Facial,verbal, and symbolic stimuli differently affect the right hemisphere preponderance of stimulus‐preceding negativity

The present study investigated whether the right hemisphere preponderance of stimulus‐preceding negativity (SPN) was affected by different categories of visual feedback stimulus. A time estimation task was performed with facial, verbal, symbolic, and no‐feedback conditions. A principal component analysis identified an early component of SPN in addition to a late component that was morphologically similar to the original SPN. Motivational scores in the verbal and facial conditions were higher than that in the symbolic condition. Significant right hemisphere preponderance of the late SPN was observed in the symbolic condition but not in the verbal condition, whereas right hemisphere preponderance of the early SPN was observed in the facial condition. The right hemisphere preponderance was influenced by the category of visual feedback stimulus through stimulus‐related activation and the effect of the motivational level.     

Preparing for saliencies: Emotional expectations under probabilistically and aversively salient situations

In humans, the expectation process in decision making has not been as thoroughly investigated as the evaluation process. The present study focused on the interaction between probabilistic saliency and motivational saliency during expectation and evaluation periods using stimulus‐preceding negativity (SPN) and reward positivity (RewP). Twenty healthy participants performed a modified monetary‐incentive delay task under reward‐approach and punishment‐avoidance conditions. Each condition was characterized by the likely outcome (reward only, punishment only) to manipulate motivational saliency. The task difficulty was regulated to control for probabilistic saliency, and the error trial was set as a probabilistically salient event (75% correct, 25% error). The results demonstrated that there was a larger SPN in the 25%‐error trial than the 75%‐correct trial and that it was left hemisphere predominant. Furthermore, there was an interaction between probabilistic and motivational saliency such that the SPN in the error trial was larger in the punishment‐avoidance than in the reward‐approach condition at Fz and at the right hemisphere. In contrast, RewP was only significantly different from zero in the 75%‐correct trial in the reward‐approach condition. These results confirm that the SPN increases with probabilistic saliency and that probabilistically salient events may intervene in the motivational saliency of the outcome; furthermore, that RewP reflects the weighted positive value of the outcome for reward but not the weighted negative value of the outcome for punishment. We discuss the interaction between probabilistic saliency and motivational saliency on SPN and its left hemisphere predominance based on the functions of the insular cortex.     

Changes in the stimulus‐preceding negativity and lateralized readiness potential during reinforcement learning

According to reinforcement learning theory, dopamine‐dependent anticipatory processes play a critical role in learning from action outcomes such as feedback or reward. To better understand outcome anticipation, we examined variation in slow cortical potentials and assessed their changes over the course of motor‐skill acquisition. Healthy young adults learned a series of precisely timed, key press sequences. Feedback was delivered at a delay of either 2.5 or 8 s, to encourage use of either the striatally mediated, habit learning system or the hippocampus‐dependent, episodic memory system, respectively. During the 2.5‐s delay, the stimulus‐preceding negativity (SPN) was shown to decline in amplitude across trials, confirming previous results from a perceptual categorization task (Morís, Luque, & Rodríguez‐Fornells, 2013). This falsifies the hypothesis that SPN reflects specific outcome predictions, on the assumption that the ability to make such predictions should improve as a task is mastered. An SPN was also evident during the 8‐s delay, but it increased in amplitude across trials. At the conclusion of the 8‐s but not the 2.5‐s prefeedback interval, a reversed‐polarity lateralized readiness potential (LRP) was noted. It was suggested that this might indicate maintenance of an action representation for comparison with the feedback display. If so, this would constitute the first direct psychophysiological evidence for a popular hypothetical construct in quantitative models of reinforcement learning, the so‐called eligibility trace.     

The role of outcome expectations in the generation of the feedback‐related negativity

The feedback‐related negativity (FRN) is thought to index activity within the midbrain dopaminergic reward‐learning system, with larger FRN magnitudes observed when outcomes are worse than expected. This view holds that the FRN is an index of neural activity coding for prediction errors, and reflects activity that can be used to adaptively alter future performance. Untested to date, however, is a key prediction of this view: the FRN should not appear in response to negative outcomes when outcome expectations are not allowed to develop. The current study tests this assumption by eliciting FRNs to win and loss feedback in conditions of participant choice, participant observation of computer choice, and, critically, simple presentation of win or loss feedback in the absence of a predictive choice cue. Whereas FRNs were observed in each of the conditions in which there was time for an expectation to develop, no FRN was observed in conditions without sufficient time for the development of an expectation. These results provide empirical support for an untested but central tenet of the reinforcement learning account of the genesis of the FRN.     

Quantifying learning‐dependent changes in the brain: Single‐trial multivoxel pattern analysis requires slow event‐related fMRI

Single‐trial analysis is particularly useful for assessing cognitive processes that are intrinsically dynamic, such as learning. Studying these processes with fMRI is problematic, as the low signal‐to‐noise ratio of fMRI requires the averaging over multiple trials, obscuring trial‐by‐trial changes in neural activation. The superior sensitivity of multivoxel pattern analysis over univariate analyses has opened up new possibilities for single‐trial analysis, but this may require different fMRI designs. Here, we measured fMRI and pupil dilation responses during discriminant aversive conditioning, to assess associative learning in a trial‐by‐trial manner. The impact of design choices was examined by varying trial spacing and trial order in a series of five experiments (total n = 66), while keeping stimulus duration constant (4.5 s). Our outcome measure was the change in similarity between neural response patterns related to two consecutive presentations of the same stimulus (within‐stimulus) and between patterns related to pairs of different stimuli (between‐stimulus) that shared a specific outcome (electric stimulation vs. no consequence). This trial‐by‐trial similarity analysis revealed clear single‐trial learning curves in conditions with intermediate (8.1–12.6 s) and long (16.5–18.4 s) intervals, with effects being strongest in designs with long intervals and counterbalanced stimulus presentation. No learning curves were observed in designs with shorter intervals (1.6–6.1 s), indicating that rapid event‐related designs—at present, the most common designs in fMRI research—are not suited for single‐trial pattern analysis. These findings emphasize the importance of deciding on the type of analysis prior to data collection.     

Differential effects of instructed and objective feedback reliability on feedback‐related brain activity

Feedback reliability refers to the probability that the same decision leads to the same positive or negative feedback in the future. Previous research has shown that unreliable feedback is associated with attenuated feedback‐related brain activity in ERPs, represented by a reduced fronto‐central valence effect (feedback‐related negativity or reward positivity) and a reduced feedback‐related P3. Here, we asked whether these effects reflect top‐down mechanisms or whether they can be explained by implicit feedback‐outcome contingency learning. In two experiments, participants performed a trial‐and‐error learning task while subjective or objective feedback reliability was varied across blocks. In Experiment 1, we manipulated instructed feedback reliability while holding objective feedback reliability constant. Low instructed feedback reliability led to an attenuation of the fronto‐central valence effect and the P3. In Experiment 2, we manipulated objective feedback reliability while holding instructed feedback reliability constant. Here, no modulation of feedback‐related brain activity was observed. These results suggest that effects of feedback reliability are driven by top‐down mechanisms based on explicit knowledge. Specifically, effects on the fronto‐central valence effect could indicate a devaluation of unreliable feedback or a bias on the generation or utilization of reward prediction errors.     

The feedback‐related negativity indexes prediction error in active but not observational learning

Reinforcement learning (RL) theory states that learning is driven by prediction errors (PEs)—the discrepancy between the predicted and actual outcome of an action. When participants learn from their own actions, PEs correlate with the feedback‐related negativity (FRN), but it is not clear if the FRN reflects a PE in observational learning. We use a model‐based regression analysis of single‐trial event‐related potentials to determine if the FRN in observational learning is PE driven. Twenty participants (16 female) learned the stimulus‐outcome contingencies for a probabilistic three‐armed bandit task. They played in pairs, with the acting and observing player switching every one to three trials. An RL‐learning algorithm was fit to participants' choices in the task to extract individual PE estimates for every trial of the experiment. In the acting condition, model‐estimated PEs covaried positively with neural signal at electrode FCz, 200–350 ms after outcome presentation, which is a typical time frame for the FRN. There was no PE effect in the observation condition in the same time frame. From 300 ms the outcome correlated negatively with the frontal P300 component at FCz and parietal P300 at Pz. At Pz the effect was greater in the acting than the observing condition. The frontal and parietal P300 components have been linked to attentional reorienting and stimulus value updating, respectively. These findings indicate that observed outcomes undergo processing that is distinguishable from directly experienced outcomes in the time windows of the FRN and P3b but that attention dedicated to the two outcomes types is comparable.     

Enhanced sensitization to animal,interpersonal, and intergroup fear‐relevant stimuli (but no evidence for selective one‐trial fear learning)

Selective sensitization has been proposed as an alternative explanation for enhanced responding to animal fear‐relevant stimuli—snakes and spiders—during extinction of Pavlovian fear conditioning. The current study sought to replicate the phenomenon using a shock workup procedure as the sensitizing manipulation and to extend it to interpersonal and intergroup fear‐relevant stimuli—angry faces and other‐race faces. Assessment of selective sensitization was followed by a one‐trial fear learning procedure. Selective sensitization, larger electrodermal responses to fear‐relevant than to control stimuli after sensitization, or a larger increase in electrodermal responding to fear‐relevant than to control stimuli after sensitization was observed across stimulus domains. However, the one‐trial fear learning procedure failed to provide evidence for enhanced fear conditioning to fear‐relevant stimuli. One‐trial fear learning was either absent or present for fear‐relevant and nonfear‐relevant stimuli. The current study confirms that electrodermal responses to fear‐relevant stimuli across stimulus domains are subject to selective sensitization.     

Electrophysiological correlates of prediction formation in anticipation of reward‐ and punishment‐related feedback signals

Feedback processing during decision making involves comparing anticipated and actual outcome. Although effects on ERPs of valence, magnitude, expectancy, and context during feedback processing have been extensively investigated, the electrophysiological processes underlying prediction formation in anticipation of feedback signals have received little attention. The aim of the present study was to explore these processes of prediction formation and their influence on subsequent feedback signals. Twenty healthy, right‐handed volunteers performed a forced‐choice task in which they had to indicate which of two presented objects was more expensive. After the volunteer's choice, an expert cue, which was accurate in 80% of trials, was presented to manipulate prediction formation about future reward and punishment. ERPs were recorded during presentation of the expert cue and during feedback. Results revealed that prediction formation of future rewards and punishments is accompanied by differences in the P2 component and a subsequent delay period. During feedback processing, the prediction‐related P2 was associated with the processing of valence reflected in the feedback‐related P2. Furthermore, the prediction‐related difference in the delay period was associated with error processing in feedback‐related medial frontal negativity. These findings suggest that prediction signals prior to feedback contain information about whether a prediction is correct or wrong (expectancy) and if the outcome will be a reward or punishment (valence).     

Brain activities associated with learning of the Monty Hall Dilemma task

The Monty Hall Dilemma (MHD) poses a counterintuitive probabilistic problem to the players of this game. In the MHD task, a participant chooses one of three options where only one contains a reward. After one of the unchosen options (always no reward) is disclosed, the participant is asked to make a final decision: either change to the remaining option or stick with their first choice. Although the probability of winning if they change is higher (2/3) compared to sticking with their first choice (1/3), most people stick with their original selection and often lose. In accordance with previous research, repetitive exposure to the MHD task increases the change behavior without any obvious understanding of the mathematical reasons why changing increases their chance of being rewarded. We recorded the stimulus‐preceding negativity (SPN), an ERP that might reflect the informative value of the feedback. In the second half of the task, feedback was predicted to be less informative because learning had taken place. Indeed, the SPN amplitude became smaller over the frontal region. Also, the SPN amplitude was larger for change than for stick trials. These results suggest that learning in the MHD might be manifest in affective‐motivational anticipation as indicated by the SPN.     

β‐catenin mutation in ovarian solid pseudopapillary neoplasm

Primaly solid pseudopapillary neoplasm (SPN) of the ovary is a rare tumor; recently 6 cases have been reported. Its pathogenesis, however, remains largely unclear. We report an additional case of primary ovarian SPN of an 18‐year‐old girl. The aim of this study is to define the difference between pancreatic and ovarian SPN by histological and molecular examination. Microscopically the tumor predominantly showed a solid pattern and focally a pseudopapillary pattern. The tumor cells showed two patterns of abundant eosinophilic cytoplasm and intracytoplasmic vacuoles. Immunohistochemistry of the tumor was positive for β‐catenin (nuclear and cytoplasmic reactivity), α1‐antitrypsin, vimentin, CD56, synaptophysin (focal weak), CD10. Mutation analyses revealed a point mutation, c.110C >T, in exon 3 of the the β‐catenin gene (CTNNB1), which causes the replacement of serine with phenylalanine at codon 37. A Ser37 point mutation is known to be one of the oncogenic somatic mutations in pancreatic SPN and the major oncogenic β‐catenin mutation. Ovarian SPN of our case was similar to pancreatic SPN histologicaly and had the same genomic characteristics. We expected that both ovarian and pancreatic SPNs shared the same oncogenesis related to Wnt/β‐catenin pathway for tumorgenesis.     

Neural response to action and reward prediction errors: Comparing the error‐related negativity to behavioral errors and the feedback‐related negativity to reward prediction violations

The error‐related negativity (ERN) is thought to index an anterior cingulate (ACC) behavioral monitoring system. The feedback ERN (FRN) is elicited to error feedback when the correct response is not known, but also when a choice outcome is suboptimal and to passive reward prediction violation, suggesting that the monitoring system may not be restricted to actions. This study used principal components analysis to show that the ERN consists of a single central component whereas the reward prediction violation FRN is comprised of central and prefrontal components. A prefrontal component is also present in action monitoring but occurs later, at the error positivity latency. This suggests that ACC monitors both actions and events for reward prediction error. Prefrontal cortex may update reward expectation based on the prediction violation with the latency difference due to differential processing time for motor and perceptual information.     

Effects of feedback delay and agency on feedback‐locked beta and theta power during reinforcement learning

Feedback‐based learning initiated by dopamine (DA) cell firing is crucial for adaptive behavior. The nature and context of feedback can vary, however, affecting how feedback is processed. For example, the feedback‐related negativity (FRN) in the ERP in humans, which has been linked to the DA system, is reduced for delayed feedback and for observational compared to active learning. Recent research suggested that oscillations in the theta and beta band over the medio‐frontal cortex reflect distinct feedback processing mechanisms. In this study, we hypothesized that the power in both frequency bands is affected by feedback delay and agency. We thus investigated effects of feedback delay (1 s vs. 7 s) on induced theta and beta band power and the FRN in a probabilistic feedback learning task in two participant groups, one learning actively and one by observation. For theta and beta, a larger power difference between negative and positive feedback for immediate than delayed feedback was found, driven by positive feedback for beta and by negative feedback for theta, while no differential modulation by agency was seen for theta or beta power following positive and negative feedback. These results indicate that feedback‐locked beta and theta both reflect neural processes that are specific for the integration of feedback and recently preceding events, possibly linked to cognitive control and memory. With respect to the FRN amplitude, we could replicate previous findings of both delay and agency modulations, suggesting that the neural processes underlying feedback‐locked ERPs and theta and beta power modulations differ.     

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.     

Approach‐motivated pregoal states enhance the reward positivity

Past work has demonstrated that the reward positivity (RewP) indexes a performance‐monitoring system sensitive to positive outcomes. However, studies have not investigated how approach‐motivated states occurring in goal pursuit influence performance monitoring. Using a modified monetary incentive delay task, participants played a reaction time game evoking approach‐motivated pregoal (reward trials) or neutral (no‐reward trials) states. Then, they received trial feedback resulting in monetary gain or no gain. Results revealed that the RewP was larger to win feedback on reward trials than win or no‐win feedback after neutral trials. P3 amplitudes were larger to infrequent feedback than frequent feedback, regardless of trial type or outcome. Furthermore, faster reaction times on reward trials related to larger RewP amplitudes after approach‐motivated pregoal states. Approach‐motivated pregoal states enhance RewP amplitudes for both successful and unsuccessful goal outcomes. Enhanced performance, as measured by faster reaction times, in approach‐motivated pregoal states relates to enhanced performance monitoring.     

Pancreatic fine‐needle aspiration cytology in patients < 35‐years of age: A retrospective review of 174 cases spanning a 17‐year period

Pancreatic lesions in young patients are relatively rare and, to our knowledge, the clinical value of pancreatic fine needle aspiration (FNA) in patients < 35 years of age has not been previously established by any other large retrospective studies. All pancreatic endoscopic ultrasound‐guided FNA (EUS‐FNA) cases performed on patients < 35 years of age were identified for a 17‐year period (1994–2010). All FNAs and all available correlating surgical pathology reports were reviewed. There were a total of 174 cases of pancreatic FNA performed on 109 females and 65 males under the age of 35 (range: 8–34, mean: 27 years). The FNA diagnoses included 37 malignant, 114 negative, nine atypia/suspicious, and 14 cases that were nondiagnostic. Of the 37 malignant FNA cases, the diagnoses included 18 pancreatic neuroendocrine tumors (PanNeT), 11 solid pseudopapillary neoplasms (SPN), five adenocarcinomas and three metastatic neoplasms. Histologic follow‐up was available in 22 of the 37 malignant cases diagnosed by FNA, and the diagnosis was confirmed in 21 cases. One pancreatoblastoma was misclassified as SPN on EUS‐FNA. False negative diagnoses were noted in three cases of low‐grade mucinous cystic neoplasm and one case of PanNeT. The most common type of neoplasms diagnosed by EUS‐FNA in patients < 35‐year old is PanNeT, followed by SPN with both tumors accounting for 75% of all the neoplasms encountered in this age group. The sensitivity and specificity for positive cytology in EUS‐FNA of the pancreas to identify malignancy and mucinous neoplasms were 90% and 100%, respectively. Diagn. Cytopathol. 2014;42:297–301. © 2013 Wiley Periodicals, Inc.     

Reward processing in gain versus loss context: An ERP study

Previous research has shown that consummatory ERP components are sensitive to contextual valence. The present study investigated the contextual valence effect across anticipatory and consummatory phases by requiring participants to play a simple gambling task during a gain context and a loss context. During the anticipatory phase, the cue‐P3 was more positive in the gain context compared to the loss context, whereas the stimulus‐preceding negativity (SPN) was comparable across the two contexts. With respect to the consummatory phase, the feedback‐related negativity (FRN) in response to the zero‐value outcome was more negative in the gain versus loss context, whereas the feedback P3 (fb‐P3) in response to the zero‐value outcome was insensitive to contextual valence. These findings suggest that contextual valence effect occurs at a relative early stage of both the reward anticipation and consumption. Moreover, across the gain and loss contexts, the SPN was selectively correlated with the FRN, whereas the cue‐P3 was selectively associated with the fb‐P3, pointing to a close association between the anticipatory and consummatory phases in reward dynamics.     

Anxiety and feedback negativity

It has been suggested that anxious individuals are more prone to feel that negative outcomes are particularly extreme and to interpret ambiguous outcomes as negative compared to nonanxious individuals. Previous studies have demonstrated that the feedback negativity (FN) component of event‐related brain potential (ERP) is sensitive to outcome evaluation and outcome expectancy. Hence, we predicted that the FN should be different between high trait‐anxiety (HTA) and low trait‐anxiety (LTA) individuals. To test our hypothesis, the ERPs were recorded during a simple monetary gambling task. The FN was measured as a difference wave created across conditions. We found that the amplitude of the FN indicating negative versus positive outcomes was significantly larger for LTA individuals compared to HTA individuals. However, there was no significant difference in the FN between groups in response to ambiguous versus positive outcomes. The results indicate that there is a relationship between the FN and individual differences in anxiety. We suggest that these results reflect the impact of anxiety on outcome expectation. Our results challenge the reinforcement learning theory of error‐related negativity, which proposes that ERN and FN reflect the same cognitive process.     

Large lateralized EDAN‐like brain potentials in a gaze‐shift detection task

Attentional cueing tasks using gaze direction as spatial cues have sometimes yielded an early directing attention negativity (EDAN) component in the ERP, presumably reflecting the initial orienting toward the cued location. However, other studies have failed to identify an EDAN component for gaze cues, yielding an inconsistent picture. In the present study, we re‐examined the EDAN to gaze cueing, using a continuous task where the specific direction of the gaze changes was task irrelevant. Face stimuli changed gaze direction several times during each trial between direct, left‐, and right‐averted positions. Participants counted the number of gaze shifts during the trial. Results showed an unusually large EDAN‐like ERP asymmetry at posterior scalp sites that was of similar amplitude for large and small gaze shifts into the periphery. Shifts from an averted position toward a direct gaze elicited a qualitatively similar but smaller effect than shifts into the periphery. Together, these findings shed new light on gaze‐elicited spatial attention as they indicate a reflexive attention orienting, following the direction of gaze motion, even when the gaze direction itself is irrelevant for the task.     

The effect of interpersonal competition on monitoring internal and external error feedback

The present study examined the effect of the social context on early emotional appraisal of performance errors and negative feedback reflected by the error‐related negativity (ERN), feedback‐related negativity (FRN), and P300. Participants performed a probabilistic learning task in which they received valid and invalid performance feedback. During one half of the task they were led to believe that they were competing online against another participant. As expected, the ERN following response errors was enhanced in the competition compared to the neutral condition. The FRN was more negative following negative compared to positive feedback and valid compared to invalid feedback, but only during competition. The P300 was larger to false positive than false negative feedback, which was independent of the social context. In conclusion, ERN and FRN, but not P300, may be sensitive to affective distress elicited by expectation violations during social interaction.