Electrophysiology of appetitive taste and appetitive taste conditioning in humans

The present study examines two novel aspects of appetitive processing and conditioning: the electrophysiological response to (a) the appetitive taste of a sweet fluid and (b) appetitively/taste conditioned visual stimuli. Event-related potentials (ERPs) were recorded from 32 subjects while they performed a taste conditioning task, in which two symbols were paired with a sweet or a neutral fluid. The results show a clear P1/N1/P2 complex, and a late positive potential (P3) with maxima at right fronto-central electrode sites, in response to the taste stimuli. Of these components particularly the P3 showed robust differences between the sweet and neutral taste. In addition, the electrophysiological response to the taste conditioned stimuli (CS), also showed the expected differences for both P2 and P3 at frontocentral electrodes. The present data demonstrate that the employed paradigm is a useful methodology to study the electrophysiological responses to unconditioned appetitive stimuli. Since appetitive conditioning is assumed to be disturbed in many psychopathological conditions, such as substance dependence, depression and eating disorders, this paradigm could be employed to get more insight in these conditions in humans.     

Different strategies underlying uncertain decision making: Higher executive performance is associated with enhanced feedback‐related negativity

The aim of the present study was to investigate the role of executive functions (EFs) in different strategies underlying risky decision making. Adult participants from a nonclinical sample were assigned to low or high EF groups based on their performance on EF tasks measuring shifting, updating, and inhibition. ERPs were recorded while participants performed the Balloon Analogue Risk Task (BART). In this task, each balloon pump was associated with either a reward or a balloon pop with unknown probability. The BART behavioral measures did not show between‐group differences. However, the feedback‐related negativity (FRN) associated with undesirable outcomes was larger in the high EF group than in the low EF group. Since the FRN represents salience prediction error, our results suggest that the high EF group formed internal models that were violated by the outcomes. Thus, we provided ERP evidence for EFs influencing risky decision‐making processes.     

Reduced premovement positivity during the stimulus‐response interval precedes errors: Using single‐trial and regression ERPs to understand performance deficits in ADHD

Brain mechanisms linked to incorrect response selections made under time pressure during cognitive task performance are poorly understood, particularly in adolescents with attention‐deficit hyperactivity disorder (ADHD). Using subject‐specific multimodal imaging (electroencephalogram, magnetic resonance imaging, behavior) during flanker task performance by a sample of 94 human adolescents (mean age = 15.5 years, 50% female) with varying degrees of ADHD symptomatology, we examined the degree to which amplitude features of source‐resolved event‐related potentials (ERPs) from brain‐independent component processes within a critical (but often ignored) period in the action selection process, the stimulus‐response interval, were associated with motor response errors (across trials) and error rates (across individuals). Response errors were typically preceded by two smaller peaks in both trial‐level and trial‐averaged ERP projections from posterior medial frontal cortex (pMFC): a frontocentral P3 peaking about 390 ms after stimulus onset, and a premovement positivity (PMP) peaking about 110 ms before the motor response. Separating overlapping stimulus‐locked and response‐locked ERP contributions using a “regression ERP” approach showed that trial errors and participant error rates were primarily associated with smaller PMP, and not with frontocentral P3. Moreover, smaller PMP mediated the association between larger numbers of errors and ADHD symptoms, suggesting the possible value of using PMP as an intervention target to remediate performance deficits in ADHD.     

Temporal prediction modulates the evaluative processing of “good” action feedback: An electrophysiological study

The present study aimed to investigate whether or not the evaluative processing of action feedback can be modulated by temporal prediction. For this purpose, we examined the effects of the predictability of the timing of action feedback on an ERP effect that indexed the evaluative processing of action feedback, that is, an ERP effect that has been interpreted as a feedback‐related negativity (FRN) elicited by “bad” action feedback or a reward positivity (RewP) elicited by “good” action feedback. In two types of experimental blocks, the participants performed a gambling task in which they chose one of two cards and received an action feedback that indicated monetary gain or loss. In fixed blocks, the time interval between the participant's choice and the onset of the action feedback was fixed at 0, 500, or 1,000 ms in separate blocks; thus, the timing of action feedback was predictable. In mixed blocks, the time interval was randomly chosen from the same three intervals with equal probability; thus, the timing was less predictable. The results showed that the FRN/RewP was smaller in mixed than fixed blocks for the 0‐ms interval trial, whereas there was no difference between the two block types for the 500‐ms and 1,000‐ms interval trials. Interestingly, the smaller FRN/RewP was due to the modulation of gain ERPs rather than loss ERPs. These results suggest that temporal prediction can modulate the evaluative processing of action feedback, and particularly good feedback, such as that which indicates monetary gain.     

Significance?... Significance! Empirical,methodological, and theoretical connections between the late positive potential and P300 as neural responses to stimulus significance: An integrative review

Event-related potential studies of emotional processing have focused on the late positive potential (LPP), a sustained positive deflection in the ERP that is increased for emotionally arousing stimuli. A prominent theory suggests that modulation of the LPP is a response to stimulus significance, defined in terms of the activation of appetitive and aversive motivational systems. The current review incorporates experimental studies showing that manipulations that alter the significance of stimuli alter LPP amplitude. Complementing these within-person studies, also included is individual differences research on depression wherein the LPP has been used to study reduced neural sensitivity to emotional stimuli. Finally, the current review builds an existing framework that the LPP observed in studies in emotional processing and the P300 observed in classic oddball studies may reflect a common response to stimulus significance. This integrative account has implications for the functional interpretation of these ERPs, their neurobiological mechanisms, and clinical applications.     

Expectancy affects the feedback‐related negativity (FRN) for delayed feedback in probabilistic learning

Learning from feedback is a prerequisite for adapting to the environment. Prediction error signals coded by midbrain dopamine (DA) neurons are projected to the basal ganglia and anterior cingulate cortex (ACC). It has been suggested that neuronal activity shifts away from the DA system when feedback is delayed. The feedback‐related negativity (FRN), an ERP that is generated in the ACC and has been shown to be sensitive to feedback valence and prediction error magnitude, was found to be reduced for delayed feedback. It has, however, not yet been investigated if the FRN for delayed feedback reflects a reward prediction error. In this study, effects of feedback delay (1 s vs. 7 s) on the processing of expected and unexpected positive and negative feedback were investigated in a between‐subjects design in healthy human participants conducting a probabilistic feedback learning task. FRN and P300 amplitudes were decreased for subjects learning from delayed compared to immediate feedback. Importantly, the FRN, extracted from the negative‐positive feedback difference wave, was significantly smaller for expected compared to unexpected feedback for both the immediate and delayed feedback conditions. Expectancy effects for the P300 were also seen, but did not interact with feedback valence. These results demonstrate an influence of feedback expectancy, and thus the prediction error, on early feedback processing even for delayed feedback, suggesting that neuronal structures underlying feedback processing are comparable for immediate and delayed feedback, at least to some extent. Modulations of the P300 by feedback delay may be linked to feedback salience.     

Event-related potential study to aversive auditory stimuli

In an auditory oddball task emotionally negative (aversive) sounds (e.g. rubbing together of polystyrene) and everyday sounds (e.g. ringing of a bicycle bell) were presented as task-irrelevant (novel) sounds. Both the aversive and the everyday sounds elicited the orientation-related P3a component of the event-related potentials (ERPs). In the 154–250 ms range the ERPs for the aversive sounds were more negative than the ERP of the everyday sounds. For the aversive sounds, this negativity was followed by a frontal positive wave (372–456 ms). The aversive sounds elicited larger late positive shift than the everyday sounds. The early negativity is considered as an initial effect in a broad neural network including limbic structures, while the later is related to the cognitive assessment of the stimuli and to memory-related processes.     

How does cognitive reappraisal affect the response to gains and losses?

To investigate the influence of cognitive reappraisal, one important kind of emotion regulation strategy, on psychological and electrophysiological responses to gains and losses, a monetary gambling task was performed in two conditions, that is, spontaneity and regulation. Event‐related potentials (ERP) and self‐rating emotional experiences to outcome feedback were recorded during the task. Cognitive reappraisal reduced self‐rating emotional experience to both gains and losses and the amplitudes of the feedback‐related negativity (FRN) and the P3 of ERPs. According to these results, we suggest that the application of cognitive reappraisal strategy significantly modulated the motivational salience of current outcomes, thus weakening the subjective emotional experience elicited. In addition, cognitive reappraisal might have changed the allocation of cognitive resources during outcome evaluation. This study extends emotion regulation studies by applying monetary outcomes as emotional stimuli, and also implicates the significance of emotion regulation in decision‐making processes.     

Conditioned reversal of reactions to normally avoided tastes

Oral motor responses, elicited by the infusion of a taste solution into a rat's mouth, can be changed through association with either other tastes or internal states. Such changes have been well established when ingestive responses, elicited by a normally preferred taste, are changed to aversive responses when the taste signals a LiCl injection. However, the converse has yet to be clearly established; that aversive responses, elicited by a normally avoided taste, can be changed to ingestive responses in a nondeprived animal, as a result of conditioning. We demonstrate here that when a normally avoided taste (quinine or HCl) signals a preferred taste (sucrose), the oral motor responses gradually undergo two types of change as a function of trials. The aversive oral motor responses elicited by the avoided taste decrease over trials and the ingestive responses increase. The two measures, ingestive and aversive responding, were obtained by recording the rat's reactions to the stimuli as they were infused directly into the oral cavity. This taste reactivity method both enabled us to use avoided stimuli in a nondeprived animal and to measure the rat's evaluation of the stimuli's aversiveness. Problems with stimulus sampling may be responsible for the dearth of conditioning experiments which utilize avoided tastes in conditioned preference studies.     

The effect of taste familiarity on intake and taste reactivity in infant rats

With infant rats, unlike with adults, increased intake of a taste after mere exposure to this stimulus is not consistently found; this has sometimes been interpreted as a failure by the immature subject to recognize tastes as familiar. We studied the effect of preexposure to a tastant, measuring taste reactivity and intake in 14‐day‐old rats. Familiarity increased hedonic response to sucrose, but also increased aversive response to quinine and ethanol. With the sucrose‐quinine compound, familiarity increased both the hedonic and the aversive reaction to the stimulus. In no case was a differential reactivity to water observed. Significant increased intake after familiarization was only found with quinine or the sucrose‐quinine compound. Results indicate that in infant rats, and with the present parameters, taste familiarity enhances responsiveness to these stimuli, an effect not always accompanied by detectable changes in intake. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 52:109–120, 2010     

Impaired conditioned taste aversion learning in APP transgenic mice

Cognition in transgenic mouse models of Alzheimer's disease (AD) has been predominantly characterized in explicit spatial orientation tasks. However, dementia in AD encompasses also implicit memory systems. In the present study a line of transgenic mice (TgCRND8) encoding a double mutated allele of the human amyloid precursor protein (APP) genes was evaluated in an implicit associative learning task of conditioned taste aversion (CTA). CTA is a form of Pavlovian classical conditioning, in which a mouse learns to avoid a novel taste of saccharine (conditioned stimulus) paired with an experimentally induced (systemic injection of lithium chloride) nausea (unconditioned stimulus). In contrast to conditioned non-Tg mice, TgCRND8 APP mice developed weaker aversion against saccharine and quickly increased its consumption in repeated tests. These results indicate that TgCRND8 mice show a significant impairment not only in explicit spatial memory, as has been previously shown [Nature 408 (2000) 979], but also in implicit memory. Control experiments confirmed that TgCRND8 and non-Tg mice had comparable taste sensitivities in response to appetitive as well as aversive tastes. The study suggests that the CTA paradigm can be a sensitive tool to evaluate deficits in implicit associative learning in APP transgenic mouse models of AD.     

Early frontal responses elicited by physical threat words in an emotional Stroop task: Modulation by anxiety sensitivity

High-density brain electrical activity elicited by physical threat, positive and neutral words were recorded in 33 healthy individuals screened for high or low anxiety sensitivity (AS) during a modified emotional Stroop task. The paradigm allowed the separate assessment of block and mixed-trial effects. In the block analysis, a significant emotional RT slowing was observed along with the modulation of a frontocentral negativity (350-400 ms) in the high AS group only. In contrast, the mixed-trial analysis revealed a positive enhancement of the ERP to threat words peaking earlier (200-300 ms) over anterior frontal scalp in the absence of RT slowing. This component was preceded by a very early positive modulation (peaking 50 ms) in the high AS group only. It is concluded that frontal ERPs to physical threat words can distinguish the contribution of emotional conflict and emotional salience, particularly in individuals with high trait-anxiety.     

The effects of performance‐based rewards on neurophysiological correlates of stimulus,error, and feedback processing in children with ADHD

Rewards have been shown to improve behavior and cognitive processes implicated in attention‐deficit hyperactivity disorder (ADHD), but the information‐processing mechanisms by which these improvements occur remain unclear. We examined the effect of performance‐based rewards on ERPs related to processing of the primary task stimuli, errors, and feedback in children with ADHD and typically developing controls. Participants completed a flanker task containing blocks with and without performance‐based rewards. Children with ADHD showed reduced amplitude of ERPs associated with processing of the flanker stimuli (P3) and errors (ERN, Pe), but did not differ in feedback‐processing (FRN). Rewards enhanced flanker‐related P3 amplitude similarly across groups and error‐related Pe amplitude differentially for children with ADHD. These findings suggest that rewards may improve cognitive deficits in children with ADHD through enhanced processing of relevant stimuli and increased error evaluation.     

Conditioned and extinguished fear modulate functional corticocardiac coupling in humans

Although the conditioned cardiac fear response is an important index of psychophysiological fear processing, underlying neural mechanisms remain unclear. N = 22 participants underwent differential fear conditioning and extinction with face pictures as conditioned stimuli (CS) and loud noise bursts as aversive unconditioned stimulus (US) on Day 1 and a recall test 1 day later. We assessed ERPs, evoked heart period (HP), and time‐lagged within‐subject correlations of single‐trial EEG amplitude and HP as index for corticocardiac coupling in response to the CS. Fear‐conditioned stimuli (CS+) triggered cardiac deceleration during fear acquisition and recall. Meanwhile, only during Day 1 acquisition, CS+ evoked larger late positivities in the ERP than CS?. Most importantly, during Day 2 recall, stimulus‐evoked single‐trial EEG responses in the time window between 250 and 500 ms predicted the magnitude of cardiac fear responses 2 to 5 s later. This marker of corticocardiac coupling selectively emerged in response to not previously extinguished CS+ but was absent in response to CS? or previously extinguished CS+. The present results provide first evidence that fear conditioning and extinction modulate functional corticocardiac coupling in humans. Underlying mechanisms may involve subcortical structures enhancing corticocardiac transmission to facilitate processing of consolidated conditioned fear.     

Olfactory associative learning in Caenorhabditis elegans is impaired in lrn-1 and lrn-2 mutants.

The C. elegans mutants, lrn-1 and lrn-2, are impaired in associative learning using conditioned taste cues. Both mutants are defective in associative learning about appetitive and aversive events, indicating that lrn-1 and lrn-2 exert effects across motivational boundaries. In a new olfactory associative learning paradigm, in which wild type worms learn to avoid a previously attractive diacetyl odor after it has been paired with an aversive acetic acid solution, lrn-1 and lrn-2 are impaired. Although defective in associative learning using a conditioned olfactory cue, nonassociative learning (habituation and dishabituation) using this same olfactory cue is unaffected. The discovery that lrn-1 and lrn-2 are defective in associative learning with both taste and olfactory cues may suggest that associative learning in different sensory modalities converges on a common genetic pathway in C. elegans that is subserved by lrn-1 and lrn-2.     

Do sensorimotor perturbations to standing balance elicit an error‐related negativity?

Detecting and correcting errors is essential to successful action. Studies on response monitoring have examined scalp ERPs following the commission of motor slips in speeded‐response tasks, focusing on a frontocentral negativity (i.e., error‐related negativity or ERN). Sensorimotor neurophysiologists investigating cortical monitoring of reactive balance recovery behavior observe a strikingly similar pattern of scalp ERPs following externally imposed postural errors, including a brief frontocentral negativity that has been referred to as the balance N1. We integrate and review relevant literature from these discrepant fields to suggest shared underlying mechanisms and potential benefits of collaboration across fields. Unlike the cognitive tasks leveraged to study the ERN, balance perturbations afford precise experimental control of postural errors to elicit balance N1s that are an order of magnitude larger than the ERN and drive robust and well‐characterized adaptation of behavior within an experimental session. Many factors that modulate the ERN, including motivation, perceived consequences, perceptual salience, expectation, development, and aging, are likewise known to modulate the balance N1. We propose that the ERN and balance N1 reflect common neural activity for detecting errors. Collaboration across fields could help clarify the functional significance of the ERN and poorly understood interactions between motor and cognitive impairments.     

Size does matter! Perceptual stimulus properties affect event‐related potentials during feedback processing

The current study investigated whether or not the physical aspect of stimulus size has an effect on neuronal correlates of feedback processing. A time estimation task was administered applying three different feedback stimulus categories: small, middle, and large size stimuli. Apart from early visual ERPs such as P1 and N1 components, later feedback processing stages were also affected by the size of feedback stimuli. In particular, small size stimuli compared to middle and large size ones led to diminished amplitudes in both FRN and P300 components, despite intact discrimination between negative and positive outcomes in these two ERPs. In contrast, time estimation performance was not influenced by feedback size. The current results indicate that small size feedback stimuli were perceived as less salient and hence were processed less deeply than the others. This suggests that future feedback studies could manipulate feedback salience simply by presenting differently sized feedback stimuli, at least when the focus lies on FRN and P300 amplitude variation.     

Taste reactivity analysis of 6-hydroxydopamine-induced aphagia: implications for arousal and anhedonia hypotheses of dopamine function

The deficits in feeding and drinking that result from 6-hydroxydopamine (6-OHDA) lesions of the mesostriatal dopamine system are often explained using either sensorimotor arousal or anhedonia hypotheses. Sensorimotor arousal hypotheses posit that dopamine systems facilitate the capacity of sensory stimuli to activate any motor output. The anhedonia hypothesis suggests that dopamine systems amplify the hedonic impact of positive reinforcers. Natural palatability-dependent ingestive and aversive actions, which are emitted by rats to tastes, provide a sensitive test that can discriminate between these hypotheses: A reduction of sensorimotor arousal should diminish the ability of tastes to elicit any actions, whereas anhedonia should shift the balance between positive and aversive actions. To directly compare these two hypotheses, taste reactivity was examined in rats made aphagic by intranigral 6-OHDA injections. The results did not support either of these predictions: Taste reactivity was essentially unchanged. The persistence of normal taste reactivity argues against both an anhedonia and a global sensorimotor arousal interpretation and provides further evidence that the capacity for hedonics can be neurologically dissociated from motivated appetitive behavior. An incentive attribution hypothesis that can account for the results is discussed, along with its implications for a wide range of phenomena associated with dopamine depletion.     

Goal relevance influences performance monitoring at the level of the FRN and P3 components

The feedback‐related negativity (FRN) provides a reliable ERP marker of performance monitoring (PM). It is usually larger for negative compared to positive feedback, and for unexpected relative to expected feedback. In two experiments, we assessed whether these effects could be modulated by goal relevance, defined as feedback informativeness (reliability) and/or impact on a person's goals. EEG (64‐channel) was recorded while 30 participants (in each experiment) performed a speeded go/no‐go task across blocks in which the feedback on task performance was deemed either relevant or not. At the ERP level, the FRN component was larger for (frequent) negative compared to (deviant) positive feedback exclusively when the feedback was relevant (Experiment 1). When the probability of positive and negative feedback was balanced (Experiment 2), this valence‐driven FRN effect was absent. However, across these two experiments, the FRN was always larger for irrelevant than relevant feedback. Moreover, the subsequent P300 component was larger for feedback in the relevant than the irrelevant blocks. This effect was valence unspecific in Experiment 1, while in Experiment 2 larger P3 amplitudes were recorded for negative than positive (relevant) feedback. Across the two experiments, a larger correct‐related negativity in the irrelevant than relevant context was also observed, suggesting that PM is flexible. These ERP findings indicate that goal relevance influences feedback (and response) processing during PM, with two nonoverlapping neurophysiological effects: It gates reward prediction error brain mechanisms (FRN effect), before enhancing subsequent motivational processes (P300 effect).     

Intensity expectation modifies gustatory evoked potentials to sweet taste: Evidence of bidirectional assimilation in early perceptual processing

Expectations can affect subjective sensory and hedonic ratings of tastes, but it is unclear whether they also shape sensory experience at a perceptual level. The neural correlates of the taste‐expectancy relationship were explored through EEG analysis. Using a trial‐by‐trial cueing paradigm, lingual delivery of 0.05 M or 0.3 M sucrose solutions was preceded by congruent or incongruent visual cues designed to promote anticipation of either a low‐sweet or high‐sweet solution. When participants were cued to expect low‐sweet, but received high‐sweet (incongruent cue), intensity ratings for high‐sweet decreased. Likewise, expectation of high‐sweet increased intensity ratings of low‐sweet solutions. Taste‐dependent, right central‐parietal gustatory ERPs were detected, with greater P1 (associated with greater right insula activation) and P2 peak amplitudes for high‐sweet tastes. Valid cue‐taste pairings led to specific reduced right‐lateralized N400 responses (associated with an attenuation in right insula activation) compared with invalid cue‐taste pairings. Finally, P1 amplitudes following invalidly cued low‐sweet tastes closely matched those generated by expected high‐sweet tastes, and P1 amplitudes for invalidly cued high‐sweet tastes resembled those generated by low‐sweet tastes. We conclude that, as well as modifying subjective ratings toward the anticipated intensity level, expectations affect cortical activity in a top‐down manner to induce bidirectional assimilation in the early perceptual processing of sweet taste and modulate N400 ERP components not previously associated with gustatory stimulation.