Getting closer to social interactions using electroencephalography in developmental cognitive neuroscience.

The field of developmental cognitive neuroscience is advancing rapidly, with large-scale, population-wide, longitudinal studies emerging as a key means of unraveling the complexity of the developing brain and cognitive processes in children. While numerous neuroscientific techniques like functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS) have proved advantageous in such investigations, this perspective proposes a renewed focus on electroencephalography (EEG), leveraging underexplored possibilities of EEG. In addition to its temporal precision, low costs, and ease of application, EEG distinguishes itself with its ability to capture neural activity linked to social interactions in increasingly ecologically valid settings. Specifically, EEG can be measured during social interactions in the lab, hyperscanning can be used to study brain activity in two (or more) people simultaneously, and mobile EEG can be used to measure brain activity in real-life settings. This perspective paper summarizes research in these three areas, making a persuasive argument for the renewed inclusion of EEG into the toolkit of developmental cognitive and social neuroscientists.

L-DOPA and oxytocin influence the neural correlates of performance monitoring for self and others.

RATIONALE: The ability to monitor the consequences of our actions for others is imperative for flexible and adaptive behavior, and allows us to act in a (pro)social manner. Yet, little is known about the neurochemical mechanisms underlying alterations in (pro)social performance monitoring. OBJECTIVE: The aim of this functional magnetic resonance imaging (fMRI) study was to improve our understanding of the role of dopamine and oxytocin and their potential overlap in the neural mechanisms underlying performance monitoring for own versus others' outcomes. METHOD: Using a double-blind placebo-controlled cross-over design, 30 healthy male volunteers were administered oxytocin (24 international units), the dopamine precursor L-DOPA (100 mg + 25 mg carbidopa), or placebo in three sessions. Participants performed a computerized cannon shooting game in two recipient conditions where mistakes resulted in negative monetary consequences for (1) oneself or (2) an anonymous other participant. RESULTS: Results indicated reduced error-correct differentiation in the ventral striatum after L-DOPA compared to placebo, independent of recipient. Hence, pharmacological manipulation of dopamine via L-DOPA modulated performance-monitoring activity in a brain region associated with reward prediction and processing in a domain-general manner. In contrast, oxytocin modulated the BOLD response in a recipient-specific manner, such that it specifically enhanced activity for errors that affected the other in the pregenual anterior cingulate cortex (pgACC), a region previously implicated in the processing of social rewards and prediction errors. Behaviorally, we also found reduced target sizes-indicative of better performance-after oxytocin, regardless of recipient. Moreover, after oxytocin lower target sizes specifically predicted higher pgACC activity when performing for others. CONCLUSIONS: These different behavioral and neural patterns after oxytocin compared to L-DOPA administration highlight a divergent role of each neurochemical in modulating the neural mechanisms underlying social performance monitoring.

Neural processing of observed performance-based errors and rewards in the context of friends and unfamiliar peers across adolescence.

Adolescence is characterized by changes in performance monitoring, whereby action outcomes are monitored to subsequently adapt behavior and optimize performance. Observation of performance-based outcomes (i.e., errors and rewards) received by others forms the basis of observational learning. Adolescence is also a period of increasing importance of peers, especially friends, and observing peers forms a crucial aspect of learning in the social context of the classroom. However, to our knowledge, no developmental fMRI studies have examined the neural mechanisms underlying observed performance monitoring of errors and rewards in the context of peers. The current fMRI study investigated the neural correlates of observing performance-based errors and rewards of peers in adolescents aged 9-16 years (N = 80). In the scanner, participants observed either their best friend or an unfamiliar peer play a shooting game resulting in performance-dependent rewards (based on hits) or losses (based on misses, i. e, errors), where outcomes affected both the player and the observing participant. Findings showed higher activation in the bilateral striatum and bilateral anterior insula when adolescents observed peers (i.e., best friend and unfamiliar peer) receive performance-based rewards compared to losses. This might reflect the heightened salience of observed reward processing in the peer context in adolescence. Our results further revealed lower activation in the left temporoparietal junction (TPJ) while adolescents observed the performance-based outcomes (rewards and losses) for their best friend than for an unfamiliar peer. Considering that observation of others' performance-based errors and rewards forms the basis of observational learning, this study provides a crucial first step in understanding and potentially improving adolescent observational learning in the peer context.

Expecting the unexpected: a review of learning under uncertainty across development.

Many of our decisions take place under uncertainty. To successfully navigate the environment, individuals need to estimate the degree of uncertainty and adapt their behaviors accordingly by learning from experiences. However, uncertainty is a broad construct and distinct types of uncertainty may differentially influence our learning. We provide a semi-systematic review to illustrate cognitive and neurobiological processes involved in learning under two types of uncertainty: learning in environments with stochastic outcomes, and with volatile outcomes. We specifically reviewed studies (N = 26 studies) that included an adolescent population, because adolescence is a period in life characterized by heightened exploration and learning, as well as heightened uncertainty due to experiencing many new, often social, environments. Until now, reviews have not comprehensively compared learning under distinct types of uncertainties in this age range. Our main findings show that although the overall developmental patterns were mixed, most studies indicate that learning from stochastic outcomes, as indicated by increased accuracy in performance, improved with age. We also found that adolescents tended to have an advantage compared with adults and children when learning from volatile outcomes. We discuss potential mechanisms explaining these age-related differences and conclude by outlining future research directions.

l-DOPA and oxytocin influence the neurocomputational mechanisms of self-benefitting and prosocial reinforcement learning.

Humans learn through reinforcement, particularly when outcomes are unexpected. Recent research suggests similar mechanisms drive how we learn to benefit other people, that is, how we learn to be prosocial. Yet the neurochemical mechanisms underlying such prosocial computations remain poorly understood. Here, we investigated whether pharmacological manipulation of oxytocin and dopamine influence the neurocomputational mechanisms underlying self-benefitting and prosocial reinforcement learning. Using a double-blind placebo-controlled cross-over design, we administered intranasal oxytocin (24 IU), dopamine precursor l-DOPA (100 mg + 25 mg carbidopa), or placebo over three sessions. Participants performed a probabilistic reinforcement learning task with potential rewards for themselves, another participant, or no one, during functional magnetic resonance imaging. Computational models of reinforcement learning were used to calculate prediction errors (PEs) and learning rates. Participants behavior was best explained by a model with different learning rates for each recipient, but these were unaffected by either drug. On the neural level, however, both drugs blunted PE signaling in the ventral striatum and led to negative signaling of PEs in the anterior mid-cingulate cortex, dorsolateral prefrontal cortex, inferior parietal gyrus, and precentral gyrus, compared to placebo, and regardless of recipient. Oxytocin (versus placebo) administration was additionally associated with opposing tracking of self-benefitting versus prosocial PEs in dorsal anterior cingulate cortex, insula and superior temporal gyrus. These findings suggest that both l-DOPA and oxytocin induce a context-independent shift from positive towards negative tracking of PEs during learning. Moreover, oxytocin may have opposing effects on PE signaling when learning to benefit oneself versus another.

Prevention is better than cure: effects of errors on memory performance during spatial learning in healthy aging.

BACKGROUND: Healthy aging is accompanied by a decline in learning ability and memory capacity. One widely-studied method to improve learning outcome is by reducing the occurrence of errors during learning (errorless learning; EL). However, there is also evidence that committing errors during learning (trial-and-error learning; TEL) may benefit memory performance. We argue that these inconsistent findings could be driven by a lack of control over the error frequency in traditional EL and TEL paradigms. AIM: This study employed a spatial learning task to study EL and TEL and to determine the impact of error frequency on memory recall in healthy older adults (OA; N = 68) and young adults (YA; N = 60). METHOD: Four groups of participants (YA-EL, YA-TEL, OA-EL, OA-TEL) were instructed to first place and memorize the locations of everyday objects in a chest of drawers presented on a computer screen, and in whom memory recall performance was later tested. In the TEL condition, the amount of errors made before the correct drawer was 'found' was predetermined, varying from 0 to 5. During the EL condition, every first attempt was correct (i.e., no errors were made). RESULTS: We found better overall performance in YA compared to OA and a beneficial effect of EL in both age groups. However, the amount of errors committed during learning did not influence accuracy of memory recall. CONCLUSION: Our results indicate that elimination of errors during learning can benefit memory performance in both YA and OA compared to TEL.

Self-centered or other-directed: Neural correlates of performance monitoring are dependent on psychopathic traits and social context.

Performing in a social context can result in negative feelings when our actions harm another person, but it can also lead to positive feelings when observing an opponent fail. The extent to which individuals scoring high on psychopathic traits, often characterized as self-centered with reduced concern for others' welfare, are sensitive to own and others' success and failure is yet unknown. However, knowledge about these processes is crucial for comprehending how these traits are involved in understanding ourselves and others during social interactions. In this functional magnetic resonance imaging (fMRI) study, healthy females scoring low or high on psychopathic traits performed a cannon-shooting game in non-social, cooperative, and competitive contexts. We hypothesized group differences regarding: (1) monitoring of own actions in a non-social context (errors that only negatively affect oneself) versus cooperative context (errors that also harm others), (2) successfully performing with either positive (shared gain) or negative consequences (selfish gain) for the co-player, and (3) observing other's performance leading to shared or selfish gain for oneself. Decreased performance-monitoring-related activations were found in posterior medial frontal cortex for females scoring high on psychopathic traits in the social versus non-social context. When observing others, striatal activations were stronger for selfish gains for high scorers and for shared gains for low scorers. The current outcomes demonstrate that performance-monitoring and reward-related brain activations importantly depend on the interplay between psychopathic traits and social context. We propose that these neural mechanisms may underlie the more self-centered behavior of individuals scoring high on psychopathic traits. As such, the current findings may open up new research avenues, which could advance our understanding of how personality traits impact performance monitoring in a wide variety of social contexts and could possibly lead to the development of interventions aimed at normalizing reduced concern for others.

Social Cognition and Obsessive-Compulsive Disorder: A Review of Subdomains of Social Functioning.

Disturbances in social cognitive processes such as the ability to infer others' mental states importantly contribute to social and functional impairments in psychiatric disorders. Yet, despite established social, emotional, and cognitive problems, the role of social cognition in obsessive-compulsive disorder is largely overlooked. The current review provides a first comprehensive overview of social (neuro)cognitive disturbances in adult patients with obsessive-compulsive disorder. Results of our review indicate various social cognitive alterations. Patients with obsessive-compulsive disorder show deficits in the recognition of affective social cues, specifically facial expressions of disgust, and more general deficits in theory of mind/mentalizing. Additionally, patients show heightened affective reactions and altered neural responding to emotions of self and others, as well as poor emotion regulation skills, which may contribute to poor social functioning of patients. However, the discrepancies in findings and scarcity of studies make it difficult to draw firm conclusions with regard to the specificity of social cognitive disturbances. The review offers directions for future research and highlights the need to investigate obsessive-compulsive disorder from an interactive social neurocognitive perspective in addition to the prevalent passive spectator perspective to advance our understanding of this intricate and burdensome disorder.

Human fecal contamination of water, soil, and surfaces in households sharing poor-quality sanitation facilities in Maputo, Mozambique.

Identifying the origin of fecal contamination can support more effective interventions to interrupt enteric pathogen transmission. Microbial source tracking (MST) assays may help to identify environmental routes of pathogen transmission although these assays have performed poorly in highly contaminated domestic settings, highlighting the importance of both diagnostic validation and understanding the context-specific ecological, physical, and sociodemographic factors driving the spread of fecal contamination. We assessed fecal contamination of compounds (clusters of 2-10 households that share sanitation facilities) in low-income neighborhoods of urban Maputo, Mozambique, using a set of MST assays that were validated with animal stool and latrine sludge from study compounds. We sampled five environmental compartments involved in fecal microbe transmission and exposure: compound water source, household stored water and food preparation surfaces, and soil from the entrance to the compound latrine and the entrances to each household. Each sample was analyzed by culture for the general fecal indicator Escherichia coli (cEC) and by real-time PCR for the E. coli molecular marker EC23S857, human-associated markers HF183/BacR287 and Mnif, and GFD, an avian-associated marker. We collected 366 samples from 94 households in 58 compounds. At least one microbial target (indicator organism or marker gene) was detected in 96% of samples (353/366), with both E. coli targets present in the majority of samples (78%). Human targets were frequently detected in soils (59%) and occasionally in stored water (17%) but seldom in source water or on food surfaces. The avian target GFD was rarely detected in any sample type but was most common in soils (4%). To identify risk factors of fecal contamination, we estimated associations with sociodemographic, meteorological, and physical sample characteristics for each microbial target and sample type combination using Bayesian censored regression for target concentration responses and Bayesian logistic regression for target detection status. Associations with risk factors were generally weak and often differed in direction between different targets and sample types, though relationships were somewhat more consistent for physical sample characteristics. Wet soils were associated with elevated concentrations of cEC and EC23S857 and odds of detecting HF183. Water storage container characteristics that expose the contents to potential contact with hands and other objects were weakly associated with human target detection. Our results describe a setting impacted by pervasive domestic fecal contamination, including from human sources, that was largely disconnected from the observed variation in socioeconomic and sanitary conditions. This pattern suggests that in such highly contaminated settings, transformational changes to the community environment may be required before meaningful impacts on fecal contamination can be realized.

Processing of performance errors predicts memory formation: Enhanced feedback-related negativities for corrected versus repeated errors in an associative learning paradigm.

Learning from errors or negative feedback is crucial for adaptive behavior. FMRI studies have demonstrated enhanced anterior cingulate cortex activity for errors that were later corrected versus repeated errors even when a substantial delay between the error and the opportunity to correct was introduced. We aimed at identifying the electrophysiological correlates of these processes by investigating the feedback-related negativity (FRN) and stimulus-locked P3. Participants had to learn and recall the location of 2-digit targets over consecutive rounds. Feedback was provided in two steps, first a color change indicated a correct or incorrect response (feedback phase) followed by presentation of the correct digit information (re-encoding phase). Behaviorally, participants improved performance from the first to the third round. FRN amplitudes time-locked to feedback were enhanced for corrected compared to repeated errors. The P3 in response to re-encoding did not differ between the two error types. The finding that FRN amplitudes positively predicted memory performance is consistent with the idea that the FRN reflects prediction errors and the need for enhanced cognitive control. Interestingly, this happens early during feedback processing and not at a later time point when re-encoding of correct information takes place. The prediction error signal reflected in the FRN is usually elicited by performance errors, but may thus also play a role in preparing/optimizing the system for memory formation. This supports the existence of a close link between action control and memory processes even when there is a substantial delay between error feedback and the opportunity to correct the error.

Enhanced error-related brain activations for mistakes that harm others: ERP evidence from a novel social performance-monitoring paradigm.

Our mistakes often have negative consequences for ourselves, but may also harm the people around us. Continuous monitoring of our performance is therefore crucial for both our own and others' well-being. Here, we investigated how modulations in responsibility for other's harm affects electrophysiological correlates of performance-monitoring, viz. the error-related negativity (ERN) and error positivity (Pe). Healthy participants (N = 27) performed a novel social performance-monitoring paradigm in two responsibility contexts. Mistakes made in the harmful context resulted in a negative consequence for a co-actor, i.e., hearing a loud aversive sound, while errors in the non-harmful context were followed by a soft non-aversive sound. Although participants themselves did not receive auditory feedback in either context, they did experience harmful mistakes as more distressing and reported higher effort to perform well in the harmful context. ERN amplitudes were enhanced for harmful compared to non-harmful mistakes. Pe amplitudes were unaffected. The present study shows that performing in a potentially harmful social context amplifies early automatic performance-monitoring processes and increases the impact of the resulting harmful mistakes. These outcomes not only further our theoretical knowledge of social performance monitoring, but also demonstrate a novel and useful paradigm to investigate aberrant responsibility attitudes in various clinical populations.

The impact of error frequency on errorless and errorful learning of object locations using a novel paradigm.

Errorless learning (EL) is an approach in which errors are eliminated or reduced as much as possible while learning of new information or skills. In contrast, during trial-and-error - or errorful - learning (TEL) errors are not reduced and are often even promoted. There is a complex and conflicting pattern of evidence whether EL or TEL may result in better memory performance. One major confound in the extant literature is that most EL studies have not controlled for the number of errors made during TEL, resulting in a large variability in the amount of errors committed. This variability likely explains why studies on the cognitive underpinnings of EL and TEL have produced mixed findings. In this study, a novel object-location learning task was employed to examine EL and TEL in 30 healthy young adults. The number of errors was systematically manipulated, allowing us to investigate the impact of frequency of errors on learning outcome. The results showed that recall from memory was significantly better during EL. However, the number of errors made during TEL did not influence the performance in young adults. Altogether, our novel paradigm is promising for measuring EL and TEL, allowing for more accurate analyses to understand the impact of error frequency on a person's learning ability and style.

Neural Mechanisms Involved in Social Conformity and Psychopathic Traits: Prediction Errors, Reward Processing and Saliency.

Aligning behavior in favor of group norms, i.e., social conformity, can help to successfully adapt to uncertain environments and may result in social approval. This may lead to enhanced feelings of belongingness and is found to be associated with reward-related activations in the brain. Individuals high on psychopathic traits violate group norms regularly. Yet, it is unclear how psychopathic traits are related to neural mechanisms involved in social conformity. This functional magnetic resonance imaging (fMRI) study includes 42 healthy females scoring low or high on the Psychopathic Personality Inventory questionnaire (PPI). Participants were asked to rate the trustworthiness of 120 faces while lying in the scanner. After rating each face, participants were presented with the group rating of European students. In an unanticipated second part participants rated all faces again, allowing us to focus on two main contrasts: (1) "Social conflict": group opinion in conflict with the participant's rating vs. group opinion aligned with participant rating; and (2) "Conformity": conflict trials followed by conformity vs. conflict trials followed by non-conformity. Behaviorally, the two groups showed similar conformity behavior. fMRI results showed that both groups activated the nucleus accumbens (NAc) following alignment, suggesting the central role of prediction errors and reward. The data also showed a significant interaction between group and conformity in the amygdala. Following conflicts, females scoring low on psychopathic traits showed a trend in enhanced amygdala activation for conformity relative to non-conformity. Additionally, results showed a trend significant group effect for non-conformity. Females scoring high on psychopathic traits showed more activation for non-conformity compared to females scoring low on psychopathic traits, suggesting altered emotional salience of experiencing conflict depending on psychopathic traits. Taken together, these results support the importance of investigating the role of relevant traits in adaptive behavior when facing uncertain social situations and the neural mechanisms involved in this process.

Risk factors for childhood enteric infection in urban Maputo, Mozambique: A cross-sectional study.

BACKGROUND: Enteric infections are common where public health infrastructure is lacking. This study assesses risk factors for a range of enteric infections among children living in low-income, unplanned communities of urban Maputo, Mozambique. METHODS & FINDINGS: We conducted a cross-sectional survey in 17 neighborhoods of Maputo to assess the prevalence of reported diarrheal illness and laboratory-confirmed enteric infections in children. We collected stool from children aged 1-48 months, independent of reported symptoms, for molecular detection of 15 common enteric pathogens by multiplex RT-PCR. We also collected survey and observational data related to water, sanitation, and hygiene (WASH) characteristics; other environmental factors; and social, economic, and demographic covariates. We analyzed stool from 759 children living in 425 household clusters (compounds) representing a range of environmental conditions. We detected ≥1 enteric pathogens in stool from most children (86%, 95% confidence interval (CI): 84-89%) though diarrheal symptoms were only reported for 16% (95% CI: 13-19%) of children with enteric infections and 13% (95% CI: 11-15%) of all children. Prevalence of any enteric infection was positively associated with age and ranged from 71% (95% CI: 64-77%) in children 1-11 months to 96% (95% CI: 93-98%) in children 24-48 months. We found poor sanitary conditions, such as presence of feces or soiled diapers around the compound, to be associated with higher risk of protozoan infections. Certain latrine features, including drop-hole covers and latrine walls, and presence of a water tap on the compound grounds were associated with a lower risk of bacterial and protozoan infections. Any breastfeeding was also associated with reduced risk of infection. CONCLUSIONS: We found a high prevalence of enteric infections, primarily among children without diarrhea, and weak associations between bacterial and protozoan infections and environmental risk factors including WASH. Findings suggest that environmental health interventions to limit infections would need to be transformative given the high prevalence of enteric pathogen shedding and poor sanitary conditions observed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02362932.

Electrophysiological correlates of oxytocin-induced enhancement of social performance monitoring.

Altered performance monitoring has been demonstrated after administration of different pharmacological compounds and in various clinical populations, such as excessive neurophysiological responses to mistakes in anxiety disorders. Here, a novel social pharmacological approach was applied to investigate whether oxytocin administration (24 IU) enhances performance monitoring for errors that have negative consequences for another individual, so-called social mistakes. Healthy male volunteers (N = 24) participated in a placebo-controlled crossover design. EEG measures were obtained while pairs of participants performed a speeded choice reaction-time task in an individual and social context. Following oxytocin administration, error-related negativity amplitudes were increased for social compared with individual mistakes. This increase was not found in the placebo condition. No effects of oxytocin were present in the individual context. The current study shows that oxytocin enhances performance monitoring specifically for social mistakes. This outcome is in line with a presumed role for oxytocin in salience attribution to social cues and underlines its context-dependency. Combining these processes may thus open up new research avenues and advance our understanding of individual differences in performance monitoring and oxytocin responses from a social neurocognitive, pharmacological and clinical perspective.

Oxytocin reduces amygdala responses during threat approach.

Oxytocin reduces amygdala responses to threatening social stimuli in males and has been suggested to facilitate approach-related processing by either decreasing anxiety or intensifying salience. The current administration study tested whether oxytocin either reduces or enhances amygdala responses during threat approach in a placebo-controlled randomized, double-blind, between-subjects design with 52 healthy males undergoing fMRI during a social approach-avoidance task. Oxytocin decreased amygdala activation during threat approach and not during threat avoidance. This neural effect supports oxytocin's social anxiolytic effects and provides a neuroendocrine mechanism promoting social approach. The findings may yield clinical implications for individuals suffering from dysregulations of social approach such as patients with anxiety disorders.

Opposite effects of cannabis and cocaine on performance monitoring.

Drug use is often associated with risky and unsafe behavior. However, the acute effects of cocaine and cannabis on performance monitoring processes have not been systematically investigated. The aim of the current study was to investigate how administration of these drugs alters performance monitoring processes, as reflected in the error-related negativity (ERN), the error positivity (Pe) and post-error slowing. A double-blind placebo-controlled randomized three-way crossover design was used. Sixty-one subjects completed a Flanker task while EEG measures were obtained. Subjects showed diminished ERN and Pe amplitudes after cannabis administration and increased ERN and Pe amplitudes after administration of cocaine. Neither drug affected post-error slowing. These results demonstrate diametrically opposing effects on the early and late phases of performance monitoring of the two most commonly used illicit drugs of abuse. Conversely, the behavioral adaptation phase of performance monitoring remained unaltered by the drugs.

Competitive Game Play Attenuates Self-Other Integration during Joint Task Performance.

Joint task performance is facilitated by sharing and integrating each other's action representations. Research has shown that the amount of this so-called self-other integration depends on situational aspects related to the social context, including differences in the social relationship between co-acting individuals. There are indications that a cooperative relationship facilitates self-other integration while a competitive relationship results in more individualistic task performance. However, findings from previous studies in which the cooperative or competitive element was manipulated during task performance are inconsistent. Therefore, the present study aimed to manipulate the social relationship between two individuals prior to performing a social Simon task. This task is frequently used to measure self-other integration and distinction processes. A mixed-within-and-between-subjects design was used in which three groups of participants performed both a standard Simon task and a social Simon task after having played a Tetris game either individually, in cooperation with a co-actor, or in competition against another participant. Performance on the standard Simon task was not affected by the Tetris manipulation. However, a sustained effect of the induced cooperative versus competitive relationship was found on the social Simon Task. Less self-other integration was found in participants who had first played a competitive Tetris game compared to participants who had played a cooperative or solo version of the game. The current study thus demonstrates that an established cooperative or competitive relationship is sufficient to modulate the degree of self-other integration on subsequent joint task performance. Importantly, by using Tetris, attention to others' actions was beneficial both during cooperative and competitive game play and can thus not explain the competition-induced reduction of self-other integration.

Acute effects of cocaine and cannabis on reversal learning as a function of COMT and DRD2 genotype.

RATIONALE: Long-term cannabis and cocaine use has been associated with impairments in reversal learning. However, how acute cannabis and cocaine administration affect reversal learning in humans is not known. OBJECTIVE: In this study, we aimed to establish the acute effects of administration of cannabis and cocaine on valence-dependent reversal learning as a function of DRD2 Taq1A (rs1800497) and COMT Val108/158Met (rs4680) genotype. METHODS: A double-blind placebo-controlled randomized 3-way crossover design was used. Sixty-one regular poly-drug users completed a deterministic reversal learning task under the influence of cocaine, cannabis, and placebo that enabled assessment of both reward- and punishment-based reversal learning. RESULTS: Proportion correct on the reversal learning task was increased by cocaine, but decreased by cannabis. Effects of cocaine depended on the DRD2 genotype, as increases in proportion correct were seen only in the A1 carriers, and not in the A2/A2 homozygotes. COMT genotype did not modulate drug-induced effects on reversal learning. CONCLUSIONS: These data indicate that acute administration of cannabis and cocaine has opposite effects on reversal learning. The effects of cocaine, but not cannabis, depend on interindividual genetic differences in the dopamine D2 receptor gene.

Acute effects of cocaine and cannabis on response inhibition in humans: an ERP investigation.

Substance abuse has often been associated with alterations in response inhibition in humans. Not much research has examined how the acute effects of drugs modify the neurophysiological correlates of response inhibition, or how these effects interact with individual variation in trait levels of impulsivity and novelty seeking. This study investigated the effects of cocaine and cannabis on behavioural and event-related potential (ERP) correlates of response inhibition in 38 healthy drug using volunteers. A double-blind placebo-controlled randomized three-way crossover design was used. All subjects completed a standard Go/NoGo task after administration of the drugs. Compared with a placebo, cocaine yielded improved accuracy, quicker reaction times and an increased prefrontal NoGo-P3 ERP. Cannabis produced opposing results; slower reaction times, impaired accuracy and a reduction in the amplitude of the prefrontal NoGo-P3. Cannabis in addition decreased the amplitude of the parietally recorded P3, while cocaine did not affect this. Neither drugs specifically affected the N2 component, suggesting that pre-motor response inhibitory processes remain unaffected. Neither trait impulsivity nor novelty seeking interacted with drug-induced effects on measures of response inhibition. We conclude that acute drug effects on response inhibition seem to be specific to the later, evaluative stages of response inhibition. The acute effects of cannabis appeared less specific to response inhibition than those of cocaine. Together, the results show that the behavioural effects on response inhibition are reflected in electrophysiological correlates. This study did not support a substantial role of vulnerability personality traits in the acute intoxication stage.