David Cucurell

Human oscillatory activity associated to reward processing in a gambling task

Previous event-related brain potential (ERP) studies have identified a medial frontal negativity (MFN) in response to negative feedback or monetary losses. In contrast, no EEG correlates have been identified related to the processing of monetary gains or positive feedback. This result is puzzling considering the large number of brain regions involved in the processing of rewards. In the present study we used a gambling task to investigate this issue with trial-by-trial wavelet-based time-frequency analysis of the electroencephalographic signal recorded non-invasively in healthy humans. Using this analysis a mediofrontal oscillatory component in the beta range was identified which was associated to monetary gains. In addition, standard time-domain ERP analysis showed an MFN for losses that was associated with an increase in theta power in the time-frequency analysis. We propose that the reward-related beta oscillatory activity signifies the functional coupling of distributed brain regions involved in reward processing.

The Impact of Catechol-O-Methyltransferase and Dopamine D4 Receptor Genotypes on Neurophysiological Markers of Performance Monitoring

Dynamic adaptations of ones behavior by means of performance monitoring are a central function of the human executive system, that underlies considerable interindividual variation. Converging evidence from electrophysiological and neuroimaging studies in both animals and humans hints at the importance of the dopaminergic system for the regulation of performance monitoring. Here, we studied the impact of two polymorphisms affecting dopaminergic functioning in the prefrontal cortex [catechol-O-methyltransferase (COMT) Val108/158Met and dopamine D4 receptor (DRD4) single-nucleotide polymorphism (SNP)-521] on neurophysiological correlates of performance monitoring. We applied a modified version of a standard flanker task with an embedded stop-signal task to tap into the different functions involved, particularly error monitoring, conflict detection and inhibitory processes. Participants homozygous for the DRD4 T allele produced an increased error-related negativity after both choice errors and failed inhibitions compared with C-homozygotes. This was associated with pronounced compensatory behavior reflected in higher post-error slowing. No group differences were seen in the incompatibility N2, suggesting distinct effects of the DRD4 polymorphism on error monitoring processes. Additionally, participants homozygous for the COMT Val allele, with a thereby diminished prefrontal dopaminergic level, revealed increased prefrontal processing related to inhibitory functions, reflected in the enhanced stop-signal-related components N2 and P3a. The results extend previous findings from mainly behavioral and neuroimaging data on the relationship between dopaminergic genes and executive functions and present possible underlying mechanisms for the previously suggested association between these dopaminergic polymorphisms and psychiatric disorders as schizophrenia or attention deficit hyperactivity disorder.

The Effects of COMT (Val108/158Met) and DRD4 (SNP −521) Dopamine Genotypes on Brain Activations Related to Valence and Magnitude of Rewards

Peoples sensitivity to reinforcing stimuli such as monetary gains and losses shows a wide interindividual variation that might in part be determined by genetic differences. Because of the established role of the dopaminergic system in the neural encoding of rewards and negative events, we investigated young healthy volunteers being homozygous for either the Valine or Methionine variant of the catechol-O-methyltransferase (COMT) codon 158 polymorphism as well as homozygous for the C or T variant of the SNP -521 polymorphism of the dopamine D4 receptor. Participants took part in a gambling paradigm featuring unexpectedly high monetary gains and losses in addition to standard gains/losses of expected magnitude while undergoing functional magnetic resonance imaging at 3 T. Valence-related brain activations were seen in the ventral striatum, the anterior cingulate cortex, and the inferior parietal cortex. These activations were modulated by the COMT polymorphism with greater effects for valine/valine participants but not by the D4 receptor polymorphism. By contrast, magnitude-related effects in the anterior insula and the cingulate cortex were modulated by the D4 receptor polymorphism with larger responses for the CC variant. These findings emphasize the differential contribution of genetic variants in the dopaminergic system to various aspects of reward processing.

On the number of trials needed for a stable feedback-related negativity

Feedback-related negativity is an event-related brain potential elicited by negative feedback. Its properties make it a valuable tool for the assessment of cognitive-affective processes that are involved in feedback and reward processing. The present study sought to determine the minimum number of trials that are required to obtain a reliable FRN component using a simple gambling paradigm. Three independent groups of young participants and one group of old participants were used. In the experimental conditions with healthy young controls, 20 trials were sufficient to measure the optimal FRN amplitude. In older participants, 50 trials were needed to obtain a reliable FRN. Whereas 20 trials would be enough to ensure a reliable FRN component in studies with nonclinical samples, the number of trials needed in clinical and cognitively impaired populations has to be determined based on the signal-to-noise ratios and the characteristics of the signals recorded.

Updating Fearful Memories with Extinction Training during Reconsolidation: A Human Study Using Auditory Aversive Stimuli

Learning to fear danger in the environment is essential to survival, but dysregulation of the fear system is at the core of many anxiety disorders. As a consequence, a great interest has emerged in developing strategies for suppressing fear memories in maladaptive cases. Recent research has focused in the process of reconsolidation where memories become labile after being retrieved. In a behavioral manipulation, Schiller et al., (2010) reported that extinction training, administrated during memory reconsolidation, could erase fear responses. The implications of this study are crucial for the possible treatment of anxiety disorders without the administration of drugs. However, attempts to replicate this effect by other groups have been so far unsuccessful. We sought out to reproduce Schiller et al., (2010) findings in a different fear conditioning paradigm based on auditory aversive stimuli instead of electric shock. Following a within-subject design, participants were conditioned to two different sounds and skin conductance response (SCR) was recorded as a measure of fear. Our results demonstrated that only the conditioned stimulus that was reminded 10 minutes before extinction training did not reinstate a fear response after a reminder trial consisting of the presentation of the unconditioned stimuli. For the first time, we replicated Schiller et al., (2010) behavioral manipulation and extended it to an auditory fear conditioning paradigm.

Genetic Variability in the Dopamine System (Dopamine Receptor D4, Catechol-O-Methyltransferase) Modulates Neurophysiological Responses to Gains and Losses

BACKGROUND Interindividual variability in the processing of reward might be partially explained by genetic differences in the dopamine system. Here, we study whether brain responses (event-related potentials [ERPs], oscillatory activity) to monetary gains and losses in normal human subjects are modulated as a function of two dopaminergic polymorphisms (catechol-O-methyltransferase [COMT] valine [Val]158methionine [Met], dopamine receptor D4 [DRD4] single nucleotide polymorphism [SNP] -521). METHODS Forty participants homozygous for the different alleles of both polymorphisms were selected from a larger population to assess the main effects and interactions. Based on the phasic/tonic dopamine hypothesis, we expected increased brain responses to losses and gains in participants homozygous for the Val/Val variant of the COMT polymorphism (related to higher enzyme activity). RESULTS The medial frontal negativity (MFN) of the ERP and the increase in beta power for gains were enhanced for participants homozygous for the COMT ValVal allele when compared with homozygous MetMet participants. In contrast, no modulations in gain- and loss-related brain activity were found to be a function of the DRD4 SNP -521 polymorphism. CONCLUSIONS The results demonstrate the role of the COMT Val/Met polymorphism in the processing of reward, consistent with theoretical explanations that suggest the possible role of dopamine in the MFN and beta power increase generation. In addition, the present results might agree with the phasic/tonic dopamine theory that predicts higher phasic dopamine responses in ValVal participants.

ADHD candidate gene (DRD4 exon III) affects inhibitory control in a healthy sample.

BackgroundDopamine is believed to be a key neurotransmitter in the development of attention-deficit/hyperactivity disorder (ADHD). Several recent studies point to an association of the dopamine D4 receptor (DRD4) gene and this condition. More specifically, the 7 repeat variant of a variable number of tandem repeats (VNTR) polymorphism in exon III of this gene is suggested to bear a higher risk for ADHD. In the present study, we investigated the role of this polymorphism in the modulation of neurophysiological correlates of response inhibition (Go/Nogo task) in a healthy, high-functioning sample.ResultsHomozygous 7 repeat carriers showed a tendency for more accurate behavior in the Go/Nogo task compared to homozygous 4 repeat carriers. Moreover, 7 repeat carriers presented an increased nogo-related theta band response together with a reduced go-related beta decrease.ConclusionsThese data point to improved cognitive functions and prefrontal control in the 7 repeat carriers, probably due to the D4 receptors modulatory role in prefrontal areas. The results are discussed with respect to previous behavioral data on this polymorphism and animal studies on the impact of the D4 receptor on cognitive functions.

Neurophysiological differences in reward processing in anhedonics

Anhedonia is characterized by a reduced capacity to experience pleasure in response to rewarding stimuli and has been considered a possible candidate endophenotype in depression and schizophrenia. However, it is still not well understood whether these reward deficits are confined to anticipatory and/or to consummatory experiences of pleasure. In the present study, we recorded electrophysiological responses (event-related brain potentials [ERPs] and oscillatory activity) to monetary gains and losses in extreme groups of anhedonic and nonanhedonic participants. The anhedonic participants showed reduced motivation to incur risky decisions, especially after monetary rewards. These sequential behavioral effects were correlated with an increased sensitivity to punishment, which psychometrically characterized the anhedonic group. In contrast, both electrophysiological measures associated with the impacts of monetary losses and gains—the feedback-related negativity (FRN) and the beta–gamma oscillatory component—clearly revealed preserved consummatory responses in anhedonic participants. However, anhedonics showed a drastic increase in frontal medial theta power after receiving the maximum monetary gain. This increase in theta oscillatory activity could be associated with an increase in conflict and cognitive control for unexpected large positive rewards, thus indexing the violation of default negative expectations built up across the task in anhedonic participants. Thus, the present results showed that participants with elevated scores on Chapman’s Physical Anhedonia Scale were more sensitive to possible punishments, showed deficits in the correct integration of response outcomes in their actions, and evidenced deficits in sustaining positive expectations of future rewards. This overall pattern suggests an effect of anhedonia in the motivational aspects of approach behavior rather than in consummatory processes.

Electrophysiological correlates of anticipating improbable but desired events

Psychological studies have emphasized that motivation is regulated by the anticipation of the emotional impact from the possible occurrence of unexpected rewarding events. Here, we scrutinized the existence of a corresponding neural signal by means of event-related potentials (ERPs) and computational modeling. In the first experiment, we designed a task that manipulated the probability of gaining a monetary reward and measured ERPs during anticipation and at reward delivery. A sustained frontocentral neural activity (i.e., the stimulus preceding negativity, SPN) was evidenced during the anticipation period. Critically, the SPN was found to increase in amplitude as the reward became more unexpected. Changes in the SPN were found to be predictive of individual differences in risk seeking, suggesting that a greater risk attitude involved a greater motivational state for receiving an improbable reward. In the second experiment, SPN results associated with unexpected monetary gains were replicated in a condition in which participants avoided monetary losses and the occurrence of unexpected rewards was also associated with an increase in the amount of self-reported pleasure. These findings support the existence of a neural ERP signature that encodes the process of tuning our motivation to the possibility of receiving a desirable but improbable rewarding outcome.

Neurophysiological markers of novelty processing are modulated by COMT and DRD4 genotypes.

Humans are faced with the dilemma to maintain a stable cognitive set on the one hand and to be able to redirect and switch attention to novel stimuli of potential importance. The dopaminergic system has been implicated in the balance between these two antagonistic constraints and in particular in novelty processing. Here we studied the impact of two polymorphisms affecting dopaminergic functioning (COMT Val108/158Met and DRD4 SNP -521) on neurophysiological correlates of novelty processing. Recording event-related potentials (ERPs) and oscillatory activity in a modified oddball task that featured infrequent but task-irrelevant novel sounds in addition to frequent standard and rare target tones, we examined participants homozygous for the Met or Val variant of COMT as well as homozygous for the C or T variant of DRD4. We found effects mainly on the P3a component to novel stimuli. A greater P3a amplitude was found for the COMT-ValVal group relative to MetMet. There was a tendency for DRD4-TT participants to show greater P3a amplitude and shorter P3a latency. Finally, DRD4-TT and COMT-ValVal participants showed the greatest increase of theta-power to novel stimuli. By contrast, the P3b component to target stimuli showed little influence of the studied polymorphism. Individual differences in dopaminergic genes explain part of the interindividual variance in the neural correlates of novelty but not target processing.