Prefrontal Neuromodulation Using rTMS Improves Error Monitoring and Correction Function in Autism

One important executive function known to be compromised in autism spectrum disorder (ASD) is related to response error monitoring and post-error response correction. Several reports indicate that children with ASD show reduced error processing and deficient behavioral correction after an error is committed. Error sensitivity can be readily examined by measuring event-related potentials (ERP) associated with responses to errors, the fronto-central error-related negativity (ERN), and the error-related positivity (Pe). The goal of our study was to investigate whether reaction time (RT), error rate, post-error RT change, ERN, and Pe will show positive changes following 12-week long slow frequency repetitive TMS (rTMS) over dorsolateral prefrontal cortex (DLPFC) in high functioning children with ASD. We hypothesized that 12 sessions of 1 Hz rTMS bilaterally applied over the DLPFC will result in improvements reflected in both behavioral and ERP measures. Participants were randomly assigned to either active rTMS treatment or wait-list (WTL) groups. Baseline and post-TMS/or WTL EEG was collected using 128 channel EEG system. The task involved the recognition of a specific illusory shape, in this case a square or triangle, created by three or four inducer disks. ERN in TMS treatment group became significantly more negative. The number of omission errors decreased post-TMS. The RT did not change, but post-error RT became slower. There were no changes in RT, error rate, post-error RT slowing, nor in ERN/Pe measures in the wait-list group. Our results show significant post-TMS differences in the response-locked ERP such as ERN, as well as behavioral response monitoring measures indicative of improved error monitoring and correction function. The ERN and Pe, along with behavioral performance measures, can be used as functional outcome measures to assess the effectiveness of neuromodulation (e.g., rTMS) in children with autism and thus may have important practical implications.     

Suppression (but Not Reappraisal) Impairs Subsequent Error Detection: An ERP Study of Emotion Regulation's Resource-Depleting Effect

Past event-related potentials (ERPs) research shows that, after exerting effortful emotion inhibition, the neural correlates of performance monitoring (e.g. error-related negativity) were weakened. An undetermined issue is whether all forms of emotion regulation uniformly impair later performance monitoring. The present study compared the cognitive consequences of two emotion regulation strategies, namely suppression and reappraisal. Participants were instructed to suppress their emotions while watching a sad movie, or to adopt a neutral and objective attitude toward the movie, or to just watch the movie carefully. Then after a mood scale, all participants completed an ostensibly unrelated Stroop task, during which ERPs (i.e. error-related negativity (ERN), post-error positivity (Pe) and N450) were obtained. Reappraisal group successfully decreased their sad emotion, relative to the other two groups. Compared with participants in the control group and the reappraisal group, those who suppressed their emotions during the sad movie showed reduced ERN after error commission. Participants in the suppression group also made more errors in incongruent Stroop trials than the other two groups. There were no significant main effects or interactions of group for reaction time, Pe and N450. Results suggest that reappraisal is both more effective and less resource-depleting than suppression.     

Altered error processing following vascular thalamic damage: evidence from an antisaccade task

Event-related potentials (ERP) research has identified a negative deflection within about 100 to 150 ms after an erroneous response--the error-related negativity (ERN)--as a correlate of awareness-independent error processing. The short latency suggests an internal error monitoring system acting rapidly based on central information such as an efference copy signal. Studies on monkeys and humans have identified the thalamus as an important relay station for efference copy signals of ongoing saccades. The present study investigated error processing on an antisaccade task with ERPs in six patients with focal vascular damage to the thalamus and 28 control subjects. ERN amplitudes were significantly reduced in the patients, with the strongest ERN attenuation being observed in two patients with right mediodorsal and ventrolateral and bilateral ventrolateral damage, respectively. Although the number of errors was significantly higher in the thalamic lesion patients, the degree of ERN attenuation did not correlate with the error rate in the patients. The present data underline the role of the thalamus for the online monitoring of saccadic eye movements, albeit not providing unequivocal evidence in favour of an exclusive role of a particular thalamic site being involved in performance monitoring. By relaying saccade-related efference copy signals, the thalamus appears to enable fast error processing. Furthermore early error processing based on internal information may contribute to error awareness which was reduced in the patients.     

Internal Consistency of Event-Related Potentials Associated with Cognitive Control: N2/P3 and ERN/Pe

Recent studies in psychophysiology show an increased attention for examining the reliability of Event-Related Potentials (ERPs), which are measures of cognitive control (e.g., Go/No-Go tasks). An important index of reliability is the internal consistency (e.g., Cronbach''s alpha) of a measure. In this study, we examine the internal consistency of the N2 and P3 in a Go/No-Go task. Furthermore, we attempt to replicate the previously found internal consistency of the Error-Related Negativity (ERN) and Positive-Error (Pe) in an Eriksen Flanker task. Healthy participants performed a Go/No-Go task and an Eriksen Flanker task, whereby the amplitudes of the correct No-Go N2/P3, and error trials for ERN/Pe were the variables of interest. This study provides evidence that the N2 and P3 in a Go/No-Go task are internally consistent after 20 and 14 trials are included in the average, respectively. Moreover, the ERN and Pe become internally consistent after approximately 8 trials are included in the average. In addition guidelines and suggestions for future research are discussed.     

Event-related potential correlates of performance-monitoring in a lateralized time-estimation task

Performance-monitoring as a key function of cognitive control covers a wide range of diverse processes to enable goal directed behavior and to avoid maladjustments. Several event-related brain potentials (ERP) are associated with performance-monitoring, but their conceptual background differs. For example, the feedback-related negativity (FRN) is associated with unexpected performance feedback and might serve as a teaching signal for adaptational processes, whereas the error-related negativity (ERN) is associated with error commission and subsequent behavioral adaptation. The N2 is visible in the EEG when the participant successfully inhibits a response following a cue and thereby adapts to a given stop-signal. Here, we present an innovative paradigm to concurrently study these different performance-monitoring-related ERPs. In 24 participants a tactile time-estimation task interspersed with infrequent stop-signal trials reliably elicited all three ERPs. Sensory input and motor output were completely lateralized, in order to estimate any hemispheric processing preferences for the different aspects of performance monitoring associated with these ERPs. In accordance with the literature our data suggest augmented inhibitory capabilities in the right hemisphere given that stop-trial performance was significantly better with left- as compared to right-hand stop-signals. In line with this, the N2 scalp distribution was generally shifted to the right in addition to an ipsilateral shift in relation to the response hand. Other than that, task lateralization affected neither behavior related to error and feedback processing nor ERN or FRN. Comparing the ERP topographies using the Global Map Dissimilarity index, a large topographic overlap was found between all considered components.With an evenly distributed set of trials and a split-half reliability for all ERP components ≥.85 the task is well suited to efficiently study N2, ERN, and FRN concurrently which might prove useful for group comparisons, especially in clinical populations.     

Deficits in Error-Monitoring by College Students with Schizotypal Traits: An Event-Related Potential Study

The present study used event-related potentials (ERPs) to investigate deficits in error-monitoring by college students with schizotypal traits. Scores on the Schizotypal Personality Questionnaire (SPQ) were used to categorize the participants into schizotypal-trait (n = 17) and normal control (n = 20) groups. The error-monitoring abilities of the participants were evaluated using the Simon task, which consists of congruent (locations of stimulus and response are the same) and incongruent (locations of stimulus and response are different) conditions. The schizotypal-trait group committed more errors on the Simon task and exhibited smaller error-related negativity (ERN) amplitudes than did the control group. Additionally, ERN amplitude measured at FCz was negatively correlated with the error rate on the Simon task in the schizotypal-trait group but not in the control group. The two groups did not differ in terms of correct-related potentials (CRN), error positivity (Pe) and correct-related positivity (Pc) amplitudes. The present results indicate that individuals with schizotypal traits have deficits in error-monitoring and that reduced ERN amplitudes may represent a biological marker of schizophrenia.     

Dopamine transporter (DAT1) and dopamine receptor D4 (DRD4) genotypes differentially impact on electrophysiological correlates of error processing

Recent studies as well as theoretical models of error processing assign fundamental importance to the brain's dopaminergic system. Research about how the electrophysiological correlates of error processing--the error-related negativity (ERN) and the error positivity (Pe)--are influenced by variations of common dopaminergic genes, however, is still relatively scarce. In the present study, we therefore investigated whether polymorphisms in the DAT1 gene and in the DRD4 gene, respectively, lead to interindividual differences in these error processing correlates. One hundred sixty participants completed a version of the Eriksen Flanker Task while a 26-channel EEG was recorded. The task was slightly modified in order to increase error rates. During data analysis, participants were split into two groups depending on their DAT1 and their DRD4 genotypes, respectively. ERN and Pe amplitudes after correct responses and after errors as well as difference amplitudes between errors and correct responses were analyzed. We found a differential effect of DAT1 genotype on the Pe difference amplitude but not on the ERN difference amplitude, while the reverse was true for DRD4 genotype. These findings are in line with predictions from theoretical models of dopaminergic transmission in the brain. They furthermore tie results from clinical investigations of disorders impacting on the dopamine system to genetic variations known to be at-risk genotypes.     

Placebo Analgesia Affects Brain Correlates of Error Processing

Placebo analgesia (PA) is accompanied by decreased activity in pain-related brain regions, but also by greater prefrontal cortex (PFC) activation, which has been suggested to reflect increases in top-down cognitive control and regulation of pain. Here we test whether PA is associated with altered prefrontal monitoring functions that could adjust nociceptive processing to a mismatch between expected and experienced pain. We recorded event-related potentials to response errors in a go/nogo task during placebo vs. a matched control condition. Error commission was associated with two well-described components, the error-related negativity (ERN) and the error positivity (Pe). Results show that the Pe, but not the ERN, was amplified during placebo analgesia compared to the control condition, with neural sources in the lateral and medial PFC. This Pe increase was driven by participants showing a placebo-induced change in pain tolerance, but was absent in the group of non-responders. Our results shed new light on the possible functional mechanisms underlying PA, suggesting a placebo-induced transient change in prefrontal error monitoring and control functions.     

In Your Face: Risk of Punishment Enhances Cognitive Control and Error-Related Activity in the Corrugator Supercilii Muscle

Cognitive control is needed when mistakes have consequences, especially when such consequences are potentially harmful. However, little is known about how the aversive consequences of deficient control affect behavior. To address this issue, participants performed a two-choice response time task where error commissions were expected to be punished by electric shocks during certain blocks. By manipulating (1) the perceived punishment risk (no, low, high) associated with error commissions, and (2) response conflict (low, high), we showed that motivation to avoid punishment enhanced performance during high response conflict. As a novel index of the processes enabling successful cognitive control under threat, we explored electromyographic activity in the corrugator supercilii (cEMG) muscle of the upper face. The corrugator supercilii is partially controlled by the anterior midcingulate cortex (aMCC) which is sensitive to negative affect, pain and cognitive control. As hypothesized, the cEMG exhibited several key similarities with the core temporal and functional characteristics of the Error-Related Negativity (ERN) ERP component, the hallmark index of cognitive control elicited by performance errors, and which has been linked to the aMCC. The cEMG was amplified within 100 ms of error commissions (the same time-window as the ERN), particularly during the high punishment risk condition where errors would be most aversive. Furthermore, similar to the ERN, the magnitude of error cEMG predicted post-error response time slowing. Our results suggest that cEMG activity can serve as an index of avoidance motivated control, which is instrumental to adaptive cognitive control when consequences are potentially harmful.     

ERP Correlates of Proactive and Reactive Cognitive Control in Treatment-Na?ve Adult ADHD

This study investigated whether treatment naïve adults with Attention Deficit Hyperactivity Disorder (ADHD; n = 33; 19 female) differed from healthy controls (n = 31; 17 female) in behavioral performance, event-related potential (ERP) indices of preparatory attention (CueP3 and late CNV), and reactive response control (Go P3, NoGo N2, and NoGo P3) derived from a visual cued Go/NoGo task. On several critical measures, Cue P3, late CNV, and NoGo N2, there were no significant differences between the groups. This indicated normal preparatory processes and conflict monitoring in ADHD patients. However, the patients had attenuated Go P3 and NoGoP3 amplitudes relative to controls, suggesting reduced allocation of attentional resources to processes involved in response control. The patients also had a higher rate of Go signal omission errors, but no other performance decrements compared with controls. Reduced Go P3 and NoGo P3 amplitudes were associated with poorer task performance, particularly in the ADHD group. Notably, the ERPs were not associated with self-reported mood or anxiety. The results provide electrophysiological evidence for reduced effortful engagement of attentional resources to both Go and NoGo signals when reactive response control is needed. The absence of group differences in ERP components indexing proactive control points to impairments in specific aspects of cognitive processes in an untreated adult ADHD cohort. The associations between ERPs and task performance provided additional support for the altered electrophysiological responses.     

Neurophysiological Evidence of Compensatory Brain Mechanisms in Early-Stage Multiple Sclerosis

Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by white matter inflammation, demyelination and neurodegeneration. Although cognitive dysfunction is a common manifestation, it may go unnoticed in recently-diagnosed patients. Prior studies suggest MS patients develop compensatory mechanisms potentially involving enhanced performance monitoring. Here we assessed the performance monitoring system in early-stage MS patients using the error-related negativity (ERN), an event-related brain potential (ERP) observed following behavioral errors. Twenty-seven early-stage MS patients and 31 controls were neuropsychologically assessed. Electroencephalography recordings were obtained while participants performed: a) a stop task and b) an auditory oddball task. Behavior and ERP measures were assessed. No differences in performance were found between groups in most neuropsychological tests or in behavior or ERP components in the auditory oddball task. However, the amplitude of the ERN associated with stop errors in the stop task was significantly higher in patients. ERN amplitude correlated positively with scores on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and negatively with the time since last relapse. Patients showed higher neuronal recruitment in tasks involving performance monitoring. Results suggest the development of compensatory brain mechanisms in early-stage MS and reflect the sensitivity of the ERN to detect these changes.     

Additive effects of the dopamine D2 receptor and dopamine transporter genes on the error-related negativity in young children

The error-related negativity (ERN) is a negative deflection in the event-related potential that occurs approximately 50 ms following the commission of an error at fronto-central electrode sites. Previous models suggest dopamine plays a role in the generation of the ERN. We recorded event-related potentials (ERPs) while 279 children aged 5-7 years completed a simple Go/No-Go task; the ERN was examined in relation to the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes. Results suggest an additive effect of the DRD2 and DAT1 genotype on ERN magnitude such that children with at least one DRD2 A1 allele and children with at least one DAT1 9 allele have an increased (i.e. more negative) ERN. These results provide further support for the involvement of dopamine in the generation of the ERN.     

The Association of Childhood Fitness to Proactive and Reactive Action Monitoring

Several studies have claimed that the positive association between childhood fitness and cognitive control is attributable to differences in the child’s cognitive control strategy, which can involve either proactive or reactive control. The present study tested this hypothesis by manipulating the probability of trial types during a modified flanker task. Preadolescent children performed mostly congruent and mostly incongruent conditions of the flanker task, with post-error task performance and error negativity/error-related negativity (Ne/ERN) being assessed. Results indicated that greater aerobic fitness was related to greater post-error accuracy and larger Ne/ERN amplitudes in the mostly congruent condition. These findings suggest that higher-fit children might be able to transiently upregulate cognitive control by recruiting reactive control in the mostly congruent condition. Further, greater fitness was related to greater modulation of Ne/ERN amplitude between conditions, suggesting that higher-fit children engaged in more proactive control in the mostly incongruent condition. This study supports the hypothesis that greater childhood fitness is associated with a more flexible shift between reactive and proactive modes of cognitive control to adapt to varying task demands.     

精神障碍的神经电生理循证医学证据

寻找客观标记物是精神医学研究最重要的课题之一,近期融合了循证医学的神经电生理研究为此提供了重要的途径,并取得了较为可观的研究成果,然而现有的研究结果仍然存在较多争议,难以取得一致共识.本文全面总结和归纳了结合以元分析(meta-analysis)为代表的循证医学方法和以脑电图(electroencephalography)为代表的神经电生理技术的精神障碍相关脑电研究成果,将事件相关电位划分为早期和晚期成分,并结合定量EEG分析,从感知加工、认知控制、情绪反应和社会认知等不同认知过程出发,系统分析和评述了精神障碍患者及高危人群的神经认知功能异常情况.我们发现:精神分裂症患者存在从早期到晚期的各种感知、情感和社会认知方面的缺陷,注意缺陷/多动障碍(ADHD)患者存在从早期到晚期的认知控制缺陷,焦虑和强迫障碍患者则存在早期的认知控制缺陷,而孤独症谱系障碍(ASD)患者则存在早期的感知加工和社会认知缺陷.此外,反映注意资源分配和认知加工速度的P300异常特征跨越了多个诊断类型,这表明该脑电成分可能反映了精神障碍的一般性认知缺陷.未来研究可利用多中心大样本数据库探寻精神疾病的神经电生理客观标记物,并融合先进的多模态精神影像技术和机器学习等人工智能方法,进一步增强精神障碍生物标记物的可靠性和有效性.     

Error-related negativity predicts reinforcement learning and conflict biases

The error-related negativity (ERN) is an electrophysiological marker thought to reflect changes in dopamine when participants make errors in cognitive tasks. Our computational model further predicts that larger ERNs should be associated with better learning to avoid maladaptive responses. Here we show that participants who avoided negative events had larger ERNs than those who were biased to learn more from positive outcomes. We also tested for effects of response conflict on ERN magnitude. While there was no overall effect of conflict, positive learners had larger ERNs when having to choose among two good options (win/win decisions) compared with two bad options (lose/lose decisions), whereas negative learners exhibited the opposite pattern. These results demonstrate that the ERN predicts the degree to which participants are biased to learn more from their mistakes than their correct choices and clarify the extent to which it indexes decision conflict.     

Cascade of neural events leading from error commission to subsequent awareness revealed using EEG source imaging

The goal of the present study was to shed light on the respective contributions of three important action monitoring brain regions (i.e. cingulate cortex, insula, and orbitofrontal cortex) during the conscious detection of response errors. To this end, fourteen healthy adults performed a speeded Go/Nogo task comprising Nogo trials of varying levels of difficulty, designed to elicit aware and unaware errors. Error awareness was indicated by participants with a second key press after the target key press. Meanwhile, electromyogram (EMG) from the response hand was recorded in addition to high-density scalp electroencephalogram (EEG). In the EMG-locked grand averages, aware errors clearly elicited an error-related negativity (ERN) reflecting error detection, and a later error positivity (Pe) reflecting conscious error awareness. However, no Pe was recorded after unaware errors or hits. These results are in line with previous studies suggesting that error awareness is associated with generation of the Pe. Source localisation results confirmed that the posterior cingulate motor area was the main generator of the ERN. However, inverse solution results also point to the involvement of the left posterior insula during the time interval of the Pe, and hence error awareness. Moreover, consecutive to this insular activity, the right orbitofrontal cortex (OFC) was activated in response to aware and unaware errors but not in response to hits, consistent with the implication of this area in the evaluation of the value of an error. These results reveal a precise sequence of activations in these three non-overlapping brain regions following error commission, enabling a progressive differentiation between aware and unaware errors as a function of time elapsed, thanks to the involvement first of interoceptive or proprioceptive processes (left insula), later leading to the detection of a breach in the prepotent response mode (right OFC).     

Abnormal Error Monitoring in Math-Anxious Individuals: Evidence from Error-Related Brain Potentials

This study used event-related brain potentials to investigate whether math anxiety is related to abnormal error monitoring processing. Seventeen high math-anxious (HMA) and seventeen low math-anxious (LMA) individuals were presented with a numerical and a classical Stroop task. Groups did not differ in terms of trait or state anxiety. We found enhanced error-related negativity (ERN) in the HMA group when subjects committed an error on the numerical Stroop task, but not on the classical Stroop task. Groups did not differ in terms of the correct-related negativity component (CRN), the error positivity component (Pe), classical behavioral measures or post-error measures. The amplitude of the ERN was negatively related to participants’ math anxiety scores, showing a more negative amplitude as the score increased. Moreover, using standardized low resolution electromagnetic tomography (sLORETA) we found greater activation of the insula in errors on a numerical task as compared to errors in a non-numerical task only for the HMA group. The results were interpreted according to the motivational significance theory of the ERN.     

Improving source localization of event-related potentials in the GO/NOGO task by modeling their cross-covariance structure

Nineteen-channel event-related potentials (ERPs) were studied in the GO/NOGO test in 517 healthy subjects. Multi-channel ERPs were decomposed into independent components by the method of modeling the cross-covariance structure of transient process. The research results showed that low-correlated ERP components could be obtained by this method with acceptable reliability. The identified components were associated with psychological processes, such as the attended sensory mismatch operation, decision making on the subsequent action, the action inhibition operation, and the conflict monitoring operation. In conclusion, decomposition of ERP recordings into independent components and the use of sLORETA help to localize ERP sources more accurately than the conventional ERP analysis.     

Electrophysiological Explorations of the Bilingual Advantage: Evidence from a Stroop Task

Bilinguals have been shown to exhibit a performance advantage on executive control tasks, outperforming their monolingual counterparts. Although a wealth of research has investigated this ‘bilingual advantage’ behaviourally, electrophysiological correlates are lacking. Using EEG with a Stroop task that manipulated the stimulus onset asynchrony (SOA) of word and colour presentation, the current study addressed two facets of the bilingual advantage. The possibility that bilinguals experience superior conflict processing relative to monolinguals (a ‘conflict-specific advantage’) was investigated by comparing behavioural interference effects as well as the amplitude of the N_inc, a conflict-related ERP component occurring from approximately 300–500 ms after the onset of conflict. In contrast, the hypothesis that bilinguals experience domain-general, conflict-independent enhancements in executive processing (a ‘non-conflict-specific advantage’) was evaluated by comparing the control condition (symbol strings) between groups. There was some significant, but inconsistent, evidence for a conflict-specific bilingual advantage. In contrast, strong evidence emerged for a non-conflict-specific advantage, with bilinguals demonstrating faster RTs and reduced ERP amplitudes on control trials compared to monolinguals. Importantly, when the control stimulus was presented before the colour, ERPs to control trials revealed group differences before the onset of conflict, suggesting differences in the ability to ignore or suppress distracting irrelevant information. This indicates that bilinguals experience superior executive processing even in the absence of conflict and semantic salience, and suggests that the advantage extends to more efficient proactive management of the environment.     

Dopamine Precursor Depletion Influences Pain Affect Rather than Pain Sensation

Pain is a multidimensional experience, which includes sensory, cognitive, and affective aspects. Converging lines of evidence indicate that dopaminergic neurotransmission plays an important role in human pain perception. However, the precise effects of dopamine on different aspects of pain perception remain to be elucidated. To address this question, we experimentally decreased dopaminergic neurotransmission in 22 healthy human subjects using Acute Phenylalanine and Tyrosine Depletion (APTD). During APTD and a control condition we applied brief painful laser stimuli to the hand, assessed different aspects of pain perception, and recorded electroencephalographic responses. APTD-induced decreases of cerebral dopaminergic activity did not influence sensory aspects of pain perception. In contrast, APTD yielded increases of pain unpleasantness. The increases of unpleasantness ratings positively correlated with effectiveness of APTD. Our finding of an influence of dopaminergic neurotransmission on affective but not sensory aspects of phasic pain suggests that analgesic effects of dopamine might be mediated by indirect effects on pain affect rather than by direct effects on ascending nociceptive signals. These findings contribute to our understanding of the complex relationship between dopamine and pain perception, which may play a role in various clinical pain states.