fMRI evidence that the neural basis of response inhibition is task-dependent

Event-related fMRI was used to investigate the hypothesis that neural activity involved in response inhibition depends upon the nature of the response being inhibited. Two different Go/No-go tasks were compared-one with a high working memory load and one with low. The 'simple' Go/No-go task with low working memory load required subjects to push a button in response to green spaceships but not red spaceships. A 'counting' Go/No-go task (high working memory load) required subjects to respond to green spaceships as well as to those red spaceships preceded by an even number of green spaceships. In both tasks, stimuli were presented every 1.5 s with a 5:1 ratio of green-to-red spaceships. fMRI group data for each task were analyzed using random effects models to determine signal change patterns associated with Go events and No-go events (corrected P< or =0.05). For both tasks, Go responses were associated with signal change in the left primary sensorimotor cortex, supplementary motor area (SMA) proper, and anterior cerebellum (right>left). For the simple task, No-go events were associated with activation in the pre-SMA; the working memory-loaded 'counting' task elicited additional No-go activation in the right dorsolateral prefrontal cortex. The findings suggest that neural contributions to response inhibition may be task dependent; the pre-SMA appears necessary for inhibition of unwanted movements, while the dorsolateral prefrontal cortex is recruited for tasks involving increased working memory load.     

Event-related fMRI study of response inhibition

Event-related functional magnetic resonance imaging (erfMRI) was employed to measure the hemodynamic response during a Go/No-go task in 16 healthy subjects. The task was designed so that Go and No-go events were equally probable, allowing an unbiased comparison of cerebral activity during these two types of trials. In accordance with prediction, anterior cingulate was active during both the Go and No-go trials, dorsolateral and ventrolateral prefrontal cortex was more active during the No-go trials, while primary motor cortex, supplementary motor area, pre-motor cortex and cerebellum were more active during Go trials. These findings are consistent with the hypothesis that the anterior cingulate cortex is principally engaged in making and monitoring of decisions, while dorsolateral and ventral lateral prefrontal sites play a specific role in response inhibition.     

fMRI of intrasubject variability in ADHD: anomalous premotor activity with prefrontal compensation

ObjectiveChildren with attention-deficit/hyperactivity disorder (ADHD) consistently display increased intrasubject variability (ISV) in response time across varying tasks, signifying inefficiency of response preparation compared to typically developing (TD) children. Children with ADHD also demonstrate impaired response inhibition; inhibitory deficits correlate with ISV, suggesting that similar brain circuits may underlie both processes. To better understand the neural mechanisms underlying increased ISV and inhibitory deficits in children with ADHD, functional magnetic resonance imaging was used to examine the neural correlates of ISV during Go/No-go task performance.MethodEvent-related functional magnetic resonance imaging was used to study 25 children with ADHD and 25 TD children ages 8 to 13 years performing a simplified Go/No-go task. Brain-behavior correlations were examined between functional magnetic resonance imaging activation and ISV within and between groups.ResultsFor TD children, increased rostral supplementary motor area (pre-supplementary motor area) activation during No-go events was associated with less ISV, whereas the reverse was true for children with ADHD for whom increased pre-supplementary motor area activation was associated with more ISV. In contrast, children with ADHD with less ISV showed greater prefrontal activation, whereas TD children with more prefrontal activation demonstrated more ISV.ConclusionsThese findings add to evidence that dysfunction of premotor systems may contribute to increased variability and impaired response inhibition in children with ADHD and that compensatory strategies eliciting increased cognitive control may improve function. However, recruitment of prefrontal resources as a compensatory mechanism for motor task performance may preclude the use of those prefrontal resources for higher order, more novel executive functions with which children with ADHD often struggle.     

Meta-analysis of Go/No-go tasks demonstrating that fMRI activation associated with response inhibition is task-dependent

FMRI studies of response inhibition consistently reveal frontal lobe activation. Localization within the frontal cortex, however, varies across studies and appears dependent on the nature of the task. Activation likelihood estimate (ALE) meta-analysis is a powerful quantitative method of establishing concurrence of activation across functional neuroimaging studies. For this study, ALE was used to investigate concurrent neural correlates of successfully inhibited No-go stimuli across studies of healthy adults performing a Go/No-go task, a paradigm frequently used to measure response inhibition. Due to the potential overlap of neural circuits for response selection and response inhibition, the analysis included only event-related studies contrasting No-go activation with baseline, which allowed for inclusion of all regions that may be critical to visually guided motor response inhibition, including those involved in response selection. These Go/No-go studies were then divided into two groups: "simple" Go/No-go tasks in which the No-go stimulus was always the same, and "complex" Go/No-go tasks, in which the No-go stimulus changed depending on context, requiring frequent updating of stimulus-response associations in working memory. The simple and complex tasks demonstrated distinct patterns of concurrence, with right dorsolateral prefrontal and inferior parietal circuits recruited under conditions of increased working memory demand. Common to both simple and complex Go/No-go tasks was concurrence in the pre-SMA and the left fusiform gyrus. As the pre-SMA has also been shown to be involved in response selection, the results support the notion that the pre-SMA is critical for selection of appropriate behavior, whether selecting to execute an appropriate response or selecting to inhibit an inappropriate response.     

Compensatory brain activation in children with attention deficit/hyperactivity disorder during a simplified Go/No-go task

Given that a number of recent studies have shown attenuated brain activation in prefrontal regions in children with ADHD, it has been recognized as a disorder in executive function. However, fewer studies have focused exclusively on the compensatory brain activation in ADHD. The present study objective was to investigate the compensatory brain activation patterns during response inhibition (RI) processing in ADHD children. In this study, 15 ADHD children and 15 sex-, age-, and IQ-matched control children were scanned with a 3-T MRI equipment while performing a simplified letter Go/No-go task. The results showed more brain activation in the ADHD group compared with the control group, whereas the accuracy and reaction time of behavioral performance were the same. Children with ADHD did not activate the normal RI brain circuits, which are thought to be predominantly located in the right middle/inferior frontal gyrus (BA46/44), right inferior parietal regions (BA40), and pre-SMA(BA6), but instead, activated brain regions, such as the left inferior frontal cortex, the right inferior temporal cortex, the right precentral gyrus, the left postcentral gyrus, the inferior occipital cortex, the middle occipital cortex, the right calcarine, the right hippocampus, the right midbrain, and the cerebellum. Our conclusion is that children with ADHD tend to compensatorily use more posterior and diffusive brain regions to sustain normal RI function.     

Differential cerebellar and cortical involvement according to various attentional load: role of educational level

Recent imaging studies have evidenced various cerebral patterns dependent on educational level during cognitive tasks in neurodegenerative diseases. Determining relationships between educational status and cerebral activation during cognitive demands in physiological conditions may help to better understand the role of education on cognitive efficacy and functional reorganisation in pathological conditions. We proposed to analyse by functional MRI (fMRI) the relationship between educational status and cerebral activation during various attentional requests in healthy young adults. Twenty healthy young adults completed four successive conditions of a Go/No-go test of increasing complexity under fMRI. An effect of education was observed on attentional performances. Both in-scanner response times and cerebral activation increased during the Go/No-go paradigm. Healthy subjects with higher education exhibited higher activity in cerebellum and lower activity in medial prefrontal and inferior parietal regions compared with the healthy subjects with lower educational levels while performing the conditions of Go/No-go task. Our data evidence the influence of education on automatized strategies in healthy adults by modulating a functional balance of activation between cerebral cortex and cerebellar regions during attentional processes.     

Children with high functioning autism show increased prefrontal and temporal cortex activity during error monitoring

Evidence exists for deficits in error monitoring in autism. These deficits may be particularly important because they may contribute to excessive perseveration and repetitive behavior in autism. We examined the neural correlates of error monitoring using functional magnetic resonance imaging (fMRI) in 8–12-year-old children with high functioning autism (HFA, n = 11) and typically developing children (TD, n = 15) during performance of a Go/No-Go task by comparing the neural correlates of commission errors versus correct response inhibition trials. Compared to TD children, children with HFA showed increased BOLD fMRI signal in the anterior medial prefrontal cortex (amPFC) and the left superior temporal gyrus (STempG) during commission error (versus correct inhibition) trials. A follow-up region of-interest analysis also showed increased BOLD signal in the right insula in HFA compared to TD controls. Our findings of increased amPFC and STempG activity in HFA, together with the increased activity in the insula, suggest a greater attention towards the internally driven emotional state associated with making an error in children with HFA. Since error monitoring occurs across different cognitive tasks throughout daily life, an increased emotional reaction to errors may have important consequences for early learning processes.     

Prefrontal unit activity during delayed conditional Go/No-go discrimination in the monkey. II. Relation to Go and No-go responses

Three monkeys were trained to perform a Go/No-go discrimination task where the animals were required to perform a muscular movement (Go) or to withhold it (No-go) depending on the previously presented signal. Single unit activity was recorded from the prefrontal cortex during the performance of the task. Among 512 task-related prefrontal units, 253 units showed differential activity in relation to the type of the trial (Go or No-go) either at the time of the response or both during the preparatory period for the response and at the time of the response. These units were classified into 3 types depending on whether the changes in unit activity were observed selectively on Go trials (Go units, n = 47), or selectively on No-go trials (No-go units, n = 28) or on both Go and No-go trials (Go/No-go units, n = 178). A small number of units from the premotor cortex (n = 31) were examined inadvertently and the 3 types of units were present in this area as well. The existence of the 3 types of prefrontal units (Go, No-go and Go/No-go) indicates that the prefrontal cortex is involved in the behavioral inhibitory mechanism besides participating in the behavioral excitatory mechanism.     

Dissociation in performance of children with ADHD and high-functioning autism on a task of sustained attention

Attention deficit hyperactivity disorder (ADHD) and autism are two neurodevelopmental disorders associated with prominent executive dysfunction, which may be underpinned by disruption within fronto-striatal and fronto-parietal circuits. We probed executive function in these disorders using a sustained attention task with a validated brain-behaviour basis. Twenty-three children with ADHD, 21 children with high-functioning autism (HFA) and 18 control children were tested on the Sustained Attention to Response Task (SART). In a fixed sequence version of the task, children were required to withhold their response to a predictably occurring no-go target (3) in a 1-9 digit sequence; in the random version the sequence was unpredictable. The ADHD group showed clear deficits in response inhibition and sustained attention, through higher errors of commission and omission on both SART versions. The HFA group showed no sustained attention deficits, through a normal number of omission errors on both SART versions. The HFA group showed dissociation in response inhibition performance, as indexed by commission errors. On the Fixed SART, a normal number of errors was made, however when the stimuli were randomised, the HFA group made as many commission errors as the ADHD group. Greater slow-frequency variability in response time and a slowing in mean response time by the ADHD group suggested impaired arousal processes. The ADHD group showed greater fast-frequency variability in response time, indicative of impaired top-down control, relative to the HFA and control groups. These data imply involvement of fronto-parietal attentional networks and sub-cortical arousal systems in the pathology of ADHD and prefrontal cortex dysfunction in children with HFA.     

The functional neuroanatomical correlates of response variability: evidence from a response inhibition task

Intra-individual performance variability may be an important index of the efficiency with which executive control processes are implemented, Lesion studies suggest that damage to the frontal lobes is accompanied by an increase in such variability. Here we sought for the first time to investigate how the functional neuroanatomy of executive control is modulated by performance variability in healthy subjects by using an event-related functional magnetic resonance imaging (ER-fMRI) design and a Go/No-go response inhibition paradigm. Behavioural results revealed that individual differences in Go response time variability were a strong predictor of inhibitory success and that differences in mean Go response time could not account for this effect. Task-related brain activation was positively correlated with intra-individual variability within a distributed inhibitory network consisting of bilateral middle frontal areas and right inferior parietal and thalamic regions. Both the behavioural and fMRI data are consistent with the interpretation that those subjects with relatively higher intra-individual variability activate inhibitory regions to a greater extent, perhaps reflecting a greater requirement for top-down executive control in this group, a finding that may be relevant to disorders of executive/attentional control.     

Response inhibition and impulsivity: an fMRI study

Aggressive, suicidal and violent behaviour have been associated with impulsive personality and difficulty in inhibiting responses. We used functional magnetic resonance imaging (fMRI) of the whole brain to examine the neural correlates of response inhibition in 19 normal subjects as they performed a Go/NoGo task. Subjects completed Eysenck’s Impulsivity Scale, Barratt’s Impulsivity Scale (BIS) and behavioural impulsivity tasks. Associations between blood oxygen level dependent (BOLD) response, trait impulsivity, task performance and National Adult Reading Test (NART) IQ were investigated. Neural response during response inhibition was most prominent in the right lateral orbitofrontal cortex. Responses were also seen in superior temporal gyrus, medial orbitofrontal cortex, cingulate gyrus, and inferior parietal lobule, predominantly on the right side. Subjects with greater scores on impulsivity scales and who made more errors had greater activation of paralimbic areas during response inhibition, while less impulsive individuals and those with least errors activated higher order association areas. Exploratory factor analysis of orbital activations, personality measures and errors of commission did not reveal a unitary dimension of impulsivity. However, the strong association between posterior orbital activation and Eysenck’s impulsivity score on a single factor suggests that greater engagement of right orbitofrontal cortex was needed to maintain behavioural inhibition in impulsive individuals. Lower IQ was more important than impulsivity scores in determining errors of commission during the task. Neuroimaging of brain activity during the Go/NoGo task may be useful in understanding the functional neuroanatomy and associated neurochemistry of response inhibition. It may also allow study of the effects of physical and psychological interventions on response inhibition in clinical conditions such as antisocial personality disorder.     

注意缺陷多动障碍儿童反应抑制功能的磁共振成像研究

目的 探讨注意缺陷多动障碍(ADHD)儿童执行高级反应抑制脑激活的模式和功能状态.方法 对12例注意缺陷多动障碍儿童(ADHD组)和12名正常对照者(对照组)检测执行持续性操作测试任务(CPT)时的功能磁共振成像(fMRT)和行为学,并采集全脑血氧水平依赖对比的fMRI扫描数据.结果 (1)行为学检测,ADHD组的击中数[(18.6±4.1)个]少于对照组[(22.8±1.8)个],反应时间[(579±56)ms]长于正常对照组[(510±35)ms;均P＜0.01],漏击数[(6.3±4.1)个]和错击数[(3.9±2.4)个]均多于对照组[(2.2±1.9)个和(1.9±1.0)个;P＜0.01～0.05].(2)fMRI检测,ADHD组扣带前回、前额叶腹外侧、尾状核和小脑激活弱于对照组(P＜0.05,未校正,体素值＞20).结论 ADHD儿童反应抑制功能存在缺陷,其扣带前回、前额叶、基底节及小脑的功能低下.     

Bilateral decrease in ventrolateral prefrontal cortex activation during motor response inhibition in mania

Mania has been frequently associated with impaired inhibitory control. The present study aimed to identify brain functional abnormalities specifically related to motor response inhibition in mania by using event-related fMRI in combination with a Go/NoGo task designed to control for extraneous cognitive processes involved in task performance. Sixteen manic patients and 16 healthy subjects, group-matched for age and sex, were imaged while performing a warned equiprobable Go/NoGo task during event-related fMRI. Between-group differences in brain activation associated with motor response inhibition were assessed using analyses of covariance. Although no significant between-group differences in task performance accuracy were observed, patients showed significantly longer response times on Go trials. After controlling for covariates, the only brain region that differentiated the two groups during motor response inhibition was the ventrolateral prefrontal cortex (VLPFC), where activation was significantly decreased in both the right and left hemispheres in manic patients. Our data suggest that response inhibition in mania is associated with a lack of engagement of the bilateral VLPFC, which is known to play a primary role in the suppression of irrelevant responses. This result might give clues to understanding the pathophysiology of dishinhibition and impulsivity that characterize mania.     

Brain network dynamics during error commission

Previous studies suggest that the anterior cingulate and other prefrontal brain regions might form a functionally-integrated error detection network in the human brain. This study examined whole brain functional connectivity to both correct and incorrect button presses using independent component analysis (ICA) of functional magnetic resonance imaging (fMRI) data collected from 25 adolescent and 25 adult healthy participants (ages 11-37) performing a visual Go/No-Go task. Correct responses engaged a network comprising left lateral prefrontal cortex, left postcentral gyrus/inferior parietal lobule, striatum, and left cerebellum. In contrast, a similar network was uniquely engaged during errors, but this network was not integrated with activity in regions believed to be engaged for higher-order cognitive control over behavior. A medial/dorsolateral prefrontal-parietal neural network responded to all No-Go stimuli, but with significantly greater activity to errors. ICA analyses also identified a third error-related circuit comprised of anterior temporal lobe, limbic, and pregenual cingulate cortices, possibly representing an affective response to errors. There were developmental differences in error-processing activity within many of these neural circuits, typically reflecting greater hemodynamic activation in adults. These findings characterize the spatial structure of neural networks underlying error commission and identify neurobiological differences between adolescents and adults.     

Adjustments of response threshold during task switching: a model-based functional magnetic resonance imaging study

Adjustment of response threshold for speed compared with accuracy instructions in two-choice decision-making tasks is associated with activation in the fronto-striatal network, including the pre-supplementary motor area (pre-SMA) and striatum (Forstmann et al., 2008). In contrast, increased response conservativeness is associated with activation of the subthalamic nucleus (STN) (Frank et al., 2007). We investigated the involvement of these regions in trial-by-trial adjustments of response threshold in humans, using a cued-trials task-switching paradigm. Fully and partially informative switch cues produced more conservative thresholds than repeat cues. Repeat cues were associated with higher activation in pre-SMA and striatum than switch cues. For all cue types, individual variability in response threshold was associated with activation level in pre-SMA, with higher activation linked to lower threshold setting. In the striatum, this relationship was found for repeat cues only. These findings support the notion that pre-SMA biases the striatum to lower response threshold under more liberal response regimens. In contrast, a high threshold for switch cues was associated with greater activation in right STN, consistent with increasing response caution under conservative response regimens. We conclude that neural models of response threshold adjustment can help explain executive control processes in task switching.     

An fMRI study of reduced left prefrontal activation in schizophrenia during normal inhibitory function

Functional magnetic resonance imaging (fMRI) was used to investigate the hypothesis that schizophrenia is associated with a dysfunction of prefrontal brain regions during motor response inhibition. Generic brain activation of six male medicated patients with schizophrenia was compared to that of seven healthy comparison subjects matched for sex, age, and education level while performing 'stop' and 'go-no-go' tasks. No group differences were observed in task performance. Patients, however, showed reduced BOLD signal response in left anterior cingulate during both inhibition tasks and reduced left rostral dorsolateral prefrontal and increased thalamus and putamen BOLD signal response during stop task performance. Despite good task performance, patients with schizophrenia thus showed abnormal neural network patterns of reduced left prefrontal activation and increased subcortical activation when challenged with motor response inhibition.     

Proactive response inhibition abnormalities in the sensorimotor cortex of patients with schizophrenia

BackgroundPrevious studies of response inhibition in patients with schizophrenia have focused on reactive inhibition tasks (e.g., stop-signal, go/no-go), primarily observing lateral prefrontal cortex abnormalities. However, recent studies suggest that purposeful and sustained (i.e., proactive) inhibition may also be affected in these patients.MethodsPatients with chronic schizophrenia and healthy controls underwent fMRI while inhibiting motor responses during multisensory (audiovisual) stimulation. Resting state data were also collected.ResultsWe included 37 patients with schizophrenia and 37 healthy controls in our study. Both controls and patients with schizophrenia successfully inhibited the majority of overt motor responses. Functional results indicated basic inhibitory failure in the lateral premotor and sensorimotor cortex, with opposing patterns of positive (schizophrenia) versus negative (control) activation. Abnormal activity was associated with independently assessed signs of psychomotor retardation. Patients with schizophrenia also exhibited unique activation of the pre–supplementary motor area (pre-SMA)/SMA and precuneus relative to baseline as well as a failure to deactivate anterior nodes of the default mode network. Independent resting-state connectivity analysis indicated reduced connectivity between anterior (task results) and posterior regions of the sensorimotor cortex for patients as well as abnormal connectivity between other regions (cerebellum, thalamus, posterior cingulate gyrus and visual cortex).LimitationsAside from rates of false-positive responses, true proactive response inhibition tasks do not provide behavioural metrics that can be independently used to quantify task performance.ConclusionOur results suggest that basic cortico-cortico and intracortical connections between the sensorimotor cortex and adjoining regions are impaired in patients with schizophrenia and that these impaired connections contribute to inhibitory failures (i.e., a positive rather than negative hemodynamic response).     

Hypoactivation in right inferior frontal cortex is specifically associated with motor response inhibition in adult ADHD

Adult ADHD has been linked to impaired motor response inhibition and reduced associated activation in the right inferior frontal cortex (IFC). However, it is unclear whether abnormal inferior frontal activation in adult ADHD is specifically related to a response inhibition deficit or reflects a more general deficit in attentional processing. Using functional magnetic resonance imaging, we tested a group of 19 ADHD patients with no comorbidities and a group of 19 healthy control volunteers on a modified go/no‐go task that has been shown previously to distinguish between cortical responses related to response inhibition and attentional shifting. Relative to the healthy controls, ADHD patients showed increased commission errors and reduced activation in inferior frontal cortex during response inhibition. Crucially, this reduced activation was observed when controlling for attentional processing, suggesting that hypoactivation in right IFC in ADHD is specifically related to impaired response inhibition. The results are consistent with the notion of a selective neurocognitive deficit in response inhibition in adult ADHD associated with abnormal functional activation in the prefrontal cortex, whilst ruling out likely group differences in attentional orienting, arousal and motivation. Hum Brain Mapp 35:5141–5152, 2014. © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.     

Altered brain activation during response inhibition in children with primary nocturnal enuresis: An fMRI study

Nocturnal enuresis is a common developmental disorder in children, and primary nocturnal enuresis (PNE) is the dominant subtype. The main purpose of this study was to investigate brain functional abnormalities specifically related to motor response inhibition in children with PNE using fMRI in combination with a Go/NoGo task. Twenty‐two children with PNE and 22 healthy children, group‐matched for age and sex, took part in this experiment. Although no significant between‐group differences in task performance accuracy were observed, PNE patients showed significantly longer response times on average. There were several brain regions with reduced activation during motor response inhibition in children with PNE: the bilateral inferior frontal gyri, right superior and middle frontal gyri, right inferior parietal lobe, bilateral cingulate gyri and insula. Our data indicate that response inhibition in children with PNE is associated with a relative lack of or delay in the maturation of prefrontal cortex circuitry that is known to suppress inappropriate responses. This result might give clues to understanding the pathophysiology of PNE. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Error processing in major depressive disorder: evidence from event-related potentials

In a previous study we showed that errors following errors activate a strategic (prefrontal) mechanism. In an error trial (trial n) following an erroneous previous trial (trial n - 1) healthy control subjects were found to have enlarged (more negative) amplitudes of the error related negativity (ERN)/error negativity (Ne), an electrophysiological correlate of response monitoring, in response to a negative feedback signal. Contrary to that, patients with major depressive disorder showed smaller (less negative) ERN/Ne amplitudes. It has been discussed controversially whether errors of choice (e.g., pressing an incorrect response button in an Eriksen flanker task) and errors of commission (e.g., pressing a button when one is not supposed to in a Go/Nogo task) are related to different ERN/Ne mechanisms. In the present study, we examined whether our previous result only holds for errors of choice in an Eriksen flankers task or extends to errors of commission in a Go/Nogo task, as well. Ten patients with DSM-IV major depressive disorder and 10 matched controls participated in a Go/Nogo task with performance feedback which signaled monetary reward. Patients with major depressive disorder again showed a less negative ERN/Ne amplitude in error trials following error trials. This result might reflect impaired response monitoring processes in major depressive disorder resulting from an impaired activation of a central reward pathway and/or a deficit in strategic reasoning.