Maria G. Veldhuizen

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. Hum Brain Mapp, 2011.

Sense of smell disorder and health-related quality of life

OBJECTIVES To compare health-related quality of life and depression between individuals with an inability to smell (anosmia) and a comparison group of individuals with a normal sense of smell. METHODS Ninety individuals from an anosmia organization (anosmia based on self-report) were compared to 89 individuals with a normal sense of smell. The SF-36 and Beck Depression Inventory-II-NL (BDI-II-NL) were administered, along with the Questionnaire for Olfactory Dysfunction (QOD) to assess the degree of problems in daily life related to the smell impairment. RESULTS Compared to the comparison group, scores in the anosmia group differed on: the QOD-subscale Life Quality (related to tasting and smelling: p < .001) and Parosmia (Smelling odors as different: p < .001); and the SF-36 subscales of Social Functioning, Vitality, Mental Health and General Health (ps < .05). Persons with anosmia scored higher on the BDI-II-NL than persons from the comparison group (p < .01). DISCUSSION Once a smell dysfunction is recognized, interventions aiming at dealing with the loss of smell as a source of information and enjoyment, as well as at improvement of emotional wellbeing, social interaction, energy, and depression should be considered.

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.

The Role of the Human Orbitofrontal Cortex in Taste and Flavor Processing

Abstract: The human orbitofrontal cortex (OFC) plays an important role in representing taste, flavor, and food reward. The primary role of the OFC in taste is thought to be the encoding of affective value and the computation of perceived pleasantness. The OFC also encodes retronasal olfaction and oral somatosensation. During eating, distinct sensory inputs fuse into a unitary flavor percept, and there is evidence that this percept is encoded in the orbital cortex. Studies examining the effect of internal state on neural representation of food and drink further suggest that processing in the OFC is critical for representing the reward value of foods. Thus, it is likely that, in addition to serving as higher‐order gustatory cortex, the OFC integrates multiple sensory inputs and computes reward value to guide feeding behavior.

Basolateral Amygdala Response to Food Cues in the Absence of Hunger Is Associated with Weight Gain Susceptibility

In rodents, food-predictive cues elicit eating in the absence of hunger (Weingarten, 1983). This behavior is disrupted by the disconnection of amygdala pathways to the lateral hypothalamus (Petrovich et al., 2002). Whether this circuit contributes to long-term weight gain is unknown. Using fMRI in 32 healthy individuals, we demonstrate here that the amygdala response to the taste of a milkshake when sated but not hungry positively predicts weight change. This effect is independent of sex, initial BMI, and total circulating ghrelin levels, but it is only present in individuals who do not carry a copy of the A1 allele of the Taq1A polymorphism. In contrast, A1 allele carriers, who have decreased D2 receptor density (Blum et al., 1996), show a positive association between caudate response and weight change. Regardless of genotype, however, dynamic causal modeling supports unidirectional gustatory input from basolateral amygdala (BLA) to hypothalamus in sated subjects. This finding suggests that, as in rodents, external cues gain access to the homeostatic control circuits of the human hypothalamus via the amygdala. In contrast, during hunger, gustatory inputs enter the hypothalamus and drive bidirectional connectivity with the amygdala. These findings implicate the BLA–hypothalamic circuit in long-term weight change related to nonhomeostatic eating and provide compelling evidence that distinct brain mechanisms confer susceptibility to weight gain depending upon individual differences in dopamine signaling.

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.

Decreased caudate response to milkshake is associated with higher body mass index and greater impulsivity

Previous investigations consistently report a negative association between body mass index (BMI) and response in the caudate nucleus during the consumption of palatable and energy dense food. Since this response has also been linked to weight gain, we sought to replicate this finding and determine if the reduced response is associated with measures of impulsivity or food reward. Two studies were conducted in which fMRI was used to measure brain response to milkshake and a tasteless control solution. In Study 1 (n=25) we also assessed self-reported impulsivity, willingness to work for food, and subjective experiences of the pleasantness of milkshake taste and aroma. Replicating prior work, we report a negative association between BMI and brain response to milkshake vs. tasteless in the caudate nucleus. The opposite pattern was observed in the ventral putamen, with greater response observed in the 13 overweight compared to the 12 healthy weight subjects. Regression of brain response against impulsivity and food reward measures revealed one significant association: in the overweight but not healthy weight group self-reported impulsivity was negatively associated with caudate response to milkshake. In Study 2 (n=14), in addition to assessing brain response to milkshake and tasteless solutions subjects completed a go/no-go task outside the scanner. As predicted, we identified an inverse relationship between caudate response to milkshake vs. tasteless and failure to inhibit responses on the no-go trials. We conclude that the inverse correlation between BMI and caudate response to milkshake is associated with impulsivity but not food reward. These findings suggest that response to milkshake in the dorsal striatum may be related to weight gain by promoting impulsive eating behavior.

Metabolic Regulation of Brain Response to Food Cues

Identification of energy sources depends upon the ability to form associations between food cues and nutritional value. As such, cues previously paired with calories elicit neuronal activation in the nucleus accumbens (NAcc), which reflects the reinforcing value of food. The identity of the physiological signals regulating this response remains elusive. Using fMRI, we examined brain response to noncaloric versions of flavors that had been consumed in previous days with either 0 or 112.5 calories from undetected maltodextrin. We report a small but perceptually meaningful increase in liking for the flavor that had been paired with calories and find that change in liking was associated with changes in insular responses to this beverage. In contrast, NAcc and hypothalamic response to the calorie-paired flavor was unrelated to liking but was strongly associated with the changes in plasma glucose levels produced by ingestion of the beverage when consumed previously with calories. Importantly, because each participant ingested the same caloric dose, the change in plasma glucose depended upon individual differences in glucose metabolism. We conclude that glucose metabolism is a critical signal regulating NAcc and hypothalamic response to food cues, and that this process operates independently from the ability of calories to condition liking.

The neural signature of satiation is associated with ghrelin response and triglyceride metabolism.

Eating behavior is guided by a complex interaction between signals conveying information about energy stores, food availability, and palatability. How peripheral signals regulate brain circuits that guide feeding during sensation and consumption of a palatable food is poorly understood. We used fMRI to measure brain response to a palatable food (milkshake) when n=32 participants were fasted and fed with either a fixed-portion or ad libitum meal. We found that larger post-prandial reductions in ghrelin and increases in triglycerides were associated with greater attenuation of response to the milkshake in brain regions regulating reward and feeding including the midbrain, amygdala, pallidum, hippocampus, insula and medial orbitofrontal cortex. Satiation-induced brain responses to milkshake were not related to acute changes in circulating insulin, glucose, or free fatty acids. The impact of a meal on the response to milkshake in the midbrain and dorsolateral prefrontal cortex differed depending upon whether meal termination was fixed or volitional, irrespective of the amount of food consumed. We conclude that satiation-induced changes in brain response to a palatable food are strongly and specifically associated with changes in circulating ghrelin and triglycerides and by volitional meal termination.

Coactivation of Gustatory and Olfactory Signals in Flavor Perception

It is easier to detect mixtures of gustatory and olfactory flavorants than to detect either component alone. But does the detection of mixtures exceed the level predicted by probability summation, assuming independent detection of each component? To answer this question, we measured simple response times (RTs) to detect brief pulses of one of 3 flavorants (sucrose [gustatory], citral [olfactory], sucrose-citral mixture) or water, presented into the mouth by a computer-operated, automated flow system. Subjects were instructed to press a button as soon as they detected any of the 3 nonwater stimuli. Responses to the mixtures were faster (RTs smaller) than predicted by a model of probability summation of independently detected signals, suggesting positive coactivation (integration) of gustation and retronasal olfaction in flavor perception. Evidence for integration appeared mainly in the fastest 60% of the responses, indicating that integration arises relatively early in flavor processing. Results were similar when the 3 possible flavorants, and water, were interleaved within the same session (experimental condition), and when each flavorant was interleaved with water only (control conditions). This outcome suggests that subjects did not attend selectively to one flavor component or the other in the experimental condition and further supports the conclusion that (late) decisional or attentional strategies do not exert a large influence on the gustatory-olfactory flavor integration.