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.     

Response inhibition in adolescents diagnosed with attention deficit hyperactivity disorder during childhood: an event-related FMRI study

OBJECTIVE: Frontostriatal neural abnormalities have been implicated in the response inhibition impairments that are characteristic of attention deficit hyperactivity disorder (ADHD). However, reports of such abnormalities in adolescents are inconsistent. The present study used behavioral and functional neuroimaging techniques to examine inhibitory control processes in adolescents who had been diagnosed with ADHD during childhood. METHOD: The authors used functional magnetic resonance imaging (fMRI) during performance of a Go/No-Go task to scan 10 male adolescents who were diagnosed with DSM-III-R ADHD when they were 7 to 11 years old and nine age-, sex-, and IQ-matched comparison subjects with no history of ADHD. Response inhibition was tested by contrasting neural activation during No-Go trials with that during Go trials. RESULTS: The inhibition of a prepotent tendency to respond produced markedly greater activation of the left anterior cingulate gyrus, bilateral frontopolar regions, bilateral ventrolateral prefrontal cortex, and left medial frontal gyrus in the adolescents with childhood ADHD than in the adolescents with no history of ADHD. Activity in the first two regions was inversely related to task performance across the study group. CONCLUSIONS: Compared with adolescents who had no history of ADHD, adolescents who were diagnosed with ADHD during childhood exhibited enhanced responses during inhibition in ventrolateral prefrontal cortical areas that subserve response inhibition, as well as in anterior cingulate and frontopolar regions implicated in other executive functions.     

Functional MRI of cerebral activation during encoding and retrieval of words

The aims of the present study were to identify the cerebral structures associated with encoding and retrieval of verbal material. To circumvent the inherent disadvantages of the conventional block designs used in functional magnetic resonance imaging (MRI), an event-related design compared activation related to randomly intermixed old and new words during recognition. To support the validity of results, both nonparametric analyses in regions of interest (ROI) and statistical parametric mapping (SPM 96) were used. Twelve healthy volunteers, ages 22-35 years, performed three tasks: intentional encoding of words, recognition of old (previously learned) words, and discrimination between words and nonwords, a task to control for visual input and motor output during recognition. Echo-planar magnetic resonance imaging of blood-level, oxygen-dependent, task-related changes was used to compare cerebral activity under active and resting conditions as well as to detect event-related activity within blocks of trials. Comparable results were obtained following nonparametric statistical analysis of selected ROI and SPM. Encoding of words was associated with increased activity in the left inferior frontal gyrus, including Broca's area and in the left parietal association cortex. Event-related data analysis revealed activation of the right medial frontal gyrus, the right anterior cingulate gyrus, and parietal association cortices during recognition of previously presented words. In the lexical decision task, words in comparison with nonwords were associated with activation of the left parietal association cortex. The right medial frontal gyrus, the right anterior cingulate gyrus, and the right parietal association cortex are likely to be involved in episodic memory functions during recognition of previously presented verbal material. The comparison of event-related activation occurring within one trial block instead of among several trial blocks may significantly improve the performance of memory studies.     

Neural processes of preparatory control for stop signal inhibition

This study investigated the preparatory control of motor inhibition and motor execution using a stop signal task (SST) and functional magnetic resonance imaging (fMRI). In the SST, a frequent “go” signal triggered a prepotent response and a less frequent “stop” signal prompted the inhibition of this response. Preparatory control of motor inhibition and execution in the stop signal trials were examined by contrasting brain activation between stop success and stop error trials during the fore‐period, in which participants prepared to respond to go or to stop. Results from 91 healthy adults showed greater activation in the right prefrontal cortex and inferior parietal lobule during preparatory motor inhibition. Preparatory motor execution activated bilateral putamen, primary motor cortices, posterior cingulate cortex, ventromedial prefrontal cortex, and superior temporal/intraparietal sulci. Furthermore, the extents of these inhibition and execution activities were inversely correlated across subjects. On the basis of a median split of the stop signal reaction time (SSRT), subjects with short SSRT showed greater activity in the right orbital frontal cortex during preparatory inhibition. These new findings suggest that the go and stop processes interact prior to target presentation in the SST, in accord with recent computational models of stop signal inhibition. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

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.     

Sustained brain activation supporting stop‐signal task performance

Stop‐signal paradigms operationalize a basic test of goal‐directed behaviour whereby an overarching stop goal that is performed intermittently must be maintained throughout ongoing performance of a reaction time go task (go goal). Previous studies of sustained brain activation during stop‐signal task performance in humans did not observe activation of the dorsolateral prefrontal cortex (DLPFC) that, in concert with the parietal cortex, is known to subserve goal maintenance. Here we explored the hypothesis that a DLPFC and parietal network has a key role in supporting ongoing stop‐signal task performance. We used a blocked functional magnetic resonance imaging design that included blocks of trials containing typical stop‐signal paradigm stimuli that were performed under three conditions: Stop condition, which required reaction time responding to go stimuli and inhibition of cued responses upon presentation of a stop signal; Go condition, identical except that the tone was ignored; and Passive condition, which required only quiescent attention to stimuli. We found that, whereas a distributed corticothalamic network was more active in Stop compared with Go, only the right DLPFC and bilateral parietal cortex survived after masking that contrast with Stop compared with Passive. These findings indicate that sustained activation of a right dominant frontoparietal network supports stop goal processes during ongoing performance of the stop‐signal task.     

Task-specific hypoactivation in prefrontal and temporoparietal brain regions during motor inhibition and task switching in medication-naive children and adolescents with attention deficit hyperactivity disorder

OBJECTIVE: A relatively small number of functional imaging studies of attention deficit hyperactivity disorder (ADHD) have shown abnormal prefrontal and striatal brain activation during tasks of motor response inhibition. However, the potential confound of previous medication exposure has not yet been addressed, and no functional imaging study exists to date on medication-naive children and adolescents with ADHD. The aim of this study was to investigate the neural substrates of a range of motor and cognitive inhibitory functions in a relatively large group of children and adolescents with ADHD who had never previously been exposed to medication. METHOD: Nineteen boys with ADHD and 27 healthy age- and IQ-matched boys underwent functional MRI to compare brain activation during performance of tasks that assessed motor response inhibition (go/no go task), cognitive interference inhibition (motor Stroop task), and cognitive flexibility (switch task). RESULTS: Boys with ADHD showed decreased activation in the left rostral mesial frontal cortex during the go/no go task and decreased activation in the bilateral prefrontal and temporal lobes and right parietal lobe during the switch task. No significant group differences were observed during motor Stroop task performance. CONCLUSION: Abnormal brain activation was observed in medication-naive children and adolescents with ADHD during tasks involving motor inhibition and task switching, suggesting that hypoactivation in this patient group is unrelated to long-term stimulant exposure. Furthermore, functional abnormalities are task-specific and extend from frontostriatal to parietal and temporal cortices.     

Serotonergic modulation of neuronal responses to behavioural inhibition and reinforcing stimuli: an fMRI study in healthy volunteers

Serotonin (5-HT) has been implicated in the aetiology of a number of psychiatric conditions, including depression, anxiety and antisocial personality disorder. The development of these disorders may arise from alterations in underlying motivational and cognitive processes such as emotional recognition, reinforcement processing and central inhibitory control. This study aimed to localize where in the brain 5-HT modulates neuropsychological processes relevant to putative 5-HT disorders, using functional magnetic resonance imaging. We examined the effect of the antidepressant mirtazapine on brain activations associated with behavioural inhibition and reinforcement processing in healthy subjects. Forty-five men were randomly allocated to receiving mirtazapine or placebo in a double-blind fashion. A Go/No-Go, Reward/No-Reward and Loss/No-loss task were performed during functional magnetic resonance imaging using a 1.5 Tesla Philips Gyroscan scanner. Blood oxygenation level dependent (BOLD) responses were analysed using SPM2. Task activations were largely consistent with previous findings. Mirtazapine modulated brain activations in the Go/No-Go and Reward/No-Reward task. During behavioural inhibition, enhanced activations were observed in the right orbitofrontal cortex (BA47). Increased activations in bilateral parietal cortex were found during the Reward task while no significant interaction was observed in the Loss task. Our results support the suggestion of an important role of serotonin in modulating basic processes involved in psychiatric disorders. Combining drug challenge with fMRI (pharmacoMRI; pMRI) is a promising tool for investigating these processes in healthy as well as patient groups.     

Error-related brain activation during a Go/NoGo response inhibition task

Inhibitory control and performance monitoring are critical executive functions of the human brain. Lesion and imaging studies have shown that the inferior frontal cortex plays an important role in inhibition of inappropriate response. In contrast, specific brain areas involved in error processing and their relation to those implicated in inhibitory control processes are unknown. In this study, we used a random effects model to investigate error-related brain activity associated with failure to inhibit response during a Go/NoGo task. Error-related brain activation was observed in the rostral aspect of the right anterior cingulate (BA 24/32) and adjoining medial prefrontal cortex, the left and right insular cortex and adjoining frontal operculum (BA 47) and left precuneus/posterior cingulate (BA 7/31/29). Brain activation related to response inhibition and competition was observed bilaterally in the dorsolateral prefrontal cortex (BA 9/46), pars triangularis region of the inferior frontal cortex (BA 45/47), premotor cortex (BA 6), inferior parietal lobule (BA 39), lingual gyrus and the caudate, as well as in the right dorsal anterior cingulate cortex (BA 24). These findings provide evidence for a distributed error processing system in the human brain that overlaps partially, but not completely, with brain regions involved in response inhibition and competition. In particular, the rostal anterior cingulate and posterior cingulate/precuneus as well as the left and right anterior insular cortex were activated only during error processing, but not during response competition, inhibition, selection, or execution. Our results also suggest that the brain regions involved in the error processing system overlap with brain areas implicated in the formulation and execution of articulatory plans.     

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.     

Progressive increase of frontostriatal brain activation from childhood to adulthood during event-related tasks of cognitive control

Higher cognitive inhibitory and attention functions have been shown to develop throughout adolescence, presumably concurrent with anatomical brain maturational changes. The relatively scarce developmental functional imaging literature on cognitive control, however, has been inconsistent with respect to the neurofunctional substrates of this cognitive development, finding either increased or decreased executive prefrontal function in the progression from childhood to adulthood. Such inconsistencies may be due to small subject numbers or confounds from age-related performance differences in block design functional MRI (fMRI). In this study, rapid, randomized, mixed-trial event-related fMRI was used to investigate developmental differences of the neural networks mediating a range of motor and cognitive inhibition functions in a sizeable number of adolescents and adults. Functional brain activation was compared between adolescents and adults during three different executive tasks measuring selective motor response inhibition (Go/no-go task), cognitive interference inhibition (Simon task), and attentional set shifting (Switch task). Adults compared with children showed increased brain activation in task-specific frontostriatal networks, including right orbital and mesial prefrontal cortex and caudate during the Go/no-go task, right mesial and inferior prefrontal cortex, parietal lobe, and putamen during the Switch task and left dorsolateral and inferior frontotemporoparietal regions and putamen during the Simon task. Whole-brain regression analyses with age across all subjects showed progressive age-related changes in similar and extended clusters of task-specific frontostriatal, frontotemporal, and frontoparietal networks. The findings suggest progressive maturation of task-specific frontostriatal and frontocortical networks for cognitive control functions in the transition from childhood to mid-adulthood.     

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.     

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.     

Neuronal correlates and serotonergic modulation of behavioural inhibition and reward in healthy and antisocial individuals

Individuals with antisocial personality disorder (ASPD) are impulsive and show impairment in reinforcement processing. There is increasing evidence for a neurobiological basis of psychopathy, which shares some of the characteristics of ASPD, but research on the neuronal correlates of neuropsychological processes in ASPD remains limited. Furthermore, no research has examined the effects of serotonergic manipulation on brain activations in antisocial groups. In this study, 25 male participants with ASPD (mean age 42.1) and 32 male control participants (mean age 30.5; 25 participants providing usable scans) were randomly allocated to receive the 5-HT_2C-agonist mCPP or placebo. Participants were scanned using functional magnetic resonance imaging (fMRI) during a behavioural inhibition (Go/NoGo) and a reward task. In comparison to healthy controls the ASPD group showed reduced task related activations in the dorsolateral prefrontal cortex (DLPFC) but increased signal in the pre/subgenual anterior cingulate cortex (ACC) in the Go/No-Go task and increased activation in OFC in the reward task. mCPP modulated brain responses in both tasks in the whole group. Interactions between group and drug occured in bilateral OFC, caudate and ventral pallidum during the reward task but no significant interactions were found in the Go/No-Go task. This suggests that ASPD involves altered serotonin modulation of reward, but not motor inhibition pathways. These findings suggest that ASPD involves altered DLPFC, ACC and OFC function. Altered serotonergic modulation of reward pathways seen in the ASPD group raises the possibility that targeting serotonin systems may be therapeutic.     

Theta oscillations within right dorsolateral prefrontal cortex contribute differently to speech versus limb inhibition

Evidence suggests that speech and limb movement inhibition are subserved by common neural mechanisms, particularly within the right prefrontal cortex. In a recent study, we found that cathodal stimulation of right dorsolateral prefrontal cortex (rDLPFC) differentially modulated P3 event-related potentials for speech versus limb inhibition. In the present study, we further analyzed these data to examine the effects of cathodal high-definition transcranial direct current stimulation (HD-tDCS) over rDLPFC on frontal theta - an oscillatory marker of cognitive control - in response to speech and limb inhibition, during a Go/No-Go task in 21 neurotypical adults. Electroencephalography data demonstrated that both speech and limb No-Go elicited prominent theta activity over right prefrontal electrodes, with stronger activity for speech compared to limb. Moreover, we found that cathodal stimulation significantly increased theta power over right prefrontal electrodes for speech versus limb No-Go. Source analysis revealed that cathodal, but not sham, stimulation increased theta activity within rDLPFC and bilateral premotor cortex for speech No-Go compared to limb movement inhibition. These findings complement our previous report and suggest (1) right prefrontal theta activity is an amodal oscillatory mechanism supporting speech and limb inhibition, (2) larger theta activity in prefrontal electrodes for speech versus limb following cathodal stimulation may reflect allocation of additional neural resources for a more complex motor task, such as speech compared to limb movement. These findings have translational implications for conditions such as Parkinson's disease, wherein both speech and limb movement are impaired.     

Event-related components of the punishment and reward sensitivity

ObjectiveThe present study investigated the properties of feedback-related negativity (FRN) and P3 component of the event-related potentials (ERPs) and their neural sources localization as neurocognitive correlates of the behavioural inhibition and behavioural activation systems (BIS/BAS). The association between BIS/BAS function and anterior cortical asymmetry was tested.MethodsFifty right-handed women were investigated with 30-channel recordings during an instrumental Go/No-Go learning task. ERPs were elicited to feedback signals indicating monetary losses and monetary gains. Learning performance, FRN, and P3 amplitude and latency measures were calculated and related to BIS and BAS measures by means of ANOVA and correlation analysis. The neural sources of FRN and P3 components of the ERPs were estimated using LORETA software. A resting EEG-alpha-power (8–13 Hz) asymmetry measure was obtained.ResultsHigh levels of Reward Responsiveness (RR), a first order factor of the BAS, were associated with shorter RTs and enhanced positive feelings. The FRN was larger to signals indicating monetary Loss as compared to monetary Gain and enhanced with higher BIS and individual learning ability. Higher RR scores were related to greater left-sided resting frontal cortical asymmetry associated with approach orientation. High-RR subjects, as compared to Low-RR ones, had a smaller P3 amplitude for Go/Loss signals. The P3 latency to No-Go/Gain signals was the best positive predictor of RR. LORETA source localization for the FRN component displayed significantly higher brain electrical activity in left-fusiform gyrus and right superior temporal gyrus to monetary Loss in comparison to monetary Gain after incorrect No-Go responses. For the P3 wave, the monetary Loss produced significantly higher activations in the left superior parietal lobule, right postcentral gyrus, and in the ACC.ConclusionThe FRN was sensitive to cues of punishment and higher BIS was uniquely related to a larger FRN amplitude on No-Go/Loss trials, linking BIS with conflict monitoring and sensitivity to No-Go cues. Furthermore, the significant interaction found between BIS and RR on FRN amplitude together with the findings linking High-RR levels with shorter RTs, smaller P3 amplitudes and enhanced positive feelings are in line with the hypothesis that both BIS and BAS have the potential to influence punishment-mediated and reward-mediated behaviour.SignificanceResults open up new perspectives for future investigations on the relationship between BIS/BAS measures and ERP components to monetary reward during learning.     

Neural networks of response shifting: influence of task speed and stimulus material

Functional magnetic resonance imaging (fMRI) was used in 14 healthy subjects to measure brain activation, while response shifting was performed. In the activation phase, subjects were asked to shift their attention between two different types of visually presented stimuli. In the baseline phase, subjects were required to attend to one stimulus type only. Subjects responded by pressing a left or right key according to the side of presentation of the target stimuli. In a verbal task, subjects were required to switch between letters and numbers. In a figural task, subjects reacted to round and square shapes. Stimuli were presented for 750 or 1500 ms. Response shifting revealed significantly increased activation compared to non-switching in the bilateral superior parietal cortex, right occipital cortex, left inferior frontal cortex, left and right striatum, and bilateral dorsolateral prefrontal cortex (DLPFC). Superior parietal and occipital cortex activation may be due to spatial analysis during response shifting. Subvocal rehearsal of the task instructions may have led to activation in the left inferior frontal cortex. Activation in the striatum was related to prefrontal activation and may represent the association between basal ganglia and prefrontal activation during executive control. However, the most important brain region involved in the execution of response shifting was the bilateral DLPFC. Higher task speed increased executive top-down attentional control and, therefore, significantly increased activity in the bilateral DLPFC. Brain activation did not differ significantly between verbal and figural stimulus material. This result suggests that brain activation in the present study illustrates the brain regions involved in the basic cognitive mechanisms of response shifting.     

ERPs to response production and inhibition

Three experiments investigating the effects of response production and inhibition on the N2 and P3 components of the ERP are reported. In the first experiment, 12 young female volunteers were presented with the words "push' and "wait' (semantic stimuli). On a separate series of trials, they were presented with arbitrary symbols assigned the same meanings (symbolic stimuli). For each stimulus series half of the stimuli were degraded. To obtain an estimate of reliability of the data, each task was repeated. Data were collected from Fz, Cz and Pz electrode sites. The P3 amplitude had a parietal maximum when the stimuli instructed subjects to respond (Go). The P3 was equal at central and parietal sites when the stimuli instructed the subjects to withhold a response (No-Go). This topographic pattern was obtained for all stimulus manipulations, simple and degraded stimuli, words and symbols, and for the first and second runs. The N2 was a frontal maximum component that was larger to the No-Go than to the Go stimuli. This result was also robust to the manipulations. A second experiment investigated the dependency of these findings on an overt motor response. In this experiment, the symbolic and semantic stimulus series were each presented twice. The subjects counted the Go stimuli and did not count the No-Go stimuli for one presentation and pressed the reaction time button as in experiment 1 for the other presentation. While counting (compared to button pressing) delayed the N2 and P3 peaks, counting and pressing produced similar results, including the Go/No-Go P3 distribution effects. A third experiment investigated the sensitivity of these findings to the orientation of the symbols instructing the subjects to respond or withhold the response. Again the pattern of results was robust to this manipulation.     

Dissociable neural effects of stimulus valence and preceding context during the inhibition of responses to emotional faces

Socially appropriate behavior requires the concurrent inhibition of actions that are inappropriate in the context. This self‐regulatory function requires an interaction of inhibitory and emotional processes that recruits brain regions beyond those engaged by either processes alone. In this study, we isolated brain activity associated with response inhibition and emotional processing in 24 healthy adults using event‐related functional magnetic resonance imaging (fMRI) and a go/no‐go task that independently manipulated the context preceding no‐go trials (ie, number of go trials) and the valence (ie, happy, sad, and neutral) of the face stimuli used as trial cues. Parallel quadratic trends were seen in correct inhibitions on no‐go trials preceded by increasing numbers of go trials and associated activation for correct no‐go trials in inferior frontal gyrus pars opercularis, pars triangularis, and pars orbitalis, temporoparietal junction, superior parietal lobule, and temporal sensory association cortices. Conversely, the comparison of happy versus neutral faces and sad versus neutral faces revealed valence‐dependent activation in the amygdala, anterior insula cortex, and posterior midcingulate cortex. Further, an interaction between inhibition and emotion was seen in valence‐dependent variations in the quadratic trend in no‐go activation in the right inferior frontal gyrus and left posterior insula cortex. These results suggest that the inhibition of response to emotional cues involves the interaction of partly dissociable limbic and frontoparietal networks that encode emotional cues and use these cues to exert inhibitory control over the motor, attention, and sensory functions needed to perform the task, respectively. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

Dissociation of inhibition from error processing using a parametric inhibitory task during functional magnetic resonance imaging

Inhibition, the process that overrides and reverses the execution of a thought, action, or emotion, is important in daily life. Sixteen healthy volunteers performed a parametrically modulated motor inhibition task during functional magnetic resonance imaging. Two results were observed: (1) increased error-related anterior cingulate cortex activation and, (2) increased inferior frontal gyrus and medial prefrontal cortex activation during inhibition, irrespective of errors. Thus, the parametric nature of the task elucidated a functional dissociation of brain structures involved in motor inhibition from those involved in error processing. Additionally, this task allowed the identification of unique areas of increased activation within specific subregions of the anterior cingulate cortex related to errors made during trials with a high (dorsal anterior cingulate cortex) and low (ventral anterior cingulate cortex) inhibitory load.