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.     

A study about the frequency of taste disorders

Although 5% of the general population exhibit a functional anosmia, little is known about the frequency of gustatory disorders. Whenever taste function has been tested within large sociodemographic studies, so far only short test versions were applied making the interpretation difficult. Using two psychophysical taste tests, the validated “taste strips” and suprathreshold taste solutions of the four basic tastes sweet, sour, salty and bitter we investigated 761 healthy subjects within the age range of 5–89 years. Prior to testing, all subjects rated their taste function. According to testing with the taste strips, 5.3% scored below the result considered as hypogeusia. All four taste sprays were correctly identified by 82.3% of all subjects. Results of the two taste tests correlated positively (r = 0.33, p < 0.001), and there was a significant negative correlation between age and test results. However, we never observed complete ageusia. Misinterpretations of tastes were surprisingly common. In summary, hypogeusia was present in 5% while complete ageusia seems to be very rare, in contrast to misinterpretations of tastes.     

Effects of gustatory deafferentation on Polycose and sucrose appetite in the rat

Recent studies have revealed that rats are strongly attracted to the taste of starch-derived polysaccharides, and suggest that the taste receptors involved differ from those that respond to sucrose. The present study examined the possibility that different gustatory nerves mediate the rat's taste and appetite for polysaccharides and sucrose. This was accomplished by measuring the effects of selective gustatory nerve transection on the intake of Polycose and sucrose solutions in nondeprived female rats. Bilateral transection of the chorda tympani nerve produced comparable reductions in Polycose and sucrose intake, but bilateral transection of the glossopharyngeal nerve selectively reduced the intake of Polycose. Bilateral transection of the greater superficial petrosal nerve, and to a lesser degree, the pharyngeal branch of the vagus nerve, increased sucrose intake without affecting Polycose intake. These results indicate that while no single gustatory nerve mediates sucrose or polysaccharide taste, there is some specialization of function within the peripheral gustatory system. Combined bilateral transections of all four gustatory nerves produced the greatest reduction in solution intake, and reduced Polycose and sucrose consumption to the same degree. The suppressive effect was only partial, however, which indicates that relatively few intact taste receptors are required to maintain the rat's appetite for sugar and polysaccharide solutions.     

Neural architecture of the primary gustatory center of Drosophila melanogaster visualized with GAL4 and LexA enhancer‐trap systems

Gustatory information is essential for animals to select edible foods and avoid poisons. Whereas mammals detect tastants with their taste receptor cells, which convey gustatory signals to the brain indirectly via the taste sensory neurons, insect gustatory receptor neurons (GRNs) send their axons directly to the primary gustatory center in the suboesophageal ganglion (SOG). In spite of this relatively simple architecture, the precise structure of the insect primary gustatory center has not been revealed in enough detail. To obtain comprehensive anatomical knowledge about this brain area, we screened the Drosophila melanogaster GAL4 enhancer‐trap strains that visualize specific subsets of the gustatory neurons as well as putative mechanosensory neurons associated with the taste pegs. Terminals of these neurons form three branches in the SOG. To map the positions of their arborization areas precisely, we screened newly established LexA::VP16 enhancer‐trap strains and obtained a driver line that labels a large subset of peripheral sensory neurons. By double‐labeling specific and landmark neurons with GAL4 and LexA strains, we were able to distinguish 11 zones in the primary gustatory center, among which 5 zones were identified newly in this study. Arborization areas of various known GRNs on the labellum, oesophagus, and legs were also mapped in this framework. The putative mechanosensory neurons terminate exclusively in three zones of these areas, supporting the notion of segregated primary centers that are specialized for chemosensory and mechanosensory signals associated with gustatory sensation. J. Comp. Neurol. 518:4147–4181, 2010. © 2010 Wiley‐Liss, Inc.     

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.     

Intranasal Insulin Boosts Gustatory Sensitivity

Intranasal insulin has been the subject of attention not only with respect to enhancing memory processes, but also for its anorexic effects, as well as its effects on olfactory sensitivity. In the present study, the influence of intranasal insulin on gustatory sensitivity was investigated using intranasal applications of insulin or placebo in a double‐blind manner alongside a control condition without any application. We hypothesised that, because it mediates satiety, intranasal insulin alters gustatory sensitivity, whereas placebo application and the control should not alter gustatory sensitivity. We did not expect the sensitivity to the different taste solutions to differ. Sweet, salty, bitter and sour liquids in four concentrations each were sprayed onto the tongue of healthy male subjects. Additionally, water with no taste was applied to enable calculation of taste sensitivity in terms of parameter d′ of signal detection theory. The task of the subject was to identify the quality of the respective tastant. Gustatory sensitivity and blood parameters were evaluated using repeated‐measures ANOVAs. Gustatory sensitivity (implying all tastants) improved significantly after intranasal insulin application compared to the application of placebo, although it did not reach significance compared to the control condition. Subjects performed best when detecting the sweet taste and worst when detecting the bitter taste. The blood parameters glucose, insulin, homeostatic model assessment and leptin did not differ with respect to insulin or placebo condition, nor did they differ regarding measurements preceding or following intranasal application, in confirmation of preserved peripheral euglycaemia during the experiment. Thus, it can be concluded that the application of intranasal insulin led to an improved gustatory sensitivity compared to placebo.     

Fast periodic visual stimulation to highlight the relationship between human intracerebral recordings and scalp electroencephalography

Despite being of primary importance for fundamental research and clinical studies, the relationship between local neural population activity and scalp electroencephalography (EEG) in humans remains largely unknown. Here we report simultaneous scalp and intracerebral EEG responses to face stimuli in a unique epileptic patient implanted with 27 intracerebral recording contacts in the right occipitotemporal cortex. The patient was shown images of faces appearing at a frequency of 6 Hz, which elicits neural responses at this exact frequency. Response quantification at this frequency allowed to objectively relate the neural activity measured inside and outside the brain. The patient exhibited typical 6 Hz responses on the scalp at the right occipitotemporal sites. Moreover, there was a clear spatial correspondence between these scalp responses and intracerebral signals in the right lateral inferior occipital gyrus, both in amplitude and in phase. Nevertheless, the signal measured on the scalp and inside the brain at nearby locations showed a 10‐fold difference in amplitude due to electrical insulation from the head. To further quantify the relationship between the scalp and intracerebral recordings, we used an approach correlating time‐varying signals at the stimulation frequency across scalp and intracerebral channels. This analysis revealed a focused and right‐lateralized correspondence between the scalp and intracerebral recordings that were specific to the face stimulation is more broadly distributed in various control situations. These results demonstrate the interest of a frequency tagging approach in characterizing the electrical propagation from brain sources to scalp EEG sensors and in identifying the cortical sources of brain functions from these recordings.     

Neural correlates of evaluative compared with passive tasting

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

Cerebral processing of gustatory stimuli in patients with taste loss

Aim was to investigate differences in the central-nervous processing of gustatory stimuli between normogeusic subjects and patients with taste disorders. Twelve subjects with normal gustatory function and eight patients suffering from hypo- to ageusia underwent one fMRI run each in a 1.5 T scanner where they received liquid gustatory stimuli. fMRI analyses were performed by means of SPM2. Across all participants clusters of activated voxels were mainly found in orbitofrontal and insular regions of interest. Even those patients who did not perceive any stimuli showed some activation of gustatory centers. Group comparisons revealed higher activation of the insular and orbitofrontal cortices in patients compared to the group of healthy subjects. While further studies are needed, this finding may be interpreted in terms of enhanced neuronal recruitment due to functional impairment in patients with gustatory loss. It may ultimately prove useful in terms of the prognostic evaluation of individual patients.     

Bilateral Ageusia in a Patient with a Left Ventroposteromedial Thalamic Infarct: Cortical Localization of Taste Sensation by Statistical Parametric Mapping Analysis of PET Images

Unilateral taste loss is usually observed on the side contralateral to a thalamic infarction, despite gustatory function being represented bilaterally. We report a rare case of bilateral taste loss in a patient with an acute left unilateral thalamic infarction, with unilateral left insular hypometabolism demonstrated by statistical parametric map analysis of PET images. Our observations suggest that the left insular cortex and left ventroposteromedial thalamic nuclei are critical to bilateral gustatory sensation.     

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.     

Time for Taste—A Review of the Early Cerebral Processing of Gustatory Perception

The first successfully recorded event-related potential (ERP) for taste, one of our basic senses, was published nearly half a century ago. Despite this large time span, surprisingly little is known about the early neural processing of taste perception. Here, we are providing a comprehensive and critical overview of over four decades of research, with a focus on the temporal dimension of cerebral taste processing in healthy humans. For this purpose, we review studies using techniques that permit a high temporal resolution, namely, electroencephalography and magnetoencephalography, ERP, and event-related magnetic fields (ERF). Our current knowledge of taste ERP is interpreted in the context of our understanding of other, nonchemical senses. Gaps in the existing literature are identified and discussed. Finally, we suggest directions for future investigations using gustatory ERP/ERF.     

Spectral and spatial changes of brain rhythmic activity in response to the sustained thermal pain stimulation

The aim of this study was to investigate the neurophysiological correlates of pain caused by sustained thermal stimulation. A group of 21 healthy volunteers was studied. Sixty‐four channel continuous electroencephalography (EEG) was recorded while the subject received tonic thermal stimulation. Spectral changes extracted from EEG were quantified and correlated with pain scales reported by subjects, the stimulation intensity, and the time course. Network connectivity was assessed to study the changes in connectivity patterns and strengths among brain regions that have been previously implicated in pain processing. Spectrally, a global reduction in power was observed in the lower spectral range, from delta to alpha, with the most marked changes in the alpha band. Spatially, the contralateral region of the somatosensory cortex, identified using source localization, was most responsive to stimulation status. Maximal desynchrony was observed when stimulation was present. The degree of alpha power reduction was linearly correlated to the pain rating reported by the subjects. Contralateral alpha power changes appeared to be a robust correlate of pain intensity experienced by the subjects. Granger causality analysis showed changes in network level connectivity among pain‐related brain regions due to high intensity of pain stimulation versus innocuous warm stimulation. These results imply the possibility of using noninvasive EEG to predict pain intensity and to study the underlying pain processing mechanism in coping with prolonged painful experiences. Once validated in a broader population, the present EEG‐based approach may provide an objective measure for better pain management in clinical applications. Hum Brain Mapp 37:2976–2991, 2016. © 2016 Wiley Periodicals, Inc.     

The use of single bipolar scalp derivation for the detection of ictal events during long‐term EEG monitoring

Aim. Epilepsy is difficult to diagnose using routine EEG recordings of short duration in patients who have low seizure frequency. Long‐term EEG may be useful but is impractical in an out‐of‐hospital setting. We investigated whether single‐channel scalp EEG placed behind the earlobe is suitable for seizure identification during prolonged EEG monitoring. Methods. Scalp EEG samples were selected from subjects over 15 years of age, and comprised two segments of either background followed by seizure or background followed by background. Bipolar EEG derivations in three directions (F8‐T8, C4‐T8 and T8‐P8) were evaluated for the presence of a seizure by two experienced reviewers. For each EEG segment containing a seizure, one pair of electrodes was oriented towards the suspected region of seizure onset, while two pairs of electrodes were oriented elsewhere. Results. The EEG data contained five frontally localized seizures, five parietal, five temporal, two occipital, and four primary or secondary generalized seizures. The sensitivity and specificity for recognition of seizures was 86% and 95% for Reviewer 1, and 79% and 99% for Reviewer 2, respectively. When identifying a seizure with the lead orientation towards the region of seizure onset, both reviewers identified 20 out of 21 seizures (95%). When the lead was not oriented towards the region of seizure onset, the reviewers identified 34 and 30 out of 42 ictal records correctly, respectively. Conclusions. These results suggest that it is possible to identify epileptic seizures by bipolar EEG derivation using only two scalp electrodes. Lead orientation towards the suspected region of seizure onset is important for optimal detection sensitivity.     

Scalp‐recorded high‐frequency oscillations in childhood sleep‐induced electrical status epilepticus

Because high‐frequency oscillations (HFOs) may affect normal brain functions, we examined them using electroencephalography (EEG) in epilepsy with continuous spike‐waves during slow‐wave sleep (CSWS), a condition that can cause neuropsychological regression. In 10 children between 6 and 9 years of age with epilepsy with CSWS or related disorders, we investigated HFOs in scalp EEG spikes during slow‐wave sleep through temporal expansion of the EEG traces with a low‐cut frequency filter at 70 Hz as well as through time‐frequency power spectral analysis. HFOs (ripples) concurrent with spikes were detected in the temporally expanded traces, and the frequency of the high‐frequency peak with the greatest power in each patient’s spectra ranged from 97.7 to 140.6 Hz. This is the first report on the detection of HFOs from scalp EEG recordings in epileptic patients. We speculate that epileptic HFOs may interfere with higher brain functions in epilepsy with CSWS.     

Taste reactivity deficit in anorexia nervosa

Aim: Anorexia nervosa is a complex psychiatric disorder posing a rapidly increasing burden on modern societies. Our purpose was to clarify perceptual‐motivational aspects of gustatory disturbances in the disease. Methods: A taste reactivity test, with the use of all five primary qualities in two concentrations, was performed in restrictive‐type anorexic patients, and their hedonic evaluations were compared to those of age‐matched healthy control subjects. Results: The patients gave significantly lower pleasantness scores for pleasant taste stimuli compared with controls. The differences were the greatest for the lower concentration sucrose, umami and sodium chloride. Ratings given for the aversive taste stimuli were similar in both experimental groups. Conclusion: Our findings contribute to a better understanding of complex symptoms of anorexia nervosa, and may also help to develop more effective cognitive‐behavioral therapies.     

Chemosensory interaction: acquired olfactory impairment is associated with decreased taste function

Olfaction, taste and trigeminal function are three distinct modalities. However, in daily life they are often activated concomitantly. In health and disease, it has been shown that in two of these senses, the trigeminal and olfactory senses, modification of one sense leads to changes in the other sense and vice versa. The objective of the study was to investigate whether and (if so) how, the third modality, taste, is influenced by olfactory impairment. We tested 210 subjects with normal (n = 107) or impaired (n = 103) olfactory function for their taste identification capacities. Validated tests were used for olfactory and gustatory testing (Sniffin’ Sticks, Taste Strips). In an additional experiment, healthy volunteers underwent reversible olfactory cleft obstruction to investigate short-time changes of gustatory function after olfactory alteration. Mean gustatory identification (taste strip score) for the subjects with impaired olfaction was 19.4 ± 0.6 points and 22.9 ± 0.5 points for those with normal olfactory function (t = 4.6, p < 0.001). The frequencies of both, smell and taste impairments interacted significantly (Chi², F = 16.4, p < 0.001), and olfactory and gustatory function correlated (r ₂₁₀ = 0.30, p < 0.001). Neither age nor olfactory impairment cause effects interfered with this olfactory–gustatory interaction. In contrast, after short-lasting induced olfactory decrease, gustatory function remained unchanged. The present study suggests that longstanding impaired olfactory function is associated with decreased gustatory function. These findings seem to extend previously described mutual chemosensory interactions also to smell and taste. It further raises the question whether chemical senses in general decrease mutually after acquired damage.     

EEG alpha map series: brain micro-states by space-oriented adaptive segmentation

The spontaneous EEG, viewed as a series of momentary scalp field maps, shows stable map configurations (of periodically reversed polarity) for varying durations, and discontinuous changes of the configurations. For adaptive segmentation of map series into spatially stationary epochs, the maps at the times of maximal map relief are selected and spatially described by the two locations of maximal and minimal (extreme) potentials; a segment ends if over time an extreme leaves its pre-set spatial window. Over 6 subjects, the resting alpha EEG showed 210 msec mean segment duration; segments longer than 323 msec covered 50% of the total time; the most prominent segment class (1.5% of all classes) covered 20% of total time (prominence varied strongly over classes; not all possible classes occurred). Spectral power and phase of averages of adaptive and pre-determined segments demonstrated the adequacy of the strategy, and the homogeneity of adaptive segment classes by their reduced within-class variance. It is suggested that different segment classes manifest different brain functional states exerting different effects on information processing. The spatially stationary segments might be basic building blocks of brain information processing, possibly operationalizing consciousness time and offering a common phenomenology for spontaneous activity and event-related potentials. The functional significance of segments might be modes or steps of information processing or performance, tested, e.g., as reaction time.     

Hunger Modulates the Responses to Gustatory Stimuli of Single Neurons in the Caudolateral Orbitofrontal Cortex of the Macaque Monkey

1. In order to determine whether the responsiveness of neurons in the caudolateral orbitofrontal cortex (a secondary cortical gustatory area) is influenced by hunger, the activity evoked by prototypical taste stimuli (glucose, NaCl, HCl, and quinine hydrochloride) and fruit juice was recorded in single neurons in this cortical area before, while, and after cynomolgous macaque monkeys were fed to satiety with glucose or fruit juice. 2. It was found that the responses of the neurons to the taste of the glucose decreased to zero while the monkey ate it to satiety during the course of which his behaviour turned from avid acceptance to active rejection. 3. This modulation of responsiveness of the gustatory responses of the neurons to satiety was not due to peripheral adaptation in the gustatory system or to altered efficacy of gustatory stimulation after satiety was reached, because modulation of neuronal responsiveness by satiety was not seen at earlier stages of the gustatory system, including the nucleus of the solitary tract, the frontal opercular taste cortex, and the insular taste cortex. 4. The decreases in the responsiveness of the neurons were relatively specific to the food with which the monkey had been fed to satiety. For example, in seven experiments in which the monkey was fed glucose solution, neuronal responsiveness decreased to the taste of the glucose but not to the taste of blackcurrant juice. Conversely, in two experiments in which the monkey was fed to satiety with fruit juice, the responses of the neurons decreased to fruit juice but not to glucose. 5. These and earlier findings lead to a proposed neurophysiological mechanism for sensory-specific satiety in which the information coded by single neurons in the gustatory system becomes more specific through the processing stages consisting of the nucleus of the solitary tract, the taste thalamus, and the frontal opercular and insular taste primary taste cortices, until neuronal responses become relatively specific for the food tasted in the caudolateral orbitofrontal cortex (secondary) taste area. Then sensory-specific satiety occurs because in this caudolateral orbitofrontal cortex taste area (but not earlier in the taste system) it is a property of the synapses that repeated stimulation results in a decreased neuronal response. 6. Evidence was obtained that gustatory processing involved in thirst also becomes interfaced to motivation in the caudolateral orbitofrontal cortex taste projection area, in that neuronal responses here to water were decreased to zero while water was drunk until satiety was produced.