohort. Future research is needed to estimate the incidence of upper GI bleeding in chronic users of ChEIs and in high-risk individuals, such as those living in long-term care residences or with a history of upper GI hemorrhage.

Neuropeptide receptors provide a signalling pathway for trigeminal modulation of olfactory transduction

The mammalian olfactory epithelium contains olfactory receptor neurons and trigeminal sensory endings. The former mediate odor detection, the latter the detection of irritants. The two apparently parallel chemosensory systems are in reality interdependent in various well‐documented ways. Psychophysical studies have shown that virtually all odorants can act as irritants, and that most irritants have an odor. Thus, the sensory perception of odorants and irritants is based on simultaneous input from the two systems. Moreover, functional interactions between the olfactory system and the trigeminal system exist on both peripheral and central levels. Here we examine the impact of trigeminal stimulation on the odor response of olfactory receptor neurons. Using an odorant with low trigeminal potency (phenylethyl alcohol) and a non‐odorous irritant (CO2), we have explored this interaction in psychophysical experiments with human subjects and in electroolfactogram (EOG) recordings from rats. We have demonstrated that simultaneous activation of the trigeminal system attenuates the perception of odor intensity and distorts the EOG response. On the molecular level, we have identified a route for this cross‐modal interaction. The neuropeptide calcitonin‐gene related peptide (CGRP), which is released from trigeminal sensory fibres upon irritant stimulation, inhibits the odor response of olfactory receptor neurons. CGRP receptors expressed by these neurons mediate this neuromodulatory effect. This study demonstrates a site of trigeminal–olfactory interaction in the periphery. It reveals a pathway for trigeminal impact on olfactory signal processing that influences odor perception.

Olfactory Function After Mild Head Injury in Children

Olfactory impairment has been shown to be linked to head injury. In addition, it is believed that measurement of olfactory function after head trauma represents a sensitive tool for measuring frontal brain damage. Aim of the study was to evaluate the effect of mild head trauma in children on olfactory function over a time period of up to 1 year after head trauma. The olfactory function of 114 children who suffered mild head trauma according to the Glasgow Coma Scale was assessed 3 times with an interval of 4 months. In addition, healthy, age-matched controls were tested for comparison of olfactory function. Patients scored significantly lower on the odor threshold test compared to the control group-but still within normal range. Between the 2 groups, no difference was found for suprathreshold testing. Neither olfactory threshold scores nor olfactory discrimination scores changed significantly over the study period of 1 year. This data prove an impact of mild head trauma on olfactory function of children. It seems unlikely that children who suffered mild head trauma will become hyposmic or anosmic.

Cross-modal integration of emotions in the chemical senses

Although the brain structures involved in integrating odorant and trigeminal stimuli are well-documented, there is still a need to clarify (1) how emotional response is represented in the human brain during cross-modal interaction between odors and trigeminal stimuli, and (2) whether the degree of congruency between the two types of stimuli influences these emotional responses and their neural processing. These questions were explored combining psychophysics, event-related potentials (ERP) and fMRI in the same group of 17 subjects under a “congruent condition” (intranasal carbon dioxide mixed with the smell of orange, a combination found in soda drinks, for example), and an “incongruent condition” (intranasal carbon dioxide mixed with the smell of rose, a combination not encountered in everyday life). Responses to the 3 constituent stimuli (carbon dioxide, orange, and rose) were also measured. Hedonic and intensity ratings were collected for all stimulations. The congruent bimodal stimulus was rated as more pleasant than the incongruent. This behavioral effect was associated with enhanced neural activity in the hippocampus and anterior cingulate gyrus, indicating that these brain areas mediate reactivation of pleasant and congruent olfactory-trigeminal associations.

A Cross-Cultural Adaptation of the Sniffin’ Sticks Olfactory Identification Test for US children

Disorders associated with smell loss are common in adolescents. However, current odor identification tests focus on children from age 6 and older and no cross-cultural test has to date been validated and fully implemented. Here, we aimed to investigate how 3-to-11-year-old US children performed to an adapted and shortened (11 odors instead of 14) version of a European odor identification test—the Sniffin’ Kids (Schriever VA, Mori E, Petters W, Boerner C, Smitka M, Hummel T. 2014. The “Sniffin’Kids” test: a 14-item odor identification test for children. Plos One. 9:e101086.). Results confirmed that cued odor identification performance increases with age and revealed little to no differences between girls and boys. Scores below 3 and below 6 may raise hyposmia concerns in US children aged 3–7 years and 8–10 years, respectively. Even though the completion rate of the task reached the 88%, suggesting that children below age 5 were able to finish the test, their performance was relatively poor. In comparing the overall identification performance of US children with that of German children, for whom the test was specifically developed, significant differences emerged, with higher scores obtained by the German sample. Analysis of errors indicated that a lack of semantic knowledge for the olfactory-presented objects may be at the root of poor identification skills in US children and therefore constitutes a problem in the development of an odor identification test for younger children valid across cultures.

Influence of Airflow Rate and Stimulus Concentration on Olfactory Event-Related Potentials (OERP) in Humans

Although the association between odor concentration and olfactory event-related potential (OERP) has been studied, less is known about the influence of airflow on OERP. The aim of this study was to investigate the influence of airflow rate and stimulus concentration on OERP in humans. Electroencephalogram data were collected from young healthy volunteers (n = 17) in separate sessions where 2-phenylethanol (PEA) was delivered in the following conditions: 8 L/min 50% v/v, 8 L/min 30% v/v, 4 L/min 100% v/v, and 4 L/min 60%v/v. Odor concentrations are referred to the %v/v achieved with air dilution and was not measured in the nose. Odor intensity ratings were recorded immediately after stimulus presentation. Data recorded at 5 electrodes (Fz, Cz, Pz, C3, and C4) were pooled and analyzed using both time-domain averaging and single-trial time-frequency domain approaches. Higher airflow rate significantly increased intensity ratings (F = 10.98, P < 0.01), and improved the signal-to-noise-ratio (F = 5.42, P = 0.025). Results from time-frequency analysis showed higher concentration versus lower concentration increased brain oscillations in the slow frequency band (1-3 Hz) at 0-600 ms; while higher airflow rates versus lower airflow rate increased theta-band oscillations (300-600 ms and 5-9 Hz) and decreased delta-band oscillations at 900-1500 ms after stimulus onset. In conclusion, compared to stimulus concentration, airflow rate was associated with improved OERP quality and more pronounced responses. The results suggest that intensity ratings and OERP are strongly related to the steepness of stimulus onset. High airflow rates are suggested for odor delivery in order to record OERP.

Time frequency analysis of olfactory induced EEG-power change

Objectives The objective of the present study was to investigate the usefulness of time-frequency analysis (TFA) of olfactory-induced EEG change with a low-cost, portable olfactometer in the clinical investigation of smell function. Materials & methods A total of 78 volunteers participated. The study was composed of three parts where olfactory stimuli were presented using a custom-built olfactometer. Part I was designed to optimize the stimulus as well as the recording conditions. In part II EEG-power changes after olfactory/trigeminal stimulation were compared between healthy participants and patients with olfactory impairment. In Part III the test-retest reliability of the method was evaluated in healthy subjects. Results Part I indicated that the most effective paradigm for stimulus presentation was cued stimulus, with an interstimulus interval of 18-20s at a stimulus duration of 1000ms with each stimulus quality presented 60 times in blocks of 20 stimuli each. In Part II we found that central processing of olfactory stimuli analyzed by TFA differed significantly between healthy controls and patients even when controlling for age. It was possible to reliably distinguish patients with olfactory impairment from healthy individuals at a high degree of accuracy (healthy controls vs anosmic patients: sensitivity 75%; specificity 89%). In addition we could show a good test-retest reliability of TFA of chemosensory induced EEG-power changes in Part III. Conclusions Central processing of olfactory stimuli analyzed by TFA reliably distinguishes patients with olfactory impairment from healthy individuals at a high degree of accuracy. Importantly this can be achieved with a simple olfactometer.

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.

Size of nostril opening as a measure of intranasal volume.

The anatomy of the human intranasal cavity is complex and anatomical variations are known to affect olfactory functions. Measurement of anatomical variations via delineation of intranasal volume is, however, technically complicated as well as time-consuming. It is well documented that size of various body parts tends to correlate within the same individual. Therefore, in the current study, we explored the relationship between intranasal volume and the size of the nares, with the aim of using the area of the nostril opening as a potential predictor of intranasal volume. Structural whole-brain T1-weighted MR images of 69 healthy volunteers (35 women) were obtained using a 1.5 T standard clinical MRI scanner. The intranasal volume, as well as the area of the nostril opening, were delineated. Our results suggest that the intranasal volume is positively correlated with the area of the nostril opening. Intranasal volume did not differ significantly between men and women although men had significant larger nostril openings. However, the correlation between intranasal volume and nostril opening was not influenced by the subjects gender. In conclusion, it is possible to obtain a good estimate of the intranasal volume using measurements of the nares.

A computer-controlled olfactometer for a self-administered odor identification test

Odor identification tests are widely used for the general screening of olfactory function. However, the administration of odor identification tests is often limited due to a lack of investigators’ time. Therefore, we attempted to design a computer-controlled olfactometer to present a self-administered odor identification test. The results produced by means of this olfactometer were evaluated in terms of validity and test–retest reliability. To test the validity, participants’ performance in the odor identification test using the olfactometer was compared with their performance in the odor identification test using the validated assessment of the “Sniffin’ Sticks” test. The ten-item odor identification test was performed two times using two different methods: (1) the self-administered test using the computer-controlled olfactometer and (2) the foreign-administered test using the “Sniffin’ sticks.” To examine test–retest reliability, 20 participants were asked to repeat these tests on a different day. Participants reached significantly higher scores on a foreign-administered odor identification test using the “Sniffin’ sticks” than on the olfactometer-based test; however, this effect was driven by two less correctly identified odors in the olfactometer-based test. The significant difference between both methods in the mean scores disappeared after excluding two odors from the analysis. In addition, both methods showed no significant difference in scores obtained during the first and second session, indicating that results were consistent between sessions. In conclusion, our findings demonstrate that the computer-controlled olfactometer designed in this study can be used for a self-administered odor identification test.