A methodological investigation of a flexible surface MRI coil to obtain functional signals from the human olfactory bulb.

BACKGROUND: Mammalian olfaction begins with transduction in olfactory receptors, continues with extensive processing in the olfactory bulb, and culminates in cortical representation. Most rodent studies on the functional neuroanatomy of olfaction have concentrated on the olfactory bulb, yet whether this structure is tuned only to basic chemical features of odorants or also to higher-order perceptual features is unclear. NEW METHOD: Whereas studies of the human brain can typically uncover involvement of higher-order feature extraction, this has not been possible in the case of the olfactory bulb, inaccessible to fMRI. The present study examined whether a novel method of acquisition using a facial coil could overcome this limitation. RESULTS: A series of experiments provided preliminary evidence of odor-driven responses in the human olfactory bulb, and found that these responses differed between individuals. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: The present preliminary technical achievement renders possible to design novel human odor fMRI studies by considering the olfactory system from the olfactory bulb to associative areas.

Differences in the central-nervous processing of olfactory stimuli according to their hedonic and arousal characteristics.

Given the strong relationship between human olfaction and emotion, it is not surprising that numerous studies have investigated human response to hedonic and arousing qualities of odors. However, neuropsychological research addressed rather the pleasant-unpleasant, and not the arousing-calming dimension of emotional states generated by odorants. The purpose of the presented fMRI study was to evaluate the differences in cerebral processing of olfactory stimuli, focusing on both of these dimensions of emotional experiences, i.e., pleasantness and arousal. We investigated the patterns of activation generated by odors differing in hedonic tone and generated arousal while controlling the stimuli intensity. This design allowed for a new insight to the emotional odor processing with imaging techniques. The pleasantness was related to activation in the cingulate gyrus, the insula, the hippocampal area, the amygdala, and the superior temporal gyrus, whereas arousal affected activation in the thalamic relay. The present study showed also that the emotional states generated by arousing qualities of odorants are an important determinant of magnitude of cerebral activation.

Source localization of event-related brain activity elicited by food and nonfood odors.

Tastes and odors influence the perception of a meal. Especially food aromas can act as potent signals to modulate our eating behavior with strong dependency on the reward produced by food. In this investigation we aimed to study the electrophysiological response to food- and non-food-related odors in healthy volunteers. Analyses revealed specific scalp potential maps for the two conditions; in particular the source of the map in the "food" condition seemed to be associated with the processing of rewards; the specific map in the "non-food" condition reflects odor characteristics excluding the reward.

Changes of olfactory abilities in relation to age: odor identification in more than 1400 people aged 4 to 80 years.

The currently presented large dataset (n = 1,422) consists of results that have been assembled over the last 8 years at science fairs using the 16-item odor identification part of the "Sniffin' Sticks". In this context, the focus was on olfactory function in children; in addition before testing, we asked participants to rate their olfactory abilities and the patency of the nasal airways. We reinvestigated some simple questions, e.g., differences in olfactory odor identification abilities in relation to age, sex, self-ratings of olfactory function and nasal patency. Three major results evolved: first, consistent with previously published reports, we found that identification scores of the youngest and the oldest participants were lower than the scores obtained by people aged 20-60. Second, we observed an age-related increase in the olfactory abilities of children. Moreover, the self-assessed olfactory abilities were related to actual performance in the smell test, but only in adults, and self-assessed nasal patency was not related to the "Sniffin' Sticks" identification score.

Spatio-temporal correlates of taste processing in the human primary gustatory cortex.

In humans the identification of the primary gustatory cortex (PGC) is still under debate. Neuroimaging studies indicate insula and overlying opercula as the best candidates but the exact position of the PGC within this region is not entirely clear. Moreover, inconsistencies appear when comparing results from studies using functional magnetic resonance imaging (fMRI), and gustatory event-related potentials (gERP), or gustatory event-related magnetic fields (gERMF). fMRI indicates activations in the anterior part of the insula and frontal operculum, while gERP and/or gERMF indicate activations at the transition between the parietal operculum and insula in its posterior part. Here it is important to note that for gERP and gERMF temporal and spatial characteristics of the stimulus must be well controlled to evoke a useful brain response. In the present study gERMF and gERP were recorded simultaneously using a whole-head system with 249 magnetometers and 32 electrodes, respectively; taste stimuli were applied using a stimulator providing excellent temporal and spatial control of the stimulus. Separate ERP and ERMF averaged waveforms were derived time-locked to the onset of the taste stimuli. The source analysis for the early time range revealed activity in the left and right anterior and mid part of the insula, where in the later time range the sources were located more in the posterior part of the insula.

Lateralized differences in olfactory bulb volume relate to lateralized differences in olfactory function.

The present study aimed to investigate whether side differences in olfactory bulb (OB) volume correlate to respective differences in olfactory function. In a total of 164 healthy volunteers volumetric measures of the OBs were performed plus lateralized measurements of odor thresholds and odor discrimination. Side differences were defined as 10% difference between the left and right OB. In 39 cases volumes on the right side were larger than on the left side, whereas in 29 cases it was the other way around. Subjects with larger right-sided OB volumes were found to be more sensitive to odorous stimulation of the right as compared to the left nostril in terms of odor thresholds and odor detection; higher sensitivity of the left nostrils (decreased odor threshold) was observed in individuals with larger OB volumes on the left side. These data appear to suggest that OB volume may be partly dependent on lateralized influences on the olfactory system, reflecting its lateralized organization.

OLAF: standardization of international olfactory tests.

Developed in the 1990 s, the "Sniffin 'Sticks" test for the assessment of olfactory threshold, odor identification and discrimination has become a widely used tool both in clinical and research settings. Originally pencil-and-paper documented, it may now be applied using a computer program. The "Filemaker" based software "OLAF" guides the examiner through any user-defined arrangement of the test battery, stores all data in a database, and offers results sheets to be printed out for convenience. The royalty-free program may be downloaded from http://www.tu-dresden.de/medkhno/riechen_schmecken/olaf.zip as a runtime solution application. It is currently available in four languages (English, French, German, and Italian) which can be toggled by a single mouse click, and is suitable for Windows as well as Apple platforms. In conclusion, the currently described software is expected to further facilitate and standardize olfactory testing with the "Sniffin' Sticks" test battery.

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.

Central processing of trigeminal activation in humans.

Although numerous fMRI studies have been performed on the processing of olfactory information, the intranasal trigeminal system so far has not received much attention. In a pilot study stimulants were presented within a constantly flowing airstream birhinally to activate the olfactory (phenylethyl alcohol, H(2)S) or the trigeminal (CO(2)) nerves. Both olfactory and trigeminal stimulation activated the ventral insular cortex. Intranasal trigeminal stimulation additionally led to an activation of the midbrain, superior temporal gyrus, anterior caudate nucleus, and the dorsolateral orbitofrontal cortex. Cerebellar activation was reduced relative to odorous stimuli. For all stimuli, right-sided activity was more pronounced. These results suggested that processing of intranasal activation follows a pattern which is, at least to some degree, similar for both trigeminal and olfactory stimulation. This and results from several other studies emphasize the fact that there is a high degree of interaction between the different aspects of the chemical senses, also in the sense that chemosensory-induced activation in the nasal cavity is processed in similar cortical networks. Interactions between the olfactory and trigeminal system can also be seen in patients with acquired olfactory loss, who exhibit reduced trigeminal sensitivity, possibly due to the lack of a central-nervous interaction. Both the orbitofrontal cortex and the rostral insula appear to be of significance in the amplification of trigeminal input, which is missing in patients with olfactory loss.

Gustatory testing for clinicians.

Gustatory testing for clinicians. By contrast with the evaluation of olfactory function, which has been standardised for almost two decades, the clinical assessment of gustatory function with psychophysical and objective testing is still in its infancy. This overview will attempt to summarise the knowledge that is important for clinicians in the awareness that progress in the field is ongoing. We focus on psychophysical testing but also discuss some recent achievements in the area of objective taste testing. There are now validated tests available for simple quick scans of gustatory function but debate continues about the extent to which such tests can be used for medico-legal purposes. In addition to emerging measures such as gustatory event-related potentials and functional imaging, routine objective gustatory testing will be needed in the future.

Trigeminal activation using chemical, electrical, and mechanical stimuli.

Tactile, proprioceptive, and nociceptive information, including also chemosensory functions are expressed in the trigeminal nerve sensory response. To study differences in the processing of different stimulus qualities, we performed a study based on functional magnetic resonance imaging. The first trigeminal branch (ophthalmic nerve) was activated by (a) intranasal chemical stimulation with gaseous CO2 which produces stinging and burning sensations, but is virtually odorless, (b) painful, but not nociceptive specific cutaneous electrical stimulation, and (c) cutaneous mechanical stimulation using air puffs. Eighteen healthy subjects participated (eight men, 10 women, mean age 31 years). Painful stimuli produced patterns of activation similar to what has been reported for other noxious stimuli, namely activation in the primary and secondary somatosensory cortices, anterior cingulate cortex, insular cortex, and thalamus. In addition, analyses indicated intensity-related activation in the prefrontal cortex which was specifically involved in the evaluation of stimulus intensity. Importantly, the results also indicated similarities between activation patterns after intranasal chemosensory trigeminal stimulation and patterns usually found following intranasal odorous stimulation, indicating the intimate connection between these two systems in the processing of sensory information.

Neural coding of stimulus concentration in the human olfactory and intranasal trigeminal systems.

Nasal chemical sensations are mediated principally by the olfactory and the trigeminal systems. Over the last few years brain structures involved in processing of trigeminal stimuli have been more and more documented. However, the exact role of individual regions in stimulus intensity processing is unclear. The present study set out to examine the neural network involved in encoding stimulus intensity in the trigeminal system and the olfactory system of humans. Participants were presented with two concentrations of relatively specific trigeminal stimuli (CO2) and olfactory (H2S), respectively. Responses were assessed by functional magnetic resonance imaging (fMRI). Whereas brain responses to stimulus intensity in the olfactory modality involved a wide neural network including cerebellum, entorhinal cortex, visual areas, and frontal regions, contrasting high and low CO2 concentrations revealed activation in a less complex network including various sub-regions of the cingulate cortex. Taken together, these results suggest separate but overlapping neural networks involved in encoding stimulus intensity in the two chemosensory systems.

Intranasal trigeminal function in subjects with and without an intact sense of smell.

The intranasal trigeminal system is involved in the perception of odors. To investigate the cerebral processing of sensory information from the trigeminal nerve in detail we studied subjects with and without olfactory function using functional magnetic resonance imaging. A normosmic group (n=12) was compared with a group of anosmic subjects (n=11). For trigeminal stimulation gaseous CO(2) was used. Following right-sided stimulation with CO(2) controls exhibited a stronger right-sided cerebral activation than anosmic subjects. Stronger activation was found in controls compared to anosmic subjects for the right prefrontal cortex, the right somatosensory cortex (SI), and the left parietal insula. In contrast, relatively higher activation was found in anosmic subjects for the left supplementary motor area in the frontal lobe, the right superior and middle temporal lobe, the left parahippocampal gyrus in the limbic lobe, and the sub-lobar region of the left putamen and right insula which was mostly due to a decreased BOLD signal of controls in these areas. Additional conjunction analysis revealed that activated areas common to the two groups were the cerebellum and the right premotor frontal cortex. These data suggest that the processing of the trigeminally mediated information is different in the presence or absence of an intact sense of smell, pointing towards the intimate connection between the two chemosensory systems.