Toni Cunillera

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.

Neurophysiological mechanisms involved in language learning in adults

Little is known about the brain mechanisms involved in word learning during infancy and in second language acquisition and about the way these new words become stable representations that sustain language processing. In several studies we have adopted the human simulation perspective, studying the effects of brain-lesions and combining different neuroimaging techniques such as event-related potentials and functional magnetic resonance imaging in order to examine the language learning (LL) process. In the present article, we review this evidence focusing on how different brain signatures relate to (i) the extraction of words from speech, (ii) the discovery of their embedded grammatical structure, and (iii) how meaning derived from verbal contexts can inform us about the cognitive mechanisms underlying the learning process. We compile these findings and frame them into an integrative neurophysiological model that tries to delineate the major neural networks that might be involved in the initial stages of LL. Finally, we propose that LL simulations can help us to understand natural language processing and how the recovery from language disorders in infants and adults can be accomplished.

Time course and functional neuroanatomy of speech segmentation in adults

The present investigation was devoted to unraveling the time-course and brain regions involved in speech segmentation, which is one of the first processes necessary for learning a new language in adults and infants. A specific brain electrical pattern resembling the N400 language component was identified as an indicator of speech segmentation of candidate words. This N400 trace was clearly elicited after a short exposure to the words of the new language and showed a decrease in amplitude with longer exposure. Two brain regions were observed to be active during this process: the posterior superior temporal gyrus and the superior part of the ventral premotor cortex. We interpret these findings as evidence for the existence of an auditory-motor interface that is responsible for isolating possible candidate words when learning a new language in adults.

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.

The effects of stress and statistical cues on continuous speech segmentation: An event-related brain potential study

The study of the processes involved in speech segmentation has gained special relevance in recent years by trying to establish what type of information listeners use to segment the speech signal into words. An event-related brain potential experiment was conducted in order to understand how two of these cues (statistical and stress cues) interact. The experiment consisted of the presentation of artificial speech streams in which words were marked either by statistical cues alone, or by a combination of statistical and stress cues. As a baseline, comparison streams were also created with the same syllables but organized in random order. Results showed an N400 component that marks the on-line segmentation of speech into words, and an increased positivity (P2 component) for languages that include both types of cues. Possible implications of these results for the process of speech segmentation are discussed.

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.

Recognition of morphologically complex words in Finnish: Evidence from event-related potentials

The temporal dynamics of processing morphologically complex words was investigated by recording event-related brain potentials (ERPs) when native Finnish-speakers performed a visual lexical decision task. Behaviorally, there is evidence that recognition of inflected nouns elicits a processing cost (i.e., longer reaction times and higher error rates) in comparison to matched monomorphemic words. We aimed to reveal whether the processing cost stems from decomposition at the early visual word form level or from re-composition at the later semantic-syntactic level. The ERPs showed no early effects for morphology, but revealed an interaction with word frequency at a late N400-type component, as well as a late positive component that was larger for inflected words. These results suggest that the processing cost stems mainly from the semantic-syntactic level. We also studied the features of the morphological decomposition route by investigating the recognition of pseudowords carrying real morphemes. The results showed no differences between inflected vs. uninflected pseudowords with a false stem, but differences in relation to those with a real stem, suggesting that a recognizable stem is needed to initiate the decomposition route.

Brain oscillatory activity associated with task switching and feedback processing

In this study, we sought to dissociate event-related potentials (ERPs) and the oscillatory activity associated with signals indicating feedback about performance (outcome-based behavioral adjustment) and the signals indicating the need to change or maintain a task set (rule-based behavioral adjustment). With this purpose in mind, we noninvasively recorded electroencephalographic signals, using a modified version of the Wisconsin card sorting task, in which feedback processing and task switching could be studied separately. A similar late positive component was observed for the switch and correct feedback signals on the first trials of a series, but feedback-related negativity was observed only for incorrect feedback. Moreover, whereas theta power showed a significant increase after a switch cue and after the first positive feedback of a new series, a selective frontal beta–gamma increase was observed exclusively in the first positive feedback (i.e., after the selection of the new rule). Importantly, for the switch cue, beta–alpha activity was suppressed rather than increased. This clear dissociation between the cue and feedback stimuli in task switching emphasizes the need to accurately study brain oscillatory activity to disentangle the role of different cognitive control processes.

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.