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.     

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.     

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.     

Modulation of olfactory perception by visual cortex stimulation

When attempting to identify an object based on smell alone, people often visualize the perceived source of the odorant. This close association between olfactory and visual functions is supported by neuroimaging studies demonstrating activation of visual cortex during performance of purely olfactory tasks. Such activation might simply reflect the correlation between olfactory percepts and the corresponding visual images, or it might reflect a causal contribution of visual processing to olfactory perception. Here we provide evidence in support of the latter possibility. Using repetitive transcranial magnetic stimulation, we show that stimulating human visual cortex improves performance on a task requiring discrimination among different odor qualities. No significant improvement is found for tasks involving discrimination between intensities of the same odor, from stimulation of auditory cortex, or from "sham" stimulation. These results are thus consistent with a specific visual cortical influence on high-level olfactory perception. They also demonstrate that unimodal perceptual tasks are influenced by processing within cortical areas of other, seemingly unrelated, sensory systems.     

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.     

Perceptual and Neural Plasticity of Odor Quality Coding in the Human Brain

Current neurobiological models of odor perception tend to emphasize the “bottom-up” contributions of odorant chemistry in determining the perceptual features of an odor. However, increasing research suggests that “top-down” effects related to learning and experience play equally important roles in human olfactory perception, implying that a given set of olfactory receptors activated by an odorant does not neatly map onto a given odor percept. Rather, odor perception may rely on more synthetic mechanisms subserved by higher order brain regions. This review article focuses on the modulatory effects of learning, context, and experience on human odor perception. Recent psychophysical and neuroimaging work from our laboratory indicates that sensory-specific information about odor quality is not static within human piriform and orbitofrontal cortices but can be rapidly updated by mere sensory exposure. This experience-dependent neural plasticity parallels behavioral improvements in odor perception, providing direct evidence for the role of learning in shaping neural representations of odor quality in the human brain.     

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.     

Response amplification in sensory-specific cortices during crossmodal binding

Integrating information across the senses can enhance our ability to detect and classify stimuli in the environment. For example, auditory speech perception is substantially improved when the speaker's face is visible. In an fMRI study designed to investigate the neural mechanisms underlying these crossmodal behavioural gains, bimodal (audio-visual) speech was contrasted against both unimodal (auditory and visual) components. Significant response enhancements in auditory (BA 41/42) and visual (V5) cortices were detected during bimodal stimulation. This effect was found to be specific to semantically congruent crossmodal inputs. These data suggest that the perceptual improvements effected by synthesizing matched multisensory inputs are realised by reciprocal amplification of the signal intensity in participating unimodal cortices.     

Tactile intensity and population codes

An important question in neuroscience is how different aspects of a stimulus are encoded at different stages of neural processing. In this review, I discuss studies investigating the peripheral neural code for perceived intensity in touch. One of the recurrent themes in this line of research is that information about stimulus intensity is encoded in the activity of populations of neurons. Not only is information integrated across afferents of a given type, but information is also combined across submodalities to yield a unified percept of stimulus intensity. The convergence of information stemming from multiple submodalities is particularly interesting in light of the fact that these are generally thought to be parallel sensory channels with distinct sensory functions and little cross-channel interactions. I discuss implications of a recently proposed model of intensity coding for psychophysical functions and for the coding of intensity in cortex. I also briefly review the peripheral coding of intensity in other sensory modalities.     

Passive perception of odors and semantic circuits

The sense of smell has been traditionally assumed to be different from other sensory modalities in that odors are encoded perceptually, without a semantic component. Recent findings of improved odor memory upon encoding with verbal cues question this view. Furthermore, familiar odors are easier to remember and discriminate than are unfamiliar ones, and odor familiarity is reported to predict odor naming. To investigate whether familiar odors are processed by different cerebral structures than those that process unfamiliar odors, (15)O H(2)O-positron emission tomography (PET) measurements of cerebral blood flow were carried out in 14 healthy men. The task was passive, birhinal, smelling of familiar odors (FAM), unfamiliar odors (uFAM), and odorless air (AIR). Significant activations (P < 0.05) were calculated using the contrasts FAM-AIR, uFAM-AIR, and FAM-uFAM, and deactivations running these contrasts in the opposite direction. In relation to AIR, both FAM and uFAM activated amygdala, piriform cortex, and parts of anterior cingulate cortex. FAM activated, in addition, left frontal cortex (Brodmann's areas 44,45,47), left parietal cortex incorporating precuneus, and right parahippocampus. Clusters covering parahippocampus and precuneus were observed also in FAM-uFAM. The activation of left frontal cortex and right parahippocampus was positively correlated with familiarity ratings. Smelling of familiar but not unfamiliar odorants seems to engage cerebral circuits mediating memory and language functions, in addition to the engagement of olfactory cortex. Already the most elemental form of odor processing, passive perception thus seems to engage semantic circuits. This is achieved by the ability of odorants to immediately elicit associations and judgments of odor characteristics.     

Distinct sensory requirements for unimodal and cross-modal homeostatic synaptic plasticity

Loss of a sensory modality elicits both unimodal changes in the deprived cortex and cross-modal alterations in the remaining sensory systems. Unimodal changes are proposed to recruit the deprived cortex for processing the remaining senses, while cross-modal changes are thought to refine processing of spared senses. Hence coordinated unimodal and cross-modal changes are likely beneficial. Despite this expectation, we report in mice that losing behaviorally relevant patterned vision is sufficient to trigger cross-modal synaptic changes in the primary somatosensory cortex barrel fields, but is insufficient to drive unimodal synaptic plasticity in visual cortex (V1), which requires a complete loss of visual activity. In addition, cross-modal changes depend on whisker inputs. Our results demonstrate that unimodal and cross-modal synaptic plasticity occur independently of each other and rely on distinct sensory requirements.     

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.     

Bimodal speech: early suppressive visual effects in human auditory cortex

While everyone has experienced that seeing lip movements may improve speech perception, little is known about the neural mechanisms by which audiovisual speech information is combined. Event-related potentials (ERPs) were recorded while subjects performed an auditory recognition task among four different natural syllables randomly presented in the auditory (A), visual (V) or congruent bimodal (AV) condition. We found that: (i) bimodal syllables were identified more rapidly than auditory alone stimuli; (ii) this behavioural facilitation was associated with cross-modal [AV-(A+V)] ERP effects around 120-190 ms latency, expressed mainly as a decrease of unimodal N1 generator activities in the auditory cortex. This finding provides evidence for suppressive, speech-specific audiovisual integration mechanisms, which are likely to be related to the dominance of the auditory modality for speech perception. Furthermore, the latency of the effect indicates that integration operates at pre-representational stages of stimulus analysis, probably via feedback projections from visual and/or polymodal areas.     

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.     

Early attention modulates perceptual interpretation of multisensory stimuli

Perceptual interpretation of the same multisensory stimuli may rely upon influence of attention on multisensory integration. We tested this hypothesis by recording the brain activity using magnetoencephalography in a passing-bouncing illusion with sound. Early activation of the attention-related brain areas and subsequent involvement of the multisensory areas were associated with the bouncing percept. Early activation of the unimodal sensory areas and later involvement of the attention-related areas were associated with the passing percept. Thus, the bouncing percept occurs when early attentional deployment facilitates multisensory integration modulating visual perception. The passing percept results from hierarchical sequence of the perceptual processes: early activation of the unimodal areas and late attentional deployment. Alternation of the perceptual interpretations may depend on spontaneous fluctuation of attention.     

The neurocognitive bases of human multimodal food perception: consciousness

This review explores how we become aware of the (integrated) flavor of food. In recent years, progress has been made understanding the neural correlates of consciousness. Experimental and computational data have been largely based on the visual system. Contemporary neurobiological frameworks of consciousness are reviewed, concluding that neural reverberation among forward- and back-projecting neural ensembles across brain areas is a common theme. In an attempt to extrapolate these concepts to the oral-sensory and olfactory systems involved with multimodal flavor perception, the integration of the sensory information of which into a flavor gestalt has been reviewed elsewhere (Verhagen, J.V., Engelen, L., 2006. The neurocognitive bases of human multimodal food perception: Sensory integration. Neurosci. Biobehav. Rev. 30(5): 613_650), I reconceptualize the flavor-sensory system by integrating it into a larger neural system termed the Homeostatic Interoceptive System (HIS). This system consists of an oral (taste, oral touch, etc.) and non-oral part (non oral-thermosensation, pain, etc.) which are anatomically and functionally highly similar. Consistent with this new concept and with a large volume of experimental data, I propose that awareness of intraoral food is related to the concomitant reverberant self-sustained activation of a coalition of neuronal subsets in agranular insula and orbitofrontal cortex (affect, hedonics) and agranular insula and perirhinal cortex (food identity), as well as the amygdala (affect and identity) in humans. I further discuss the functional anatomy in relation essential nodes. These formulations are by necessity to some extent speculative.     

Experience induces functional reorganization in brain regions involved in odor imagery in perfumers

Areas of expertise that cultivate specific sensory domains reveal the brain's ability to adapt to environmental change. Perfumers are a small population who claim to have a unique ability to generate olfactory mental images. To evaluate the impact of this expertise on the brain regions involved in odor processing, we measured brain activity in novice and experienced (student and professional) perfumers while they smelled or imagined odors. We demonstrate that olfactory imagery activates the primary olfactory (piriform) cortex (PC) in all perfumers, demonstrating that similar neural substrates were activated in odor perception and imagination. In professional perfumers, extensive olfactory practice influences the posterior PC, the orbitofrontal cortex, and the hippocampus; during the creation of mental images of odors, the activity in these areas was negatively correlated with experience. Thus, the perfumers' expertise is associated with a functional reorganization of key olfactory and memory brain regions, explaining their extraordinary ability to imagine odors and create fragrances.     

Understanding smell—The olfactory stimulus problem

The main problem with sensory processing is the difficulty in relating sensory input to physiological responses and perception. This is especially problematic at higher levels of processing, where complex cues elicit highly specific responses. In olfaction, this relationship is particularly obfuscated by the difficulty of characterizing stimulus statistics and perception. The core questions in olfaction are hence the so-called stimulus problem, which refers to the understanding of the stimulus, and the structure–activity and structure–odor relationships, which refer to the molecular basis of smell. It is widely accepted that the recognition of odorants by receptors is governed by the detection of physico-chemical properties and that the physical space is highly complex. Not surprisingly, ideas differ about how odor stimuli should be classified and about the very nature of information that the brain extracts from odors. Even though there are many measures for smell, there is none that accurately describes all aspects of it. Here, we summarize recent developments in the understanding of olfaction. We argue that an approach to olfactory function where information processing is emphasized could contribute to a high degree to our understanding of smell as a perceptual phenomenon emerging from neural computations. Further, we argue that combined analysis of the stimulus, biology, physiology, and behavior and perception can provide new insights into olfactory function. We hope that the reader can use this review as a competent guide and overview of research activities in olfactory physiology, psychophysics, computation, and psychology. We propose avenues for research, particularly in the systematic characterization of receptive fields and of perception.     

Olfactory processing in a changing brain

The perception of odorant molecules provides the essential information that allows animals to explore their surrounding. We describe here how the external world of scents may sculpt the activity of the first central relay of the olfactory system, i.e., the olfactory bulb. This structure is one of the few brain areas to continuously replace one of its neuronal populations: the local GABAergic interneurons. How the newly generated neurons integrate into a pre-existing neural network and how basic olfactory functions are maintained when a large percentage of neurons are subjected to continuous renewal, are important questions that have recently received new insights. Furthermore, we shall see how the adult neurogenesis is specifically subjected to experience-dependent modulation. In particular, we shall describe the sensitivity of the bulbar neurogenesis to the activity level of sensory inputs from the olfactory epithelium and, in turn, how this neurogenesis may adjust the neural network functioning to optimize odor information processing. Finally, we shall discuss the behavioral consequences of the bulbar neurogenesis and how it may be appropriate for the sense of smell. By maintaining a constitutive turnover of bulbar interneurons subjected to modulation by environmental cues, we propose that adult ongoing neurogenesis in the olfactory bulb is associated with improved olfactory memory. These recent findings not only provide new fuel for the molecular and cellular bases of sensory perception but should also shed light onto cellular bases of learning and memory.     

Crossmodal influences in somatosensory cortex: Interaction of vision and touch

Previous research has shown that information from one sensory modality has the potential to influence activity in a different modality, and these crossmodal interactions can occur early in the cortical sensory processing stream within sensory‐specific cortex. In addition, it has been shown that when sensory information is relevant to the performance of a task, there is an upregulation of sensory cortex. This study sought to investigate the effects of simultaneous bimodal (visual and vibrotactile) stimulation on the modulation of primary somatosensory cortex (SI), in the context of a delayed sensory‐to‐motor task when both stimuli are task‐relevant. It was hypothesized that the requirement to combine visual and vibrotactile stimuli would be associated with an increase in SI activity compared to vibrotactile stimuli alone. Functional magnetic resonance imaging (fMRI) was performed on healthy subjects using a 3T scanner. During the scanning session, subjects performed a sensory‐guided motor task while receiving visual, vibrotactile, or both types of stimuli. An event‐related design was used to examine cortical activity related to the stimulus onset and the motor response. A region of interest (ROI) analysis was performed on right SI and revealed an increase in percent blood oxygenation level dependent signal change in the bimodal (visual + tactile) task compared to the unimodal tasks. Results of the whole‐brain analysis revealed a common fronto‐parietal network that was active across both the bimodal and unimodal task conditions, suggesting that these regions are sensitive to the attentional and motor‐planning aspects of the task rather than the unimodal or bimodal nature of the stimuli. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.