Superadditive opercular activation to food flavor is mediated by enhanced temporal and limbic coupling

Food perception is characterized by a transition from initially separate sensations of the olfactory and gustatory properties of the object toward their combined sensory experience during consumption. The holistic flavor experience, which occurs as the smell and taste merge, extends beyond the mere addition of the two chemosensory modalities, being usually perceived as more object‐like, intense and rewarding. To explore the cortical mechanisms which give rise to olfactory–gustatory binding during natural food consumption, brain activation during consumption of a pleasant familiar beverage was contrasted with presentation of its taste and orthonasal smell alone. Convergent activation to all presentation modes was observed in executive and chemosensory association areas. Flavor, but not orthonasal smell or taste alone, stimulated the frontal operculum, supporting previous accounts of its central role in the formation of the flavor percept. A functional dissociation was observed in the insula: the anterior portion was characterized by sensory convergence, while mid‐dorsal sections activated exclusively to the combined flavor stimulus. psycho‐physiological interaction analyses demonstrated increased neural coupling between the frontal operculum and the anterior insula during flavor presentation. Connectivity was also increased with the lateral entorhinal cortex, a relay to memory networks and central node for contextual modulation of olfactory processing. These findings suggest a central role of the insular cortex in the transition from mere detection of chemosensory convergence to a superadditive flavor representation. The increased connections between the frontal operculum and medial temporal memory structures during combined olfactory–gustatory stimulation point to a potential mechanism underlying the acquisition and modification of flavor preferences. Hum Brain Mapp 36:1662–1676, 2015. © 2014 Wiley Periodicals, Inc.     

The representation of pleasant touch in the brain and its relationship with taste and olfactory areas

Although there has been much investigation of brain pathways involved in pain, little is known about the brain mechanisms involved in processing somatosensory stimuli which feel pleasant. Employing fMRI it was shown that pleasant touch to the hand with velvet produced stronger activation of the orbitofrontal cortex than affectively neutral touch of the hand with wood. In contrast, the affectively neutral but more intense touch produced more activation of the primary somatosensory cortex than the pleasant stimulus. This indicates that part of the orbitofrontal cortex is concerned with representing the positively affective aspects of somatosensory stimuli, and in further experiments it was shown that this orbitofrontal area is different from that activated by taste and smell. The finding that three different primary or unlearned types of reinforcer (touch, taste, and smell) are represented in the orbitofrontal cortex helps to provide a firm foundation for understanding the neural basis of emotions, which can be understood in terms of states elicited by stimuli which are rewarding or punishing.     

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.     

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.     

Cerebral blood flow changes associated with attribution of emotional valence to pleasant, unpleasant, and neutral visual stimuli in a PET study of normal subjects.

OBJECTIVE: To assist in the development of a model for the psychopathology of emotions, the present study sought to identify the neural circuits associated with the evaluation of visual stimuli for emotional valence. METHOD: Seventeen healthy individuals were shown three sets of emotionally laden pictures carrying pleasant, unpleasant, and neutral content. While subjects evaluated the picture set for emotional valence, regional cerebral blood flow was measured with the use of [15O] water positron emission tomography. Subjective ratings of the emotional valence of the picture sets were recorded. Data were analyzed by comparing the images acquired during the neutral condition with the unpleasant and pleasant image sets and the unpleasant and pleasant conditions with each other. RESULTS: Processing of pleasant stimuli was associated with increased blood flow in the dorsal-lateral, orbital, and medial frontal cortex relative to the unpleasant condition and in the cingulate, precuneus, and visual cortex relative to the neutral condition. Evaluation of unpleasant stimuli activated the amygdala, visual cortex, and cerebellum relative to the pleasant condition and the nucleus accumbens, precuneus, and visual cortex relative to the neutral condition. CONCLUSIONS: Observing and assigning emotional value to unpleasant stimuli produced activations in subcortical limbic regions, whereas evaluation of pleasant stimuli produced activations in cortical limbic areas. These findings are consistent with the notion of a subcortical and archaic danger recognition system and a system detecting pleasantness in events and situations that is phylogenetically younger, involving primarily the prefrontal cortex.     

Investigating emotion with music: an fMRI study

The present study used pleasant and unpleasant music to evoke emotion and functional magnetic resonance imaging (fMRI) to determine neural correlates of emotion processing. Unpleasant (permanently dissonant) music contrasted with pleasant (consonant) music showed activations of amygdala, hippocampus, parahippocampal gyrus, and temporal poles. These structures have previously been implicated in the emotional processing of stimuli with (negative) emotional valence; the present data show that a cerebral network comprising these structures can be activated during the perception of auditory (musical) information. Pleasant (contrasted to unpleasant) music showed activations of the inferior frontal gyrus (IFG, inferior Brodmann's area (BA) 44, BA 45, and BA 46), the anterior superior insula, the ventral striatum, Heschl's gyrus, and the Rolandic operculum. IFG activations appear to reflect processes of music-syntactic analysis and working memory operations. Activations of Rolandic opercular areas possibly reflect the activation of mirror-function mechanisms during the perception of the pleasant tunes. Rolandic operculum, anterior superior insula, and ventral striatum may form a motor-related circuitry that serves the formation of (premotor) representations for vocal sound production during the perception of pleasant auditory information. In all of the mentioned structures, except the hippocampus, activations increased over time during the presentation of the musical stimuli, indicating that the effects of emotion processing have temporal dynamics; the temporal dynamics of emotion have so far mainly been neglected in the functional imaging literature.     

Selective attention to affective value alters how the brain processes taste stimuli

How does selective attention to affect influence sensory processing? In an fMRI investigation, when subjects were instructed to remember and rate the pleasantness of a taste stimulus, 0.1 m monosodium glutamate, activations were greater in the medial orbitofrontal and pregenual cingulate cortex than when subjects were instructed to remember and rate the intensity of the taste. When the subjects were instructed to remember and rate the intensity, activations were greater in the insular taste cortex. An interaction analysis showed that this dissociation of taste processing, depending on whether attention to pleasantness or intensity was relevant, was highly significant (P < 0.0002). Thus, depending on the context in which tastes are presented and whether affect is relevant, the brain responds to a taste differently. These findings show that, when attention is paid to affective value, the brain systems engaged to represent the sensory stimulus of taste are different from those engaged when attention is directed to the physical properties of a stimulus such as its intensity. This differential biasing of brain regions engaged in processing a sensory stimulus, depending on whether the cognitive demand is for affect‐related vs. more sensory‐related processing, may be an important aspect of cognition and attention. This has many implications for understanding the effects not only of taste but also of other sensory 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.     

Critical role of insular cortex in taste but not odour aversion memory

Conditioned odour aversion (COA) and conditioned taste aversion (CTA) result from the association of a novel odour or a novel taste with delayed visceral illness. The insular cortex (IC) is crucial for CTA memory, and the present experiments sought to determine whether the IC is required for the formation and the retrieval of COA memory as it is for CTA. We first demonstrated that ingested odour is as effective as taste for single-trial aversion learning in rats conditioned in their home cage. COA, like CTA, tolerates long intervals between the ingested stimuli and the illness and is long-lasting. Transient inactivation of the IC during acquisition spared COA whereas it greatly impaired CTA. Similarly, blockade of protein synthesis in IC did not affect COA but prevented CTA consolidation. Moreover, IC inactivation before retrieval tests did not interfere with COA memory expression when performed either 2 days (recent memory) or 36 days after acquisition (remote memory). Similar IC inactivation impaired the retrieval of either recent or remote CTA memory. Altogether these findings indicate that the IC is not necessary for aversive odour memory whereas it is essential for acquisition, consolidation and retrieval of aversive taste memory. We propose that the chemosensory stimulations modulate IC recruitment during the formation and the retrieval of food aversive memory.     

Taste and olfactory status in a gourmand with a right amygdala lesion

In a patient with a lesion of the right amygdala and temporal pole who had the characteristics of the gourmand syndrome, sensory and hedonic testing was performed to examine the processing of taste, olfactory, and some emotional stimuli. The gourmand syndrome describes a preoccupation with food and a preference for fine eating and is associated with right anterior lesions. It was found that the taste thresholds for sweet, salt, bitter, and sour were normal; that the patient did not dislike the taste of salt (NaCl) at low and moderate concentrations as much as age-matched controls; that this also occurred for monosodium glutamate (MSG); that there were some olfactory differences from normal controls; and that there was a marked reduction in the ability to detect face expressions of disgust.     

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.     

From affective value to decision-making in the prefrontal cortex

Representing the affective value of a reward on a continuous scale may occur separately from making a binary, for example yes vs no, decision about whether to choose the reward. To investigate whether these are separable processes, we used functional magnetic resonance imaging to measure activations produced by pleasant warm, unpleasant cold, and affectively complex combinations of these stimuli applied to the hand. On some trials the affective value was rated on a continuous scale, and on different trials a yes-no decision was made about whether the stimulus should be repeated in future. Decision-making contrasted with just rating the affective stimuli revealed activations in the medial prefrontal cortex area 10, implicating this area in binary decision-making. Activations related to the pleasantness ratings and which were not influenced when a binary decision was made were found in the pregenual cingulate and parts of the orbitofrontal cortex, implicating these regions in the continuous representation of affective value. When a decision was yes vs. no, effects were found in the dorsal cingulate cortex, agranular (anterior) insula and ventral tegmental area, implicating these areas in initiating actions to obtain goals.     

Pleasant or Unpleasant: Attentional Modulation of Odor Perception

Using positron emission tomography, we investigated whether regional brain activations differ as a function of attending to pleasant versus unpleasant components of odors. There were two experimental (attention to pleasantness and attention to unpleasantness) and one control (baseline) condition. The stimuli presented during the two experimental conditions were exactly the same (three binary mixtures, each consisting of one pleasant and one unpleasant compound), but the affective property to which participants?? attention was directed was different: They indicated with a mouse click whether each stimulus contained a pleasant (during attention to pleasantness) or unpleasant (during attention to unpleasantness) odor. During baseline, odorless stimuli were presented, and participants pressed the mouse button randomly after each one. Several brain regions were involved in both types of attention, and these included ventral striatum, right orbitofrontal cortex, and anterior cingulate cortex. Subtle differences were also revealed: Attending to pleasantness was associated preferentially with a sensory/perceptual network (piriform cortex and amygdala), whereas attending to unpleasantness engaged a component of the attentional (right parietal) network. Thus, we delineate neural substrates of attending to olfactory pleasantness and unpleasantness, some of which are common to both and others that are specific to pleasantness or to unpleasantness. Our results suggest that the view of the mesolimbic dopaminergic system as the reward network that responds selectively to positive reinforcers is somewhat limited: Our findings are more in keeping with a view of this set of structures as the salience system of the brain.     

Intracellularly-recorded effects of glutamate and aspartate on neurones in the guinea-pig olfactory cortex slice

The effects of bath-applied glutamate, aspartate (and some related amino acids) on neurones of the guinea pig olfactory cortex slice were recorded intracellularly. Neurones were activated either by intracellularly-applied current or orthodromically by stimulating the lateral olfactory tract. In response to orthodromic stimuli several neurones displayed a late hyperpolarizing potential (LHP) after the usual sequence of EPSP, spike and IPSP. Glutamate and aspartate evoked 3 types of response: (a) a depolarization with apparent increase in input conductance; (b) a depolarization with no detectable conductance change; and (c) a hyperpolarization with conductance increase. Some possible mechanisms by which these 3 response-types could be generated are discussed. Depolarizations evoked by the glutamate analogue, kainate, were usually irreversible. Our results emphasize that glutamate and aspartate can evoke a variety of neuronal responses from olfactory cortex neurones. Several of these responses were previously undetected in experiments based on extracellular recordings.     

Presynaptic kainate and N-methyl-d-aspartate receptors regulate excitatory amino acid release in the olfactory cortex

The potassium-evoked release of endogenous aspartate, glutamate and GABA from olfactory cortex slices has been monitored. Release of aspartate alone is significantly reduced by N-methyl-d-aspartate (NMDA) whilst kainate significantly increases release of both aspartate and glutamate. These effects, which are blocked by appropriate receptor antagonists, suggest that presynaptic NMDA and kainate receptors regulate excitatory amino acid release in the olfactory cortex.     

Biological complexity and adaptability of simple mammalian olfactory memory systems

Chemosensory systems play vital roles in the lives of most mammals, including the detection and identification of predators, as well as sex and reproductive status and the identification of individual conspecifics. All of these capabilities require a process of recognition involving a combination of innate (kairomonal/pheromonal) and learned responses. Across very different phylogenies, the mechanisms for pheromonal and odour learning have much in common. They are frequently associated with plasticity of GABA-ergic feedback at the initial level of processing the chemosensory information, which enhances its pattern separation capability. Association of odourant features into an odour object primarily involves anterior piriform cortex for non-social odours. However, the medial amygdala appears to be involved in both the recognition of social odours and their association with chemosensory information sensed by the vomeronasal system. Unusually not only the sensory neurons themselves, but also the GABA-ergic interneurons in the olfactory bulb are continually being replaced, with implications for the induction and maintenance of learned chemosensory responses.     

Locus coeruleus activation modulates firing rate and temporal organization of odour-induced single-cell responses in rat piriform cortex

Piriform cortex (PCx) is the primary cortical projection region for olfactory information and has bidirectional monosynaptic connections with olfactory bulb and association cortices. PCx neurons display a complex receptive field, responding to odours rather than their molecular components, suggesting that these neurons are involved in higher order olfactory processing. Neuromodulators, especially noradrenaline (NA), have important influences on sensory processing in other cortical regions and might be responsible for the plasticity observed in PCx during learning. The present study is the first attempt to examine in vivo the actions of NA on sensory responses in the PCx. Stimulation of the noradrenergic nucleus locus coeruleus (LC) was used to induce release of NA in the forebrain in urethane-anaesthetized rats. Extracellular recording of single units was made simultaneously in anterior and posterior PCx. The responses to an odour stimulus were measured over 25 trials. Twenty-five subsequent odour presentations were preceded by stimulation of the ipsilateral LC through a bipolar electrode, previously placed in the LC under electrophysiological control. This priming stimulation modified the activity of 77 of the 135 recorded neurons. For most cells, LC stimulation enhanced cortical responses to odour in terms of both spike count and temporal organization, with some differential effects in anterior and posterior regions. These results are the first to show enhancement of sensory responses in the olfactory cortex by LC activation. Spontaneous activation of LC neurons such as occurs during learning could serve to enhance olfactory perception and promote learning.     

Sensory-specific satiety-related olfactory activation of the human orbitofrontal cortex

When a food is eaten to satiety, its reward value decreases. This decrease is usually greater for the food eaten to satiety than for other foods, an effect termed sensory-specific satiety. In an fMRI investigation it was shown that for a region of the orbitofrontal cortex the activation produced by the odour of the food eaten to satiety decreased, whereas there was no similar decrease for the odour of a food not eaten in the meal. This effect was shown both by a voxel-wise SPM contrast (p<0.05 corrected) and an ANOVA performed on the mean percentage change in BOLD signal in the identified clusters of voxels (p<0.006). These results show that activation of a region of the human orbitofrontal cortex is related to olfactory sensory-specific satiety.     

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.     

Sensory-specific satiety-related olfactory activation of the human orbitofrontal cortex

When a food is eaten to satiety, its reward value decreases. This decrease is usually greater for the food eaten to satiety than for other foods, an effect termed sensory-specific satiety. In an fMRI investigation it was shown that for a region of the orbitofrontal cortex the activation produced by the odour of the food eaten to satiety decreased, whereas there was no similar decrease for the odour of a food not eaten in the meal. This effect was shown both by a voxel-wise SPM contrast (p <0.05 corrected) and an ANOVA performed on the mean percentage change in BOLD signal in the identified clusters of voxels (p <0.006). These results show that activation of a region of the human orbitofrontal cortex is related to olfactory sensory-specific satiety.