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The goal of the present study was to investigate whether the psychophysical evaluation of taste stimuli using magnitude estimation influences the pattern of cortical activation observed with neuroimaging. That is, whether different brain areas are involved in the magnitude estimation of pleasantness relative to the magnitude estimation of intensity. fMRI was utilized to examine the patterns of cortical activation involved in magnitude estimation of pleasantness and intensity during hunger in response to taste stimuli. During scanning, subjects were administered taste stimuli orally and were asked to evaluate the perceived pleasantness or intensity using the general Labeled Magnitude Scale (Green 1996, Bartoshuk et al. 2004). Image analysis was conducted using AFNI. Magnitude estimation of intensity and pleasantness shared common activations in the insula, rolandic operculum, and the medio dorsal nucleus of the thalamus. Globally, magnitude estimation of pleasantness produced significantly more activation than magnitude estimation of intensity. Areas differentially activated during magnitude estimation of pleasantness versus intensity included, e.g., the insula, the anterior cingulate gyrus, and putamen; suggesting that different brain areas were recruited when subjects made magnitude estimates of intensity and pleasantness. These findings demonstrate significant differences in brain activation during magnitude estimation of intensity and pleasantness to taste stimuli. An appreciation for the complexity of brain response to taste stimuli may facilitate a clearer understanding of the neural mechanisms underlying eating behavior and over consumption.

Neural bases of human olfactory memory are poorly understood. Very few studies have examined neural substrates associated with correct odor recognition, and none has tackled neural networks associated with incorrect odor recognition. We investigated the neural basis of task performance during a yes-no odor recognition memory paradigm in young and elderly subjects using event-related functional magnetic resonance imaging. We explored four response categories: correct (Hit) and incorrect false alarm (FA) recognition, as well as correct (CR) and incorrect (Miss) rejection, and we characterized corresponding brain responses using multivariate analysis and linear regression analysis. We hypothesized that areas of the medial temporal lobe were differentially involved depending on the accuracy of odor recognition. In young adults, we found that significant activity in the hippocampus and the parahippocampal gyrus was associated with correct (true) recognition of odors, whereas the perirhinal cortex was associated with FAs and Misses. These findings are consistent with literature regarding hypothetical functional organization for memory processing. We also found that for correct recognition and rejection responses, the involvement of the hippocampus decreased when memory performances improved. In contrast to young individuals, elderly subjects were more prone to false memories and exhibited less specific activation patterns for the four response categories. Activation in the hippocampus and the parahippocampal gyrus was positively correlated with response bias scores for true and false recognition, demonstrating that conservative subjects produced an additional search effort leading to more activation of these two medial temporal lobe regions. These findings demonstrate that correct and incorrect recognition and rejection induce distinct neural signatures.

Impaired ability to remember what has gone before is one of the most distressing aspects of the aging process. Odor recognition memory is particularly vulnerable to the effects of aging, yet the underlying neural substrate is unknown. This study investigated the neural substrate of cross-modal olfactory recognition memory in young and older adults using fMRI. Participants were presented with 16 familiar odors immediately before entering the scanner, and were then tested for retrieval with words, either names of odors previously presented (targets) or names of new odors (foils), while being scanned at 3 T. Activation was reduced in the old subjects, both in regions involved in episodic memory retrieval and in regions involved in olfactory processing. Greater activation in the cerebellum of older adults was observed, suggesting increased response to attentional demands or compensatory mechanisms. Unlike in a number of studies in other sensory modalities, no increase in activation in frontal areas in older adults was observed during retrieval.

Classic psychophysical studies have provided significant information on the psychophysical functions for taste stimuli. With the advent of fMRI, studies are being conducted that provide insight into central processing of gustation in humans. However, fMRI experiments impose physical limitations on stimulus delivery. In the present study, we compared psychophysical functions relating perceived intensity to concentration, derived from previous studies that used the traditional sip-and-spit and dorsal flow delivery techniques, to psychophysical functions generated in this study using a simulated stimulus delivery technique (SSDT). The SSDT delivered minute quantities of taste stimuli to the dorsal surface of the tongue, just as in an fMRI scanner. As was hypothesized, the results indicated that slopes of intensity functions were dependent on the type of stimulus delivery technique. The SSDT resulted in slopes that were more similar to those generated by dorsal flow than by sip-and-spit stimulus delivery techniques, suggesting the importance of considering the influence of stimulus delivery on psychophysical response in designing and interpreting experiments.

This event-related functional magnetic resonance imaging (er-fMRI) study investigated BOLD signal change in response to a series of pure gustatory stimuli that varied in stimulus quality when subjects were hungry and sated with a nutritional pre-load. Group analyses showed significant differences in activation in the hunger minus satiety condition in response to sucrose, caffeine, saccharin, and citric acid within the thalamus, hippocampus, and parahippocampus. When examining the hunger and satiety conditions, activation varied as a function of stimulus, with the majority of the stimuli exhibiting significantly greater activation in the hunger state within the insula, thalamus, and substantia nigra, in contrast to decreased activation in the satiated state within the parahippocampus, hippocampus, amygdala, and anterior cingulate. Region of interest (ROI) analysis revealed two significant interactions, ROI by physiology and ROI by physiology by stimulus. In the satiety condition, the primary (inferior and superior insulae) and secondary (OFC 11 and OFC 47) taste regions exhibited significantly greater brain activation in response to all stimuli than regions involved in processing eating behavior (hypothalamus), affect (amygdala), and memory (hippocampus, parahippocampus and entorhinal cortex). These same regions demonstrated significantly greater activation within the hunger condition than the satiety condition, with the exception of the superior insula. Furthermore, the patterns of activation differed as a function taste stimulus, with greater activation in response to sucrose than to the other stimuli. These differential patterns of activation suggest that the physiological states of hunger and satiety produce divergent activation in multiple brain areas in response to different pure gustatory stimuli.

An experimental method for event-related functional magnetic resonance imaging that allows for the presentation of several chemosensory stimuli in the oral cavity during the same run, the collection of psychophysical measures (intensity or pleasantness) during the presentation of the stimuli, and the analysis of the data in an event-related fashion are described. The automatic pumps used to present taste stimuli allowed for multiple tastes to be delivered in small amounts under computer control. Psychophysical ratings of pleasantness or intensity were collected after each presentation of a taste stimulus and water, with the general labeled magnitude scale, using a joystick that controlled the movement of an arrow on the visual display. Performing these cognitive tasks required that the participant remained focused, and aided in the interpretation of the data collected. The perceived pleasantness differed across stimuli for all conditions; however, pleasantness ratings for the same stimulus displayed consistency, over the duration of the run and before each scan on separate days. Activation in response to sucrose and caffeine while the participant rated pleasantness was found in the insula, frontal operculum, rolandic operculum and orbitofrontal cortex which is consistent with previous taste fMRI studies.

Ten young adults (aged 20 to 25 years) participated in a functional Magnetic Resonance Imaging (fMRI) study to investigate neural substrates of cross-modal olfactory recognition memory. Before entering the scanner, participants were presented with 16 familiar odors selected from the COLT (Murphy, C., Nordin, S., Acosta, L., 1997. Odor learning, recall, and recognition memory in young and elderly adults. Neuropsychology 11, 126-137) and were then scanned for 3 runs according to a paradigm derived from Stark and Squire (Stark, C.E., Squire, L.R., 2000. Functional magnetic resonance imaging (fMRI) activity in the hippocampal region during recognition memory. J. Neurosci. 20, 7776-7781). During each run, participants were shown names of odors presented (targets) or not presented (foils) at encoding. Participants distinguished targets from foils via button press. Each run alternated 4 'ON' periods containing 7 targets and 2 foils (36 s) and 4 'OFF' periods with 7 foils and 2 targets (36 s). Data were processed with AFNI (Cox, R.W., 1996. AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput. Biomed. Res. 29, 162-173) and compared ON and OFF periods, extracting activation in regions that responded during the cross-modal olfactory recognition memory task. Group analysis showed that regions activated during the first run included right hippocampus, piriform/amygdalar area, superior temporal gyrus, anterior cingulate gyrus, inferior frontal/orbitofrontal gyrus, superior/medial frontal gyrus, and bilateral parahippocampal gyrus, inferior parietal lobule, supramarginal gyrus, cerebellum, lingual/fusiform area and middle/posterior cingulate gyrus. Region of interest analysis showed that degree of activation significantly decreased from run 1 to run 3 in the right hippocampus, fusiform gyrus, lingual gyrus, parahippocampal gyrus and middle frontal gyrus but not in other regions, suggesting that these regions sustain a specific function in olfactory recognition memory that attenuates as foils become more familiar with repeated presentation.

Neuroimaging and in particular functional magnetic resonance imaging (fMRI) of olfactory function relies on the ability to model the time course of brain responses elicited by odor stimuli. In this study we compared two templates of olfactory brain activation by comparing levels of correlation in regions critical to olfactory processing with either a stimulation-based template or a perception-based template, derived from perception profiles acquired off-line during a simulated fMRI session. fMRI signal was more correlated with the perception-based template than with the stimulation-based template in all regions. This effect was not observed when comparing correlations obtained with the exact same templates shifted in time by 12 s. Therefore, the improvement due to the use of the perception-based template was not only caused by a difference of shape between the stimulation-based and the perception-based template but was specifically related to the olfactory stimulation performed. These results suggest that the perception-based template better represents brain activity in response to olfactory stimulation and might help improve data processing of fMRI studies investigating olfactory function.

A protocol suited to the investigations of odor-taste interactions in a functional magnetic resonance imaging (fMRI) scanner is described and results that confirm the validity of that protocol are presented. Stimuli were dissolved in water and presented to the mouth of the participant through plastic syringes and plastic tubes as 50 microl every 3 s for 18 s. Participants were lying on the back to simulate the conditions in a fMRI scanner and gave pleasantness and intensity ratings in response to each stimulus using a Labeled Magnitude Scale (LMS). Stimuli were three concentrations of two tastants (i.e., sucrose and NaCl) and two odorants [i.e., ethyl butyrate (fruity) and citral (citrus)] and all possible odor-taste mixtures. Results showed that additivity of intensity in odor-taste mixtures was linear and did not depend on the pleasantness of the mixture. This study showed the feasibility of acquiring reliable psychophysical data with a stimulation device compatible with the fMRI environment and provided the foundation for the interpretation of future fMRI investigations of odor-taste interactions in flavor.

Olfactory function is affected by aging and deficits often result in decreasing quality of life, health and safety. The present study investigated the cortical substrate of olfactory deficits related to aging with functional Magnetic Resonance Imaging (fMRI), with a retronasal olfactory stimulation protocol using flavored aqueous solutions presented to the mouth. Activation was found in young subjects in the piriform/amygdalar region and in the orbitofrontal cortex and in other areas previously found activated in neuroimaging studies using odorized air, including insula and cerebellum. Activation was seen in similar areas in old subjects but the degree of activation was significantly lower in regions receiving primary olfactory projections (piriform cortex, entorhinal cortex, and amygdala). This result supports the hypothesis of dysfunction and/or degeneration in areas critical to olfactory processing as a major cause of olfactory deficits in the older population.

During food intake flavor perception results from simultaneous stimulation of the gustatory, olfactory and trigeminal systems. Olfactory stimulation occurs mainly through the retronasal pathway and the resulting perception is often interpreted as a taste perception, thus leading to the well-known sensory confusion between taste and olfaction. The present experiment was designed to study, with functional magnetic resonance imaging (fMRI), the cortical representation of olfactory perception in humans in response to retronasal stimulation by odorants delivered in aqueous solution. Psychophysical evaluation confirmed that the stimuli acted as pure olfactory stimuli through the retronasal pathway and did not present any taste component. Results showed activation in all brain regions previously described with neuroimaging techniques using olfactory stimulation with an odorized air flow. Piriform and orbitofrontal cortex were found activated as well as the hippocampal region, the amygdala, the insular lobe, the cingulate gyrus and the cerebellum. These results demonstrate the feasibility of efficiently stimulating the olfactory system in an fMRI scanner through the retronasal pathway with liquids delivered to the oral cavity. The presentation of olfactory stimuli in liquids to the mouth is a realistic model for the study of food-related flavor perception. This stimulation protocol furthermore allows presenting taste and olfactory stimuli separately or combined, thus allowing for direct comparisons between single modality representation, taste or olfaction, and representation of multi-modality mixtures.

The present study has investigated interaction at the cortical level in the human between two major components of flavor perception, pure chemical gustatory and lingual somatosensory perception. Twelve subjects participated in a functional magnetic resonance imaging study and tasted six stimuli, applied on the whole tongue, among which four were pure gustatory stimuli (NaCl, aspartame, quinine and HCl, pH 2.4 or 2.2) and two were both taste and lingual somatosensory stimuli, i.e. somato-gustatory stimuli (HCl, pH 1.6 or 1.5, and aluminum potassium sulfate). Functional images were acquired with an echo planar sequence on a 3 T system and were individually processed by correlation with the temporal perception profile. Both sets of stimuli showed activation in the same cortical areas, namely the insula, the rolandic operculum (base of the pre- and post-central gyri), the frontal operculum and the temporal operculum, confirming a wide overlap of taste and lingual somatosensory representations. However, the relative activation across areas and the analysis of co-activated areas across all runs for each set of stimuli allowed discrimination of taste and somatosensory modalities. Factor analysis of correspondences indicated different patterns of activation across the sub-insular and opercular regions, depending on the gustatory or somato-gustatory nature of the stimuli. For gustatory stimuli different activation patterns for the superior and inferior parts of the insula suggested a difference in function between these two insular sub-regions. Furthermore, the left inferior insula was co-activated with the left angular gyrus, a structure involved in semantic processing. In contrast, only somato-gustatory stimuli specifically produced a simultaneous and symmetrical activation of both the left and right rolandic opercula, which include a part of the sensory homunculus dedicated to the tactile representation of oral structures.

Whole-brain functional magnetic resonance imaging was used to detect local hemodynamic changes reflecting cortical activation in five left handed and five right handed human subjects during bilateral stimulation of the tongue with various tastes. Activation was found bilaterally in the insula and the perisylvian region. These regions correspond to the primary taste cortical areas identified with electrophysiological recordings in monkeys and suggested from former clinical observations in human subjects. Moreover, a unilateral projection was described for the first time in the inferior part of the insula of the dominant hemisphere, according to the subject's handedness.

Ten healthy subjects aged 20-25 including five right-handed and five left-handed according to the Dellatolas test participated in this functional magnetic resonance imaging (fMRI) study. A 3 Tesla whole-body MR scanner allowed echo planar imaging (EPI)-64 x 64 pixels, repetition time (TR) = 6 s, field of view (FOV) = 20 x 20 cm2--associated to acute anatomical localization of activated foci (256 x 256 pixels). Subjects were bilaterally stimulated with NaCl 85 mM, aspartame 2 mM, quinine hydrochloride 1 mM, glycyrrhizic acid 0.5 mM, guanosine monophosphate 1 mM and D-threonine 250 mM alternating with water. Stimuli and rinse were continuously pushed as bolus of 50 microliters every 3 s to the subject's mouth through microsyringes. We detected brain activated areas by correlation of the MR signal to an on-line perception profile recorded for each experiment and each subject with the finger-span method. We found most activations in the insula and the perisylvian region in agreement with previous electrophysiological studies on monkeys and clinical reports in humans. The superior part of the insula was bilaterally activated, in accordance with a whole-mouth stimulation. A striking lateralization related to handedness was found in a lower part of the insula. This projection in the dominant hemisphere, located in the same coronal plane as the upper insular activation, is the first evidence of a functional lateralization of brain processing involved in taste perception.

We used 3 Tesla functional magnetic resonance imaging (fMRI) with echo planar imaging to map taste projections in the human. Activations were found surrounding and buried in the sylvian fissure; the upper part of insula, the frontal operculum, and the foot of the pre- and postcentral gyri were usually activated. Moreover, we could describe, for the first time, a lateralized associative projection located in the lower part of the dominant hemisphere of the subject (n = 10). We also observed activations in the anterior cingulate gyrus, the centromedial thalamus, and other areas related to emotional or cognitive processes. Thirty subjects were submitted to a familiarization experiment sampling neophobic and nonneophobic stimuli. Measurements of isointense concentrations, magnitude estimates and hedonic values were assessed repetitively for 10 weeks. Five subjects performed 3 fMRI experiments, before, during and after familiarization. Psychophysical data showed a relationship between the evolution of the hedonic assessment and the intensity of the perception, and fMRI results showed a relationship between the evolution of the hedonic assessment and the evolution of the percent of activated pixels in taste cortical area.

In BOLD fMRI a detailed analysis of the MRI signal time course sometimes shows time differences between different activated regions. Some researchers have suggested that these latencies could be used to infer the temporal order of activation of these cortical regions. Several effects must be considered, however, before interpreting these latencies. The effect of a slice-dependent time shift (SDTS) with multi-slice acquisitions, for instance, may be important for regions located on different slices. After correction for this SDTS effect the time dispersion between activated regions is significantly decreased and the correlation between the MRI signal time course and the stimulation paradigm is improved. Another effect to consider is the latency which may exist between perception and stimulus presentation. It is shown that the control of perception can be achieved using a finger-spanning technique during the fMRI acquisition. The use of this perception profile rather than an arbitrary waveform derived from the paradigm proves to be a powerful alternative to fMRI data processing, especially with chemical senses studies, when return to baseline is not always correlated to stimulus suppression. This approach should also be relevant to other kinds of stimulation tasks, as a realistic way of monitoring the actual task performance, which may depend on attention, adaptation, fatigue or even variability of stimulus presentation.

A five-year prospective study of cutaneous leishmaniasis in an endemic area of Brazil revealed an annual incidence of disease of 8.1 per 1000 inhabitants and a prevalence of 14.9%. The disease fluctuated as a series of mini-epidemics. Most disease occurred in individuals who were 10-30 years of age. Mucosal disease occurred in 2.7% of patients with primary lesions and occurred a median of six years after this lesion. Disease was more common in males, in those with either large or multiple antecedent skin lesions, and in those with incomplete antimony therapy for the primary lesions. An ELISA was positive in 85% of those tested during the first two years after the primary lesion and remained positive for five to 40 years in 27% of patients. Skin testing was positive in 96% of patients with recent lesions and remained positive in 70% of patients. All patients with mucosal disease had positive serological and skin tests.