Cue Response Research Articles

Homeostatic circuits selectively gate food cue responses in insular cortex.

Physiological needs bias perception and attention to relevant sensory cues. This process is 'hijacked' by drug addiction, causing cue-induced cravings and relapse. Similarly, its dysregulation contributes to failed diets, obesity, and eating disorders. Neuroimaging studies in humans have implicated insular cortex in these phenomena. However, it remains unclear how 'cognitive' cortical representations of motivationally relevant cues are biased by subcortical circuits that drive specific motivational states. Here we develop a microprism-based cellular imaging approach to monitor visual cue responses in the insular cortex of behaving mice across hunger states. Insular cortex neurons demonstrate food-cue-biased responses that are abolished during satiety. Unexpectedly, while multiple satiety-related visceral signals converge in insular cortex, chemogenetic activation of hypothalamic 'hunger neurons' (expressing agouti-related peptide (AgRP)) bypasses these signals to restore hunger-like response patterns in insular cortex. Circuit mapping and pathway-specific manipulations uncover a pathway from AgRP neurons to insular cortex via the paraventricular thalamus and basolateral amygdala. These results reveal a neural basis for state-specific biased processing of motivationally relevant cues.

The role of hunger state and dieting history in neural response to food cues: An event-related potential study

A history of dieting to lose weight has been shown to be a robust predictor of future weight gain. A potential factor in propensity towards weight gain is the nature of people's reactions to the abundance of highly palatable food cues in the environment. Event Related Potentials (ERPs) have revealed differences in how the brain processes food cues between obese and normal weight individuals, as well as between restrained and unrestrained eaters. However, comparisons by weight status are not informative regarding whether differences predate or follow weight gain in obese individuals and restrained eating has not consistently been found to predict future weight gain. The present study compared ERP responses to food cues in non-obese historic dieters (HDs) to non-obese never dieters (NDs). HDs showed a blunted N1 component relative to NDs overall, and delayed N1 and P2 components compared to NDs in the hungry state, suggesting that early, perceptual processing of food cues differs between these groups, especially when food-deprived. HDs also showed a more hunger-dependent sustained ERP (LPP) compared to NDs. Future research should test ERP-based food cue responsivity as a mediator between dieting history and future weight gain to better identify those most at risk for weight gain as well as the nature of their vulnerability.

Running promotes spatial bias independently of adult neurogenesis.

Different memory systems offer distinct advantages to navigational behavior. The hippocampus forms complex associations between environmental stimuli, enabling flexible navigation through space. In contrast, the dorsal striatum associates discrete cues and favorable behavioral responses, enabling habit-like, automated navigation. While these two systems often complement one another, there are instances where striatal-dependent responses (e.g. approach a cue) conflict with hippocampal representations of spatial goals. In conflict situations, preference for spatial vs. response strategies varies across individuals and depends on previous experience, plasticity and the integrity of these two memory systems. Here, we investigated the role of adult hippocampal neurogenesis and exercise on mouse search strategies in a water maze task that can be solved with either a hippocampal-dependent place strategy or a striatal-dependent cue-response strategy. We predicted that inhibiting adult neurogenesis would impair hippocampal function and shift behavior towards striatal-dependent cue responses. However, blocking neurogenesis in a transgenic nestin-TK mouse did not affect strategy choice. We then investigated whether a pro-neurogenic stimulus, running, would bias mice towards hippocampal-dependent spatial strategies. While running indeed promoted spatial strategies, it did so even when neurogenesis was inhibited in nestin-TK mice. These findings indicate that exercise-induced increases in neurogenesis are not always required for enhanced cognitive function. Furthermore, our data identify exercise as a potentially useful strategy for promoting flexible, cognitive forms of memory in habit-related disorders that are characterized by excessive responding to discrete cues.

Differential regulation of muscle protein turnover in response to emphysema and acute pulmonary inflammation

BackgroundExacerbations in COPD are often accompanied by pulmonary and systemic inflammation, and associated with increased susceptibility to and prevalence of weight loss and muscle wasting. Muscle mass loss during disease exacerbations may contribute to emphysema-associated muscle atrophy. However, whether pulmonary inflammation in presence of emphysema differentially affects skeletal muscle, including protein synthesis and degradation signaling pathways has not previously been addressed. The aims of this study were to 1) develop a mouse model of disease exacerbation-associated muscle wasting, 2) evaluate whether emphysema and muscle wasting can be monitored non-invasively and 3) assess alterations in muscle protein turnover regulation.MethodsEmphysema was induced by three, weekly intra-tracheal (IT) elastase (E) or vehicle control (vc) instillations, followed by one single IT-LPS bolus (L) or vc instillation to mimic pulmonary inflammation-driven disease exacerbation. Consequently, four experimental groups were defined: vc/vc (‘C’), E/vc (‘E’), vc/LPS (‘L’), E/LPS (‘E + L’). Using micro cone-beam CT-scans, emphysema development and muscle mass changes were monitored, and correlated to muscle weight 48 h after LPS instillation. Protein turnover signaling was assessed in muscle tissue collected 24 h post LPS instillation.ResultsMicro-CT imaging correlated strongly with established invasive measurements of emphysema and muscle atrophy. Pulmonary inflammation following LPS instillation developed irrespective of emphysema and body and muscle weight were similarly reduced in the ‘L’ and ‘E + L’ groups. Accordingly, mRNA and protein expression levels of genes of the ubiquitin-proteasome pathway (UPS) and the autophagy-lysosomal pathway (ALP) were upregulated in skeletal muscle following IT-LPS (‘L’ and ‘E + L’). In contrast, mTOR signaling, which controls ALP and protein synthesis, was reduced by pulmonary inflammation (‘L’ and ‘E + L’) as well as emphysema as a single insult (‘E’) compared to control.ConclusionChanges in lung tissue density and muscle mass can be monitored non-invasively to evaluate emphysema and muscle atrophy longitudinally. Acute loss of muscle mass evoked by pulmonary inflammation is similar in control and emphysematous mice. Although muscle atrophy cues in response to pulmonary inflammation are not altered by emphysema, emphysema itself affects protein synthesis and ALP signaling, which may interfere with muscle mass recovery and impair maintenance of muscle mass in emphysema.

Anti-predator responses of amphipods are more effective in the presence of conspecific chemical cues

Predators have been widely demonstrated to influence developmental plasticity in aquatic prey. We investigated the body size of the amphipod Hyalella azteca raised with predatory sunfish by exposing solitary or groups of three amphipods to sunfish kairomones or a control for 30 days. Field studies indicate that small body size in H. azteca is likely an adaptive response to size-selective sunfish predation. Grouped amphipods chronically exposed to the kairomones had significantly smaller body lengths than grouped amphipods exposed to controls, while individual amphipods exhibited no significant differences. Behavioral trials revealed that grouped amphipods sought refuge less than solitary amphipods. To examine if a conspecific chemical cue was related to the reduction in body size of the grouped amphipods exposed to kairomones, individual amphipods were exposed to a combination of conspecific chemical cues and kairomones or to controls for 30 days. Amphipods exposed to kairomones in combination with conspecific cues had significantly smaller body length than amphipods exposed to conspecific cues alone. These results mirrored the group versus individual exposure experiment, suggesting that a conspecific chemical cue is required to induce an anti-predator response. The present study highlights the importance of conspecific cues for plastic responses to predators.

Not equal in the face of habitat change: closely related fishes differ in their ability to use predation-related information in degraded coral.

Coral reefs are biodiversity hotpots that are under significant threat due to the degradation and death of hard corals. When obligate coral-dwelling species die, the remaining species must either move or adjust to the altered conditions. Our goal was to investigate the effect of coral degradation on the ability of coral reef fishes to assess their risk of predation using alarm cues from injured conspecifics. Here, we tested the ability of six closely related species of juvenile damselfish (Pomacentridae) to respond to risk cues in both live coral or dead-degraded coral environments. Of those six species, two are exclusively associated with live coral habitats, two are found mostly on dead-degraded coral rubble, while the last two are found in both habitat types. We found that the two live coral associates failed to respond appropriately to the cues in water from degraded habitats. In contrast, the cue response of the two rubble associates was unaffected in the same degraded habitat. Interestingly, we observed a mixed response from the species found in both habitat types, with one species displaying an appropriate cue response while the other did not. Our second experiment suggested that the lack of responses stemmed from deactivation of the alarm cues, rather than the inability of the species to smell. Habitat preference (live coral versus dead coral associates) and phylogeny are good candidates for future work aimed at predicting which species are affected by coral degradation. Our results point towards a surprising level of variation in the ability of congeneric species to fare in altered habitats and hence underscores the difficulty of predicting community change in degraded habitats.

Erratum to: Palatable food consumption in children: interplay between (food) reward motivation and the home food environment.

To understand the importance of the home food environment on unhealthy food consumption in children high in reward sensitivity, this study tested the hypothesis that the home availability of unhealthy food moderates the effect of reward sensitivity on children’s fast-food consumption frequency, exerted via food cue responsiveness. Children between 7.5 and 14 years (n = 174, 50.6% boys) reported on reward sensitivity and food cue responsiveness (by means of the subscale ‘external eating’). Their height and weight were measured. Parents reported on their children’s fast-food consumption frequency, food cue responsiveness (by means of the subscale ‘food responsiveness’), and on the home availability of unhealthy foods. Two moderated mediation models were conducted, one with the parent- and one with the child-reported food cue responsiveness as mediator. Findings suggested that with a high home availability of unhealthy foods, (a) a higher fast-food consumption frequency was found in children high in reward sensitivity and (b) the relation between reward sensitivity and the fast-food consumption frequency was mediated by external eating. Conclusions: The findings point at the importance of the home food environment in children high in reward sensitivity. They suggest to limit the home availability of unhealthy foods.

Response Preparation, Response Conflict, and the Effects of Irrelevant Flanker Stimuli.

The present study explored how response preparation modulates the effects of response conflict as induced by irrelevant flanker stimuli. In Experiments 1 and 2, an unreliable response cue (i.e., valid in 75% of trials but invalid in 25% of trials) preceded the stimulus display containing a target stimulus and different types (i.e., identical, neutral, compatible, or incompatible) flanker stimuli. In Experiment 3, a fully reliable response cue (i.e., valid in 100% of trials) or a neutral cue preceded the stimulus display. There were two major findings. First, valid response cues always improved performance in terms of speed and accuracy when compared to invalid or neutral cues, indicating that the cues were used to selectively prepare the indicated response. Second, response preparation with unreliable response cues did not modulate flanker-induced response conflict in reaction times (RTs; and not consistently in error percentages), whereas response preparation with reliable cues eliminated flanker-induced response conflict. According to these results, only extreme levels of response preparation modulate (flanker-induced) response conflict. The results of computer simulations suggest some boundary conditions for our conclusion.

Activity patterns of serotonin neurons underlying cognitive flexibility.

Serotonin is implicated in mood and affective disorders. However, growing evidence suggests that a core endogenous role is to promote flexible adaptation to changes in the causal structure of the environment, through behavioral inhibition and enhanced plasticity. We used long-term photometric recordings in mice to study a population of dorsal raphe serotonin neurons, whose activity we could link to normal reversal learning using pharmacogenetics. We found that these neurons are activated by both positive and negative prediction errors, and thus report signals similar to those proposed to promote learning in conditions of uncertainty. Furthermore, by comparing the cue responses of serotonin and dopamine neurons, we found differences in learning rates that could explain the importance of serotonin in inhibiting perseverative responding. Our findings show how the activity patterns of serotonin neurons support a role in cognitive flexibility, and suggest a revised model of dopamine-serotonin opponency with potential clinical implications.

Higher BMI is associated with stronger effects of social cues on everyday snacking behaviour

Discretionary food choices (snacks) contribute up to a third of the daily energy intake and potentially contribute to energy imbalance and weight gain. Individual snack intake behaviour is guided by internal and external cues, with social cues (seeing others eat, being alone) consistently showing large effects. A wide body of (mainly laboratory-based) research suggests marked differences in people's response to eating cues based on BMI. Here, we show that these BMI differences in cue responsiveness also pertain to everyday snacking behaviour. In two combined ecological momentary assessment studies, 122 participants with BMIs ranging from 18.34 to 45.71 kg/m2 logged their everyday snacking behaviour in real-time over two weeks along with the presence or absence of social cues. Random-effects modelling showed that people with higher BMI were more likely to consume high-energy snacks when alone, and were more likely to consume low-energy snacks in the presence of others eating. This suggests BMI differences in cue responsiveness that are in line with impression management theory and underlines the importance of social cues for snacking behaviour and provides avenues for both theory and intervention development.

The nose knows: linking sensory cue use, settlement decisions, and post-settlement survival in a temperate reef fish.

Habitat selection by animals that migrate or disperse ultimately determines the biotic and abiotic environment they will experience in subsequent life stages. Intuitively, for habitat selection to be adaptive, animals should respond positively to cues produced by habitat characteristics that will enhance their fitness in the new environment. However, there are many examples of dispersing animals where individuals are attracted to cues produced by factors that reduce their fitness after arrival. In this study, we use a temperate reef fish to examine the relative importance of habitat-associated cues in habitat selection decisions, and assess whether use of these cues is adaptive across early life stages. We used a series of laboratory- and field-based manipulative experiments to test: (1) what habitat-associated cues are likely used to locate suitable habitat; (2) whether in situ settlement patterns reflect the cue response tested in the laboratory; and (3) whether the aspects of the habitat that stimulate settlement are the same as those that maximize survival. We observed a positive response to multiple habitat-associated cues, with conspecific cues eliciting the strongest behavioral response in laboratory choice experiments, and a strong inverse density-dependent relationship at settlement. Macroalgal cues also elicited a positive response at settlement, but were associated with higher mortality after settlement, suggesting that habitat selection decisions are not always adaptive. We argue that this non-intuitive behavior may still be adaptive if it improves fitness at an earlier life stage, as habitat selection behavior is the result of tradeoffs in fitness costs across multiple stages.

Prefrontal cortex output circuits guide reward seeking through divergent cue encoding.

The prefrontal cortex is a critical neuroanatomical hub for controlling motivated behaviours across mammalian species. In addition to intra-cortical connectivity, prefrontal projection neurons innervate subcortical structures that contribute to reward-seeking behaviours, such as the ventral striatum and midline thalamus. While connectivity among these structures contributes to appetitive behaviours, how projection-specific prefrontal neurons encode reward-relevant information to guide reward seeking is unknown. Here we use in vivo two-photon calcium imaging to monitor the activity of dorsomedial prefrontal neurons in mice during an appetitive Pavlovian conditioning task. At the population level, these neurons display diverse activity patterns during the presentation of reward-predictive cues. However, recordings from prefrontal neurons with resolved projection targets reveal that individual corticostriatal neurons show response tuning to reward-predictive cues, such that excitatory cue responses are amplified across learning. By contrast, corticothalamic neurons gradually develop new, primarily inhibitory responses to reward-predictive cues across learning. Furthermore, bidirectional optogenetic manipulation of these neurons reveals that stimulation of corticostriatal neurons promotes conditioned reward-seeking behaviour after learning, while activity in corticothalamic neurons suppresses both the acquisition and expression of conditioned reward seeking. These data show how prefrontal circuitry can dynamically control reward-seeking behaviour through the opposing activities of projection-specific cell populations.

Observed infant food cue responsivity: Associations with maternal report of infant eating behavior, breastfeeding, and infant weight gain

Infant obesity and the rate of weight gain during infancy are significant public health concerns, but few studies have examined eating behaviors in infancy. Food cue responsivity has been described as a key contributor to obesity risk in school age children and adults, but has been rarely examined during infancy. The purpose of the current study was to test among 30 infants aged 6–12 months the hypotheses that infants would show greater interest in food versus non-food stimuli, and that greater birth weight, greater rate of weight gain during infancy, greater mother-reported food responsiveness, being formula versus breastmilk fed, and higher maternal body mass index, would each be associated with greater interest in the food versus non-food stimulus. Results showed that overall infants showed a preference for the food versus non-food stimulus. Preference for the food versus non-food stimulus was predicted by greater infant rate of weight gain since birth, greater maternal-reported infant food responsiveness, and having been exclusively formula-fed, but not by any other factor tested. Results are discussed with regard to theoretical implications for the study of infant obesity and applied prevention implications.

Palatable food consumption in children: interplay between (food) reward motivation and the home food environment.

The findings point at the importance of the home food environment in children high in reward sensitivity. They suggest to limit the home availability of unhealthy foods. What is Known: • Reward sensitivity (RS) is positively associated with children's palatable food consumption • In adolescents, this effect is mediated by food cue responsiveness, which determines the strength of an individual's motivation to obtain food when perceiving food cues What is New: • Children high in RS may be more vulnerable to palatable food cues in their everyday food environment because of a higher food cue responsiveness • The home food environment may be an important determining factor of the palatable food consumption of these children.

Opposite initialization to novel cues in dopamine signaling in ventral and posterior striatum in mice.

Dopamine neurons are thought to encode novelty in addition to reward prediction error (the discrepancy between actual and predicted values). In this study, we compared dopamine activity across the striatum using fiber fluorometry in mice. During classical conditioning, we observed opposite dynamics in dopamine axon signals in the ventral striatum ('VS dopamine') and the posterior tail of the striatum ('TS dopamine'). TS dopamine showed strong excitation to novel cues, whereas VS dopamine showed no responses to novel cues until they had been paired with a reward. TS dopamine cue responses decreased over time, depending on what the cue predicted. Additionally, TS dopamine showed excitation to several types of stimuli including rewarding, aversive, and neutral stimuli whereas VS dopamine showed excitation only to reward or reward-predicting cues. Together, these results demonstrate that dopamine novelty signals are localized in TS along with general salience signals, while VS dopamine reliably encodes reward prediction error.

Alarm cue specificity and response ontogeny in juvenile rainbow trout (Oncorhynchus mykiss)

Many aquatic prey animals release chemical cues upon being captured by a predator. These chemical cues, referred to as alarm cues, may act to warn nearby individuals of danger. For the cues to be useful, fish must be able to discern if they are indicative of a real threat; cues from conspecifics in different age groups may be irrelevant due to size- and habitat-related shifts in predation risk. We test the response of newly-hatched rainbow trout,Oncorhynchus mykiss, to three concentrations of alarm cues from conspecifics from two age groups: newly-hatched versus six-month-old juveniles. Newly-hatched trout demonstrated a significant fright response to all three concentrations of alarm cues, but showed no difference in strength of response based on either concentration or age of the cue donor. We propose that the newly-hatched trout did not respond differently because of the high risk of predation that they face during this life stage.

Identifying stimuli that cue multiple responses triggers the congruency sequence effect independent of response conflict.

According to most accounts of executive control, resisting distraction requires enhancing task-relevant processing, reducing task-irrelevant processing, or both. Consistent with this view, the congruency effect in Stroop-like tasks-a putative measure of distraction-is often smaller after highly distracting incongruent trials than after less distracting congruent trials. Competing accounts of executive control, however, differ on which aspect of an incongruent trial triggers this congruency sequence effect (CSE). The activation-suppression account posits the activation of an incorrect response. In contrast, the response cueing account posits identifying stimuli that cue multiple responses. To distinguish between these accounts, we conducted 2 experiments involving a modified prime-probe task wherein participants respond to the distracter in occasional catch trials. We found that the CSE is triggered by identifying stimuli that cue multiple responses, rather than by the activation of an incorrect response. Further, we observed this effect while ruling out an alternative "response conflict" trigger. These findings are more consistent with the response cueing account than with the activation-suppression account. (PsycINFO Database Record

Erratum to: Elevated carbon dioxide has the potential to impact alarm cue responses in some freshwater fishes

Erratum to: Elevated carbon dioxide has the potential to impact alarm cue responses in some freshwater fishes

Individual differences in food cue responsivity are associated with acute and repeated cocaine-induced vocalizations, but not cue-induced vocalizations.

Individuals prone to attribute incentive salience to food-associated stimuli ("cues") are also more sensitive to cues during drug seeking and drug taking. This may be due in part to a difference in sensitivity to the affective or other stimulus properties of the drug. In rats, these properties are associated with 50-kHz ultrasonic vocalizations (USVs), in that they are elicited during putative positive affective and motivational states, including in response to drugs of abuse. We sought to determine whether individual differences in the tendency to attribute incentive salience to a food cue (as measured by approach) were associated with differences in cocaine-induced USVs. We also tested whether the food cue would elicit USVs and if this response was related to approach to the food cue. In experiment 1, rats underwent Pavlovian conditioned approach (PavCA) training where they learned to associate a cue (an illuminated lever) with the delivery of a food pellet into a food cup. Subjects were categorized based on their approach to the cue ("sign-trackers") or to the food cup ("goal-trackers"). Rats subsequently underwent nine testing days in which they were given saline or cocaine (10mg/kg i.p) and placed into a locomotor chamber. In experiment 2, rats were first tested in the locomotor chambers for one saline-treated day followed by one cocaine-treated day and then trained in PavCA. USVs were recorded from a subset of individuals during the last day of PavCA to determine if the food cue would elicit USVs. Sign-trackers produced 5-24 times more cocaine-induced 50kHz USVs compared to goal-trackers for all days of experiment 1, and this response sensitized with repeated cocaine, only in sign-trackers. Similarly in experiment 2, individuals that produced the most cocaine-induced USVs on a single exposure also showed the greatest tendency to sign-track during PavCA. Lastly, while sign-trackers produced more USVs during PavCA generally, the cue itself did not elicit additional USVs in sign- or goal-trackers. These results indicate a robust and consistent relationship between approach to a food cue and cocaine-induced USV production. Thus, these USVs may index the neurobiological differences underlying the behavioral distinctions of sign- and goal-trackers.

The Effect of Forensic Expertise and Time Pressure on Fraud Risk Assessment and Responsiveness

Professional standards direct auditors to consult with forensic specialists to enhance the quality of fraud decisions. However, research underlying this prescription is limited. We address this gap by examining the effect of forensic expertise and time pressure on fraud cue identification and responsiveness in an experiment manipulating forensic expertise (forensic specialist versus auditor) and time pressure (present versus absent). The results show that forensic specialists identify more fraud cues than auditors, although this did not result in differential fraud risk assessment. Further, auditors not only plan less effective audit procedures than forensic specialists but also the performance difference is more substantial in the more realistic time pressure condition. However, as with prior studies, we did not find an association between fraud risk assessment and the planning of audit procedures for both groups. Taken together, the results provide evidence that consulting forensic specialists can enhance fraud decision quality and the performance difference is attributable to fraud cue identification and program planning but not through differential assessment of fraud risk assessment or its linkage to program planning.