Johannes Frasnelli

Detection of presymptomatic Parkinson's disease: Combining smell tests, transcranial sonography, and SPECT

Olfactory loss is among the early signs of Parkinsons disease (PD). We investigated whether “idiopathic” olfactory dysfunction might relate to signs of nigral degeneration. Olfactory tests were combined with transcranial sonography of the substantia nigra and single photon emission computed tomography (SPECT) imaging. Thirty patients diagnosed with idiopathic olfactory loss participated. Eleven of these patients exhibited an increased echogenicity of the SN in the transcranial sonography. In 10 of these 11 patients, SPECT scans with 123I‐FP‐CIT were performed. Median uptake ratios in the basal ganglia were pathological in 5 patients, 2 patients exhibited borderline findings, and 3 patients had normal results. Considering patients with idiopathic olfactory dysfunction, noninvasive transcranial sonography seems to be helpful in identifying patients potentially at risk to develop PD. Longitudinal follow‐up studies are necessary to estimate the ratio of patients with dopaminergic cell loss in the basal ganglia who will develop PD in the future.

Effects of olfactory function, age, and gender on trigeminally mediated sensations: a study based on the lateralization of chemosensory stimuli

The present investigation aimed to compare trigeminal nasal function of anosmic and hyposmic patients to healthy controls. Further, we aimed to study effects of age and gender on trigeminally mediated sensations following intranasal chemosensory stimulation. Participants were 35 patients with olfactory dysfunction (n=13: functional anosmia; n=22: hyposmia; age 28-69 years, mean age 56 years). Their results were compared with 17 normosmic subjects (28-82 years, mean 52 years). To analyze effects of age and gender in healthy subjects, an additional 24 healthy subjects were included (19-27 years; mean 24 years). Olfactory function was assessed using the Sniffin Sticks test kit (butanol odor threshold, odor discrimination, odor identification). The subjects ability to lateralize odors was investigated for benzaldehyde and eucalyptol. Patients with olfactory dysfunction had lower scores in the lateralization task than controls (P<0.001) indicating decreased trigeminal sensitivity. Among anosmic patients scores were not different in relation to different causes of olfactory dysfunction (P>0.29). There was a weak, but significant, correlation between localization of eucalyptol and duration of olfactory dysfunction (P=0.017). When investigating normosmic subjects only, no gender-related difference was apparent for lateralization scores. However, older subjects had lower scores than younger ones (P<0.01). Results of partial correlational analyses controlling for age suggested a relation between the trigeminal and the olfactory systems. In conclusion, results of the present study indicate that patients with olfactory dysfunction have lower trigeminal sensitivity compared with normosmic controls. This seems to be independent of the cause of olfactory loss. The deficit appears to improve with duration of the olfactory dysfunction, possibly indicating adaptive mechanisms. Further, the data suggest an age-related decrease of intranasal trigeminal sensitivity in healthy subjects. Analyses additionally indicate a correlation between olfactory and trigeminal sensitivity.

Olfactory dysfunction and daily life.

The objective of the present study was to investigate the hypothesis that subjects with parosmia suffer more in their daily life than patients who experience only quantitative olfactory loss. Two hundred five outpatients of the Smell and Taste Clinic and 25 healthy controls were included. The newly developed Questionnaire of Olfactory Disorders (QOD) was administered in combination with other psychometric tests (Beck Depression Inventory, “Befindlichkeitsskala” and the Short Form-36 Health Survey) along with an olfactory test (“Sniffin’ Sticks”). Results of the QOD were found to be an appropriate and valid measure of the impact of olfactory dysfunction on daily life. Patients with parosmia and quantitative olfactory dysfunction show higher rates of daily life complaints when compared to patients suffering from quantitative olfactory impairment only (QOD-PS: P=0.005). In addition, hyposmic and anosmic patients indicated significantly more complaints compared to patients with normosmia. Further, female patients seemed to suffer more from olfactory dysfunction than male patients. In conclusion, the assessment of the degree of qualitative olfactory dysfunction may be possible by the use of instruments based on questionnaires regarding daily life problems.

Crossmodal plasticity in sensory loss.

In this review, we describe crossmodal plasticity following sensory loss in three parts, with each section focusing on one sensory system. We summarize a wide range of studies showing that sensory loss may lead, depending of the affected sensory system, to functional changes in other, primarily not affected senses, which range from heightened to lowered abilities. In the first part, the effects of blindness on mainly audition and touch are described. The latest findings on brain reorganization in blindness are reported, with a particular emphasis on imaging studies illustrating how nonvisual inputs recruit the visually deafferented occipital cortex. The second part covers crossmodal processing in deafness, with a special focus on the effects of deafness on visual processing. In the last portion of this review, we present the effects that the loss of a chemical sense have on the sensitivity of the other chemical senses, that is, smell, taste, and trigeminal chemosensation. We outline how the convergence of the chemical senses to the same central processing areas may lead to the observed reduction in sensitivity of the primarily not affected senses. Altogether, the studies reviewed herein illustrate the fascinating plasticity of the brain when coping with sensory deprivation.

The neuronal correlates of intranasal trigeminal function—an ALE meta-analysis of human functional brain imaging data

Almost every odor we encounter in daily life has the capacity to produce a trigeminal sensation. Surprisingly, few functional imaging studies exploring human neuronal correlates of intranasal trigeminal function exist, and results are to some degree inconsistent. We utilized activation likelihood estimation (ALE), a quantitative voxel-based meta-analysis tool, to analyze functional imaging data (fMRI/PET) following intranasal trigeminal stimulation with carbon dioxide (CO(2)), a stimulus known to exclusively activate the trigeminal system. Meta-analysis tools are able to identify activations common across studies, thereby enabling activation mapping with higher certainty. Activation foci of nine studies utilizing trigeminal stimulation were included in the meta-analysis. We found significant ALE scores, thus indicating consistent activation across studies, in the brainstem, ventrolateral posterior thalamic nucleus, anterior cingulate cortex, insula, precentral gyrus, as well as in primary and secondary somatosensory cortices-a network known for the processing of intranasal nociceptive stimuli. Significant ALE values were also observed in the piriform cortex, insula, and the orbitofrontal cortex, areas known to process chemosensory stimuli, and in association cortices. Additionally, the trigeminal ALE statistics were directly compared with ALE statistics originating from olfactory stimulation, demonstrating considerable overlap in activation. In conclusion, the results of this meta-analysis map the human neuronal correlates of intranasal trigeminal stimulation with high statistical certainty and demonstrate that the cortical areas recruited during the processing of intranasal CO(2) stimuli include those outside traditional trigeminal areas. Moreover, through illustrations of the considerable overlap between brain areas that process trigeminal and olfactory information; these results demonstrate the interconnectivity of flavor processing.

Odor Localization and Sniffing

For humans, the localization of an odorant seems only possible if the odorant also stimulates the trigeminal nerve. There is, however, some evidence that active sniffing may affect this ability and facilitate the localization of pure odorants. Therefore, we tested the ability of 40 subjects to localize a pure odorant and a mixed olfactory/trigeminal stimulus under 2 stimulation conditions: either odors were blown into the subjects nostrils (passive) or subjects had to actively sniff the odors (active). Subjects could only reliably localize the mixed olfactory/trigeminal stimulus. However, we found a significant interaction between stimulation condition and nature of the odorant. So, the mixed olfactory/trigeminal stimulus was more localizable in the passive condition, whereas the pure odorant was better localized in the active condition. Interestingly, subjects had more correct answers after stimulation of the right nostril than of the left nostril (where subjects performed significantly below chance when stimulated with the pure odorant), suggesting possible laterality effects. These results suggest that active sniffing may affect our ability to localize odors. Other than mixed olfactory trigeminal stimuli, pure odorants are, however, not localizable even in active condition of sniffing.

The fish is bad: Negative food odors elicit faster and more accurate reactions than other odors

Dissociating between good or bad odors is arguable of crucial value for human survival, since unpleasant odors often signal danger. Therefore, negative odors demand a faster response in order to quickly avoid or move away from negative situations. We know from other sensory systems that this effect is most evident for stimuli from ecologically-relevant categories. In the olfactory system the classification of odors into the food or non-food category is of eminent importance. We therefore aimed to explore the link between odor processing speed and accuracy and odor edibility and valence by assessing response time and detection accuracy. We observed that reaction time and detection accuracy are influenced by both pleasantness and edibility. Specifically, we showed that an unpleasant food odor is detected faster and more accurately than odors of other categories. These results suggest that the olfactory system reacts faster and more accurately to ecologically-relevant stimuli that signal a potential danger.

Responsiveness of human nasal mucosa to trigeminal stimuli depends on the site of stimulation

There is evidence that functionally different areas can be distinguished within the nasal mucosa with regard to stimulation site and stimulus properties. The aim of the present study was the comparison of electrophysiological and psychophysical measures obtained in response to mechanical and chemosomatosensory stimulation of two different regions of the nasal mucosa. A total of 40 volunteers participated in this study (age range 21-36 years). Chemosomatosensory event-related potentials (ERPs) were recorded using gaseous CO2 as stimulant, while somatosensory ERPs were recorded in response to intranasal mechanical stimuli (air puffs). Stimuli were released to the anterior portion and to the posterior portion of the nasal cavity. A significant interaction between stimulus properties and site of stimulation could be detected after analysis of ERP parameters and intensity ratings. Thus, the chemosensory stimulus was perceived as stronger in the anterior portion of the nasal cavity whereas this was not the case for mechanosensory stimuli. In addition, mechanosensory stimuli were found to evoke ERPs with shorter latencies. These results underline the idea that the respiratory mucosa should not be seen as a homogeneous tissue. It exhibits varying sensitivities to trigeminal stimulation depending on stimulus quality and site of stimulation. Hence, perception of chemosensory stimuli seems to be most accurate in the anterior portion of the nasal cavity, while sensitivity to mechanical stimuli appears to be highest in the posterior portion. In addition, these differences within the respiratory mucosa may contribute to differences in the perception of orthonasal and retronasal odorous stimulation.

Clinical presentation of qualitative olfactory dysfunction

Many patients with olfactory dysfunction not only experience quantitative reduction of olfactory function, but also suffer from distorted olfactory sensations. This qualitative dysfunction is referred to as parosmia (also called “troposmia”) or phantosmia, with the major difference that distorted olfactory sensations are experienced in the presence or absence of an odor, respectively. Our clinical observations corroborate the literature in terms of a general underestimation of the incidence of olfactory distortions. Based on selected cases we try to show that olfactory distortions exhibit a large variance in their clinical appearance. Further, emphasis is placed on the fact that only a detailed and directed history of the patient can provide cues to the correct diagnosis.

Gustatory Function in Chronic Inflammatory Middle Ear Diseases

Hypothesis: Changes of gustatory function after ear surgery have been studied extensively. However, little is known on the influence of repeated/chronic inflammation within the middle ear on taste.