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Influence of response variability on the coding performance of central gustatory neurons.

We explored how variability in responding to taste stimuli could impact the signaling of taste quality information by neuron types and individual cells in the nucleus of the solitary tract. One hundred sixty-two neurons recorded from anesthetized rats were grouped using multivariate analysis of taste responses to the following (in m): 0.5 sucrose, 0.1 NaCl, 0.01 HCl, and 0.01 quinine-HCl. Neurons fell into one of three groups corresponding to cell types that responded optimally to sucrose, NaCl, or HCl. A statistical model was used to examine whether responses observed among neurons within each group could be correctly attributed to the optimal stimulus or another tastant on the basis of spike count. Results revealed poor classification performance in some cases attributable to wide variations in the sensitivities of neurons that compose a cell type. This outcome leads us to question whether neuron types could faithfully encode a single taste quality. We then theoretically explored whether a hypothetical observer of individual neurons could discriminate between spiking rates to different tastants during the first second of stimulus processing. Spike rate was found to be an unreliable predictor of stimulus quality for each neuron tested. However, additional analyses suggested that taste stimuli could be identified by a reader that attends to the relative spiking activities of different kinds of neurons in parallel. Rather than assigning meaning to individual neurons or categories of them, central gustatory circuits may signal quality information using a strategy that involves the relative activities of neurons with different sensitivities to tastants.

Action Potentials↗

No relationship between sequence variation in protein coding regions of the Tas1r3 gene and saccharin preference in rats.

Nearly all mammalian species like sweet-tasting foods and drinks, but there are differences in the degree of 'sweet tooth' both between species and among individuals of the same species. Some individual differences can be explained by genetic variability. Polymorphisms in a sweet taste receptor (Tas1r3) account for a large fraction of the differences in consumption of sweet solutions among inbred mouse strains. We wondered whether mice and rats share the same Tas1r3 alleles, and whether this gene might explain the large difference in saccharin preference among rats. We conducted three experiments to test this. We examined DNA sequence differences in the Tas1r3 gene among rats that differed in their consumption of saccharin in two-bottle choice tests. The animals tested were from an outbred strain (Sprague-Dawley; experiment 1), selectively bred to be high- or low-saccharin consumers (HiS and LoS; experiment 2), or from inbred strains with established differences in saccharin preference (FH/Wjd and ACI; experiment 3). Although there was considerable variation in saccharin preference among the rats there was no variation in the protein-coding regions of the Tas1r3 gene. DNA variants in intronic regions were detected in 1 (of 12) outbred rat with lower-than-average saccharin preference and in the ACI inbred strain, which also has a lower saccharin preference than the FH/Wjd inbred partner strain. Possible effects of these intronic nucleotide variants on Tas1r3 gene expression or the presence of T1R3 protein in taste papillae were evaluated in the ACI and FH/Wjd strains. Based upon the results of these studies, we conclude that polymorphisms in the protein-coding regions of the sweet receptor gene Tas1r3 are uncommon and do not account for individual differences in saccharin preference for these strains of rats. DNA variants in intron 4 and 5 are more common but appear to be innocuous.

Animals↗

Spike train metrics.

Quantifying similarity and dissimilarity of spike trains is an important requisite for understanding neural codes. Spike metrics constitute a class of approaches to this problem. In contrast to most signal-processing methods, spike metrics operate on time series of all-or-none events, and are, thus, particularly appropriate for extracellularly recorded neural signals. The spike metric approach can be extended to multineuronal recordings, mitigating the 'curse of dimensionality' typically associated with analyses of multivariate data. Spike metrics have been usefully applied to the analysis of neural coding in a variety of systems, including vision, audition, olfaction, taste and electric sense.

Action Potentials↗

Patient evaluation of the hotel function of hospitals.

BACKGROUND: A means of measuring patient satisfaction is essential in the effort to improve the quality of health care delivered in our nation's hospitals. Accurate feedback allows employers to better meet patients' needs and allows hospital administrators to improve service delivery. Patients are empowered by having a voice in the manner in which their health care is delivered. Moreover, improving the efficiency of the health care delivery system decreases health care costs. Hospital comparisons can be made readily available to a large audience through the Internet, resulting in empowerment of the patient and a universal improvement in hospital care. This is the first multi-institutional analysis of patient satisfaction among New York City and northern New Jersey area tertiary care hospitals. In this study, we evaluated the patient-assessed hotel function of hospitals in a single geographic region to determine whether clinically and statistically significant differences would be revealed that could provide beneficial information to stakeholders in the healthcare system. METHODS: Patients (n = 261) who had spent a night during the past year in one of eleven hospitals within 60 miles of New York City were chosen at random from doctors' waiting rooms. On average, 24 patients from each hospital were surveyed. They were asked to complete a questionnaire that rated the various departments in the hospital on qualities such as courtesy, promptness, and cleanliness. The questionnaire also rated important characteristics of the patient experience, such as the ease of parking and the taste of the food. Each item on the survey was coded on a scale of 1 to 10 with 10 being the most positive response. The 26 specific questions were divided into 14 domains. Averages in each domain were compared by gender, age, and hospital identity, attractiveness, and setting. All statistical calculations were performed using SPSS/PC, and means were compared using t-tests. RESULTS: Analysis designed to evaluate outcomes between each of the possible 54 pairs of hospitals comparisons revealed statistically significant differences as often as 44% of the time in some outcomes measures (logistics), but as rarely as 7% of the time in others (billing function). Clinically significant differences (>2 units per scale) were frequently evident, although the ranges differed dramatically depending on the domains surveyed. Although age, gender, and race/ethnicity were generally not predictive of satisfaction, non-urban setting was correlated with greater patient satisfaction. CONCLUSION: By having access to patient satisfaction comparisons among hospitals, patients are empowered to make better choices, employers can identify and adapt to patient preferences, and administrators can improve the services delivered and decrease health care costs by improving efficiency. Although our study was somewhat limited by patient selection biases, the study's results suggest that Internet-based tools of comparison will enable patients to make free and informed decisions about their health care by comparing local hospitals and voting on their impressions of the facilities from which they receive care.

Data Collection↗

Chemoreceptors expressed in taste, olfactory and male reproductive tissues.

We have identified three genes encoding previously uncharacterized chemoreceptors expressed in rat sensory and reproductive tissues using a reverse transcriptase polymerase chain reaction strategy. Degenerate oligonucleotides designed from conserved sequences in the rat olfactory receptor gene family were used to amplify candidate receptor gene products expressed in taste tissue. Sequence analysis of three distinct clonal isolates revealed that the gene products from taste bud were 30-75% identical to previously identified olfactory receptor genes. The genomic coding sequences predicted protein structures with seven membrane spanning regions that have strong conservation relative to other members of the G-protein-coupled olfactory receptor gene family. Transcripts for each of the three gene products were detected exclusively in taste, olfactory and male reproductive tissue. Sequence analysis of the polymerase chain reaction products confirmed that identical transcripts were expressed in all three tissues. These findings are the first demonstration that identical olfactory receptor-like gene are expressed in three distinct tissues.

Amino Acid Sequence↗

Neurobiology of the gustatory systems of Drosophila and some terrestrial insects.

Insects have been favorites for the study of taste perception in the last few decades. They have been used for anatomical, behavioral, developmental, genetic, and physiological studies related to gustation and feeding response. Several genes known to affect the formation of gustatory sensilla or alter the feeding behavior of insects such as Drosophila are known. Studies related to signal transduction, coding of gustatory information, and the nature and constitution of genes involved in taste perception have also been taken up with insects in recent years. The understanding of basic mechanisms of taste perception in insects is likely to lead to better management of useful as well as harmful insects.

Animals↗

Gustatory responses of cortical neurons in rats. III. Neural and behavioral measures compared.

The responses of 39 cortical neurons to 13 kinds of taste stimuli including the four putative basic taste solutions (sucrose, NaCl, HCl, and quinine HCl) applied to the anterior portion of the tongue were recorded extracellularly in lightly anesthetized rats. The neural responses were analyzed in terms of the four hypotheses of quality coding: across-neuron response pattern, labeled-line, matrix pattern, and across-region response pattern notions. Animals were given a conditioned taste aversion to one of the 11 stimuli by pairing it with a gastrointestinal illness caused by intraperitoneal injection of 0.15 M LiCl. Behavioral taste profiles were constructed for each stimulus from the suppression of rate of drinking, which indicates the extent of generalization of aversion to each of the four basic taste stimuli. Neural taste profiles of each taste stimulus, which indicate the relation of the taste of a stimulus to each taste of the four basic stimuli, differed more or less depending on the kind of quality-coding notions employed. Among the four analyses, across-region correlation coefficients that were derived from an across-region response-pattern theory showed the highest correlation with the behavioral suppression rates. Therefore we conclude that processing of taste information in the cortex involves differences in both response magnitude across neurons and the spatial localization of those neurons. Fluid intake per day of each of the 12 taste solutions was measured by the single-bottle preference method. When the amount of intake was described in terms of an hedonic index (HI), which indicates the hedonic aspect of the taste of each solution, HI's for sucrose, NaCl, HCl, and quinine were 1.17, 0.43, -0.49, and -0.89, respectively. These values represent the degree of deviation of solution intake above (i.e., preferable) or below (aversive) the standard water intake. Then, HI's were calculated for each of the 12 taste stimuli based on the neural taste profiles and actual HI's for each of the four basic taste stimuli. The correlations between the calculated and the actual (or behaviorally obtained) HI's were very high (ranging from 0.832 to 0.941). This result suggests that the hedonic dimension of taste can be matched well by any one of the four proposed hypotheses.

Animals↗

Identification of G protein-coupled receptor genes from the human genome sequence.

We have identified novel G protein-coupled receptors (GPCRs) with no introns in the coding region from the human genome sequence: 322 olfactory receptors; 22 taste receptors; 128 registered GPCRs for endogenous ligands; 50 novel GPCR candidates homologous to registered GPCRs for endogenous ligands; and 59 novel GPCR candidates not homologous to registered GPCRs. The total number of GPCRs with and without introns in the human genome was estimated to be approximately 950, of which 500 are odorant or taste receptors and 450 are receptors for endogenous ligands.

Adult↗

Concept of neuron types in gustation in the rat.

1. In taste neurophysiology, from Pfaffmann's (49, 50) pioneering work until the present, the possibility of types of neurons corresponding in some sense with the "primary" taste qualities of Henning (33) has been entertained: recently types of gustatory neurons in peripheral nerves have been established according to which of the four classical stimuli is the "best stimulus." However, considerable variation occurs in the response profiles within neurons classified as belonging to the same type. The purpose of this research is to determine, using mathematical techniques where appropriate, if the within-type variation is spurious or, instead, indicates the absence of a typology of taste neurons. The data used were counts of the spike discharges of 50 individual taste neurons in the nucleus of the solitary tract of the rat, evoked by 32 diverse chemical stimuli. 2. Using as input the matrix of Pearson r correlation coefficients calculated for the responses of all pairings of neurons to all stimuli, multidimensional scaling analysis revealed a two-dimensional space in which no clear groupings of neurons occurred. 3. In a hierarchical cluster analysis of the neuron response profile similarities, no evidence of grouping was found, suggesting a more-or-less continuous variation among neurons. 4. When the organization of the 32 stimuli utilized was studied by the same techniques, no clear evidence for stimulus types was found, although the possibility of two stimulus types--"sweet" and "nonsweet"--was raised. 5. Construction of a joint neuron-stimulus space supported a spatial model of taste neuron-stimulus interaction, while analysis of the number and pattern of high correlations among neurons--even after allowance for attenuation due to measurement error--failed to support the notion of types of taste neurons with identical response profiles. 6. Aspects of the logical role of types of neurons in gustatory coding were discussed, and the results and methods of the present investigation were related to classification schemes for neurons in general. Suggestions for a formal taxonomy of neurons were given. 7. It should be emphasized that the present study and conclusions are of second-order, CNS neurons, whereas the studies advocating the presence of neurons types were of peripheral neurons. Taken together, the implication to be drawn from these studies is that if neural types do exist in peripheral taste nerves, the typology is lost at the first synapse and is thus unavailable to the CNS for coding purposes, at least in the rat.

Animals↗

Haplotypes at the Tas2r locus on distal chromosome 6 vary with quinine taste sensitivity in inbred mice.

BACKGROUND: The detection of bitter-tasting compounds by the gustatory system is thought to alert animals to the presence of potentially toxic food. Some, if not all, bitter stimuli activate specific taste receptors, the T2Rs, which are expressed in subsets of taste receptor cells on the tongue and palate. However, there is evidence for both receptor-dependent and -independent transduction mechanisms for a number of bitter stimuli, including quinine hydrochloride (QHCl) and denatonium benzoate (DB). RESULTS: We used brief-access behavioral taste testing of BXD/Ty recombinant inbred (RI) mouse strains to map the major quantitative trait locus (QTL) for taste sensitivity to QHCl. This QTL is restricted to a ~5 Mb interval on chromosome 6 that includes 24 genes encoding T2Rs (Tas2rs). Tas2rs at this locus display in total 307 coding region single nucleotide polymorphisms (SNPs) between the two BXD/Ty RI parental strains, C57BL/6J (quinine-sensitive) and DBA/2J (quinine insensitive); approximately 50% of these mutations are silent. Individual RI lines contain exclusively either C57BL/6J or DBA/2J Tas2r alleles at this locus, and RI lines containing C57BL/6J Tas2r alleles are more sensitive to QHCl than are lines containing DBA/2J alleles. Thus, the entire Tas2r cluster comprises a large haplotype that correlates with quinine taster status. CONCLUSION: These studies, the first using a taste-salient assay to map the major QTL for quinine taste, indicate that a T2R-dependent transduction cascade is responsible for the majority of strain variance in quinine taste sensitivity. Furthermore, the large number of polymorphisms within coding exons of the Tas2r cluster, coupled with evidence that inbred strains exhibit largely similar bitter taste phenotypes, suggest that T2R receptors are quite tolerant to variation.

Animals↗

Facial Expressivity at 4 Months: A Context by Expression Analysis.

The specificity predicted by differential emotions theory (DET) for early facial expressions in response to 5 different eliciting situations was studied in a sample of 4-month-old infants (n = 150). Infants were videotaped during tickle, sour taste, jack-in-the-box, arm restraint, and masked-stranger situations and their expressions were coded second by second. Infants showed a variety of facial expressions in each situation; however, more infants exhibited positive (joy and surprise) than negative expressions (anger, disgust, fear, and sadness) across all situations except sour taste. Consistent with DET-predicted specificity, joy expressions were the most common in response to tickling, and were less common in response to other situations. Surprise expressions were the most common in response to the jack-in-the-box, as predicted, but also were the most common in response to the arm restraint and masked-stranger situations, indicating a lack of specificity. No evidence of predicted specificity was found for anger, disgust, fear, and sadness expressions. Evidence of individual differences in expressivity within situations, as well as stability in the pattern across situations, underscores the need to examine both child and contextual factors in studying emotional development. The results provide little support for the DET postulate of situational specificity and suggest that a synthesis of differential emotions and dynamic systems theories of emotional expression should be considered.

Journal Article↗

The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception.

Individual differences in perception are ubiquitous within the chemical senses: taste, smell, and chemical somesthesis . A hypothesis of this fact states that polymorphisms in human sensory receptor genes could alter perception by coding for functionally distinct receptor types . We have previously reported evidence that sequence variants in a presumptive bitter receptor gene (hTAS2R38) correlate with differences in bitterness recognition of phenylthiocarbamide (PTC) . Here, we map individual psychogenomic pathways for bitter taste by testing people with a variety of psychophysical tasks and linking their individual perceptions of the compounds PTC and propylthiouracil (PROP) to the in vitro responses of their TAS2R38 receptor variants. Functional expression studies demonstrate that five different haplotypes from the hTAS2R38 gene code for operatively distinct receptors. The responses of the three haplotypes we also tested in vivo correlate strongly with individuals' psychophysical bitter sensitivities to a family of compounds. These data provide a direct molecular link between heritable variability in bitter taste perception to functional variations of a single G protein coupled receptor that responds to compounds such as PTC and PROP that contain the N-C=S moiety. The molecular mechanisms of perceived bitterness variability have therapeutic implications, such as helping patients to consume beneficial bitter-tasting compounds-for example, pharmaceuticals and selected phytochemicals.

Animals↗

Understanding the food choice process of adolescents in the context of family and friends.

PURPOSE: To understand from the adolescents' own perspective the decision-making processes they use to make food choices on an everyday basis and how they resolve their need for personal control over food choices with the values of family and peers. METHODS: A sample of 108 adolescents, aged 11-18 years, were individually interviewed. They were asked in a simulated task to choose a lunch from a menu of offerings and give reasons for their choices. In addition, open-ended questions probed for meal structures, dinners, perceptions of degree of choice, role of family and peers. Interviews were audio-taped, transcribed, coded, and analyzed for emerging themes. RESULTS: Primary food choice criteria were taste, familiarity/habit, health, dieting, and fillingness. Lunches had a definite structure, and lunches differed from dinners. The food choice process involved personal food decision-making rules such as trade-offs among choice criteria within a meal (e.g., taste for core items and health for secondary items), and between lunches with peers (taste) and family dinners (health); negotiation patterns with the family (autonomy versus family needs); and interactions with peers. CONCLUSIONS: The food choice process for most adolescents seemed to involve cognitive self-regulation where conflicting values for food choices were integrated and brought into alignment with desired consequences. Educators and practitioners should recognize the dilemmas adolescents face in making food choices and help them develop strategies for balancing less healthful with more healthful food items, through: (a) personal food decision-making rules, (b) effective negotiations with family members; and (c) appropriate interaction patterns with peers.

Adolescent↗

Gustatory neural coding in the monkey cortex: stimulus quality.

1. Extracellular action potentials were recorded from 50 single neurons in the insular-opercular cortex of two alert cynomolgus monkeys during gustatory stimulation of the tongue and palate. 2. Sixteen stimuli, including salts, sugars, acids, alkaloids, monosodium glutamate, and aspartame, were chosen to represent a wide range of taste qualities. Concentrations were selected to elicit a moderate gustatory response, as determined by reference to previous electrophysiological data or to the human psychophysical literature. 3. The cortical region over which taste-evoked activity could be recorded included the frontal operculum and anterior insula, an area of approximately 75 mm3. Taste-responsive cells constituted 50 (2.7%) of the 1,863 neurons tested. Nongustatory cells responded to mouth movement (20.7%), somatosensory stimulation of the tongue (9.6%), stimulus approach or anticipation (1.7%), and tongue extension (0.6%). The sensitivities of 64.6% of these cortical neurons could not be identified by our stimulation techniques. 4. Taste cells had low spontaneous activity levels (3.7 +/- 3.0 spikes/s, mean +/- SD) and showed little inhibition. They were moderately broadly tuned, with a mean entropy coefficient of 0.76 +/- 0.17. Excitatory responses were typically not robust. 5. Hierarchical cluster analysis was used to determine whether neurons could be divided into discrete types, as defined by their response profiles to the entire stimulus array. There was an apparent division of response profiles into four general categories, with primary sensitivities to sodium (n = 18), glucose (n = 15), quinine (n = 12), and acid (n = 5). However, these categories were not statistically independent. Therefore the notion of functionally distinct neuron types was not supported by an analysis of the distribution of response profiles. It was the case, however, that neurons in the sodium category could be distinguished from other neurons by their relative specificity. 6. The similarity among the taste qualities represented by this stimulus array was assessed by calculating correlations between the activity profiles they elicited from these 50 neurons. The results generally confirmed expectations derived from human psychophysical studies. In a multidimensional representation of stimulus similarity, there were groups that contained acids, sodium salts, and chemicals that humans label bitter and sweet. 7. The small proportion of insular-opercular neurons that are taste sensitive and the low discharge rates that taste stimuli are able to evoke from them suggest a wider role for this cortical area than just gustatory coding.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Divergence of T2R chemosensory receptor families in humans, bonobos, and chimpanzees.

T2R (Tas2R) genes encode a family of G protein-coupled gustatory receptors, several involved in bitter taste perception. So far, few ligands for these receptors have been identified, and the specificity of most T2Rs is unclear. Differences between individual T2Rs result in altered taste perception in either specificity or sensitivity. All 33 human T2Rs are characterized by significant sequence homology. However, with a total of eight pseudogenes and >83 coding region single-nucleotide polymorphisms, the family displays broad diversity. The underlying variability of individual T2Rs might be the source for personalized taste perception. To test this hypothesis and also to identify T2Rs that possibly function beyond bitter taste, we compared all human T2R genes with those of the closely related primate species Pan paniscus (bonobo) and Pan troglodytes (chimpanzee). The differences identified range from large sequence alterations to nonsynonymous and synonymous changes of single base pairs. In contrast to olfactory receptors, no human-specific loss of the amount of functional genes was observed. Taken together, the results indicate ongoing evolutionary diversification of T2R receptors and a role for T2Rs in dietary adaptation and personalized food uptake.

Adenosine↗

On a neural mechanism for cortical processing of taste quality in the rat.

The responses of 31 chorda tympani fibers and 47 cortical neurons were recorded in response to 6 concentrations of NaCl, and single concentrations of sucrose, HCl, and quinine hydrochloride solutions applied to the anterior portion of the tongue in rats. The neural responses were analyzed in terms of the two hypotheses of quality coding: across-neuron response pattern and across-region response pattern notions. In a behavioral experiment, animals were given a conditioned taste aversion to one of 5 concentrations of NaCl solution by pairing it with a gastrointestinal illness caused by i.p. injection of 0.15 M LiCl. Behavioral taste profiles were constructed for each stimulus from the suppression of drinking, which indicates the extent of generalization of aversion to each of the 4 basic taste stimuli. Among the two neural analyses employed for the chorda tympani and cortical units, across-region correlation coefficients for cortical neurons that were derived from the across-region response pattern theory showed the highest correlation (r = 0.89) with the behavioral suppression rates. Across-neuron correlation coefficients in the chorda tympani fibers also showed a good correlation (r = 0.81) with the behavioral data. However, the taste profile for 1.0 M NaCl in chorda tympani fibers was very similar to that for the lower concentrations of NaCl, in spite of the suggestion from the behavioral experiment and the neural analyses of cortical responses that 1.0 M NaCl has HCl and quinine components besides the NaCl component. The present result confirmed the idea that processing of taste information in the cortex involves differences in both response magnitude across neurons and the spatial localization of those neurons.

Animals↗

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.

Journal Article↗

Differential calming responses to sucrose taste in crying infants with and without colic.

BACKGROUND: Colic is a behavioral syndrome of early infancy of unknown etiology whose core symptom is increased crying. Both clinical anecdotal descriptions and controlled observations converge in suggesting that a defining characteristic of the crying behavior is the longer duration of the crying bouts, especially during the second month of life when colic is at its peak. This implies that, once infants with colic begin crying, they do not calm as well as infants without colic. To investigate this difference objectively, we used response to sucrose taste as a probe of colic-normal differences in regulation of crying for three reasons. First, sucrose taste has been shown to be a potent regulator of crying in human newborns. Second, convergent evidence from studies in both nonhuman and human infants suggests that sucrose calming reflects the function of central distress regulatory systems that are opioid-dependent. Third, effectiveness of sucrose calming diminishes in normal infants by 4 to 6 weeks of age, consistent with the developmental increase in crying duration common to infants with and without colic. Consequently we predicted that, if the regulation of crying by sucrose taste is relevant to the crying of infants with colic, calming responses to sucrose taste should be less effective in 6-week-old infants with colic compared with those without. OBJECTIVES: To investigate the clinical observation that infants with and without colic differ in their ability to regulate their crying behavior, our primary objective was to determine if there were differential crying responses to intraoral sucrose tastes (relative to water) in crying infants with and without colic. Based on previous studies of calming responses to sucrose taste, it was predicted that sucrose-specific calming before a feeding would be less effective in infants with colic than in those without. A secondary and more exploratory aim was to assess calming responses to sucrose (relative to water) on spontaneous crying after a feed in both groups. METHODS: Nineteen infants meeting modified Wessel's criteria for colic were compared with 19 age- and sex-matched normal infants without colic in a within-subject controlled observation of calming and mouthing responses to both intraoral sucrose and water tastes. Both before and after two feedings on the same day, each infant was observed until she or he cried continuously for 15 consecutive seconds, at which time three 250-microL tastes of 48% sucrose solution or sterile water were administered 30 seconds apart, and infant responses videotaped. Outcome measures derived from second-by-second coding of the videorecordings were percent time crying per minute for 4 minutes and percent time mouthing per minute for 2 minutes after stimulus administration. RESULTS: As predicted, the crying of infants with colic was less affected than the crying of infants without colic after sucrose but not water tastes before feedings. After feedings, the crying of infants with colic was less affected than the crying of infants without colic for both sucrose and water tastes, and sucrose was more effective than water in both groups of infants. These calming differences could not be attributed to differences in mouthing responses because the calming effects persisted after mouthing ceased, and there were no differences in mouthing responses between groups before or after feedings. CONCLUSIONS: As in newborns, a significant calming effect of sucrose taste that persisted beyond the cessation of mouthing could be elicited in crying 6-week-old infants, but it required a stronger taste stimulus to do so. As predicted, infants with colic were less effectively calmed by sucrose taste than infants without. These differential effects could not be accounted for by differences in crying when the stimulus was applied or by differences in mouthing behavior. Before a feed, these differences in calming were specific to sucrose taste. After a feed, infants with c

Colic↗