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.     

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.     

No altered dorsal anterior cingulate activation in bipolar II disorder patients during a Go/No-go task: an fMRI study

Objectives:  It has been reported that one of the core features in patients with bipolar disorder II (BD II) is increased impulsivity. The aim of this study was to investigate whether patients with BD II showed decreased activation in the dorsal anterior cingulate cortex (dACC) as compared to healthy controls when performing a task sensitive to impulsivity.
Methods:  Twenty-seven BD II patients and 28 healthy controls performed a Go/No-go task during a functional magnetic resonance imaging (fMRI) session. Eleven of the patients were unmedicated, and possible group differences between medicated and unmedicated patients were also assessed.
Results:  The groups did not differ in behavioral performance on the Go/No-go task.
Both BD II subjects and healthy controls demonstrated dACC activity during the task, and analyses revealed no statistically significant group differences. Medicated and unmedicated patients also did not differ in the degree of fMRI activation.
Conclusions:  These findings do not support the hypothesis of abnormal dACC activity during a Go/No-go task in BD II patients.     

Relation of a negative ERP component to response inhibition in a Go/No-go task.

Previous studies have suggested that a negative component (N2) of the event-related potential (ERP), whose peak latency is 200-300 msec after stimulus onset, may vary in amplitude depending on the neuronal activity required for response inhibition. To confirm this, ERPs were recorded in a Go/No-go paradigm in which subjects of one group (HI, n = 10) were asked to respond to Go stimuli with key pressing within a shorter period (less than 300 msec) than those of the other group (LI, n = 10) whose upper limit of the reaction time was relatively longer (less than 500 msec). All subjects had to withhold the Go response to the No-go stimuli without making overt muscle activities. The N2 component was recorded superposed on the initial descending limb of the P300 and other slow deflections, which were attenuated with a digital filter to measure the amplitude of N2. The N2 amplitude was significantly larger to the No-go stimulus than to the Go stimulus in both groups, but the N2 to the No-go stimulus was significantly larger in the HI group than in the LI group. These differences in N2 amplitude between conditions or groups were thought to be independent of other ERP components such as P300 and CNV. These results suggest that at least to some extent N2, which increased in amplitude when a greater effort was required to withhold the Go response, reflects the activity of a response inhibition system of the brain.     

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.     

Cortical rhythm of No-go processing in humans: An MEG study

ObjectiveWe investigated the characteristics of cortical rhythmic activity in No-go processing during somatosensory Go/No-go paradigms, by using magnetoencephalography (MEG).MethodsTwelve normal subjects performed a warning stimulus (S1) – imperative stimulus (S2) task with Go/No-go paradigms. The recordings were conducted in three conditions. In Condition 1, the Go stimulus was delivered to the second digit, and the No-go stimulus to the fifth digit. The participants responded by pushing a button with their right thumb for the Go stimulus. In Condition 2, the Go and No-go stimuli were reversed. Condition 3 was the resting control.ResultsA rebound in amplitude was recorded in the No-go trials for theta, alpha, and beta activity, peaking at 600–900 ms. A suppression of amplitude was recorded in Go and No-go trials for alpha activity, peaking at 300–600 ms, and in Go and No-go trials for beta activity, peaking at 200–300 ms.ConclusionThe cortical rhythmic activity clearly has several dissociated components relating to different motor functions, including response inhibition, execution, and decision-making.SignificanceThe present study revealed the characteristics of cortical rhythmic activity in No-go processing.     

Evaluating implicit spider fear associations using the Go/No-go Association Task

The Go/No-go association task (GNAT) [Nosek, B.A., & Banaji, M.R. (2001). The Go/No-go Association Task. Social Cognition, 19, 625-666], which measures automatic associations in memory, was administered to participants who were high (N=17) versus low (N=17) in spider fear along with other established fear measures to validate the tool as a proxy measure for fear schemata. The GNAT involves participants classifying stimuli into superordinate categories and looking at speed of categorization when categories match, versus contradict, participants' hypothesized implicit fear associations. Results showed that the GNAT successfully differentiated the fear groups, indicating its convergent validity, and there was no group difference on a GNAT control fear task, supporting its discriminant validity. In addition, the GNAT spider fear task was associated with questionnaire measures of spider fear, self-reported anxiety during a behavioral avoidance test (approaching a live spider), and whether or not participants touched the spider during the behavioral test, supporting the task's predictive validity. Findings suggest the GNAT provides an effective, single-target measure of involuntary fear associations.     

Single unit activity during a Go/NoGo task in the "prefrontal cortex" of pigeons.

Single unit activity was recorded during a delayed auditory/visual Go/NoGo task from the neostriatum caudolaterale (NCL) of pigeons, a multimodal associative avian forebrain structure comparable to the prefrontal cortex (PFC). The animals were trained to mandibulate (to open their beak) during the Go period after which they received a drop of water as reward. Neuronal activity changes were observed during the delay period (DELAY) between auditory and visual stimulation, to the onset of the visual stimulus or to the delivery of the reward. In some neurons, responses were related to the behavioral significance of the stimulus such that the neuronal activity was statistically different between Go and NoGo trials. Moreover, some units anticipated the upcoming reward or changed their firing frequency in a correlated manner prior to beak movements. These neuronal activity patterns suggest that the NCL provides a neural network that participates in the integration and processing of external stimuli in order to generate goal directed behavior.     

Single unit activity during a Go/NoGo task in the “prefrontal cortex” of pigeons

Single unit activity was recorded during a delayed auditory/visual Go/NoGo task from the neostriatum caudolaterale (NCL) of pigeons, a multimodal associative avian forebrain structure comparable to the prefrontal cortex (PFC). The animals were trained to mandibulate (to open their beak) during the Go period after which they received a drop of water as reward. Neuronal activity changes were observed during the delay period (DELAY) between auditory and visual stimulation, to the onset of the visual stimulus or to the delivery of the reward. In some neurons, responses were related to the behavioral significance of the stimulus such that the neuronal activity was statistically different between Go and NoGo trials. Moreover, some units anticipated the upcoming reward or changed their firing frequency in a correlated manner prior to beak movements. These neuronal activity patterns suggest that the NCL provides a neural network that participates in the integration and processing of external stimuli in order to generate goal directed behavior.     

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.     

Functional brain correlates of response time variability in children

During tasks requiring response inhibition, intra-individual response time variability, a measure of motor response preparation, has been found to correlate with errors of commission, such that individuals with higher variability show increased commission errors. This study used fMRI to examine the neural correlates of response variability in 30 typically developing children, ages 8-12, using a simplified Go/No-go task with minimal cognitive demands. Lower variability was associated with Go activation in the anterior cerebellum (culmen) and with No-go activation in the rostral supplementary motor area (pre-SMA), the postcentral gyrus, the anterior cerebellum (culmen) and the inferior parietal lobule. For both Go and No-go events, higher variability was associated with activation in prefrontal cortex and the caudate. The findings have implications for neuropsychiatric disorders such as ADHD and suggest that during response inhibition, children with more consistent performance are able to rely on premotor circuits involving the pre-SMA, important for response selection; those with less consistent performance instead recruit prefrontal circuits involved in more complex aspects of behavioral control.     

Event-related potentials in a No-go task involving response-tendency conflict.

Event-related potentials (ERPs) were recorded while 13 subjects completed a color discrimination task. In task one, subjects were asked to press a button when the presented stimulus was a red or a green spot (Go stimulus), and inhibited any motor response when the stimulus was a yellow or a white spot (No-go stimulus). In task two, subjects were instructed to count the number of the Go stimuli, not to count the No-go stimuli. In order to investigate the influence of probability on ERP components, two sessions were designed in each task. In session one, the probability of the four kinds of stimuli was equal. In session two, the probability of red, green, yellow, and white were 10%, 10%, 10%, and 70% respectively. An enhanced negative potential in the frontal area was recorded in the 200-400 ms range both following No-go stimuli and following No-count stimuli, which was not influenced by the stimulus probability. The result cast doubt on the interpretation of the frontal negative potential enhancement as reflecting response-inhibition processes. The potential might be related to the information processing of response-tendency conflict rather than the suppression of motor execution.     

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.     

Participation of the red nucleus in motor initiation: unit recording and cooling in cats

Cats were trained to release (Go) or not to release (No-go) a lever after a brief auditory signal, depending on the presence of an additional tone (No-go cue). Unit recording and cooling were made in the red nucleus (RN) contralateral to the performing limb. Three major results were found: (1) in the Go condition, we observed phasic increases of rubral firing, with a constant latency after the auditory signal and with an amplitude correlated to the latency of motor triggering (i.e. reaction time, RT); the tonic activity preceding the auditory signal could also be correlated to the RTs for some units; (2) in the No-go condition, there was no phasic increase of rubral firing after the auditory signal; the tonic activity during the presentation of the No-go cue was markedly decreased compared to the Go trials; (3) cooling of the RN increased the RTs and could also block the motor triggering. These results suggest that the RN is involved in setting and triggering a conditioned motor response according to sensory cues.     

Prefrontal representation of stimulus attributes during delay tasks. I. Unit activity in cross-temporal integration of sensory and sensory-motor information

The activity of 294 single units was recorded from the dorsolateral prefrontal cortex of monkeys performing two visual discrimination tasks with delayed response. One task, delayed matching-to-sample (DMS), required memory of a colored cue for later (18 s) matching and choice of color; the cue did not connote the location of the delayed response. The other task, delayed conditional position discrimination (DCPD), required memory of a colored cue for later (18 s) choice of spatial response; the cue did connote delayed-response location. All 4 cues (red and green in DMS, yellow and blue in DCPD) were isoluminous and appeared in identical location at trial start. Differential unit reactions to the two DCPD cues were more common than those to the two DMS cues (samples). During the delay period, 15% of all units showed, in one task or the other, differential discharge depending on the cue. In DCPD, a large proportion of the units showing direction-related activity at the time of motor response also reacted with a firing frequency change to one or both (spatially identical) trial-initiating cues. Some units showed coherence of cue-related and response-related changes in accord with the behavioral association between color and direction of response (i.e., yellow-right, blue-left). The reactivity of some units was correlated with the behavioral performance of the tasks in terms of correctness or incorrectness of response. The results indicate that, during visual delay tasks, neurons in the dorsolateral prefrontal cortex may process both spatial and non-spatial information. Because of their protracted differential discharge between cue and response (i.e., during the delay), some units seem involved in the transfer of sensory information across time. These findings suggest the role of prefrontal neurons in the representation of multiple attributes of sensory stimuli, including their associated motor connotations, and the overlap of the cortical representations of different attributes. They are also consistent with the role of the prefrontal cortex in the cross-temporal mediation of sensory-motor contingencies and, therefore, the temporal organization of behavior.     

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.     

Neuronal Activity in the Premotor Cortex of Monkeys Reflects Both Cue Salience and Motivation for Action Generation and Inhibition

Reward prospect weighs on motor decision processes, enhancing the selection of appropriate actions and the inhibition of others. While many studies have investigated the neuronal basis of reward representations and of cortical control of actions, the neuronal correlates of the influences of reward prospect on motor decisions are less clear. We recorded from the dorsal premotor cortex (PMd) of 2 male macaque monkeys performing a modified version of the Stop-signal (countermanding) task. This task challenges motor decisions by requiring responding to a frequent Go stimulus, but to suppress this response when a rare Stop signal is presented during the reaction time. We unbalanced the motivation to respond or to suppress the response by presenting a cue informing on three different rewards schedules: in one case, Go trials were rewarded more than Stop trials; in another case, Stop trials were rewarded more than Go trials; in the last case, both types of trials were rewarded equally. Monkeys adopted different strategies according to reward information provided by the cue: the higher the reward for Stop trials, the higher their ability to suppress the response and the slower their response to Go stimuli. PMd neuronal activity evolved in time and correlated with the behavior: PMd signaled first the cue salience, representing the chance to earn the highest reward at stake, then reflected the shaping of the motor choice by the motivation to move or to stop. These findings represent a neuronal correlate of the influence of reward information on motor decision.SIGNIFICANCE STATEMENT The motivation to obtain rewards drives how animals act over their environment. To explore the involvement of motor cortices in motivated behaviors, we recorded high-resolution neuronal activity in the premotor cortex of monkeys performing a task that manipulated the motivation to generate/withhold a movement through different cued reward probabilities. Our results show the presence of neuronal signals dynamically reflecting the salience of the cue, in the time immediately following its presentation, and a motivation-related activity in performing (or cancelling) a motor program, while the behavioral response approached. The encoding of multiple reward-related signals in this region leads to consider an important role of premotor areas in the reward circuitry supporting action.     

ERPs to stimuli requiring response production and inhibition: effects of age, probability and visual noise

Sixty-six normal adults ranging in age from 20 to 85 years were presented with stimuli containing explicit instructions to initiate or to inhibit a motor response (the words 'push' or 'wait'). In one task, the effect of stimulus probability was investigated by varying probability between 0.25 and 0.75 for both Go and No-go stimuli. In another task, the effect of visual noise was investigated by degrading the stimuli with ampersands on half of the trials. Regression analysis was used to examine the effects of age on P3 amplitude and latency for each stimulus type. The effects of stimulus variables on P3, independent of age, were examined by standardizing each subject's data to those expected for a 20 year old. P3 latency to all stimuli and RT to Go stimuli increased with age. The latency of P3s to No-go stimuli was less sensitive to age than Go stimuli. P3 amplitude at Cz and Pz (but not Fz) diminished with age. P3s to Go stimuli were maximal at Pz and earlier than P3s to No-go stimuli. P3s to No-go stimuli were maximal at Cz. These differences between Go and No-go stimuli remained true under visual noise and probability manipulations. Visual noise prolonged the latency of Go and No-go P3. Less probable Go and No-go stimuli elicited larger and later P3s than more probable stimuli. Decreasing the probability of the No-go stimulus enhanced its central distribution.     

Executive functions with different motor outputs in somatosensory Go/Nogo tasks: an event-related functional MRI study

The aim of this event-related functional magnetic resonance imaging (fMRI) study was to investigate and compare executive functions with different motor outputs in somatosensory Go/Nogo tasks: (1) Button press and (2) Count. Go and Nogo stimuli were presented with an even probability. We observed a common network for Movement and Count Go trials in several regions of the brain including the dorsolateral (DLPFC) and ventrolateral prefrontal cortices (VLPFC), supplementary motor area (SMA), posterior parietal cortex (PPC), inferior parietal lobule (IPL), Insula, and superior temporal gyrus (STG). Direct comparison revealed that primary sensorimotor area (SMI), premotor area (PM), and anterior cingulate cortex (ACC) were more activated during Movement than Count Go trials. In contrast, the VLPFC was more activated during Count than Movement Go trials. Our results suggest that there were two neural networks for the supramodal executive function, common and uncommon, depending on the required response mode.