Taste-olfactory convergence, and the representation of the pleasantness of flavour, in the human brain

The functional architecture of the central taste and olfactory systems in primates provides evidence that the convergence of taste and smell information onto single neurons is realized in the caudal orbitofrontal cortex (and immediately adjacent agranular insula). These higher-order association cortical areas thus support flavour processing. Much less is known, however, about homologous regions in the human cortex, or how taste-odour interactions, and thus flavour perception, are implemented in the human brain. We performed an event-related fMRI study to investigate where in the human brain these interactions between taste and odour stimuli (administered retronasally) may be realized. The brain regions that were activated by both taste and smell included parts of the caudal orbitofrontal cortex, amygdala, insular cortex and adjoining areas, and anterior cingulate cortex. It was shown that a small part of the anterior (putatively agranular) insula responds to unimodal taste and to unimodal olfactory stimuli, and that a part of the anterior frontal operculum is a unimodal taste area (putatively primary taste cortex) not activated by olfactory stimuli. Activations to combined olfactory and taste stimuli where there was little or no activation to either alone (providing positive evidence for interactions between the olfactory and taste inputs) were found in a lateral anterior part of the orbitofrontal cortex. Correlations with consonance ratings for the smell and taste combinations, and for their pleasantness, were found in a medial anterior part of the orbitofrontal cortex. These results provide evidence on the neural substrate for the convergence of taste and olfactory stimuli to produce flavour in humans, and where the pleasantness of flavour is represented in the human brain.     

An fMRI Study of the Interactions Between the Attention and the Gustatory Networks

In a prior study, we showed that trying to detect a taste in a tasteless solution results in enhanced activity in the gustatory and attention networks. The aim of the current study was to use connectivity analyses to test if and how these networks interact during directed attention to taste. We predicted that the attention network modulates taste cortex, reflecting top-down enhancement of incoming sensory signals that are relevant to goal-directed behavior. fMRI was used to measure brain responses in 14 subjects as they performed two different tasks: (1) trying to detect a taste in a solution or (2) passively perceiving the same solution. We used psychophysiological interaction analysis to identify regions demonstrating increased connectivity during a taste attention task compared to passive tasting. We observed greater connectivity between the anterior cingulate cortex and the frontal eye fields, posterior parietal cortex, and parietal operculum and between the anterior cingulate cortex and the right anterior insula and frontal operculum. These results suggested that selective attention to taste is mediated by a hierarchical circuit in which signals are first sent from the frontal eye fields, posterior parietal cortex, and parietal operculum to the anterior cingulate cortex, which in turn modulates responses in the anterior insula and frontal operculum. We then tested this prediction using dynamic causal modeling. This analysis confirmed a model of indirect modulation of the gustatory cortex, with the strongest influence coming from the frontal eye fields via the anterior cingulate cortex. In summary, the results indicate that the attention network modulates the gustatory cortex during attention to taste and that the anterior cingulate cortex acts as an intermediary processing hub between the attention network and the gustatory cortex.     

Identification of human gustatory cortex by activation likelihood estimation

Over the last two decades, neuroimaging methods have identified a variety of taste-responsive brain regions. Their precise location, however, remains in dispute. For example, taste stimulation activates areas throughout the insula and overlying operculum, but identification of subregions has been inconsistent. Furthermore, literature reviews and summaries of gustatory brain activations tend to reiterate rather than resolve this ambiguity. Here, we used a new meta-analytic method [activation likelihood estimation (ALE)] to obtain a probability map of the location of gustatory brain activation across 15 studies. The map of activation likelihood values can also serve as a source of independent coordinates for future region-of-interest analyses. We observed significant cortical activation probabilities in: bilateral anterior insula and overlying frontal operculum, bilateral mid dorsal insula and overlying Rolandic operculum, and bilateral posterior insula/parietal operculum/postcentral gyrus, left lateral orbitofrontal cortex (OFC), right medial OFC, pregenual anterior cingulate cortex (prACC) and right mediodorsal thalamus. This analysis confirms the involvement of multiple cortical areas within insula and overlying operculum in gustatory processing and provides a functional "taste map" which can be used as an inclusive mask in the data analyses of future studies. In light of this new analysis, we discuss human central processing of gustatory stimuli and identify topics where increased research effort is warranted.     

Adult-like complexity of the larval antennal lobe of D. melanogaster despite markedly low numbers of odorant receptor neurons

We provide a detailed analysis of the larval head chemosensory system of Drosophila melanogaster, based on confocal microscopy of cell-specific reporter gene expression in P[GAL4] enhancer trap lines. In particular, we describe the neuronal composition of three external and three pharyngeal chemosensory organs, the nerve tracts chosen by their afferents, and their central target regions. With a total of 21 olfactory and 80 gustatory neurons, the sensory level is numerically much simpler than that of the adult. Moreover, its design is different than in the adult, showing an association between smell and taste sensilla. In contrast, the first-order relay of the olfactory afferents, the larval antennal lobe (LAL), exhibits adult-like features both in terms of structure and cell number. It shows a division into approximately 30 subunits, reminiscent of glomeruli in the adult antennal lobe. Taken together, the design of the larval chemosensory system is a "hybrid," with larval-specific features in the periphery and central characteristics in common with the adult. The largely reduced numbers of afferents and the similar architecture of the LAL and the adult antennal lobe, render the larval chemosensory system of Drosophila a valuable model system, both for studying smell and taste and for examining the development of its adult organization.     

Flavor and the Formation of Category-Specific Processing in Olfaction

The perception of flavor occurs when objects, such as food and drink, are placed in the mouth. Although the sensation that ensues depends upon inputs from multiple sensory modalities, due to a combination of oral referral and common sensory qualities (e.g., odors and tastes can both be sweet), it is experienced as a unitary flavor perception. In this paper, it is proposed that neural processing within the somatomotor mouth area of the Rolandic operculum mediates oral referral and causes the neural binding of multimodal inputs to create a flavor percept. It is further proposed that unimodal taste and unimodal smell neurons alter the selectivity of bimodal taste/smell cells only if the binding mechanism in the somatomotor mouth area is active. The encoded flavor object is thus represented by a bounded pattern of response that includes the sculpted bimodal cells as well as the unimodal responses distributed across the insula, operculum, anterior cingulate cortex, and orbitofrontal cortex. Once an odor is encoded in this way, the odor acquires the ability to reactivate this encoded percept, whether experienced orthonasally or retronasally. Finally, it is proposed that one manifestation of this process is the existence of category-specific processing in olfaction.     

It’s in the eye of the beholder: selective attention to drink properties during tasting influences brain activation in gustatory and reward regions

Statements regarding pleasantness, taste intensity or caloric content on a food label may influence the attention consumers pay to such characteristics during consumption. There is little research on the effects of selective attention on taste perception and associated brain activation in regular drinks. The aim of this study was to investigate the effect of selective attention on hedonics, intensity and caloric content on brain responses during tasting drinks. Using functional MRI brain responses of 27 women were measured while they paid attention to the intensity, pleasantness or caloric content of fruit juice, tomato juice and water. Brain activation during tasting largely overlapped between the three selective attention conditions and was found in the rolandic operculum, insula and overlying frontal operculum, striatum, amygdala, thalamus, anterior cingulate cortex and middle orbitofrontal cortex (OFC). Brain activation was higher during selective attention to taste intensity compared to calories in the right middle OFC and during selective attention to pleasantness compared to intensity in the right putamen, right ACC and bilateral middle insula. Intensity ratings correlated with brain activation during selective attention to taste intensity in the anterior insula and lateral OFC. Our data suggest that not only the anterior insula but also the middle and lateral OFC are involved in evaluating taste intensity. Furthermore, selective attention to pleasantness engaged regions associated with food reward. Overall, our results indicate that selective attention to food properties can alter the activation of gustatory and reward regions. This may underlie effects of food labels on the consumption experience of consumers.     

Trial measurement of brain activity underlying olfactory–gustatory synchrony perception using event-related potentials from five female participants

Temporal synchrony between odor and taste plays an important role in flavor perception. When we investigate temporal synchrony between odor and taste, it is necessary to pay attention not only to physical simultaneity of the presentation of olfactory and gustatory stimuli, but also to the perceptual simultaneity between the two stimuli. In this study, we examined short-latency brain activity underlying synchrony perception for olfactory–gustatory combinations. While five female participants performed a simultaneity judgment (SJ) task using soy sauce odor and salt solution, single-channel event-related potentials (ERPs) were recorded at the position of Cz. In each trial, the participant was asked whether olfactory and gustatory stimuli were perceived simultaneously or successively. Based on the judgment responses acquired from participants (i.e., simultaneous or successive), ERP data were classified into two datasets. The means of ERPs from each participant were calculated for each type of judgment response, considering the onset of olfactory or gustatory stimuli (OERPs or GERPs, respectively) as the starting point. The latencies of the P1 component of GERPs were very similar between simultaneous and successive judgment responses, whereas the P1 amplitudes differed significantly. These results indicated that neural activity affecting SJ for an olfactory–gustatory combination is generated during a period of about 130 ms from the onset of gustatory stimulus. Thus, olfactory and gustatory information processing related to flavor perception (more specially, synchrony perception between odor and taste) might be initiated at a relatively early stage of the central pathway.     

Taste representation in the human cortex and the central control of appetite

The control of food intake and the mechanisms of energy homeostasis are now known to depend on a series of peripheral signals that act directly on the central nervous system leading to appropriate adaptive responses. However, in humans, the increasing occurrence of associated pathologies due to abnormal food-intake preferences such as obesity and anorexia implies that food intake control depend also on cortical processing. Recent functional neuroimaging studies on human volunteers reveal that the central processing of gustatory information in humans is performed in similar areas to those of other primates, with primary gustatory cortical areas in the frontal operculum/anterior insula complex responding efficiently to stimulus decoding by isolating peripheral signals on internal physiological states whereas regions of the ventromedial prefrontal cortex seem to integrate information on the sensory aspects of taste stimuli with the abovementioned peripheral signals on the current homeostatic state of the organism.     

Use of an Immediate Swallow Protocol to Assess Taste and Aroma Integration in fMRI Studies

Perception of flavor is a complex process involving the integration of taste and aroma. Few functional magnetic resonance imaging (fMRI) studies have assessed the crossmodal interactions which result in flavor perception, and all previous studies have used a retro-nasal aroma delivery with a delayed swallow, which delays retro-nasal aroma release, and thus, alters taste and aroma integration. In this paper, we assess crossmodal interactions in flavor processing using an immediate swallow fMRI paradigm in 13 healthy volunteers. We compare unimodal taste (sucrose) and unimodal retro-nasal aroma stimuli, with a congruent taste and aroma combination (flavor), to assess crossmodal flavor interactions using an immediate swallow paradigm. Subtraction and conjunction analysis methods are described, and the use of a control stimulus is addressed. Subtraction analysis was found to reveal areas of anterior insula, frontal operculum, anterior cingulate, and orbitofrontal cortex, whilst the conjunction analysis revealed additional active areas in oral somatosensory areas (SI), rolandic operculum and posterior cingulate, supporting the hypothesis that taste, olfactory, and tactile sensations are integrated to produce a flavor percept.     

On-line psychophysical data acquisition and event-related fMRI protocol optimized for the investigation of brain activation in response to 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.     

Age‐related changes of gustatory function depend on alteration of neuronal circuits

Studies on age‐related gustatory function report a reduction of the taste function, but the degeneration of the peripheral papillae alone cannot explain this reduction. In the present study, we apply psychophysics and gustatory event–related potentials (gERPs) to explore age‐related differences in the processing of gustatory information as indicated by the cerebral sources of the gERP. A total of 96 subjects (47 female), subdivided into four groups with increasing age, participated in the study. After olfactory and gustatory screening for normal function, the subjects were invited to two sessions of gERP acquisition. They received a randomized combination of five isointense basic tastants that were presented at a medium level. At the same time, we recorded scalp electroencephalography (EEG) from 128 scalp locations. Psychophysical testing for smell and taste function exhibited a significant decrease with age. Topographical analyses of the EEG delineated four basic topographical maps that explained the processing of taste in the pre‐decline age range, with sources inside the relevant gustatory areas. The age‐related change of gustatory processing was associated with the absence of a specific map with sources inside the cerebellum and posterior insula, and the temporal broadening of a map with sources in the bilateral inferior frontal gyrus. These results confirm the hypothesis that the reduction of taste function with aging is not only due to degradation of gustatory peripheral tissues but is also related to different neural signatures in the central nervous system.     

Orosensory and Homeostatic Functions of the Insular Taste Cortex

The gustatory aspect of the insular cortex is part of the brain circuit that controls ingestive behaviors based on chemosensory inputs. However, the sensory properties of foods are not restricted to taste and should also include salient features such as odor, texture, temperature, and appearance. Therefore, it is reasonable to hypothesize that specialized circuits within the central taste pathways must be involved in representing several other oral sensory modalities in addition to taste. In this review, we evaluate current evidence indicating that the insular gustatory cortex functions as an integrative circuit, with taste-responsive regions also showing heightened sensitivity to olfactory, somatosensory, and even visual stimulation. We also review evidence for modulation of taste-responsive insular areas by changes in physiological state, with taste-elicited neuronal responses varying according to the nutritional state of the organism. We then examine experimental support for a functional map within the insular cortex that might reflect the various sensory and homeostatic roles associated with this region. Finally, we evaluate the potential role of the taste insular cortex in weight-gain susceptibility. Taken together, the current experimental evidence favors the view that the insular gustatory cortex functions as an orosensory integrative system that not only enables the formation of complex flavor representations but also mediates their modulation by the internal state of the body, playing therefore a central role in food intake regulation.     

Functional anatomy of chemical senses in the alert monkey revealed by positron emission tomography

Functional imaging technique using positron emission tomography (PET) has made it possible to localize functional brain regions in the human brain by detecting changes in regional cerebral blood flow (rCBF). Performing PET studies in the monkey will aid in integrating monkey electrophysiological research with human PET studies. We examined changes in rCBF during olfactory or combined olfactory and gustatory (flavour) stimulation using PET in the alert rhesus monkey. Olfactory or flavour stimulation with acetic acid or apple increased rCBF in the prepyriform area, substantia innominata and amygdala. Besides these areas, flavour stimulation increased rCBF in the anterior insula and frontal operculum, orbitofrontal cortex, inferior frontal gyrus and cerebellum. Apple odour or flavour stimuli increased rCBF in the inferior occipital gyrus in addition to the above areas. These findings suggest that the increases of rCBF in response to neural activities in the primary olfactory and gustatory cortices are detectable by the use of PET. In addition, regions activated by apple stimuli suggest that higher brain function might be detected with PET in the alert monkey.     

Neural correlates of evaluative compared with passive tasting

We used functional magnetic resonance imaging to test the hypothesis that the nature of the neural response to taste varies as a function of the task the subject is asked to perform. Subjects received sweet, sour, salty and tasteless solutions passively and while evaluating stimulus presence, pleasantness and identity. Within the insula and overlying operculum the location of maximal response to taste vs. tasteless varied as a function of task; however, the primary taste cortex (anterior dorsal insula/frontal operculum – AIFO), as well as a more ventral region of anterior insula, responded to taste vs. tasteless irrespective of task. Although the response here did not depend upon task, preferential connectivity between AIFO and the amygdala (bilaterally) was observed when subjects tasted passively compared with when they performed a task. This suggests that information transfer between AIFO and the amygdala is maximal during implicit processing of taste. In contrast, a region of the left lateral orbitofrontal cortex (OFC) responded preferentially to taste and to tasteless when subjects evaluated pleasantness, and was preferentially connected to earlier gustatory relays (caudomedial OFC and AIFO) when a taste was present. This suggests that processing in the lateral OFC organizes the retrieval of gustatory information from earlier relays in the service of computing perceived pleasantness. These findings show that neural encoding of taste varies as a function of task beyond that of the initial cortical representation.     

Convergent gustatory and viscerosensory processing in the human dorsal mid‐insula

The homeostatic regulation of feeding behavior requires an organism to be able to integrate information from its internal environment, including peripheral visceral signals about the body's current energy needs, with information from its external environment, such as the palatability of energy‐rich food stimuli. The insula, which serves as the brain's primary sensory cortex for representing both visceral signals from the body and taste signals from the mouth and tongue, is a likely candidate region in which this integration might occur. However, to date it has been unclear whether information from these two homeostatically critical faculties is merely co‐represented in the human insula, or actually integrated there. Recent functional neuroimaging evidence of a common substrate for visceral interoception and taste perception within the human dorsal mid‐insula suggests a model whereby a single population of neurons may integrate viscerosensory and gustatory signals. To test this model, we used fMRI‐Adaptation to identify whether insula regions that exhibit repetition suppression following repeated interoception trials would then also exhibit adapted responses to subsequent gustatory stimuli. Multiple mid and anterior regions of the insula exhibited adaptation to interoceptive trials specifically, but only the dorsal mid‐insula regions exhibited an adapted gustatory response following interoception. The discovery of this gustatory‐interoceptive convergence within the neurons of the human insula supports the existence of a heretofore‐undocumented neural pathway by which visceral signals from the periphery modulate the activity of brain regions involved in feeding behavior. Hum Brain Mapp 38:2150–2164, 2017. © 2017 Wiley Periodicals, Inc.     

Intensity‐related distribution of sweet and bitter taste fMRI responses in the insular cortex

The human gustatory cortex analyzes the chemosensory properties of tastants, particularly the quality, intensity, and affective valence, to determine whether a perceived substance should be ingested or rejected. Among previous studies, the spatial distribution of taste intensity‐related activations within the human insula has been scarcely addressed. To spatially characterize a specialized or distributed nature of the cortical responses to taste intensities, a functional magnetic resonance imaging study was performed at 3 T in 44 healthy subjects where sweet and bitter tastants were administered at five increasing concentrations and cortex‐based factorial and parametric analyses were performed. Two clusters in the right middle‐posterior and left middle insula were found specialized for taste intensity processing, exhibiting a highly nonlinear profile across concentrations. Multiple clusters were found activated by sweet and bitter taste stimuli at most concentrations, in the anterior, middle‐posterior, and inferior portion of the bilateral insula. Across these clusters, respectively, for the right and left insula, a superior‐to‐inferior and an anterior‐to‐posterior spatial gradient for high‐to‐low concentrations were observed for the most responsive intensity of both tastes. These findings may gather new insights regarding how the gustatory cortex is spatially organized during the perceptual processing of taste intensity for two basic tastants.     

Improved methods for fMRI studies of combined taste and aroma stimuli

Previous neuroimaging studies of the cortical representation of gustatory and olfactory stimuli have often delivered tastants to the mouth in very small quantities or stimulated olfaction orthonasally. In studies of retro-nasal olfaction, swallowing was generally delayed to reduce head motion artefacts. The present fMRI study aims to improve upon such methodological limitations to allow investigation of the cortical representation of flavour (taste and aroma combination) as it typically occurs during the consumption of liquid foods. For this purpose we used (1) a novel, automated, sprayed stimulus delivery system and a larger volume of liquid sample (containing sweet tastants and banana/pear aroma volatiles) to achieve more extensive stimulation of the oral cavity taste receptors, (2) a pseudo-natural delivery paradigm that included prompt swallowing after each sample delivery to obtain physiological retro-nasal olfactory stimulation, (3) fMRI acquisition with wide brain coverage and double-echo EPI to improve sensitivity. We validated our paradigm for the delivery of volatiles using atmospheric pressure chemical ionisation mass spectrometry. This showed that the main retro-nasal delivery of volatiles in the paradigm occurs immediately after the swallow. Several brain areas were found to be activated, including the insula, frontal operculum, rolandic operculum/parietal lobe, piriform, dorsolateral prefrontal cortex, anterior cingulate cortex, ventro-medial thalamus, hippocampus and medial orbitofrontal cortex.     

Gustatory stimulation influences the processing of intranasal stimuli

OBJECTIVES: Taste and smell interact. The aim of this study was to examine this interaction using gustatory and olfactory stimuli applied at the same time, which exhibited perceptual compatibility and incompatibility. METHODS: Thirty-two, young, healthy normosmic subjects (16 men, 16 women) took part in two randomized sessions. Event-related potentials (ERP) were recorded in response to vanillin, or gaseous CO2. These two conditions were combined with three "taste conditions" including sweet taste, sour taste, and the intraoral presentation of an empty taste dispenser. RESULTS: Vanillin responses were largest for the "sweet" condition, while they were smaller for the "sour condition". In contrast, responses to CO2 were largest under the "sour" condition, and smallest under the "sweet" condition. Moreover, during the "sweet" condition the latencies of P1 and N1 were shorter than in the "sour" condition, which was the other way around for CO2. CONCLUSIONS: Results of the present investigation suggested that (1) the early processing of intranasal chemosensory stimuli is modulated through concomitant gustatory stimulation, and that (2) this modulation may depend, at least in part, on the contextual compatibility between intranasal and intraoral stimuli.     

The Representation of Information About Taste and Odor in the Orbitofrontal Cortex

Complementary neurophysiological recordings in macaques and functional neuroimaging in humans show that the primary taste cortex in the rostral insula and adjoining frontal operculum provides separate and combined representations of the taste, temperature, and texture (including viscosity and fat texture) of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are for some neurons combined by learning with olfactory and visual inputs, and these neurons encode food reward in that they only respond to food when hungry and in that activations here correlate with subjective pleasantness and with individual differences in and cognitive modulation of the hedonic value of food. Information theory analysis shows a robust representation of taste in the orbitofrontal cortex, with an average mutual information of 0.45 bits for each neuron about which of six tastants (glucose, NaCl, HCl, quinine-HCl, monosodium glutamate, and water) was present, averaged across 135 gustatory neurons. The information increased with the number of neurons in the ensemble, but less than linearly, reflecting some redundancy. There was less information per neuron about which of six odors was present from orbitofrontal olfactory neurons, but the code was robust in that the information increased linearly with the number of neurons, reflecting independent information encoded by different neurons. Although some neurons were sharply tuned to individual tastants, the average encoding was quite distributed.     

Interoceptive accuracy and its impact on neuronal responses to olfactory stimulation in the insular cortex

The insular cortex plays a key role in the integration of multimodal information and in interoceptive and exteroceptive processing. For instance, neurons in the central dorsal insula that are active during interoceptive tasks, also show an adaptation to gustatory stimulation. We tested the link between interoception and exteroception for the olfactory system (i.e., the second domain of chemosensation). In a sample of 31 participants, olfactory function was assessed in a two dimensional approach while the Heartbeat Perception Task served as a measurement for cardiac interoceptive accuracy. Subsequent fMRI sessions were performed on a 3‐Tesla MR scanner containing 12–15 olfactory stimulation trials with a mildly pleasant food‐related odor (coffee). Persons scoring high in the cardiac interoceptive accuracy task presented stronger smelling abilities as well as enhanced BOLD responses following olfactory stimulation. The olfactory stimulation triggered enhanced insular activation patterns in the central dorsal insular cortex. Consistent with prior findings on the coherence of gustatory and interoceptive processing in the central dorsal insula, these results base the insula as a common region for the integration of interoception and exteroception. We propose an explanatory model of how exteroception triggers the integration of intero‐ and exteroceptive sensations in the central dorsal insular cortex.