Re-examination of the human taste region: a positron emission tomography study.

There is considerable uncertainty regarding the cortical areas in the human brain that are involved in gustatory processing. Evidence from nonhuman primates indicates that parts of the peri-central opercular region (secondary somatosensory cortex) and insular cortex may be important for gustatory processing. The aim of the study was to examine changes in cerebral blood flow during gustatory stimulation (with sucrose or water) in the insulo-opercular region of the human brain with positron emission tomography using only movement of the tongue and mouth as control conditions. This is important because subtractions of responses to one gustatory stimulus from those to another may mask gustatory activity that is common to both stimuli, even when the control stimulus is an apparently tasteless one (e.g. water). Bilateral increases in activity were observed in the insulo-opercular region and, consistent with animal work, they indicate that there are a number of separate foci within this general area where primary gustatory inputs may be processed.     

Neurons in the posterior insular cortex are responsive to gustatory stimulation of the pharyngolarynx, baroreceptor and chemoreceptor stimulation, and tail pinch in rats

Extracellular unit responses to gustatory stimulation of the pharyngolaryngeal region, baroreceptor and chemoreceptor stimulation, and tail pinch were recorded from the insular cortex of anesthetized and paralyzed rats. Of the 32 neurons identified, 28 responded to at least one of the nine stimuli used in the present study. Of the 32 neurons, 11 showed an excitatory response to tail pinch, 13 showed an inhibitory response, and the remaining eight had no response. Of the 32 neurons, eight responded to baroreceptor stimulation by an intravenous (i.v.) injection of methoxamine hydrochloride (Mex), four were excitatory and four were inhibitory. Thirteen neurons were excited and six neurons were inhibited by an arterial chemoreceptor stimulation by an i.v. injection of sodium cyanide (NaCN). Twenty-two neurons were responsive to at least one of the gustatory stimuli (deionized water, 1.0 M NaCl, 30 mM HCl, 30 mM quinine HCl, and 1.0 M sucrose); five to 11 excitatory neurons and three to seven inhibitory neurons for each stimulus. A large number of the neurons (25/32) received converging inputs from more than one stimulus among the nine stimuli used in the present study. Most neurons (23/32) received converging inputs from different modalities (gustatory, visceral, and tail pinch). The neurons responded were located in the insular cortex between 2.0 mm anterior and 0.2 mm posterior to the anterior edge of the joining of the anterior commissure (AC); the mean location was 1.2 mm (n=28) anterior to the AC. This indicates that most of the neurons identified in the present study seem to be located in the region posterior to the taste area and anterior to the visceral area in the insular cortex. These results indicate that the insular cortex neurons distributing between the taste area and the visceral area receive convergent inputs from gustatory, baroreceptor, chemoreceptor, and nociceptive organs.     

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.     

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.     

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

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

Insular cortex and neuropsychiatric disorders: a review of recent literature.

The insular cortex is located in the centre of the cerebral hemisphere, having connections with the primary and secondary somatosensory areas, anterior cingulate cortex, amygdaloid body, prefrontal cortex, superior temporal gyrus, temporal pole, orbitofrontal cortex, frontal and parietal opercula, primary and association auditory cortices, visual association cortex, olfactory bulb, hippocampus, entorhinal cortex, and motor cortex. Accordingly, dense connections exist among insular cortex neurons. The insular cortex is involved in the processing of visceral sensory, visceral motor, vestibular, attention, pain, emotion, verbal, motor information, inputs related to music and eating, in addition to gustatory, olfactory, visual, auditory, and tactile data. In this article, the literature on the relationship between the insular cortex and neuropsychiatric disorders was summarized following a computer search of the Pub-Med database. Recent neuroimaging data, including voxel based morphometry, PET and fMRI, revealed that the insular cortex was involved in various neuropsychiatric diseases such as mood disorders, panic disorders, PTSD, obsessive-compulsive disorders, eating disorders, and schizophrenia. Investigations of functions and connections of the insular cortex suggest that sensory information including gustatory, olfactory, visual, auditory, and tactile inputs converge on the insular cortex, and that these multimodal sensory information may be integrated there.     

Aversive taste stimuli facilitate extracellular acetylcholine release in the insular gustatory cortex of the rat: a microdialysis study

The release of extracellular acetylcholine (ACh) in the insular gustatory cortex of conscious rats during taste stimulation was measured using the microdialysis technique. The mean basal release of ACh before stimulation was 273 ± 21 fmol/10 μl (mean ± S.E.M., n = 25). Intraorally applied taste stimuli or distilled water significantly increased the release of ACh. Among them, infusion of 0.001 M quinine HCl produced a marked increase in the release of ACh up to 355% of baseline levels. Infusion of 0.01 M saccharin to the subjects that had acquired an aversion to this taste also caused a prominent increase in ACh up to 343% of basal levels. In contrast, saccharin infusion to the naive subjects moderately increased ACh up to 243% of baseline. Water infusion resulted in the smallest increase in ACh up to 175% of baseline. Although intraoral infusions of quinine or distilled water caused a significant increase in ACh in the parietal cortex, the magnitude of increased ACh was smaller than that in the gustatory cortex. These results suggest that ACh release in the insular gustatory cortex is related to behavioral expression to aversive taste stimuli.     

Brain systems for baroreflex suppression during stress in humans

The arterial baroreflex is a key mechanism for the homeostatic control of blood pressure (BP). In animals and humans, psychological stressors suppress the capacity of the arterial baroreflex to control short-term fluctuations in BP, reflected by reduced baroreflex sensitivity (BRS). While animal studies have characterized the brain systems that link stressor processing to BRS suppression, comparable human studies are lacking. Here, we measured beat-to-beat BP and heart rate (HR) in 97 adults who performed a multisource interference task that evoked changes in spontaneous BRS, which were quantified by a validated sequence method. The same 97 participants also performed the task during functional magnetic resonance imaging (fMRI) of brain activity. Across participants, task performance (i) increased BP and HR and (ii) reduced BRS. Analyses of fMRI data further demonstrated that a greater task-evoked reduction in BRS covaried with greater activity in brain systems important for central autonomic and cardiovascular control, particularly the cingulate cortex, insula, amygdala, and midbrain periaqueductal gray (PAG). Moreover, task performance increased the functional connectivity of a discrete area of the anterior insula with both the cingulate cortex and amygdala. In parallel, this same insula area showed increased task-evoked functional connectivity with midbrain PAG and pons. These novel findings provide human evidence for the brain systems presumptively involved in suppressing baroreflex functionality, with relevance for understanding the neurobiological mechanisms of stressor-related cardiovascular reactivity and associated risk for essential hypertension and atherosclerotic heart disease.     

Fluctuations of the spontaneous discharge in the posterior insular cortex neurons are associated with changes in the cardiovascular system in rats

Extracellular neuronal responses were recorded from the posterior insular cortex. In three of 20 neurons, fluctuations in their spontaneous discharge were observed during recording without stimulation. In these recordings, fluctuations were also observed in arterial blood pressure (BP) and heart rate (HR) recorded simultaneously. For 3 neurons, the relationships among the fluctuations in the spontaneous discharge of the insular cortex neuron (INSneu), mean arterial pressure (MAP), and HR were analyzed using Pearson's correlation coefficient (r). In unit A, there was a negative correlation between INSneu and MAP (r = -0.30). The r between INSneu and HR was -0.02. In unit B, the data were divided into two groups according to HR (HR < 400 and HR > or = 400). The differential results in the correlations for INSneu-MAP were obtained in the two groups (r = -0.2, HR < 400; r = 0.51, HR > or = 400). For unit C, the INSneu was positively correlated with BP (r = 0.31) and HR (r = 0.36). From the correlation analysis concerning the time, changes in INSneu seem to precede (or delay) changes in BP. These results showed that fluctuations in neuronal activity in the posterior insular cortex are positively or negatively correlated with BP (or HR). The data suggest that some of the neurons in the posterior insular cortex may play a role in the homeostatic (and/or regulatory) control of the autonomic system.     

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

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

Insular cortex and amygdala lesions differentially affect acquisition on inhibitory avoidance and conditioned taste aversion

These experiments examined the effects of NMDA-induced lesions of the amygdala and insular (gustatory) cortex (IC) on inhibitory avoidance learning and conditioned taste aversion (CTA) in rats. IC lesions, but not amygdala lesions, disrupted CTA. In contrast, lesions of either brain region disrupted inhibitory avoidance learning. These findings support the view that the IC is strongly involved in the acquisition of external as well as visceral aversively motivated behavior. Despite extensive functional interconnections, these 2 brain regions appear to have different roles in mediating different forms of aversively based learning.     

What is odd in the oddball task? Prefrontal cortex is activated by dynamic changes in response strategy

In the "oddball" target detection task, subjects respond to target stimuli that occur infrequently and irregularly within a series of standard stimuli. Although detection of these targets reliably evokes transient activity in prefrontal cortical regions, it has not been established whether this activity is due to selection of an infrequent response or to changes in response strategy. We investigated this issue using a novel variant of the oddball task that incorporated the Simon effect, while measuring hemodynamic brain activity in prefrontal cortex using functional magnetic resonance imaging (fMRI). Subjects viewed a series of circles and squares that required left and right button presses, respectively. On 90% of trials ("standard" trials), the stimuli were presented in the same visual hemifield as the hand of response, but on 10% of trials ("strategy-change" trials) they were presented in the opposite visual hemifield. Significant activation to the infrequent strategy-change trials was found in the anterior middle frontal gyrus (MFG), the posterior inferior frontal gyrus (IFG) and adjacent insular cortex, and in the anterior cingulate gyrus (ACG). These regions, which correspond to previous reports of oddball-related activation, were consistent across subjects. Behavioral results supported our interpretation that subjects potentiated a position-based response strategy, which was inhibited on the strategy-change trials. Activity within the MFG and ACG was much greater on error trials than on correct trials, while IFG activity was similar between error and correct trials. We conclude that the dorsolateral prefrontal cortex (dlPFC) is associated with dynamic changes in the mapping of stimuli to responses (e.g. response strategies), independently of any changes in behavior.     

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.     

Dynamic and strategic aspects of executive processing

Executive cognitive functions have been postulated to include both dynamic behavioral selection and strategic goal-setting or response preparation. To investigate the relation between these aspects of executive processing, we embedded an event-related oddball paradigm within a blocked design. Subjects responded to infrequent targets presented within a series of standard stimuli that required no response; this task alternated with a visually similar nontask condition. Using functional magnetic resonance imaging (fMRI), we found that a set of brain regions including dorsolateral prefrontal cortex (dlPFC), insular cortex, cingular cortex, and the basal ganglia demonstrated transient activation both to target stimuli and to the onset of task blocks. Within the parietal cortex, there was a dissociation such that the supramarginal gyrus exhibited greater activity to the target stimuli than to block onsets, while the converse pattern was observed in the intraparietal sulcus. Sustained positive activity during task blocks was present in the caudate and supplementary motor area, while sustained negative activity was present in the precuneus and medial parietal cortex. We conclude that dlPFC and related brain regions mediate both dynamic and strategic processing, through the preparation and selection of rules for behavior.     

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.     

The anterior insular cortex represents breaches of taste identity expectation

Despite the importance of breaches of taste identity expectation for survival, its neural correlate is unknown. We used fMRI in 16 women to examine brain response to expected and unexpected receipt of sweet taste and tasteless/odorless solutions. During expected trials (70%), subjects heard "sweet" or "tasteless" and received the liquid indicated by the cue. During unexpected trials (30%), subjects heard sweet but received tasteless or they heard tasteless but received sweet. After delivery, subjects indicated stimulus identity by pressing a button. Reaction time was faster and more accurate after valid cuing, indicating that the cues altered expectancy as intended. Tasting unexpected versus expected stimuli resulted in greater deactivation in fusiform gyri, possibly reflecting greater suppression of visual object regions when orienting to, and identifying, an unexpected taste. Significantly greater activation to unexpected versus expected stimuli occurred in areas related to taste (thalamus, anterior insula), reward [ventral striatum (VS), orbitofrontal cortex], and attention [anterior cingulate cortex, inferior frontal gyrus, intraparietal sulcus (IPS)]. We also observed an interaction between stimulus and expectation in the anterior insula (primary taste cortex). Here response was greater for unexpected versus expected sweet compared with unexpected versus expected tasteless, indicating that this region is preferentially sensitive to breaches of taste expectation. Connectivity analyses confirmed that expectation enhanced network interactions, with IPS and VS influencing insular responses. We conclude that unexpected oral stimulation results in suppression of visual cortex and upregulation of sensory, attention, and reward regions to support orientation, identification, and learning about salient stimuli.     

A fMRI study of brain activations during non-noxious and noxious electrical stimulation of the sciatic nerve of rats

An acute pain animal model for fMRI study would provide useful spatial and temporal information for studying the supraspinal nociceptive neuronal responses. The aim of the present study was to investigate whether the nociceptive responses in different brain areas can be differentiated by using functional magnetic resonance imaging (fMRI) in anesthetized rats. Functional changes in brain regions activated by noxious or non-noxious stimuli of the sciatic nerve were investigated using fMRI in a 4.7 T MR system in alpha-chloralose anaesthetized rats. To determine the electrical intensity for noxious and non-noxious stimuli, compound action potential recording was employed to reveal the type of fibers activated by graded electrical stimulation of sciatic nerve. It showed that innocuous A-beta fibers were excited by two times the muscle twitch threshold and nociceptive A-delta and C fibers were recruited and excited by 10 and 20 times threshold, respectively. A series of four-slice gradient echo images were acquired during innocuous (two times threshold) and noxious (10 and 20 times threshold) stimuli in a 4.7 T MR system. Contralateral somatosensory cortex was the most prominent brain area activated by innocuous stimuli. Both signal intensity and activated areas were significantly increased in the somatosensory cortex, cingulate cortex, medial thalamus and hypothalamus during noxious stimuli. These four brain areas activated by noxious stimuli were significantly suppressed by prior intravenous injection of morphine (5 mg/kg). The present findings demonstrated that the difference of the innocuous and nociceptive responses in the brain could be detected and localized by an in vivo spatial map using fMRI. Results suggest that fMRI may be an invaluable tool for studying pain in anesthetized animals.     

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.     

Cardiovascular responses to gustatory and mechanical stimulation of the nasopharynx in rats

The effects of natural (mechanical and gustatory) stimulation of the nasopharynx or electrical stimulation of the pharyngeal branch of the glossopharyngeal (PH-IXth) nerve on the changes in heart rate (HR) and arterial blood pressure (BP) were investigated in paralyzed and anesthetized rats. Afferent responses in the PH-IXth nerve were also investigated. Electrical stimulation of the PH-IXth nerve elicited a tachycardia and an increase in BP. Among the gustatory (1.0 M NaCl, 0.03 M HCl, 0.03 M QHCl, 1.0 M sucrose, H₂O, and 0.9% NaCl) and mechanical stimuli applied to the nasopharynx, 1.0 M sucrose and 0.9% NaCl were ineffective in changing HR and BP; the rest of the stimuli were strongly effective as was the case with electrical stimulation of the PH-IXth nerve. Responses were evoked in the PH-IXth nerve by nasopharyngeal stimulation with the stimuli which were effective in producing cardiovascular responses. On the other hand, 1.0 M sucrose and 0.9% NaCl, which were ineffective stimuli for cardiovascular responses, did not produce any response in the PH-IXth nerve. There was a high correlation between the magnitude of the responses in the PH-IXth nerve and those of the cardiovascular system. These results indicate that gustatory and mechanical information carried in the PH-IXth nerve innervating the nasopharynx plays an important role in cardiovascular regulation as well as the sense of taste.     

GABA-mediated corticofugal inhibition of taste-responsive neurons in the nucleus of the solitary tract

The nucleus of the solitary tract (NST) receives descending connections from several forebrain targets of the gustatory system, including the insular cortex. Many taste-responsive cells in the NST are inhibited by gamma-aminobutyric acid (GABA). In the present study, we investigated the effects of cortical stimulation on the activity of gustatory neurons in the NST. Multibarrel glass micropipettes were used to record the activity of NST neurons extracellularly and to apply the GABA(A) antagonist bicuculline methiodide (BICM) into the vicinity of the cell. Taste stimuli were 0.032 M sucrose (S), 0.032 M NaCl (N), 0.00032 M citric acid (H), and 0.032 M quinine hydrochloride (Q), presented to the anterior tongue. Each of 50 NST cells was classified as S-, N-, H-, or Q-best on the basis of its response to chemical stimulation of the tongue. The ipsilateral insular cortex was stimulated both electrically (0.5 mA, 100 Hz, 0.2 ms) and chemically (10 mM DL-homocysteic acid, DLH), while the spontaneous activity of each NST cell was recorded. The baseline activity of 34% of the cells (n=17) was modulated by cortical stimulation: eight cells were inhibited and nine were excited. BICM microinjected into the NST blocked the cortical-induced inhibition but had no effect on the excitatory response. Although the excitatory effects were distributed across S-, N-, and H-best neurons, the inhibitory effects of cortical stimulation were significantly more common in N-best cells. These data suggest that corticofugal input to the NST may differentially inhibit gustatory afferent activity through GABAergic mechanisms.