Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

INTRODUCTION: Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. METHODS: Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. RESULTS: Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p < .001). Exploratory analyses indicated withdrawal increased time to initiate the next trial following unexpected punishment trials (p < .001) and response time on reward trials during withdrawal was positively related to nicotine dependence (p < .001). CONCLUSIONS: Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. IMPLICATIONS: Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and unpleasant stimuli may be particularly effective for alleviating nicotine withdrawal.

Medial frontal event-related potentials and reward prediction: do responses matter?

Medial frontal event-related potentials (ERPs) following rewarding feedback index outcome evaluation. The majority of studies examining the feedback related medial frontal negativity (MFN) employ active tasks during which participants' responses impact their feedback, however, the MFN has been elicited during passive tasks. Many of the studies examining the MFN show enhanced effects when an error in reward prediction occurs (i.e. expected rewards are not delivered). To clarify the roles of reward prediction error and active responding in producing the MFN, the current study employed a reward prediction design with active and passive task blocks. Following the presentation of a reward predictor, participants (active task) or the computer (passive task) indicated whether participants would receive the outcome associated with a stimulus presented on the left or right of the reward predictor. The MFN was largest when the trial outcome was worse than predicted and this effect was enhanced when the participant, rather than the computer, made the choice. These results show that both reward prediction error and active choice impact the neural system of outcome monitoring with the largest MFN when the individual's decision led to the negative outcome.

Event-related potentials to rare visual targets and negative symptom severity in a transdiagnostic psychiatric sample.

OBJECTIVES: Negative psychiatric symptoms are often resistant to treatments, regardless of the disorder in which they appear. One model for a cause of negative symptoms is impairment in higher-order cognition. The current study examined how particular bottom-up and top-down mechanisms of selective attention relate to severity of negative symptoms across a transdiagnostic psychiatric sample. METHODS: The sample consisted of 130 participants: 25 schizophrenia-spectrum disorders, 26 bipolar disorders, 18 unipolar depression, and 61 nonpsychiatric controls. The relationships between attentional event-related potentials following rare visual targets (i.e., N1, N2b, P2a, and P3b) and severity of the negative symptom domains of anhedonia, avolition, and blunted affect were evaluated using frequentist and Bayesian analyses. RESULTS: P3b and N2b mean amplitudes were inversely related to the Positive and Negative Syndrome Scale-Negative Symptom Factor severity score across the entire sample. Subsequent regression analyses showed a significant negative transdiagnostic relationship between P3b amplitude and blunted affect severity. CONCLUSIONS: Results indicate that negative symptoms, and particularly blunted affect, may have a stronger association with deficits in top-down mechanisms of selective attention. SIGNIFICANCE: This suggests that people with greater severity of blunted affect, independent of diagnosis, do not allocate sufficient cognitive resources when engaging in activities requiring selective attention.

Electrophysiological responses to appetitive and aversive outcomes: A comparison of college drinkers and non-drinkers.

The current study compared electrophysiological responses (the feedback-related negativity [FRN]) to appetitive and aversive outcomes between a group of college drinkers and non-drinkers. 50 undergraduate students completed a passive, slot machine-like task while their electroencephalographic data was recorded to extract the FRN to unexpected appetitive and aversive outcomes. In the appetitive condition, participants could expectedly or unexpectedly win $1 or not win $1 and in the aversive condition participants could expectedly or unexpectedly be exposed to a loud noise burst or silence. The FRN was recorded in response to a cue indicating the outcome. Participants also reported on the number of drinks they consumed in a typical week to establish drinking status (drinker/non-drinker). Results showed that non-drinkers had a larger FRN in the aversive task compared to the appetitive task while drinkers had similar FRNs between the tasks. Drinkers had a significantly smaller aversive outcome related FRN compared to non-drinkers. Neural sensitivity to aversive outcomes might be a marker of decreased punishment sensitivity in college drinkers compared to non-drinkers, contributing to unhealthy drinking behavior.

Impulsivity in Decision-Making: An Event-Related Potential Investigation.

Impulsive individuals make risky choices, motivated more by immediate reward than potential long-term negative consequences. We used event-related potentials to study the impact of reward and punishment sensitivity in impulsivity on risky decision-making in a two-card choice task in groups of 14 high and 14 low impulsive undergraduates formed by a median split on the Barratt Impulsiveness Scale score. The high impulsives had a larger P3 and the low impulsives a smaller P3 to the cards when making a low-risk choice suggesting that the high-risk option was the default choice of the high impulsives and the low-risk choice the default for the low impulsives. The low, but not the high impulsives had a larger error-related negativity following high-risk choice indicating that the low impulsives evaluated the risky choice as a poor decision. The results indicate that high impulsive individuals are biased towards immediate reward during option evaluation but are less sensitive to the negative consequences of their choices.

A test of dopamine hyper- and hyposensitivity in alcohol use.

Biases in outcome processing, mediated by the mesocortical dopaminergic (DA) system, may predict individual differences in the frequency and quantity of alcohol use. We tested the hypothesis that genetic markers associated with increased DA neurotransmission contribute to reduced neural sensitivity to costs and increased alcohol use in an undergraduate sample. We created a DA transmission score using five genetic markers related to DA transmission and assessed neural sensitivity to cost using the feedback-related negativity (FRN), an event-related potential implicated in neural outcome evaluation, on both passive evaluative and active decision-making tasks. Self-reported alcohol use was assessed using the Daily Drinking Questionnaire-Revised. Participants with a higher DA transmission score reported increased alcohol consumption and exhibited a more blunted FRN on both the passive and active tasks. While dopamine hyposensitivity is common among chronic alcohol users, these data provide preliminary evidence that hypersensitivity of the dopamine system may underlie increased alcohol use in those who have not yet developed a chronic alcohol use disorder.

Parallel perceptual enhancement and hierarchic relevance evaluation in an audio-visual conjunction task.

Attention directs limited-capacity information processing resources to a subset of available perceptual representations. The mechanisms by which attention selects task-relevant representations for preferential processing are not fully known. Triesman and Gelade's [Triesman, A., Gelade, G., 1980. A feature integration theory of attention. Cognit. Psychol. 12, 97-136.] influential attention model posits that simple features are processed preattentively, in parallel, but that attention is required to serially conjoin multiple features into an object representation. Event-related potentials have provided evidence for this model showing parallel processing of perceptual features in the posterior Selection Negativity (SN) and serial, hierarchic processing of feature conjunctions in the Frontal Selection Positivity (FSP). Most prior studies have been done on conjunctions within one sensory modality while many real-world objects have multimodal features. It is not known if the same neural systems of posterior parallel processing of simple features and frontal serial processing of feature conjunctions seen within a sensory modality also operate on conjunctions between modalities. The current study used ERPs and simultaneously presented auditory and visual stimuli in three task conditions: Attend Auditory (auditory feature determines the target, visual features are irrelevant), Attend Visual (visual features relevant, auditory irrelevant), and Attend Conjunction (target defined by the co-occurrence of an auditory and a visual feature). In the Attend Conjunction condition when the auditory but not the visual feature was a target there was an SN over auditory cortex, when the visual but not auditory stimulus was a target there was an SN over visual cortex, and when both auditory and visual stimuli were targets (i.e. conjunction target) there were SNs over both auditory and visual cortex, indicating parallel processing of the simple features within each modality. In contrast, an FSP was present when either the visual only or both auditory and visual features were targets, but not when only the auditory stimulus was a target, indicating that the conjunction target determination was evaluated serially and hierarchically with visual information taking precedence. This indicates that the detection of a target defined by audio-visual conjunction is achieved via the same mechanism as within a single perceptual modality, through separate, parallel processing of the auditory and visual features and serial processing of the feature conjunction elements, rather than by evaluation of a fused multimodal percept.

Medial frontal cortex response to unexpected motivationally salient outcomes.

The medial frontal cortex (MFC) plays a central role allocating resources to process salient information, in part by responding to prediction errors. While there is some recent debate, the feedback-related negativity (FRN) is thought to index a reward prediction error by signaling outcomes that are worse than expected. A recent study utilizing electric shock provided data inconsistent with these accounts and reported that the omission of both appetitive (money) and aversive outcomes (electric shocks) elicited a medial frontal negativity. These data suggest that the ERPs within this time range support a salience prediction error that responds to unexpected events regardless of valence. To compare the reward and salience prediction error models, we employed a design that delivered both appetitive (monetary) and aversive (noise burst) outcomes. Participants completed a passive S1/S2 prediction design where S1 predicted S2 with 80% accuracy and S2 predicted the outcome with 100% accuracy. We compared both earlier and later ERP responses over the medial frontal cortex to compare the salience and reward prediction hypotheses. Considering both time windows, the ERP response to S2 in the early time window was most positive when S2 signaled that an outcome was unexpectedly delivered and in the later time window, was most negative when an outcome was unexpectedly withheld, regardless of outcome valence. Thus, these results are more consistent with a salience prediction error rather than a reward prediction error.

Preliminary evidence that digit length ratio (2D:4D) predicts neural response to delivery of motivational stimuli.

Reduced relative length of the 2nd to 4th digits (2D:4D) is thought to partially reflect fetal testosterone (FT) exposure, a process suspected to promote relatively permanent effects on the brain and behavior via structural and functional neuroadaptations. We examined the effect of 2D:4D on neural response - assessed by P2a and feedback-related negativity (FRN) event-related potentials (ERPs) - to motivational stimuli (reward or punishment) using two counterbalanced conditions of a passive S1/S2 outcome prediction design. P2a to expected and unexpected delivered rewards or punishments ($1 or white noise burst, respectively) and FRN to withheld rewards or punishments ($0 or silence, respectively) were observed in undergraduates. Lower left 2D:4D and greater 2D:4DR-L predicted amplified P2a to the delivery (but not FRN to the omission) of motivationally salient stimuli, regardless of valence and probability. These preliminary findings suggest that FT may organize dopamine neurons to respond more strongly to the delivery of motivational stimuli.

Disruption of auditory and visual attention in schizophrenia.

Disruption of attention is a hallmark symptom of schizophrenia, and event-related potentials have been instrumental in studying this cognitive deficit. Event-related potentials (ERPs) have been used to study attention and its disruption in schizophrenia, with the most common finding of a reduced P300 component in auditory tasks. Some studies have found sparing of the P300 in visual attention, but reduction of an earlier attention-sensitive N2b, suggesting that the N2b may be a more sensitive index of attention disruption in schizophrenia. The current study compared visual and auditory attention using both unimodal and bimodal stimulus presentation in the same participants to examine the impact of schizophrenia on attention at both the early N2b and later P300 stages. Both N2b and P300 showed attention effects, being larger to targets than non-targets in all tasks. The N2b was reduced in the patient group in all tasks except the bimodal attend visual task, while the P300 was not reduced in the patients in any condition. This indicates that early attention, as indexed by the N2b, is differentially impaired in patients with schizophrenia, even when later attention, indexed by the P300, is intact.

Self-reported impulsivity in Huntington's disease patients and relationship to executive dysfunction and reward responsiveness.

INTRODUCTION: Few studies have directly investigated impulsivity in Huntington's disease (HD) despite known changes in dopaminergic and frontal functioning, changes that have been associated with impulsivity in other disorders and in the normal population. This study sought to further categorize impulsivity in HD through examining differences in self-reported impulsivity between community controls and HD patients, the relationship between executive dysfunction and impulsivity, and the relationship of a reward/punishment behavioral inhibition task in relation to these self-report measures. It was expected that HD patients would report higher impulsivity and executive dysfunction and that these measures would relate to a reward/punishment behavioral inhibition task. METHOD: The Barratt Impulsivity Scale (BIS-11) and Behavioral Inhibition/Behavioral Activation Scale (BIS/BAS) were completed, and the Mini-Mental State Examination (MMSE) and a reward-based flanker task with punishing and rewarding conditions were administered to 22 HD patients and 14 control participants. RESULTS: HD patients reported higher trait impulsivity (BIS-11) and executive dysfunction (Frontal Systems Behavior Scale, FrSBE) but not increased impulsivity on the BIS/BAS relative to controls. Higher BIS-11 scores were related to increased self-reported executive dysfunction and the attention/working memory factor of the MMSE. On a reward/punishment behavioral inhibition task, BAS was uniquely related to increased accuracy on rewarding trials of the flanker task, but was not related to punishing trials in HD patients. CONCLUSIONS: The relationships found suggest that trait impulsivity is reported higher in HD and may not be driven by altered reward evaluation and the appetitive nature of stimuli but rather by increased executive dysfunction and lack of sensitivity to punishment. Impulsivity in HD may represent a combination of trait impulsivity, altered dopaminergic circuitry, and executive dysfunction. Understanding impulsivity in HD is important as it is related to increased risk to the patient and difficult behaviors for the caregiver, and sheds light on the disease process.

Neural outcome processing of peer-influenced risk-taking behavior in late adolescence: Preliminary evidence for gene × environment interactions.

Adolescent brains are particularly susceptible to the rewarding properties of risky decisions in social contexts. Individual differences in genetic influences on dopamine transmission moderate neural outcome processing of risky decisions and may exert pronounced effects on adolescent risk-taking behavior (RTB) and corresponding neural outcome processing in peer contexts, a process called gene-environment interaction (G × E). Eighty-five undergraduate students completed a behavioral risk task alone and in the presence of a confederate peer providing "risky" feedback. We tested for G × E effects using a polygenic risk index that included 3 candidate genetic variations associated with high dopamine transmission efficiency, as well as the moderating role of family history of behavioral disinhibition. Difference waves for the P300 and FRN (i.e., feedback-related negativity) were examined as indices of neural outcome processing. A G × E effect was observed for RTB and the P300, but not the FRN. Family history of behavioral disinhibition also interacted with peer influence to predict P300 amplitude. These data provide preliminary evidence for G × E for peer-influenced RTB and neural outcome processing during late adolescence. Genetic influences on dopaminergic function may be particularly relevant for attentional and motivational neural systems, as indexed by the P300, which exert downstream effects on peer-influenced RTB. (PsycINFO Database Record

Reduced punishment sensitivity in neural systems of behavior monitoring in impulsive individuals.

This study measured the response-locked event-related potential during a flanker task with performance-based monetarily rewarding and punishing trials in 37 undergraduate students separated into high- and low-impulsive groups based on a median split on self-reported Barrett Impulsiveness Scale. The high-impulsive group had a smaller medial frontal error-related negativity (ERN) on punishment trials than the low-impulsive group. The medial prefrontal neural system of behavior monitoring, indexed by the ERN, appears less sensitive to punishment signals in normal impulsivity. This reduced punishment sensitivity in impulsivity, a personality variation associated with several mental and personality disorders including ADHD and substance abuse may be related to the tendency to select short-term rewards despite potential long-term negative consequences in these individuals.

Event-related potentials to auditory and visual selective attention in schizophrenia.

BACKGROUND: Prior studies have shown a consistent reduction of the auditory P300 in schizophrenia, while the visual attention findings have been mixed. Both the auditory and visual N2b, an earlier, modality-specific attention index, are reduced in schizophrenia, sometimes despite sparing of the visual P300. Thus there may be a dissociation between the N2b and P300 attention effects in auditory and visual modalities in schizophrenia. METHODS: Thirteen patients and thirteen controls observed symbols appearing on a screen, paired with simultaneous tones. In some blocks subjects responded to one of the symbols, in others to one of the tones. The N2b was predicted to be reduced in the patient group in both auditory and visual attention but the P300 reduced only while attending to tones. RESULTS: Results showed a reduction of the N1 component in the patient group in the auditory condition but not in the visual. There was a reduction of the N2b target-minus-non-target difference wave in the patients in both auditory and visual target conditions. The P300 component was larger overall in the control group in both modalities, but did not show the usual enhancement to auditory targets in the control group. CONCLUSIONS: These findings suggest that the ability to selectively attend to a target in one modality while ignoring the other is compromised in patients with schizophrenia. Perceptual processing appears to be impacted in the auditory modality while remaining intact in the visual. The N2b appears more vulnerable than the P300 in both auditory and visual attention in schizophrenia.

The role of the neural reward system in attention selection.

The prefrontal cortex may play a role in attention selection using motivational information from the mesotelencephalic dopamine system, a neural system that responds to reward prediction violations. If so, neural indices of attention selection and reward prediction violation should have overlapping spatiotemporal distributions. Attention selection elicits a frontal event-related potential component around 200-300 ms, the frontal selection positivity. A component with similar spatiotemporal characteristics, the reward positivity is elicited in reward prediction designs to outcomes that are better than expected. The current study used dense sensor array recording in a sample of 41 participants performing visual oddball (attention) and a reward prediction 'slot machine-like' design to compare the spatiotemporal distributions of the frontal selection positivity and the reward positivity. The components did not differ in their peak latencies and had overlapping scalp topographies, supporting the hypothesis that these positivities represent attachment of incentive salience to perceptual representations in the prefrontal cortex.

Transdiagnostic Psychiatric Symptoms and Event-Related Potentials following Rewarding and Aversive Outcomes.

There is a need for a better understanding of transdiagnostic psychiatric symptoms that relate to neurophysiological abnormalities following rewarding and aversive feedback in order to inform development of novel targeted treatments. To address this need, we examined a transdiagnostic sample of 44 adults (mean age: 35.52; 57% female), which consisted of individuals with broadly-defined schizophrenia-spectrum disorders (n = 16), bipolar disorders (n = 10), other mood and anxiety disorders (n = 5), and no history of a psychiatric disorder (n = 13). Participants completed a Pavlovian monetary reward prediction task during 32-channel electroencephalogram recording. We assessed the event-related potentials (ERPs) of feedback-related negativity (FRN), feedback-related positivity (FRP), and the late positive potential (LPP), following better and worse than expected outcomes. Examination of symptom relationships using stepwise regressions across the entire sample revealed that an increase in the clinician-rated Negative Symptoms factor score from the Positive and Negative Syndrome Scale, was related to a decreased LPP amplitude during better than expected (i.e., rewarding) outcomes. We also found that increased self-reported scores on the Schizotypal Personality Questionnaire (Brief-Revised) Disorganized factor related to an increased FRN amplitude during worse than expected (i.e., aversive) outcomes. Across the entire sample, the FRP component amplitudes did not show significant relationships to any of the symptoms examined. Analyses of the three diagnostic groups of schizophrenia-spectrum disorders, bipolar disorders, and nonpsychiatric controls did not reveal any statistically significant differences across the ERP amplitudes and conditions. These findings suggest relationships between specific neurophysiological abnormalities following rewarding and aversive outcomes and particular transdiagnostic psychiatric symptoms.

Disruption of neural systems of visual attention in schizophrenia.

BACKGROUND: Patients with schizophrenia show attention deficits. The frontal P2a and posterior N2b event-related potential components are early indices of activity in neural systems supporting attention and they are reduced in schizophrenia in auditory tasks. However, the auditory P300 is reduced as well. Thus, the P2a and N2b reductions may simply reflect a general event-related potential amplitude reduction. The visual P300, however, is often spared in schizophrenia. If neural systems supporting attention are specifically disrupted in schizophrenia, the attention-sensitive P2a and N2b should be differentially reduced in patients, compared with the P300, in a visual attention task. METHODS: We analyzed 64-channel event-related potentials from 14 schizophrenic patients and 14 control subjects in a visual object-spatial attention task. We examined the amplitude of the P2a, N2b, and P300 components in the target minus standard difference wave to see if there was a differential reduction of the P2a and N2b compared with the P300. RESULTS: Both the P2a and N2b waveforms were reduced in the patient group (81% [control mean, 1.99 microV; patient mean, 0.38 microV] and 95% [control mean, 0.55 microV; patient mean, 0.03 microV], respectively) while the P300 was not reduced. Measured at the peak of the frontal P2a, the N2b was larger dorsally in the spatial task and larger ventrally in the object task in the control group. CONCLUSIONS: The spatial distribution of the P2a and N2b was consistent with activity in the prefrontal cortex and modality-specific posterior cortex, respectively. The differential reduction of the P2a and N2b waveforms supports the hypothesis of specific disruption in neural systems of visual attention in schizophrenia.

Effects of dialect on merger perception: ERP and behavioral correlates.

Native speakers of a language are often unable to consciously perceive, and have altered neural responses to, phonemic contrasts not present in their language. This study examined whether speakers of dialects of the same language with different phoneme inventories also show measurably different neural responses to contrasts not present in their dialect. Speakers with (n=11) and without (n=11) an American English I/E (pin/pen) vowel merger in speech production were asked to discriminate perceptually between minimal pairs of words that contrasted in the critical vowel merger and minimal pairs of control words while their event-related potential (ERPs) were recorded. Compared with unmerged dialect speakers, merged dialect speakers were less able to make behavioral discriminations and exhibited a reduced late positive ERP component (LPC) effect to incongruent merger vowel stimuli. These results indicate that between dialects of a single language, the behavioral response differences may reflect neural differences related to conscious phonological decision processes.

On the roles of distinctiveness and semantic expectancies in episodic encoding of emotional words.

We examined the factors that contribute to enhanced recall for emotionally arousing words by analyzing behavioral performance, the P300 as an index of distinctiveness, and the N400 as an index of semantic expectancy violation in a modified Von Restorff paradigm. While their EEG was recorded, participants studied three list types (1) neutral words including one emotionally arousing isolate (either positive or negative), (2) arousing, negative words including one neutral isolate, or (3) arousing, positive words including one neutral isolate. Immediately after each list, free recall was tested. Negative, but not positive, words exhibited enhanced recall when presented as isolates in lists of neutral words and elicited a larger P300 for subsequently recalled than not-recalled words. This suggests that arousing, negative words stand out and that their distinctiveness contributes to their superior recall. Positive valence had an enhancing effect on recall only when the list contained mostly other positive words. Neutral isolates placed in either positive or negative lists elicited an N400, suggesting that semantic expectations developed in emotional word lists regardless of valence. However, semantic relatedness appeared to more strongly contribute to recall for positive than negative words. Our results suggest that distinctiveness and semantic relatedness contribute to episodic encoding of arousing words, but the impact of each factor depends on both a word's valence and its context.

Reward sensitivity in impulsivity.

Impulsive individuals choose immediate small over delayed larger rewards, suggesting reward hypersensitivity. Single-unit studies have shown increased ventral tegmental activity to rewards and reward predictors and decreased activity when predicted rewards are withheld. The orbitofrontal ventral tegmental cortical target also responds to reward and expectation in single-unit and neuroimaging studies. The anterior P2a event-related potential component is a proposed index of reward-related orbitofrontal activity. In this reward prediction study in high and low impulsive subjects, the P2a localized to orbitofrontal cortex and was largest to non-predicted rewards and smallest in the absence of predicted rewards in subjects higher on self-reported impulsiveness, consistent with a P2a index of orbitofrontal reward processing and with reward hypersensitivity in impulsivity.