A common gustatory and interoceptive representation in the human mid‐insula

The insula serves as the primary gustatory and viscerosensory region in the mammalian cortex. It receives visceral and gustatory afferent projections through dedicated brainstem and thalamic nuclei, which suggests a potential role as a site for homeostatic integration. For example, while human neuroimaging studies of gustation have implicated the dorsal mid‐insular cortex as one of the primary gustatory regions in the insula, other recent studies have implicated this same region of the insula in interoception. This apparent convergence of gustatory and interoceptive information could reflect a common neural representation in the insula shared by both interoception and gustation. This idea finds support in translational studies in rodents, and may constitute a medium for integrating homeostatic information with feeding behavior. To assess this possibility, healthy volunteers were asked to undergo fMRI while performing tasks involving interoceptive attention to visceral sensations as well as a gustatory mapping task. Analysis of the unsmoothed, high‐resolution fMRI data confirmed shared representations of gustatory and visceral interoception within the dorsal mid‐insula. Group conjunction analysis revealed overlapping patterns of activation for both tasks in the dorsal mid‐insula, and region‐of‐interest analyses confirmed that the dorsal mid‐insula regions responsive for visceral interoception also exhibit strong responses to tastants. Hum Brain Mapp 36:2996–3006, 2015. © 2015 Wiley Periodicals, Inc.     

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.     

Bilateral Rolandic operculum processing underlying heartbeat awareness reflects changes in bodily self‐consciousness

Exteroceptive bodily signals (including tactile, proprioceptive and visual signals) are important information contributing to self‐consciousness. Moreover, prominent theories proposed that visceral signals about internal bodily states are equally or even more important for self‐consciousness. Neuroimaging studies have described several brain regions which process signals related to bodily self‐consciousness (BSC) based on the integration of exteroceptive signals (e.g. premotor cortex, angular gyrus, supramarginal gyrus and extrastriate body area), and that another brain region, the insula/operculum which is involved in interoception and interoceptive awareness, processes signals critical for self‐awareness. Providing evidence for the integration of exteroceptive and interoceptive bodily signals, recent behavioral experiments have demonstrated that the manipulation of interoceptive (e.g. cardiac) signals, coupled with exteroceptive (e.g. visual) signals, also modulates BSC. Does this integration occur within or outside the structures described above? To this end, we adapted a recently designed protocol that uses cardio‐visual stimulation to induce altered states of BSC to fMRI. Additionally, we measured neural activity in a classical interoceptive task. We found six brain regions (bilateral Rolandic operculum, bilateral supramarginal gyrus, right frontal inferior operculum and left temporal superior gyrus) that were activated differently during the interoception task as opposed to a control task. The brain regions which showed the highest selectivity for BSC based on our cardio‐visual manipulation were found in the bilateral Rolandic operculum. Given our findings, we propose that the Rolandic operculum processes integrated exteroceptive–interoceptive signals that are necessary for interoceptive awareness as well as BSC.     

Two systems of resting state connectivity between the insula and cingulate cortex

The insula and cingulate cortices are implicated in emotional, homeostatic/allostatic, sensorimotor, and cognitive functions. Non‐human primates have specific anatomical connections between sub‐divisions of the insula and cingulate. Specifically, the anterior insula projects to the pregenual anterior cingulate cortex (pACC) and the anterior and posterior mid‐cingulate cortex (aMCC and pMCC); the mid‐posterior insula only projects to the posterior MCC (pMCC). In humans, functional neuroimaging studies implicate the anterior insula and pre/subgenual ACC in emotional processes, the mid‐posterior insula with awareness and interoception, and the MCC with environmental monitoring, response selection, and skeletomotor body orientation. Here, we tested the hypothesis that distinct resting state functional connectivity could be identified between (1) the anterior insula and pACC/aMCC; and (2) the entire insula (anterior, middle, and posterior insula) and the pMCC. Functional connectivity was assessed from resting state fMRI scans in 19 healthy volunteers using seed regions of interest in the anterior, middle, and posterior insula. Highly correlated, low‐frequency oscillations (< 0.05 Hz) were identified between specific insula and cingulate subdivisions. The anterior insula was shown to be functionally connected with the pACC/aMCC and the pMCC, while the mid/posterior insula was only connected with the pMCC. These data provide evidence for a resting state anterior insula–pACC/aMCC cingulate system that may integrate interoceptive information with emotional salience to form a subjective representation of the body; and another system that includes the entire insula and MCC, likely involved in environmental monitoring, response selection, and skeletomotor body orientation. Human Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.     

Neural correlates of interoception: Effects of interoceptive focus and relationship to dimensional measures of body awareness

Interoception has been defined as the sensing of the physiological condition of the body, with interoceptive sensibility (IS) characterizing an individual's self‐reported awareness of internal sensation. IS is a multidimensional construct including not only the tendency to be aware of sensation but also how sensations are interpreted, regulated, and used to inform behavior, with different dimensions relating to different aspects of health and disease. Here we investigated neural mechanisms of interoception when healthy individuals attended to their heartbeat and skin temperature, and examined the relationship between neural activity during interoception and individual differences in self‐reported IS using the Multidimensional Scale of Interoceptive Awareness (MAIA). Consistent with prior work, interoception activated a network involving insula and sensorimotor regions but also including occipital, temporal, and prefrontal cortex. Differences based on interoceptive focus (heartbeat vs skin temperature) were found in insula, sensorimotor regions, occipital cortex, and limbic areas. Factor analysis of MAIA dimensions revealed 3 dissociable components of IS in our dataset, only one of which was related to neural activity during interoception. Reduced scores on the third factor, which reflected reduced ability to control attention to body sensation and increased tendency to distract from and worry about aversive sensations, was associated with greater activation in many of the same regions as those involved in interoception, including insula, sensorimotor, anterior cingulate, and temporal cortex. These data suggest that self‐rated interoceptive sensibility is related to altered activation in regions involved in monitoring body state, which has implications for disorders associated with abnormality of interoception. Hum Brain Mapp 38:6068–6082, 2017. © 2017 Wiley Periodicals, Inc.     

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.     

Interoceptive awareness enhances neural activity during empathy

Empathy is a multicomponent function that includes sensorimotor, affective, and cognitive components. Although especially the affective component may implicate interoception and interoceptive awareness, the impact of interoception on empathy has never been evaluated behaviorally or neurophysiologically. Here, we tested how a preceding period of interoceptive awareness impacts and modulates neural activity during subsequent empathy. We used functional magnetic resonance imaging (fMRI) and measured the sequential interaction between interoception and empathy using fMRI in 18 healthy subjects. We found that the preceding interoceptive awareness period significantly enhanced neural activity during empathy in bilateral anterior insula and various cortical midline regions. The enhancement of neural activity during empathy in both interoceptive and empathy networks by preceding interoceptive awareness suggests a close relationship between interoception and empathy; thereby, interoception seems to be implicated to yielding empathy. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Multilevel convergence of interoceptive impairments in hypertension: New evidence of disrupted body–brain interactions

Interoception, the sensing of visceral body signals, involves an interplay between neural and autonomic mechanisms. Clinical studies into this domain have focused on patients with neurological and psychiatric disorders, showing that damage to relevant brain mechanisms can variously alter interoceptive functions. However, the association between peripheral cardiac‐system alterations and neurocognitive markers of interoception remains poorly understood. To bridge this gap, we examined multidimensional neural markers of interoception in patients with early stage of hypertensive disease (HTD) and healthy controls. Strategically, we recruited only HTD patients without cognitive impairment (as shown by neuropsychological tests), brain atrophy (as assessed with voxel‐based morphometry), or white matter abnormalities (as evidenced by diffusion tensor imaging analysis). Interoceptive domains were assessed through (a) a behavioral heartbeat detection task; (b) measures of the heart‐evoked potential (HEP), an electrophysiological cortical signature of attention to cardiac signals; and (c) neuroimaging recordings (MRI and fMRI) to evaluate anatomical and functional connectivity properties of key interoceptive regions (namely, the insula and the anterior cingulate cortex). Relative to controls, patients exhibited poorer interoceptive performance and reduced HEP modulations, alongside an abnormal association between interoceptive performance and both the volume and functional connectivity of the above regions. Such results suggest that peripheral cardiac‐system impairments can be associated with abnormal behavioral and neurocognitive signatures of interoception. More generally, our findings indicate that interoceptive processes entail bidirectional influences between the cardiovascular and the central nervous systems.     

Differential functional brain network connectivity during visceral interoception as revealed by independent component analysis of fMRI time‐series

Influential theories of brain‐viscera interactions propose a central role for interoception in basic motivational and affective feeling states. Recent neuroimaging studies have underlined the insula, anterior cingulate, and ventral prefrontal cortices as the neural correlates of interoception. However, the relationships between these distributed brain regions remain unclear. In this study, we used spatial independent component analysis (ICA) and functional network connectivity (FNC) approaches to investigate time course correlations across the brain regions during visceral interoception. Functional magnetic resonance imaging (fMRI) was performed in thirteen healthy females who underwent viscerosensory stimulation of bladder as a representative internal organ at different prefill levels, i.e., no prefill, low prefill (100 ml saline), and high prefill (individually adapted to the sensations of persistent strong desire to void), and with different infusion temperatures, i.e., body warm (～37°C) or ice cold (4–8°C) saline solution. During Increased distention pressure on the viscera, the insula, striatum, anterior cingulate, ventromedial prefrontal cortex, amygdalo‐hippocampus, thalamus, brainstem, and cerebellar components showed increased activation. A second group of components encompassing the insula and anterior cingulate, dorsolateral prefrontal and posterior parietal cortices and temporal‐parietal junction showed increased activity with innocuous temperature stimulation of bladder mucosa. Significant differences in the FNC were found between the insula and amygdalo‐hippocampus, the insula and ventromedial prefrontal cortex, and the ventromedial prefrontal cortex and temporal‐parietal junction as the distention pressure on the viscera increased. These results provide new insight into the supraspinal processing of visceral interoception originating from an internal organ. Hum Brain Mapp 36:4438–4468, 2015. © 2015 Wiley Periodicals, Inc.     

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.     

Affective interoceptive inference: Evidence from heart‐beat evoked brain potentials

The perception of internal bodily signals (interoception) is central to many theories of emotion and embodied cognition. According to recent theoretical views, the sensory processing of visceral signals such as one's own heartbeat is determined by top‐down predictions about the expected interoceptive state of the body (interoceptive inference). In this EEG study we examined neural responses to heartbeats following expected and unexpected emotional stimuli. We used a modified stimulus repetition task in which pairs of facial expressions were presented with repeating or alternating emotional content, and we manipulated the emotional valence and the likelihood of stimulus repetition. We found that affective predictions of external socially relevant information modulated the heartbeat‐evoked potential, a marker of cardiac interoception. Crucially, the HEP changes highly relied on the expected emotional content of the facial expression. Thus, expected negative faces led to a decreased HEP amplitude, whereas such an effect was not observed after an expected neutral face. These results suggest that valence‐specific affective predictions, and their uniquely associated predicted bodily sensory state, can reduce or amplify cardiac interoceptive responses. In addition, the affective repetition effects were dependent on repetition probability, highlighting the influence of top‐down exteroceptive predictions on interoception. Our results are in line with recent models of interoception supporting the idea that predicted bodily states influence sensory processing of salient external information.     

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.     

Mindfulness-based training attenuates insula response to an aversive interoceptive challenge

Neuroimaging studies of mindfulness training (MT) modulate anterior cingulate cortex (ACC) and insula among other brain regions, which are important for attentional control, emotional regulation and interoception. Inspiratory breathing load (IBL) is an experimental approach to examine how an individual responds to an aversive stimulus. Military personnel are at increased risk for cognitive, emotional and physiological compromise as a consequence of prolonged exposure to stressful environments and, therefore, may benefit from MT. This study investigated whether MT modulates neural processing of interoceptive distress in infantry marines scheduled to undergo pre-deployment training and deployment to Afghanistan. Marines were divided into two groups: individuals who received training as usual (control) and individuals who received an additional 20-h mindfulness-based mind fitness training (MMFT). All subjects completed an IBL task during functional magnetic resonance imaging at baseline and post-MMFT training. Marines who underwent MMFT relative to controls demonstrated a significant attenuation of right anterior insula and ACC during the experience of loaded breathing. These results support the hypothesis that MT changes brain activation such that individuals process more effectively an aversive interoceptive stimulus. Thus, MT may serve as a training technique to modulate the brain’s response to negative interoceptive stimuli, which may help to improve resilience.     

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.     

Dynamic functional network connectivity reveals unique and overlapping profiles of insula subdivisions

The human insular cortex consists of functionally diverse subdivisions that engage during tasks ranging from interoception to cognitive control. The multiplicity of functions subserved by insular subdivisions calls for a nuanced investigation of their functional connectivity profiles. Four insula subdivisions (dorsal anterior, dAI; ventral, VI; posterior, PI; middle, MI) derived using a data‐driven approach were subjected to static‐ and dynamic functional network connectivity (s‐FNC and d‐FNC) analyses. Static‐FNC analyses replicated previous work demonstrating a cognition‐emotion‐interoception division of the insula, where the dAI is functionally connected to frontal areas, the VI to limbic areas, and the PI and MI to sensorimotor areas. Dynamic‐FNC analyses consisted of k‐means clustering of sliding windows to identify variable insula connectivity states. The d‐FNC analysis revealed that the most frequently occurring dynamic state mirrored the cognition‐emotion‐interoception division observed from the s‐FNC analysis, with less frequently occurring states showing overlapping and unique subdivision connectivity profiles. In two of the states, all subdivisions exhibited largely overlapping profiles, consisting of subcortical, sensory, motor, and frontal connections. Two other states showed the dAI exhibited a unique connectivity profile compared with other insula subdivisions. Additionally, the dAI exhibited the most variable functional connections across the s‐FNC and d‐FNC analyses, and was the only subdivision to exhibit dynamic functional connections with regions of the default mode network. These results highlight how a d‐FNC approach can capture functional dynamics masked by s‐FNC approaches, and reveal dynamic functional connections enabling the functional flexibility of the insula across time. Hum Brain Mapp 37:1770–1787, 2016. © 2016 Wiley Periodicals, Inc .     

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.     

Transgenic labeling of higher order neuronal circuits linked to phospholipase C‐β2–expressing taste bud cells in medaka fish

The sense of taste plays a pivotal role in the food‐selecting behaviors of vertebrates. We have shown that the fish ortholog of the phospholipase C gene (plc‐β2) is expressed in a subpopulation of taste bud cells that transmit taste stimuli to the central nervous system to evoke favorable and aversive behaviors. We generated transgenic medaka expressing wheat germ agglutinin (WGA) under the control of a regulatory region of the medaka plc‐β2 gene to analyze the neuronal circuit connected to these sensory cells. Immunohistochemical analysis of the transgenic fish 12 days post fertilization revealed that the WGA protein was transferred to cranial sensory ganglia and several nuclei in the hindbrain. WGA signals were also detected in the secondary gustatory nucleus in the hindbrain of 3‐month‐old transgenic fish. WGA signals were observed in several diencephalic and telencephalic regions in 9‐month‐old transgenic fish. The age‐dependent increase in the labeled brain regions strongly suggests that labeling occurred at taste bud cells and progressively extended to cranial nerves and neurons in the central nervous system. These data are the first to demonstrate the tracing of higher order gustatory neuronal circuitry that is associated with a specific subpopulation of taste bud cells. These results provide insight into the basic neuronal architecture of gustatory information processing that is common among vertebrates. J. Comp. Neurol. 521:1781–1802, 2013. © 2012 Wiley Periodicals, Inc.     

Cerveau maternel : Théorie bayésienne de l’intéroception maternelle pendant la grossesse et le postpartum

The perinatal period, including pregnancy and postpartum, causes major morphological, endocrinal, and thermal transitions in women. As the fetus grows, abdominal muscle fibers stretch, internal organs such as the bladder or colon move, and the uterine anatomy changes. Many of these changes involve interoception, the perception of internal body signals such as muscle and visceral sensations. Despite the importance of these interoceptive signals, few studies have explored perinatal interoception. We propose an innovative theory of maternal interoception based on recent findings in neuroscience. We show that interoceptive signals processing during pregnancy is crucial for understanding perinatal phenomenology and psychopathology, such as maternal perception of fetal movements, maternal-infant bonding, denial of pregnancy, phantom fetal movements after childbirth, pseudocyesis or even puerperal delusion. Knowing the importance of these interoceptive mechanisms, clinicians in obstetrics, gynecology and mental health should be particularly vigilant to maternal interoception during the perinatal period.     

Insular and gustatory inputs to the caudal ventral striatum in primates

The ventral striatum mediates goal-directed behaviors based, in part, on inputs from the amygdala. However, striatal areas caudal to the ventral striatum also receive inputs from the amygdala. In primates, the amygdala projects to the central ventral putamen, lateral amygdalostriatal area, and caudal ventral putamen, suggesting that these regions are also "limbic-related." The anterior insula, which integrates sensory and amygdaloid inputs, projects to the classic ventral striatum. We used retrograde and anterograde tract tracing techniques to determine the extent to which specific subdivisions of the insula influence the caudal ventral striatum in the primate. The anterior (agranular and rostral dysgranular) insula has significant inputs to caudal ventral striatal regions that receive projections from the amygdala. In contrast, the posterior (granular) insula has sparse projections. Within the agranular insula, the posteromedial agranular (Iapm), lateral agranular (Ial), and posterolateral agranular (Iapl) subdivisions have the strongest inputs. These subdivisions mediate olfactory, gustatory, and visceral information processing (Carmichael and Price JL [1996b] J. Comp. Neurol. 363:642-640). In contrast, the intermediate agranular subdivision (Iai) is relatively devoid of visceral/gustatory inputs and has few inputs. In summary, caudal ventral striatal areas that receive amygdaloid inputs also receive significant innervation by agranular and dysgranular insula subdivisions that are themselves connected with the amygdala. Within this projection, the Ial, Iapm, and Iapl make the strongest contribution, suggesting that highly processed visceral/autonomic information, taste, and olfaction influence behavioral responses mediated by the caudal ventral striatum.     

Thermal taster status: Evidence of cross‐modal integration

Thermal taster status refers to the finding that, in some individuals, thermal stimulation of the tongue elicits a phantom taste. Little is known regarding the mechanism for this, it is hypothesised to be a result of cross‐wiring between gustatory and trigeminal nerves whose receptors co‐innervate papillae on the tongue. To address this, we use functional magnetic resonance imaging to perform the first study of whether the cortical response to gustatory‐trigeminal samples is altered with thermal taster status. We study the response to cold (6°C) gustatory (sweet) samples at varying levels of trigeminal stimulation elicited by CO₂ (no CO₂, low CO₂, high CO₂) in thermal taster (TT) and thermal non‐taster (TnT) groups, and evaluate associated behavioural measures. Behaviourally, the TT group perceived gustatory and trigeminal stimuli significantly more intense than TnTs, and were significantly more discriminating of CO₂ level. fMRI data revealed elevated cortical activation to the no CO₂ sample for the TT group compared to TnT group in taste, oral somatosensory and reward areas. In TnTs, a significant positive modulation in cortical response with increasing level of CO₂ was found across taste, somatosensory and reward areas. In contrast, in TTs, a reduced positive modulation with increasing level of CO₂ was found in somatosensory areas (SI, SII), whilst a significant negative modulation was found in taste (anterior insula) and reward (ACC) areas. This difference in cortical response to trigeminal stimuli supports cross‐modal integration in TTs, with gustatory and trigeminal nerves highly stimulated by cold gustatory samples due to their intertwined nature. Hum Brain Mapp 37:2263–2275, 2016. © 2016 Wiley Periodicals, Inc.