ERP correlates of response inhibition to elemental and configural stimuli in a negative patterning task.

OBJECTIVE: The present experiment examined the ERP correlates of response inhibition to elemental and configural Nogo stimuli in a Go/Nogo task. DESIGN AND METHODS: Event-related potentials (ERPs) were recorded while 8 subjects completed a visual Go/Nogo task. Nogo stimuli required the inhibition of a response to stimuli that differed from Go stimuli (A+, B+) either on the basis of each of two physical features (elemental Nogo stimuli; CD-) or on the basis of the conjunction of features represented in the Go stimuli (configural Nogo stimuli; AB-). Behavioural data and ERP component measures (amplitude and latency) were analysed using analysis of variance. RESULTS: An enhanced N2 component and an enhanced fronto-centrally distributed P3 component were elicited following elemental Nogo stimuli relative to Go stimuli, consistent with a number of studies examining ERPs during Go/Nogo tasks. In contrast, an enhanced late frontal negative/parietal positive slow wave was elicited following configural Nogo stimuli relative to Go stimuli. CONCLUSIONS: These results cast doubt on the interpretation of the N2 enhancement as reflecting response inhibition processes per se. The pattern of results was interpreted as providing support for the unique cue model of learning rather than the configural model of learning and was discussed in the context of a recent model of executive functioning.     

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.     

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

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

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.     

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

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

Is better preservation of eccentric strength after stroke due to altered prefrontal function?

ABSTRACT

Ventrolateral prefrontal cortex (VLPFC) is part of a network that exerts inhibitory control over the motor cortex (MC). Recently, we demonstrated that VLPFC was more activated during imagined maximum eccentric than during imagined concentric contractions in healthy participants. This was accompanied with lower activation levels within motor regions during imagined eccentric contractions. The aim was to test a novel hypothesis of an involvement of VLPFC in contraction mode-specific modulation of force. Functional magnetic resonance imaging was used to examine differences in VLPFC and motor regions during the concentric and the eccentric phases of imagined maximum contractions in a selected sample of subjects with stroke (n = 4). The subjects were included as they exhibited disturbed modulation of force. The previously demonstrated pattern within VLPFC was evident only on the contralesional hemisphere. On the ipsilesional hemisphere, the recruitment in VLPFC was similar for both modes of contractions. The findings support a hypothesis of the involvement of VLPFC in contraction mode-specific modulation of maximum force production. A disturbance of this system might underlie the lack of contraction mode-specific modulation commonly found among stroke subjects, often expressed as an increased ratio between eccentric and concentric strength.     

Differential cerebral activation during observation of expressive gestures and motor acts

We compared brain activation involved in the observation of isolated right hand movements (e.g. twisting a lid), body-referred movements (e.g. brushing teeth) and expressive gestures (e.g. threatening) in 20 healthy subjects by using functional magnetic resonance imaging (fMRI). Perception-related areas in the occipital and inferior temporal lobe but also the mirror neuron system in the lateral frontal (ventral premotor cortex and BA 44) and superior parietal lobe were active during all three conditions. Observation of body-referred compared to common hand actions induced increased activity in the bilateral posterior superior temporal sulcus (STS), the left temporo-parietal lobe and left BA 45. Expressive gestures involved additional areas related to social perception (bilateral STS, temporal poles, medial prefrontal lobe), emotional processing (bilateral amygdala, bilateral ventrolateral prefrontal cortex (VLPFC), speech and language processing (Broca's and Wernicke's areas) and the pre-supplementary motor area (pre-SMA). In comparison to body-referred actions, expressive gestures evoked additional activity only in the left VLPFC (BA 47). The valence-ratings for expressive gestures correlated significantly with activation intensity in the VLPFC during expressive gesture observation. Valence-ratings for negative expressive gestures correlated with right STS-activity. Our data suggest that both, the VLPFC and the STS are coding for differential emotional valence during the observation of expressive gestures.     

Proactive and reactive cognitive control rely on flexible use of the ventrolateral prefrontal cortex

The role of ventral versus dorsolateral prefrontal regions in instantiating proactive and reactive cognitive control remains actively debated, with few studies parsing cue versus probe‐related activity. Rapid sampling (460 ms), long cue–probe delays, and advanced analytic techniques (deconvolution) were therefore used to quantify the magnitude and variability of neural responses during the AX Continuous Performance Test (AX‐CPT; N = 46) in humans. Behavioral results indicated slower reaction times during reactive cognitive control (AY trials) in conjunction with decreased accuracy and increased variability for proactive cognitive control (BX trials). The anterior insula/ventrolateral prefrontal cortex (aI/VLPFC) was commonly activated across comparisons of both proactive and reactive cognitive control. In contrast, activity within the dorsomedial and dorsolateral prefrontal cortex was limited to reactive cognitive control. The instantiation of proactive cognitive control during the probe period was also associated with sparse neural activation relative to baseline, potentially as a result of the high degree of neural and behavioral variability observed across individuals. Specifically, the variability of the hemodynamic response function (HRF) within motor circuitry increased after the presentation of B relative to A cues (i.e., late in HRF) and persisted throughout the B probe period. Finally, increased activation of right aI/VLPFC during the cue period was associated with decreased motor circuit activity during BX probes, suggesting a possible role for the aI/VLPFC in proactive suppression of neural responses. Considered collectively, current results highlight the flexible role of the VLPFC in implementing cognitive control during the AX‐CPT task but suggest large individual differences in proactive cognitive control strategies.     

The effect of strategies,goals and stimulus material on the neural mechanisms of emotion regulation: A meta-analysis of fMRI studies

Emotion regulation comprises all extrinsic and intrinsic control processes whereby people monitor, evaluate and modify the occurrence, intensity and duration of emotional reactions. Here we sought to quantitatively summarize the existing neuroimaging literature to investigate a) whether different emotion regulation strategies are based on different or the same neural networks; b) which brain regions in particular support the up- and down-regulation of emotions, respectively; and c) to which degree the neural networks realising emotion regulation depend on the stimulus material used to elicit emotions. The left ventrolateral prefrontal cortex (VLPFC), the anterior insula and the supplementary motor area were consistently activated independent of the regulation strategy. VLPFC and posterior cingulate cortex were the main regions consistently found to be recruited during the up-regulation as well as the down-regulation of emotion. The down-regulation compared to the up-regulation of emotions was associated with more right-lateralized activity while up-regulating emotions more strongly modulated activity in the ventral striatum. Finally, the process of emotion regulation appeared to be unaffected by stimulus material.     

Evidence for an altered architecture and a hierarchical modulation of inhibitory control processes in ADHD

Inhibitory control deficits are a hallmark in ADHD. Yet, inhibitory control includes a multitude of entities (e.g. ‘inhibition of interferences’ and ‘action inhibition’). Examining the interplay between these kinds of inhibitory control provides insights into the architecture of inhibitory control in ADHD. Combining a Simon task and a Go/Nogo task, we assessed the interplay of ‘inhibition of interferences’ and ‘action inhibition’. This was combined with EEG recordings, EEG data decomposition and source localization. Simon interference effects in Go trials were larger in ADHD. At the neurophysiological level, this insufficient inhibition of interferences in ADHD related to the superior parietal cortex. Simon interference effects were absent in action inhibition (Nogo) trials in ADHD, compared to controls. This was supported by bayesian statistics. The power of effects was higher than 95%. The differential effects between the groups were associated with modulations of neurophysiological response selection processes in the superior frontal gyrus. ADHD is not only associated with deficits in inhibitory control. Rather, the organization and architecture of the inhibitory control system is different in ADHD. Distinguishable inhibitory control processes operate on a hierarchical ‘first come, first serve’ basis and are not integrated in ADHD. This is a new facet of ADHD.     

Temporal dynamics of neural activity in motor execution and inhibition processing

Although many neuroimaging studies using functional magnetic resonance imaging have shown the neuronal networks for motor execution and inhibition processing, the precise activation timing of each brain region is not yet well understood. In the present study, we investigated the temporal dynamics of neural activities in multiple brain regions using magnetoencephalography (MEG) and electroencephalography (EEG) simultaneously during somatosensory Go/No‐go paradigms. The results of MEG showed that neural activities in the bilateral premotor area at approximately 150 ms and in the primary motor cortex at approximately 250 ms were only detected in Go trials, while brain responses in the bilateral prefrontal cortex at approximately 170 ms were only observed in No‐go trials. In addition, the amplitudes of the N140 and P300 components in EEG was significantly larger in No‐go trials than in Go trials, and the latencies of N140 and P300 were significantly later in No‐go trials than in Go trials. Our results indicated the time courses of neural processing in response execution and inhibition processing, and revealed differences in their underlying neural mechanisms.     

Executive control deficit in depression: event-related potentials in a Go/Nogo task

Growing evidence suggests an impairment of executive control functions in depression. The aim of this study was to investigate whether depressive patients show a specific impairment of executive control in a response inhibition task and to investigate its neurophysiological correlates using event-related potentials. We analyzed data from 16 patients with unipolar depression and 16 healthy controls using an auditory Go/Nogo task. High resolution event-related potentials (ERPs) were recorded. Depressive patients performed similar to controls in the Go task, but worse in the Nogo task, which required response inhibition. ERPs revealed the neurophysiological correlate of this deficit. Both groups showed the same voltage pattern in the Go task. However, in the Nogo task depressive patients showed a reduction of an early fronto-temporal positivity in the N2 time window, which was associated with response inhibition in healthy subjects. This effect could not be explained by increased task difficulty in the Nogo task. There was no difference between groups in later stages of processing as indexed by the P3 complex. Therefore, the findings suggest a specific deficit in response inhibition, which requires executive control. This deficit is thought to reflect dysfunctional activation of the network subserving executive control during an early stage of cortical processing.     

Blunted activation in right ventrolateral prefrontal cortex during motor response inhibition in schizophrenia

OBJECTIVES: Previous functional magnetic resonance imaging (fMRI) studies have reported abnormal brain activation in individuals with schizophrenia during performance of motor inhibition tasks. We aimed to clarify brain functional abnormalities related to motor response inhibition in schizophrenia by using event-related fMRI in combination with a Go-NoGo task designed to control for non-inhibitory cognitive processes involved in task performance. METHOD: We studied 21 schizophrenic patients and 21 healthy subjects, group-matched for age, sex, and performance accuracy on a Go-NoGo task during event-related fMRI. The task was designed so that Go and NoGo events were equally probable. Between-group activation differences were assessed using ANCOVAs with response time and IQ as covariates of non-interest. RESULTS: Compared to healthy subjects, schizophrenic patients exhibited a significant decrease in activation during motor response inhibition in the right ventrolateral prefrontal cortex (VLPFC) only. There were no areas of increased brain activation in patients compared to healthy subjects. CONCLUSIONS: Schizophrenic patients demonstrate a blunted activation in the right VLPFC, a region known to play a critical role in motor response inhibition. Further research should ascertain the contribution of the VLPFC dysfunction to the impulsive behavior observed in schizophrenia.     

On the relevance of EEG resting theta activity for the neurophysiological dynamics underlying motor inhibitory control

The modulation of theta frequency activity plays a major role in inhibitory control processes. However, the relevance of resting theta band activity and of the ability to spontaneously modulate this resting theta activity for neural mechanisms underlying inhibitory control is elusive. Various theoretical conceptions suggest to take these aspects into consideration. In the current study, we examine whether the strength of resting theta band activity or the ability to modulate the resting state theta activity affects response inhibition. We combined EEG‐time frequency decomposition and beamforming in a conflict‐modulated Go/Nogo task. A sample of N = 66 healthy subjects was investigated. We show that the strength of resting state theta activity modulates the effects of conflicts during motor inhibitory control. Especially when resting theta activity was low, conflicts strongly affected response inhibition performance and total theta band activity during Nogo trials. These effects were associated with theta‐related activity differences in the superior (BA7) and inferior parietal cortex (BA40). The results were very specific for total theta band activity since evoked theta activity and measures of intertrial phase coherency (phase‐locking factor) were not affected. The data suggest that the strength of resting state theta activity modulates processing of a theta‐related alarm or surprise signal during inhibitory control. The ability to voluntarily modulate theta band activity did not affect conflict‐modulated inhibitory control. These findings have important implications for approaches aiming to optimize human cognitive control.     

Long-term impact of prenatal exposure to chemotherapy on executive functioning: An ERP study

ObjectiveThis study examines the long-term impact of prenatal exposure to chemotherapy on executive functioning and the contribution of late-prematurity to this effect, using event-related potentials.MethodsMothers of the prenatal-exposed children (n = 20) were diagnosed with cancer and received chemotherapeutic treatment during pregnancy. We recruited healthy controls (n = 20) who were matched on a 1:1 ratio regarding prematurity, age and sex.We assessed executive functioning at the age of nine, using two event-related potential paradigms: a Go/Nogo paradigm to investigate processes of response inhibition and conflict monitoring, as well as a Posner paradigm to investigate spatial attention.ResultsLower potentials were found in prenatal-exposed children compared to controls in the Go/Nogo P3 and Posner positive slow wave. Moreover, prenatal-exposed children responded slower on the Posner paradigm compared to controls (p < .033), with more incorrect responses (p = .023). In the control group, the N2 Go/Nogo wave was more pronounced in children born after a longer gestation.ConclusionsThis is the first study that demonstrates an effect of prenatal exposure to chemotherapy on the development of executive functioning, not limited to the effect of late-prematurity.SignificanceThis study emphasizes the necessity of a long-term follow-up of prenatal-exposed children to re-inform clinical practice on the costs and benefits of late-premature induction over treatment during pregnancy.     

Basal ganglia-thalamocortical circuitry disruptions in schizophrenia during delayed response tasks.

BACKGROUND: Schizophrenia is characterized by executive functioning deficits, presumably mediated by prefrontal cortex dysfunction. For example, schizophrenia participants show performance deficits on ocular motor delayed response (ODR) tasks, which require both inhibition and spatial working memory for correct performance. METHODS: The present functional magnetic resonance imaging (fMRI) study compared neural activity of 14 schizophrenia and 14 normal participants while they performed ODR tasks. RESULTS: Schizophrenia participants generated: 1) more trials with anticipatory saccades (saccades made during the delay period), 2) memory saccades with longer latencies, and 3) memory saccades of decreased accuracy. Increased blood oxygenation level-dependent (BOLD) signal changes were observed in both groups in ocular motor circuitry (e.g., supplementary eye fields [SEF], lateral frontal eye fields [FEF], inferior parietal lobule [IPL], cuneus, and precuneus). The normal, but not the schizophrenia, group demonstrated BOLD signal changes in dorsolateral prefrontal regions (right Brodmann area [BA] 9 and bilateral BA 10), medial FEF, insula, thalamus, and basal ganglia. Correlations between percentage of anticipatory saccade trials and BOLD signal changes were more similar between groups for subcortical regions and less similar for cortical regions. CONCLUSIONS: These results suggest that executive functioning deficits in schizophrenia may be associated with dysfunction of the basal ganglia-thalamocortical circuitry, evidenced by decreased prefrontal cortex, basal ganglia, and thalamus activity in the schizophrenia group during ODR task performance.     

Anatomical Functional Changes in a Patient Presenting a Complex Malformation of Cortical Development

The authors describe a case of right fronto‐parietal micropoligyria associated with small schizencephaly clefts and the presence of a frontal open‐lip schizencephaly with corpus callosum agenesis. A functional magnetic resonance imaging (fMRI) study was performed to evaluate the possible reorganization of cortical functions in a patient presentinga complex malformation pattern and to investigate which cortical areas were activated during left finger movements. An fMRI study was performed during the execution of a repetitive index finger‐to‐thumb opposition movement with the right hand and the left hand in 2 separate sessions. Movement of the right hand induced a normal motor activation pattern involving the contralateral left sensory‐motor cortex. Movement of the left hand produced significant activation of brain cortex. This fMRI study highlights the compensatory role of the ipsilateral cortical pathways in hand movements in the case of a complex brain malformation that involves the main motor activation areas.     

Event-related potential correlates selectively reflect cognitive dysfunction in schizophrenics

Summary. Schizophrenics show event-related potential (ERP) and particularly P3 abnormalities. To study the more detailed relationships between these ERP alterations and cognitive dysfunction we recorded and analyzed ERPs using a particular experimental approach. In 34 schizophrenics and 25 controls ERPs were obtained by a visual Go/Nogo task requiring response inhibition and were decomposed into temporally independent topographical components using Independent Component Analysis (ICA). ICA disentangled different subcomponents of P3. Subcomponent P3b with a parietal maximum amplitude was significantly reduced in the schizophrenics, probably reflecting their attentional deficits. Subcomponent P3ng with a frontal maximum amplitude and enhanced during Nogo condition appeared as an electrophysiological index of response inhibition. A significantly reduced P3ng enhancement, found in schizophrenics, probably reflects their impaired response control. Conclusions: ICA can successfully identify ERP subcomponents with distinct scalp topographies representing significant differential indices of normal and abnormal cognitive processing. Involvement of frontal brain areas in disturbed executive control in schizophrenics is supported by our ICA findings.     

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.     

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.