Response inhibition in borderline personality disorder: event-related potentials in a Go/Nogo task

Borderline personality disorder (BPD) has been related to a dysfunction of anterior cingulate cortex, amygdala, and prefrontal cortex and has been associated clinically with impulsivity, affective instability, and significant interpersonal distress. We examined 17 patients with BPD and 17 age-, sex-, and education matched control participants with no history of Axis I or II psychopathology using event-related potentials (ERPs). Participants performed a hybrid flanker-Go/Nogo task while multichannel EEG was recorded. Our study focused on two ERP components: the Nogo-N2 and the Nogo-P3, which have been discussed in the context of response inhibition and response conflict. ERPs were computed on correct Go trials (button press) and correct Nogo trials (no button press), separately. Groups did not differ with regard to the Nogo-N2. However, BPD patients showed reduced Nogo-P3 amplitudes. For the entire group (n = 34) we found a negative correlation with the Barratt Impulsiveness Scale (BIS-10) and Becks's depression inventory (BDI). The present study is the first to examine Nogo-N2 and Nogo-P3 in BPD and provides further evidence for impaired response inhibition in BPD patients.     

Executive control in obsessive-compulsive disorder: event-related potentials in a Go/Nogo task

Summary Obsessive-compulsive disorder (OCD) has been related to a hyperactive cortico-striatal-pallidal-thalamic circuitry resulting clinically in an impaired inhibition of repetitive thoughts and behaviors. We examined thirteen patients with OCD and thirteen age-, sex-, and education matched healthy controls using event-related potentials (ERPs). Participants performed a hybrid flanker-Go/Nogo task while multichannel EEG was recorded. Our study focused on two ERP components: the Nogo-N2 and the Nogo-P3, which have been discussed in the context of response inhibition and response conflict. Artifact-free EEG-segments were used to compute ERPs on correct Go trials (button press) and correct Nogo trials (no button press), separately. Patients with OCD showed enhanced (more negative) Nogo-N2 amplitudes than controls, and a significant difference in amplitudes between Nogo-N2 and Go-N2 trials (more negative for Nogo trials) at central midline electrode positions. However, groups did not differ with regard to the Nogo-P3 and Go-P3. The present study replicates and extends previous findings of altered executive control processes in OCD patients.     

ERP indices for response inhibition are related to anxiety-related personality traits

Anxiety is often associated with impaired cognitive control and avoidance behaviour. The aim of this study was to investigate the effect of anxiety-related personality traits, such as anxiety sensitivity and trait anxiety, on event-related potentials of response inhibition in a standard Go/Nogo-paradigm. We focused on the Nogo-N2 and Nogo-P3 components, which probably represent different sub-processes of response inhibition. The Nogo-N2 was mainly influenced by trait anxiety, while it was slightly affected by anxiety sensitivity. In contrast, the Nogo-P3 was significantly associated with anxiety sensitivity, but was less affected by trait anxiety. Thus, anxious subjects seem to maintain a higher level of cognitive control to prepare and to monitor the outcome of their actions, which is differentially reflected in Nogo-N2 and Nogo-P3 potentials. Our results show that anxiety-related personality traits modulate electrophysiological responses related to cognitive control processes and should be taken into consideration in studies investigating response inhibition.     

Information processing differences and similarities in adults with dyslexia and adults with Attention Deficit Hyperactivity Disorder during a Continuous Performance Test: A study of cortical potentials

Twenty male adults with ADHD, 16 dyslexic adults, 15 comorbid adults, and 16 normal controls were compared on performance and underlying brain responses, during a cued Continuous Performance Test (O-X CPT), with the aim of discovering features of information processing differentiating between the groups. The study evaluated both cue- and target-related processes by analysing performance measures (errors, reaction time, and variability of reaction time), and event-related potentials (ERPs). Cue-related ERP components included the Cue-N2, Cue-P3, contingent negative variation (CNV) consisting of the CNV1, related to cue orienting, and the CNV2, related to response preparation. For targets, a distinction was made between response-related (Go), and inhibitory (Nogo) processing. Target-related components included the Go-P3, Nogo-N2, and Nogo-P3.Performance deficits were found only for the ADHD group, who demonstrated a faster decline in response speed with time-on-task and greater overall within-subject variability. No group differences were found for cue-related ERP components. Yet, controlling for group differences in internalising problems, inhibitory control was reduced in all clinical groups compared to controls, as demonstrated by an absence of frontal amplification of P3 in the Nogo condition, relative to the Go condition. For the ADHD group, in contrast to the comorbid and the dyslexic group, this effect remained after controlling for externalising symptoms, indicating that only for the ADHD group deficiencies in inhibitory control were not explained by externalising behaviour.     

Impulsiveness and ERP components in a Go/Nogo task

Impulsiveness has been linked to fast guesses and premature responses in reaction time tasks like the Eriksen flanker task or the Go/Nogo task. In the present study, healthy subjects without history of DSM-IV Axis I or II psychopathology were examined. Impulsiveness was determined by calculating individual reaction times (as a function of general response speed) in order to split the entire group (n = 26) in a subgroup with a more controlled response style (low impulsiveness [LI] group; n = 13) and a subgroup with a more impulsive response style (high impulsiveness [HI] group; n = 13). Subjects performed a Go/Nogo task while a multi-channel EEG was recorded. Two event-related potentials (ERP) were of special interest: the Nogo-N2 and -P3 component. HI subjects had significantly reduced (less positive) Nogo-P3 amplitudes compared to LI subjects whereas groups did not differ with regard to the Nogo-N2. These results corroborate previous findings of reduced Nogo-P3 amplitudes in samples with enhanced levels of impulsiveness. Moreover, present data suggest that there is a broader range of impulsiveness even in healthy subjects which might mask or pronounce between-group differences in clinical studies. Therefore, different levels of impulsiveness in control groups should be carefully taken into account in further ERP studies.     

Source localization of the Nogo-N2: a developmental study.

OBJECTIVE: The aim of the present study was to investigate whether similar neural sources are involved in generating Nogo-N2 scalp topography in children and adults. METHODS: Source analysis was performed on the Nogo-N2 data from two groups of children (sixteen 6/7 year-olds and seventeen 9/10 year-olds) and seventeen young adults (aged 19-23 years) that were obtained in a prior study by Jonkman LM. The development of preparation, conflict monitoring and inhibition from early childhood to young adulthood; a go/nogo ERP study. Brain Res 2006;1097:181-93. RESULTS: In both children and adults a bilateral source pair in the medial frontal cortex (near ACC) was involved in the generation of Nogo-N2 activity. However, children needed an additional, posteriorly located source pair to adequately explain the Nogo-N2 distribution. In 6/7 year-olds this posterior source was localized in occipito-temporal areas, whereas in 9/10 year-olds the posterior sources shifted to parietal locations. CONCLUSIONS: Although children recruit similar frontal regions as adults in the Nogo-N2 time window, the additional activation of posterior sources might indicate that early executive control performance is less automatic or requires more effortful control in children. This in turn might cause them to rely on more basic stimulus processing or to activate additional attention-related areas. SIGNIFICANCE: Results from the present study show that in children, a more diffuse brain network is involved in executive control processing (conflict monitoring) in the Nogo-N2 time window than in adults.     

Inhibitory processing during the Go/NoGo task: an ERP analysis of children with attention-deficit/hyperactivity disorder.

OBJECTIVE: Previous event-related potential (ERP) research on inhibitory functioning in attention-deficit/hyperactivity disorder (AD/HD) has often failed to use tasks which optimally assess inhibition. We report on an improved measure of inhibitory function, involving inhibition of a prepotent response, in children with AD/HD. METHODS: Twelve males with AD/HD and 12 control males, aged 7-12 years, completed a cued Go/NoGo task where Go stimuli were presented on 70% of trials. ERP and behavioural measures were collected, together with reading, spelling and full-scale IQ scores. RESULTS: The behavioural performance of children with AD/HD was not significantly different from normal controls, although children with AD/HD made faster responses and more errors. Group differences were apparent in the early processing components (P1, N1, P2) of responses to Warning, Go and NoGo stimuli. For the frontally maximal N2, a NoGo>Go effect was found, consistent with previous work linking this component with inhibitory processing. In control children this effect was particularly strong in the right frontal region, while children with AD/HD showed a much larger NoGo>Go effect, and an earlier N2 peak, than controls, with a focal shift to the left frontal region. CONCLUSIONS: Compared with normal controls, children with AD/HD demonstrate early stimulus processing atypicalities, suggesting problems with sensory registration and identification of stimuli. Further, N2 results suggest that children with AD/HD must trigger the inhibition process earlier and more strongly than controls to perform at a comparable behavioural level. SIGNIFICANCE: The results support the theory that behavioural inhibition is deficient in AD/HD, as children with AD/HD show abnormalities in inhibitory ERP components relating to the effort involved in inhibiting a prepotent response.     

首发精神分裂症执行功能异常的心理生理机制

目的探讨首发精神分裂症患者大脑执行功能的缺陷机制。方法采用病例对照研究，选取年龄、性别、文化程度等匹配的精神分裂症患者组和对照组各30例。被试接受Go／Nogo测验，同时记录事件相关脑电位N2、P3的波幅和潜伏期及行为学数据。结果精神分裂症组Nogo反应错误数（12±9）高于对照组（8±5），Go反应时（372±79）Ins明显长于对照组（320±63）ms，差异均有统计学意义（f分别为2．13，2．81；P〈0．05）；重复测量方差分析，发现组别的主效应（F1,58=7．13，P〈0．01）以及组别与组块之间的交互效应（F1,58=6．14，P〈0．05）均有统计学意义；精神分裂症组Fz电极Nogo-N2波幅（6．64±3．29）／LV比对照组（9．45±6．71）μV降低，Nogo-P3波幅（7．93±6．81）μV也比对照组下降（10．69±5．24）μV，差异均有统计学意义（t分别为2．06，2．89；P〈0．05）。Nogo-P3波幅在组别与组块之间的交互效应有统计学意义（F1,58=5．28，P〈0．05）。结论首发精神分裂症患者存在执行功能缺陷，反应时及Nogo-N2、P3可能可作为精神分裂症早期诊断指标。     

Source analysis of the N2 in a cued Go/NoGo task

Previous source analyses of event-related potential (ERP) data elicited in Go/NoGo tasks have suggested that the anterior cingulate cortex (ACC) plays an important role in response inhibition. So far, however, source models were derived for the difference wave Go stimulus minus NoGo stimulus. This difference wave is confounded with motor- and attention-related activity. To avoid these confounds, we alternatively derived source models for NoGo stimuli only. The problem of the NoGo-N2 being superimposed on a positive deflection was addressed in two ways. First, a baseline correction was applied using the time points just preceding and succeeding the NoGo-N2. Second, a separate source model was derived at the maximum amplitude of this positive deflection. Subjects were presented with a cued version of the continuous performance task (CPT; ABX). In a second study, the probability of the Go stimulus was gradually increased to heighten subjects' tendency to respond and, as a consequence, to enhance the amplitude of the NoGo-N2. The source models of the NoGo-N2 consistently indicated bilateral dipole pairs in medial frontal regions. This is in accordance with a generator in the anterior cingulate cortex.     

The development of preparation, conflict monitoring and inhibition from early childhood to young adulthood: a Go/Nogo ERP study

The present developmental study aimed to trace changes in response expectation, preparation, conflict monitoring and subsequent response inhibition from 6 years of age to adulthood. In two groups of children (6-7 and 9-10 years old) and young adults (19-23 years old), behavior and event-related brain activity (ERP) in a CPT-AX task was measured. Hits, false alarms, inattention and impulsivity scores and ERP measures of conflict monitoring and inhibition (Nogo-N2 and P3), cue-orientation and prestimulus target expectation (cue-P2 and P3) and response preparation (Contingent Negative Variation; CNV) were collected. Behavioral measures indicated that attention processes developed most strongly before age 10, whereas impulsive behavior only started to diminish after the age of 10. Nogo-N2 effects were largest and more widely distributed across fronto-parietal electrodes in 6-7-year olds and decreased linearly with age. Nogo-P3 effects showed an opposite pattern by being absent in the youngest children, starting to develop at age 9-10 and reaching maturity in young adulthood. These developmental behavioral and ERP results are supportive of links between Nogo-N2 and conflict monitoring and Nogo-P3 and response inhibition and suggest that both are liable to different developmental progress. Furthermore, enhanced cue-P3 activity in both 6-7 and 9-10-year olds was argued to reflect a higher level of Go-stimulus expectation, that might cause them to experience more conflict on subsequent Nogo-trials, when the 'not-expected' stimulus appears. On the other hand, young children's reduced preparatory CNV activity was interpreted as a sign of reduced response priming caused by yet immature fronto-parietal networks involved in motor regulation.     

Effects of stimulus–response compatibility on inhibitory processes in Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative basal ganglia disorder accompanied by deficits in cognitive functions. One important executive function is the inhibition of responses. Due to basal ganglia damage, processes related to the selection of response are also dysfunctional. However, the relevance of deficits in response selection to processes related to response inhibition in PD is not clear. In this study we examined these processes by means of event-related potentials (ERPs) in two Go/Nogo tasks. In one task the stimulus–response mapping was compatible and in the other task it was incompatible with the meaning of the stimuli. The behavioural results show that PD patients were unaffected in the compatible response inhibition task but encountered problems in the incompatible one. In the ERPs the N2, generally reflecting response selection, was delayed for the PD compared to the control group. This suggests that response selection is delayed in PD. Moreover, the N2 was specifically enhanced in Nogo trials. This indicates that premotor inhibition, which is probably reflected by the Nogo-N2, is intensified in PD. The P3 was specifically attenuated and delayed after Nogo stimuli in the incompatible condition for PDs. Assuming that the Nogo-P3 reflects the evaluation of successful motor inhibition, our data show that this process is attenuated and delayed in PD but mainly in the incompatible task. The results suggest that inhibitory deficits in PD are only evident in complex (incompatible) stimulus–response mappings. These effects are probably due to an overstrain of striatal processes.     

Response inhibition and attention processing in 5- to 7-year-old children with and without symptoms of ADHD: An ERP study

ObjectiveResponse inhibition and attention processing in 5- to 7-year-old children with or without symptoms of attention-deficit hyperactivity disorder (ADHD) were examined.MethodsTwelve children with ADHD symptoms and 15 control children performed a CPT-AX task. Behavioral measures of inattention and impulsivity and ERP measures of conflict monitoring and inhibition (Nogo-N2 and Nogo-P3), cue-orientation and prestimulus target expectation (Cue-P2 and P3) and response preparation (CNV) were collected.ResultsADHD children detected fewer targets and had higher Inattention scores accompanied by reduced centro-parietal Cue- and Go-P3 activity. Occipital CNV amplitude was larger in ADHD children. At fronto-central leads, strong and comparable fronto-parietal Nogo-N2 effects were found in both groups, whereas the Nogo-P3 was only marginally significant in both groups.ConclusionsThe attenuated Cue- and Go-P3 effects in the ADHD-symptom group are interpreted as early signs of delayed attention development, resulting in less preparation and less alertness to detect significant events. Whereas the Nogo-N2 effects were interpreted as signs of comparable levels of conflict processing in both groups, the small Nogo-P3 suggests that inhibitory processing is still immature at this age.SignificanceThe present study shows that specific attention problems can already be detected in the behavior and brain activity of 5- to 7-year-old children with symptoms of ADHD performing a CPT-AX task, and might be better indicators for the risk of developing ADHD than impulsivity measures.     

Altered response control and anterior cingulate function in attention-deficit/hyperactivity disorder boys.

OBJECTIVE: To investigate mechanisms and structures underlying prefrontal response control and inhibition in boys suffering from attention-deficit/hyperactivity disorder (ADHD). METHOD: Sixteen boys with ADHD and 19 healthy controls were investigated electrophysiologically during performance of a visual Go-Nogo task (Continuous Performance Test, CPT). An electrophysiological source localization method was employed to further analyze the data. RESULTS: The ADHD boys showed a significantly diminished central Nogo-P3, due to a lack of Nogo-related frontalization of the positive brain electrical field in this group. This two-dimensional effect was associated with a significantly reduced activation of the anterior cingulate cortex (ACC) in the ADHD boys in the Nogo condition of the CPT. Both groups did not significantly differ regarding the amplitude of the Nogo-N2. CONCLUSIONS: The results indicate deficits in prefrontal response control in unmedicated ADHD boys that do not seem to be specifically inhibitory in nature. A supposed dysfunction of the ACC in ADHD was confirmed.     

Caffeine strengthens action monitoring: evidence from the error-related negativity

The medial frontal cortex, especially the anterior cingulate cortex (ACC), is involved in action monitoring. We studied the role of moderate amounts of caffeine in action monitoring as expressed by the error-related negativity (ERN), an event-related brain component that reflects ACC activity. In a double-blind, placebo-controlled, within-subjects experiment, two caffeine doses (3 and 5 mg/kg body weight) and a placebo were administered to habitual coffee drinkers. Compared with placebo, both caffeine doses enlarged the ERN. Amplitudes of the P2 and P3 components were not affected by caffeine. Thus, the enlarged ERN after caffeine reflects a specific effect on action monitoring. We conclude that consumption of a few cups of coffee strengthens central information processing, specifically the monitoring of ongoing cognitive processes for signs of erroneous outcomes. Brain areas related to action monitoring such as the ACC presumably mediate these caffeine effects.     

Response inhibition subprocesses and dopaminergic pathways: Basal ganglia disease effects

Response inhibition is a component of executive functions, which can be divided into distinct subprocesses by means of event-related potentials (ERPs). These subprocesses are (pre)-motor inhibition and inhibition monitoring, which are probably reflected by the Nogo-N2 and Nogo-P3, respectively. Here we ask, if these subprocesses may depend on distinct basal ganglia subsystems. We examined response inhibition processes in an extended sample of young and elderly subjects, patients with Parkinson's disease (PD) and Huntington’ disease (HD). This combination of groups also allow us to study whether, and to what degree, pathological basal ganglia changes and healthy aging have similar and/or different effects on these processes. We show that subprocesses of response inhibition are differentially modulated by distinct basal ganglia circuits. Processes related to (pre)-motor inhibition appear to be modulated by the nigrostriatal system, and are sensitive to aging and age-related basal ganglia diseases (i.e. PD). Parkinson's disease induces additive effects of aging and pathology. In contrast, inhibition monitoring is most likely modulated by the mesocortico-limbic dopamine system. These processes are equally affected in healthy aging and both basal ganglia diseases (i.e. PD, HD).     

Functional lesions and human action monitoring: combining repetitive transcranial magnetic stimulation and event-related brain potentials.

OBJECTIVE: Electrophysiological recordings of the error-related negativity (ERN) and functional imaging data point to an involvement of medial frontal cortex (including the anterior cingulate cortex, ACC) and dorsolateral prefrontal cortex (DLPFC) in the detection and correction of performance errors. Here, we studied this network by applying trains of rapid transcranial magnetic stimulation (rTMS) prior to the recording of the ERN. METHODS: Low-frequency (0.9 Hz) rTMS was applied to medial frontal or lateral frontal regions (different sessions) for 60 s immediately before each 3 min ERN recording in 11 healthy young subjects. The ERN was obtained by multichannel recordings in a typical Eriksen flanker task with instructions calling for immediate error correction in case a performance error was detected by the subject. Event-related potentials were quantified and statistically evaluated using standard methodology. RESULTS: Compared to a no-stimulation control condition, medial frontal stimulation led to a small but reliable decrease in the number of corrected errors as well as to an attenuation of the ERN and an increase of the subsequent error-positivity (Pe). No effect on these components was seen after lateral frontal stimulation. No reliable effects on the lateralized readiness potential were observed. CONCLUSIONS: Functional lesions by rTMS appear to interfere with the functions of the medial frontal cortex in error detection and correction.     

Inhibitory control in children with attention-deficit/hyperactivity disorder: event-related potentials identify the processing component and timing of an impaired right-frontal response-inhibition mechanism.

BACKGROUND: A core deficit in inhibitory control may account for a wide range of dysfunctional behaviors in attention-deficit/hyperactivity disorder (ADHD). METHODS: Event-related potentials were measured in 10 children with ADHD and 10 healthy children during a task specifically involving response inhibition (Stop signal task). RESULTS: In response to all Stop signals, control participants produced a large negative wave at 200 msec (N200) over right inferior frontal cortex, which was markedly reduced in ADHD children. The N200 amplitude was significantly correlated across subjects with response-inhibition performance. In response to the Go stimuli, ADHD children showed a reduced slow positive wave (250-500 msec) in anticipation of failed inhibitions over right frontal scalp regions. CONCLUSIONS: ADHD children appear to have an abnormality in an early-latency, right inferior frontal processing component critical to the initiation of normal response-inhibition operations. They also appear to have a right frontal abnormality associated to the covert processing of Go stimuli preceding failed inhibitions. By providing timing and processing component specificity, these results extend the findings of recent functional MRI studies of inhibitory control reporting right frontal abnormalities in ADHD.     

戒断期海洛因依赖者额叶认知功能的功能磁共振成像研究

目的 研究戒断期海洛因依赖者(AHD)的脑认知功能.方法 采用3.0 T磁共振成像系统,对30例AHD(AHD组)和18名健康对照者(对照组)在完成Go/NoGo任务时行全脑功能磁共振成像(fMRI)扫描,记录反应时间(RT).结果 (1)RT:AHD组在完成Go/NoGo任务时的RT[(394±34)ms]长于对照组[(374±26)ms;P<0.05].(2)fMRI:对照组在完成Go/NoGo任务时,诱发激活双侧前额叶内侧回、前扣带回以及双侧额下回等脑区;AHD组全脑活动普遍低,仅有双侧额上回和左侧额中回激活.两组间比较,AHD组激活显著低于对照组的区域主要位于在双侧额内侧回、前扣带回、额下回及双侧颞叶等脑区(P<0.005).结论 戒断期海洛因依赖者反应抑制功能障碍仍然存在,促进其认知功能的恢复可能成为戒毒、抗复吸的有效策略.     

Attentional control of task and response in lateral and medial frontal cortex: Brain activity and reaction time distributions

It is unclear whether task conflict is reflected in the anterior cingulate cortex (ACC) or in more dorsal regions of the medial frontal cortex (MFC). When participants switch between tasks involving incongruent, congruent, and neutral stimuli, it is possible to examine both response conflict (incongruent vs. congruent) and task conflict (congruent vs. neutral). Here, we report an event-related functional magnetic resonance imaging (fMRI) study that examined which areas in frontal cortex, including MFC, are implicated in response conflict, task conflict, or both. Stimuli were incongruent and congruent arrow-word combinations, or arrows and words only in a neutral condition. Participants responded manually to the arrow or word. The task varied every second trial. The behavioral data revealed response conflict (incongruent > congruent) and task conflict (congruent > neutral) in mean reaction times and ex-Gaussian latency distribution components. The imaging data revealed activity in both the ACC and a more dorsal region in the MFC (the medial superior frontal gyrus) related to response conflict as well as task conflict. These conflict effects were observed independent of the task performed (arrow or word) or the trial type (repeat or switch). In lateral prefrontal cortex (LPFC), response conflict was associated with activity in ventral LPFC, whereas task conflict activated both ventral and dorsal regions. Thus, whereas the type of conflict (response vs. task) was differentiated in LPFC, no such differentiation was found in MFC, including the ACC. Models of ACC functioning may require modification to take account of these findings.     

Arousal-state modulation in children with AD/HD

ObjectiveTo investigate the effect of arousal-state modulation, via manipulation of stimulus event-rate, on response inhibition in children with Attention-Deficit/Hyperactivity disorder (AD/HD) using behavioural and ERP measures.MethodsEighteen children with AD/HD, aged 7–14 years, and 18 age-and sex-matched controls performed a cued visual Go/Nogo task (70% Go) with stimuli presented at fast, medium and slow event-rates. Task performance and ERPs to Warning, Go and Nogo stimuli, as well as preparation between the S1–S2 interval, were examined for group differences.ResultsAD/HD subjects displayed poorer response inhibition during the fast condition, accompanied by a reduced Nogo P3. Group differences during the fast rate extended to Warning cues, with the AD/HD group showing ERP evidence of atypical orienting/preparation, as indexed by the early and late CNV, and early sensory/attentive processing prior to S2.ConclusionsAlthough deficient response inhibition has been proposed as the core deficit in AD/HD, the results of the present study highlight the key role of energetic factors. Furthermore, group differences found to cues suggest that this effect extends to the processing of task-irrelevant stimuli.SignificanceThis was the first ERP Go/Nogo task investigation using three event-rates, and the results support the theory that state factors may contribute to response inhibition deficits in AD/HD.