Multisensory Processing of Gustatory Stimuli

The brain’s processing of gustatory stimuli is inherently multimodal, since at approximately the same time that intraoral stimuli activate receptors on taste cells, somatosensory information is concurrently conveyed to the central nervous system. We first present evidence that throughout the oral cavity, often a single chemical stimulus will concomitantly activate different receptors expressed on taste cells and somatosensory nerve terminals. We then argue that gustatory perception is intrinsically linked to concurrent somatosensory processing. Finally, we review evidence showing that central gustatory pathways are sites where multisensory integration occurs, with particular emphasis on somatosensory responses in the gustatory cortex.     

Representation of Salty Taste Stimulus Concentrations in the Primary Gustatory Area in Humans

The relationship between neuronal activity in the human gustatory cortex and the concentrations of taste stimuli is not well understood. In this study, we recorded changes in the magnetic fields of the human brain in response to four concentrations of NaCl (30 mM, 100 mM, 300 mM, and 1 M) and measured the magnitude and shortest latency of the equivalent current dipole (ECD) in the primary gustatory area of the cerebral cortex (PGA). The average magnitude of ECDs in the PGA increased in a concentration-dependent manner throughout the entire range of NaCl concentrations. The shortest latency of the ECD, however, did not vary with the stimulus concentration.     

Human forebrain activation by visceral stimuli.

Visceral function is essential for survival. Discreet regions of the human brain controlling visceral function have been postulated from animal studies (Cechetto and Saper [1987] J. Comp. Neurol. 262:27-45) and suspected from lethal cardiac arrythmias (Cechetto [1994] Integr. Physiol. Behv. Sci. 29:362-373). However, these visceral sites remain uncharted in the normal human brain. We used 4-Tesla functional magnetic resonance imaging (fMRI) to identify changes in activity in discrete regions of the human brain previously identified in animal studies to be involved in visceral control. Five male subjects underwent heart rate (HR) and/or blood pressure (BP) altering tests: maximal inspiration (MX), Valsalva's maneuver (VM), and isometric handgrip (HG). Increased neuronal activity was observed during MX, VM, and HG, localized in the insular cortex, in the posterior regions of the thalamus, and in the medial prefrontal cortex. To differentiate special visceral (taste) regions from general visceral (HR, BP) regions in these areas, response to gustatory stimulation was also examined; subjects were administered saline (SAL) and sucrose (SUC) solutions as gustatory stimuli. Gustatory stimulation increased activity in the ventral insular cortex at a more inferior level than the cardiopulmonary stimuli. The observed neural activation is the first demonstration of human brain activity in response to visceral stimulation as measured by fMRI.     

An fMRI study investigating cognitive modulation of brain regions associated with emotional processing of visual stimuli

Brain regions modulated by cognitive tasks during emotional processing were investigated using fMRI. Participants performed indirect and direct emotional processing tasks on positive and negative faces and pictures. We used a multivariate technique, partial least squares (PLS) to determine spatially distributed patterns of brain activity associated with different tasks and stimulus conditions, as well as the interaction between the two. The pattern of brain activity accounting for the most task-related covariance represented a task x stimulus interaction and distinguished indirect processing of pictures and direct processing of faces from direct processing of pictures and indirect processing of faces. The latter two conditions were characterised by limbic (e.g. amygdala, insula, thalamus) and temporal lobe activity, in addition to greater activity in the ventral prefrontal cortex. Indirect and direct processing of pictures and faces, respectively, were represented by more dorsal prefrontal and parietal activity. These findings indicate that brain activity during processing of emotional content is critically dependent on both the type of stimulus and processing task. In addition, these results support the idea that the pattern of activity in the emotional network can be influenced in a 'top-down' fashion via cognitive factors such as attentional control, and as such, have important clinical implications for emotional disorders, such as depression and anxiety.     

Neural networks of response shifting: influence of task speed and stimulus material

Functional magnetic resonance imaging (fMRI) was used in 14 healthy subjects to measure brain activation, while response shifting was performed. In the activation phase, subjects were asked to shift their attention between two different types of visually presented stimuli. In the baseline phase, subjects were required to attend to one stimulus type only. Subjects responded by pressing a left or right key according to the side of presentation of the target stimuli. In a verbal task, subjects were required to switch between letters and numbers. In a figural task, subjects reacted to round and square shapes. Stimuli were presented for 750 or 1500 ms. Response shifting revealed significantly increased activation compared to non-switching in the bilateral superior parietal cortex, right occipital cortex, left inferior frontal cortex, left and right striatum, and bilateral dorsolateral prefrontal cortex (DLPFC). Superior parietal and occipital cortex activation may be due to spatial analysis during response shifting. Subvocal rehearsal of the task instructions may have led to activation in the left inferior frontal cortex. Activation in the striatum was related to prefrontal activation and may represent the association between basal ganglia and prefrontal activation during executive control. However, the most important brain region involved in the execution of response shifting was the bilateral DLPFC. Higher task speed increased executive top-down attentional control and, therefore, significantly increased activity in the bilateral DLPFC. Brain activation did not differ significantly between verbal and figural stimulus material. This result suggests that brain activation in the present study illustrates the brain regions involved in the basic cognitive mechanisms of response shifting.     

Segregation of gustatory cortex in response to salt and umami taste studied through event-related potentials

In this study, we report gustatory event-related potentials in response to stimulation with monosodium glutamate (MSG) and salt (NaCl). We investigated differences in event-related potential related to stimulus quality, stimulus concentration, cortical topography, and participants' sex. Our results showed that amplitudes P1N1 and N1P2 were significantly larger in response to stimulation with NaCl compared with stimulation with MSG and the topographical distribution of amplitudes varied significantly for the two stimuli. In addition, responses were significantly larger in the right hemisphere compared with the left hemisphere for both stimuli, suggesting right hemispheric dominance for gustatory processing. In conclusion, this study shows significant differences in cerebral processing of MSG and NaCl in the human brain.     

Neural mechanisms involved in odor pleasantness and intensity judgments

Olfactory processing in the human brain was examined using positron emission tomography. Twelve normal volunteers were scanned while smelling pairs of odors: they were asked to judge which odor was more pleasant in one condition, and which was more intense in a second condition; they also were scanned while sniffing an odorless stimulus. As in prior studies, greater cerebral blood flow was found in the right orbitofrontal cortex during both pleasantness and intensity judgments as compared to baseline. Cerebellar activity was also seen, but contrary to expectations no activity was detected in the primary olfactory (piriform) cortex. Only the pleasantness judgment elicited additional activity within the hypothalamus, suggesting that this structure may be involved in affective processing that requires access to information about internal state.     

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.     

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.     

Decreased activity in inferotemporal cortex during explicit memory: dissociating priming,novelty detection,and recognition

Studies of non-human primates have shown that activity in inferotemporal (IT) brain regions decrease over repeated stimulus exposure, a phenomenon known as repetition suppression. In the present study, repetition suppression was examined during recognition of personally experienced events (explicit memory). Brain activity was measured while subjects encoded and subsequently recognized scenic pictures. First, two recognition conditions were compared; one that mainly included familiar pictures and one that mainly included novel pictures. Responses derived from this contrast may reflect recognition memory, perceptual priming, or novelty detection. To test specifically for responses associated with recognition memory, subjects encoded a new set of pictures followed by two recognition tests. All test pictures had been presented during the course of the experiment, and the subjects identified pictures that appeared in the second encoding list. Since all pictures were familiar, repetition suppression was specifically associated with recognition memory. In the first contrast, relative change in brain activity was observed in inferotemporal, extra-striate, and hippocampal regions during recognition of familiar versus novel pictures. In the second contrast, decreased activity in IT cortex was found. The location of this region overlapped with that for the region identified in the first contrast, and a conjunction analysis showed that reduced activity in left IT cortex was common to both contrasts. These results suggest that repetition suppression in IT cortex reflects recognition memory, and that such a response is not a simple function of stimulus repetition but can be modulated by top-down processing.     

Error-related brain activation during a Go/NoGo response inhibition task

Inhibitory control and performance monitoring are critical executive functions of the human brain. Lesion and imaging studies have shown that the inferior frontal cortex plays an important role in inhibition of inappropriate response. In contrast, specific brain areas involved in error processing and their relation to those implicated in inhibitory control processes are unknown. In this study, we used a random effects model to investigate error-related brain activity associated with failure to inhibit response during a Go/NoGo task. Error-related brain activation was observed in the rostral aspect of the right anterior cingulate (BA 24/32) and adjoining medial prefrontal cortex, the left and right insular cortex and adjoining frontal operculum (BA 47) and left precuneus/posterior cingulate (BA 7/31/29). Brain activation related to response inhibition and competition was observed bilaterally in the dorsolateral prefrontal cortex (BA 9/46), pars triangularis region of the inferior frontal cortex (BA 45/47), premotor cortex (BA 6), inferior parietal lobule (BA 39), lingual gyrus and the caudate, as well as in the right dorsal anterior cingulate cortex (BA 24). These findings provide evidence for a distributed error processing system in the human brain that overlaps partially, but not completely, with brain regions involved in response inhibition and competition. In particular, the rostal anterior cingulate and posterior cingulate/precuneus as well as the left and right anterior insular cortex were activated only during error processing, but not during response competition, inhibition, selection, or execution. Our results also suggest that the brain regions involved in the error processing system overlap with brain areas implicated in the formulation and execution of articulatory plans.     

Visual activation in prefrontal cortex is stronger in monkeys than in humans

The prefrontal cortex supports many cognitive abilities, which humans share to some degree with monkeys. The specialized functions of the prefrontal cortex depend both on the nature of its inputs from other brain regions and on distinctive aspects of local processing. We used functional MRI to compare prefrontal activity between monkey and human subjects when they viewed identical images of objects, either intact or scrambled. Visual object-related activation of the lateral prefrontal cortex was observed in both species, but was stronger in monkeys than in humans, both in magnitude (factors 2-3) and in spatial extent (fivefold or more as a percentage of prefrontal volume). This difference was observed for two different stimulus sets, at two field strengths, and over a range of tasks. These results suggest that there may be more volitional control over visual processing in humans than in monkeys.     

Motion direction tuning in human visual cortex

A number of electrophysiological studies have been conducted in recent years in order to clarify the dynamics of visual motion processing in the human brain. Using a variety of event-related potential (ERP) measures, several parameters such as onset, offset, contrast and velocity have been investigated, while a critical aspect of visual motion, that of direction, has received less attention. Here we used multichannel electroencephalography and distributed source localization to study brain activity for different directions of visual motion using random dot stimuli. Our data reveal differential extrastriate activation at 164–226 ms after motion onset that coded for motion direction with different ERP maps and underlying electrical generators for each tested direction. This activation was paralleled initially (164–186 ms) by a distinct extrastriate activation encoding whether the motion stimulus consisted of directed motion stimuli (as above) or contained undirected incoherent motion (control stimulus). Application of a linear inverse solution localized the brain activity for each tested motion direction to distinct brain regions within the same larger network of extrastriate brain regions. These regions included bilateral temporo-occipital and bilateral parieto-occipital cortex. The present data in healthy subjects are compatible with extrastriate activity that is tuned to different directions of visual motion. This extends previous clinical data and suggests the presence of distributed macroscopic motion direction tuning in primate extrastriate cortex that may complement the classical microscopic motion tuning at the columnar level.     

Selective and divided attention during visual discriminations of shape, color, and speed: functional anatomy by positron emission tomography

Positron emission tomography (PET) was used to identify the neural systems involved in discriminating the shape, color, and speed of a visual stimulus under conditions of selective and divided attention. Psychophysical evidence indicated that the sensitivity for discriminating subtle stimulus changes in a same-different matching task was higher when subjects selectively attended to one attribute than when they divided attention among the attributes. PET measurements of brain activity indicated that modulations of extrastriate visual activity were primarily produced by task conditions of selective attention. Attention to speed activated a region in the left inferior parietal lobule. Attention to color activated a region in the collateral sulcus and dorsolateral occipital cortex, while attention to shape activated collateral sulcus (similarly to color), fusiform and parahippocampal gyri, and temporal cortex along the superior temporal sulcus. Outside the visual system, selective and divided attention activated nonoverlapping sets of brain regions. Selective conditions activated globus pallidus, caudate nucleus, lateral orbitofrontal cortex, posterior thalamus/colliculus, and insular-premotor regions, while the divided condition activated the anterior cingulate and dorsolateral prefrontal cortex. The results in the visual system demonstrate that selective attention to different features modulates activity in distinct regions of extrastriate cortex that appear to be specialized for processing the selected feature. The disjoint pattern of activations in extravisual brain regions during selective- and divided-attention conditions also suggests that preceptual judgements involve different neural systems, depending on attentional strategies.     

A supramodal limbic-paralimbic-neocortical network supports goal-directed stimulus processing

Limited processing resources are allocated preferentially to events that are relevant for behavior. Research using the novelty "oddball" paradigm suggests that a widespread network of limbic, paralimbic, and association areas supports the goal-directed processing of task-relevant target events. In that paradigm, greater activity in diverse brain areas is elicited by rare task-relevant events that require a subsequent motor response than by rare task-irrelevant novel events that require no response. Both stimulus infrequency (unexpectedness) and novelty, however, may contribute to the pattern of activity observed using that paradigm. The goal of the present study was to examine the supramodal neural activity elicited by regularly occurring, equiprobable, and non-novel stimuli that differed in the subsequent behavior they prescribed. We employed event-related functional magnetic resonance imaging (fMRI) during auditory and visual versions of a Go/NoGo task. Participants made a motor response to the designated "Go" (target) stimulus, and no motor response to the equiprobable "NoGo" (nontarget) stimulus. We hypothesized that task-relevant Go events would elicit relatively greater hemodynamic activity than would NoGo events throughout a network of limbic, paralimbic, and association areas. Indeed, Go events elicited greater activity than did NoGo events in the amygdala-hippocampus, paralimbic cortex at the anterior superior temporal sulcus, insula, posterior orbitofrontal cortex, and anterior and posterior cingulate cortex, as well as in heteromodal association areas located at the temporoparietal junction, anterior intraparietal sulcus and precuneus, and premotor cortex. Paralimbic cortex offers an important site for the convergence of motivational/goal-directed influences from limbic cortex with stimulus processing and response selection mediated within the frontoparietal areas.     

Taste neurons in the cortex of the alert cynomolgus monkey.

The activity of single neurons in the gustatory cortex of alert cynomolgus monkeys was analyzed. Taste-evoked activity in response to the four prototypical taste stimuli was recorded from a cortical gustatory area comprising the frontal operculum and adjoining anterior insula. Spontaneous activity for 364 gustatory neurons was 3.9 +/- 4.9 (mean +/- SD) spikes/s. Mean net (gross minus spontaneous) discharge rates for all gustatory neurons were: 1.0 M glucose = 4.9 +/- 11.6, 0.3 M NaCl = 3.2 +/- 7.1, M quinine HCl = 2.6 +/- 5.8, and 0.01 M HCl = 1.7 +/- 4.6. The results from intensity-response functions imply that the perception of each basic taste quality in the nonhuman primate is based on the activity of the appropriate neural subgroup rather than on the mean activity of all taste cells. Therefore a more meaningful index of the effectiveness of a stimulus may be the discharge rate it evokes from the subset of gustatory neurons for which it is the best stimulus. Glucose was the best stimulus for 142 cells (including ties), from which it elicited a mean net response of 10.3 spikes/s; NaCl was best for 107 neurons which gave a mean 8.7 spikes/s; quinine HCl evoked 6.2 spikes/s from the 74 cells that responded best to it; HCl elicited 5.9 spikes/s from the 49 neurons for which it served as best stimulus. The response characteristics of cortical taste cells indicate heterogeneous features, and significantly different patterns from those reported in other nonchemical sensory systems.     

The Role of the Anterior Cingulate Cortex in Prediction Error and Signaling Surprise

In the past two decades, reinforcement learning (RL) has become a popular framework for understanding brain function. A key component of RL models, prediction error, has been associated with neural signals throughout the brain, including subcortical nuclei, primary sensory cortices, and prefrontal cortex. Depending on the location in which activity is observed, the functional interpretation of prediction error may change: Prediction errors may reflect a discrepancy in the anticipated and actual value of reward, a signal indicating the salience or novelty of a stimulus, and many other interpretations. Anterior cingulate cortex (ACC) has long been recognized as a region involved in processing behavioral error, and recent computational models of the region have expanded this interpretation to include a more general role for the region in predicting likely events, broadly construed, and signaling deviations between expected and observed events. Ongoing modeling work investigating the interaction between ACC and additional regions involved in cognitive control suggests an even broader role for cingulate in computing a hierarchically structured surprise signal critical for learning models of the environment. The result is a predictive coding model of the frontal lobes, suggesting that predictive coding may be a unifying computational principle across the neocortex.     

Automatic activation in the human primary motor cortex synchronized with movement preparation.

The human primary motor cortex during a unilateral finger reactive movement to visual stimuli was examined by magnetoencephalography (MEG) measurement. The brain activity related to movement execution (the motor activity contralateral to the movement side) was estimated based on movement onset conditions and reaction times. The movement onset conditions were: (1) a simple reaction time task with a visual stimulus, (2) a Go/NoGo task with different colored stimuli and (3) a Go/NoGo task with different position stimuli. Dipole source estimation was done, and the time course of the motor activity was calculated. The results showed that not only the visual response but also the contralateral motor activity was evoked by the stimulus in all cases, and even when the NoGo stimulus was given. The motor activity in the primary motor cortex was conjectured to consist of two dominant components: the first component for the movement preparation and the second component for the movement execution. Because the first component happened with a constant delay time from the stimulus even in the NoGo case, the first component, coming through a fast pathway for signals from visual stimulus processing to the motor cortex without any intervening cognitive processing, was conjectured to make the motor cortex prepare for the forthcoming movement onset automatically regardless of the stimulus instruction.     

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.