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.     

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.     

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.     

Response inhibition and response selection: two sides of the same coin

Response inhibition refers to the suppression of actions that are inappropriate in a given context and that interfere with goal-driven behavior. Studies using a range of methodological approaches have implicated executive control processes mediated by frontal-subcortical circuits as being critical to response inhibition; however, localization within the frontal lobe has been inconsistent. In this review, we present evidence from behavioral, lesion, neuroimaging, electrophysiology, and neurological population studies. The findings lay the foundation for a construct in which response inhibition is akin to response selection, such that pre-SMA circuits are critical to selection of appropriate behavior, including both selecting to engage appropriate motor responses and selecting to withhold (inhibit) inappropriate motor responses. Recruitment of additional prefrontal and posterior cortical circuits, necessary to guide response selection, varies depending on the cognitive and behavioral demands of the task.     

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.     

Functional magnetic resonance imaging evidence for abnormalities in response selection in attention deficit hyperactivity disorder: differences in activation associated with response inhibition but not habitual motor response

Impaired response inhibition is thought to be a core deficit in attention deficit hyperactivity disorder (ADHD). Prior imaging studies investigating response inhibition in children with ADHD have used tasks involving different cognitive resources, thereby complicating the interpretation of their findings. In this study, a classical go/no-go task with a well-ingrained stimulus-response association (green = go; red = no-go) was used in order to minimize extraneous cognitive demands. Twenty-five children with ADHD and 25 typically developing (TD) children between the ages of 8 and 13 years and group-matched for IQ and performance on the go/no-go task were studied using event-related functional magnetic resonance imaging (fMRI). Analyses were used to examine differences in activation between the ADHD and TD groups for "go" (habitual motor response) and "no-go" (requiring inhibition of the motor response) events. Region-of-interest analyses revealed no between-group difference in activation in association with "go" events. For "no-go" events, the children with ADHD demonstrated significantly less activation than did TD controls within a network important for inhibiting a motor response to a visual stimulus, with frontal differences localized to the pre-supplementary motor area. Although blood oxygenation level-dependent fMRI data show no differences between children with ADHD and TD children in association with a habituated motor "go" response, during "no-go" events, which require selecting not to respond, children with ADHD show diminished recruitment of networks important for response inhibition. The findings suggest that abnormalities in circuits important for motor response selection contribute to deficits in response inhibition in children with ADHD and lend support to the growing awareness of ADHD-associated anomalies in medial frontal regions important for the control of voluntary actions.     

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.     

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.     

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.     

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.     

The NoGo P300 'anteriorization' effect and response inhibition.

OBJECTIVE: The P300 event-related potential shows anterior P300 increases on NoGo tasks (target stimulus=withhold response) relative to Go tasks (target stimulus=commit response). This 'NoGo anteriorization' has been hypothesized to reflect response inhibition. However, silent-count tasks show similar P300 anteriorization. The P300 anteriorization on silent-count tasks relative to Go tasks cannot reflect inhibition-related processes, and questions the degree to which anteriorization observed on NoGo trials can be ascribed to response inhibition. Comparison of anteriorization between the silent-count and NoGo tasks is thus essential. P300 topography on NoGo and silent-count tasks has not been previously compared. METHODS: P300 on Go, NoGo, and silent-count auditory oddball tasks were compared. If the NoGo P300 anteriorization reflects response inhibitory processes, the NoGo P300 should be larger anteriorly than the Go P300 (overt responses) and the silent-count P300s (covert responses). If anteriorization primarily reflects negative voltage Go task motor activity that reduces the normal frontal P300 amplitude, then the Go task P300 should be smaller than both the NoGo and silent-count P300s, which should not differ from one another. RESULTS: The Go task elicited a bilaterally reduced frontal P300 and asymmetrical frontal P300 relative to both the NoGo and silent-count tasks. The NoGo task P300 and silent-count task P300 showed similar amplitude and topography. P300 and slow wave on the NoGo task were not asymmetrical. CONCLUSIONS: The increased frontal P300 in NoGo tasks cannot be attributed solely to a positive-going inhibitory process, but likely reflects negative voltage response execution processes on Go trials. However, the alternative explanation that memory-related processes increase the silent-count P300 anteriorly to the same degree as NoGo inhibitory processes cannot be ruled out.     

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.     

An evaluation of distinct volumetric and functional MRI contributions toward understanding age and task performance: a study in the basal ganglia

Prior work by our group and others has implicated the basal ganglia as important in age-related differences in tasks involving motor response control. The present study used structural and functional MRI approaches to analyze this region of interest (ROI) toward better understanding the contributions of structural and functional MRI measures to understanding age-related and task performance-related cognitive differences. Eleven healthy elders were compared with 11 healthy younger adults while they completed the "go" portion of a complex Go/No-go task. Separate ROI's in the bilateral caudate (C) and putamen/globus pallidus (PGp) were studied based upon previous findings of age-related functional MRI differences in basal ganglia for this portion of the task. Structural volumes and functional activation (in percent area under the curve during correct responses) were independently extracted for these ROI's. Results showed that age correlated with ROI volume in bilateral PGp and C, while multiple task performance measures correlated with functional activation in the left PGp. The Go/No-go task measures were also significantly correlated with traditional attention and executive functioning measures. Importantly, fMRI activation and volumes from each ROI were not significantly inter-correlated. These findings suggest that structural and functional MRI make unique contributions to the study of performance changes in aging.     

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.     

Neural mechanisms of inhibitory control continue to mature in adolescence

Inhibition is a fundamental executive function necessary for self-management of behaviour. The ability to withhold prepotent responses shows protracted development, extending through childhood and into adulthood. Using magnetoencephalography (MEG) with co-registered MRI, the spatiotemporal neural processes involved in inhibitory control were examined in 15 adolescents and 15 adults during a Go/No-go task. Two tasks were run that contained inverse ratios of Go to No-go trials for the experimental (2:1) and control conditions (1:2). Using vector beamforming, images of neural activation between No-go and Go trials were compared for both age-groups and revealed recruitment of the right inferior frontal gyrus in adults (BA 45; 200–250 ms), but delayed recruitment of the left inferior frontal gyri in adolescents (BA 45; 250–300 ms). Left anticipatory-related activity near the hand motor region (BA 6) was present in both adolescents and adults, but for a longer duration in adults. Adolescents additionally recruited the right middle and superior temporal gyri (BA21, BA22), while adults engaged the right temporal gyrus (BA41) but for a much briefer duration. These findings of delayed recruitment of canonical inhibitory control areas with supplementary and prolonged involvement of temporal areas in adolescents compared to adults indicate an immature inhibitory network even in adolescence.     

Neural correlates of inhibitory control in adult attention deficit/hyperactivity disorder: evidence from the Milwaukee longitudinal sample

Only a few studies have investigated the neural substrate of response inhibition in adult attention deficit hyperactivity disorder (ADHD) using Stop-Signal and Go/No-Go tasks. Inconsistencies and methodological limitations in the existing literature have resulted in limited conclusions regarding underlying pathophysiology. We examined the neural basis of response inhibition in a group of adults diagnosed with ADHD in childhood and who continue to meet criteria for ADHD. Adults with ADHD (n=12) and controls (n=12) were recruited from an ongoing longitudinal study and were matched for age, IQ, and education. Individuals with comorbid conditions were excluded. Functional magnetic resonance imaging (fMRI) was used to identify and compare the brain activation patterns during correct trials of a response-inhibition task (Go/No-Go). Our results showed that the control group recruited a more extensive network of brain regions than the ADHD group during correct inhibition trials. Adults with ADHD showed reduced brain activation in the right frontal eye field, pre-supplementary motor area, left precentral gyrus, and the inferior parietal lobe bilaterally. During successful inhibition of an inappropriate response, adults with ADHD display reduced activation in fronto-parietal networks previously implicated in working memory, goal-oriented attention, and response selection. This profile of brain activation may be specifically associated with ADHD in adulthood.     

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.     

Negative correlation between right prefrontal activity during response inhibition and impulsiveness: A fMRI study

Behavioral disinhibition in Go/No-Go task is thought to be associated with impulsiveness in humans. Recent imaging studies showed that neural circuits involving diverse areas of the frontal cortex and other association cortex sites such as the parietal cortex are implicated in the inhibition of response during No-Go trials. The aim of the present study was to investigate the association between regional cerebral activation during No-Go trials and impulsiveness. Seventeen right-handed healthy volunteers participated in the study. We used functional magnetic resonance imaging to measure the brain activation during a Go/No-Go task. The Barratt Impulsiveness Scale, 11(th) version (BIS-11) was used to measure impulsiveness. Activated regions included the right middle frontal gyrus and the inferior parietal lobe, which is consistent with previous neuroimaging studies. A negative correlation was observed between the motor impulsiveness of BIS-11 and No-Go-related activation in the right dorsolateral prefrontal cortex (RDLPFC). Our results suggest that the RDLPFC is the area most sensitive to differences in individual motor impulsiveness and its activity may be an indicator of the individual capacity for response inhibition.     

Posttraumatic stress symptoms and brain function during a response-inhibition task: an fMRI study in youth

Youth who experience interpersonal trauma and have posttraumatic stress symptoms (PTSS) can exhibit difficulties in executive function and physiological hyperarousal. Response inhibition has been identified as a core component of executive function. In this study, we investigate the functional neuroanatomical correlates of response inhibition in youth with PTSS. Thirty right‐handed medication‐naïve youth between the ages of 10 and 16 years underwent a 3‐Tesla Functional Magnetic Resonance Imaging scan during a response‐inhibition (Go/No‐Go) task. Youth with PTSS (n = 16) were age and gender matched to a control group of healthy youth (n = 14). Between‐groups analyses were conducted to identify brain regions of greater activation in the No/Go‐Go contrasts. PTSS and control youth performed the task with similar accuracy and response times. Control subjects had greater middle frontal cortex activation when compared with PTSS subjects. PTSS subjects had greater medial frontal activation when compared with control subjects. A sub‐group of youth with PTSS and a history of self‐injurious behaviors demonstrated increased insula and orbitofrontal activation when compared with those PTSS youth with no self‐injurious behaviors. Insula activation correlated positively with PTSS severity. Diminished middle frontal activity and enhanced medial frontal activity during response‐inhibition tasks may represent underlying neurofunctional markers of PTSS. Depression and Anxiety 0:1–13, 2007. Published 2007 Wiley‐Liss, Inc.     

Dysfunction of response inhibition in eating disorders

Introduction: Response inhibition in eating disorders (ED) has been studied using methods such as Go/No-go tasks and cognitive conflict tasks, but the results have been inconsistent with regard to the presence or absence of impaired response inhibition in ED. This may be due to variation across the studies in the characteristics of the tasks and in the degree of underweight of ED participants. Method: We investigated the presence or absence of impaired response inhibition in an ED patient group, including many severe cases (body mass index <15 kg/m²), by comparing the interference effect of ED patients and healthy participants with an arrow–space interference task as the cognitive conflict task. Results: There was a significant interference effect on response time in healthy participants and ED patients, with no significant intergroup difference in response times. However, the interference effect on error rate was significantly greater in ED patients than healthy participants. There was no significant difference in this trend across different ED subtypes (restricting type anorexia nervosa, binge-eating/purging type anorexia nervosa, and eating disorder not otherwise specified). Conclusions: Attentional control such as focused attention and sustained attention are preserved in ED patients, but there appears to be dysfunction of response inhibition. This might be the basis of poor impulse control in the eating behavior of ED patients.