No-go Events Research Articles

Enhancing Safety of a System-Wide In Situ Simulation Program Using No-Go Considerations.

A large-scale in situ simulation initiative on cardiac arrest in pregnancy was implemented across NYC Health + Hospitals. In situ simulation must be safely balanced with clinical conditions such as through application of no-go considerations or standardized reasons to cancel or postpone the simulation. Our objective is to describe our findings on the application of no-go considerations during this simulation initiative. NYC Health + Hospitals/Simulation Center developed an in situ simulation program focused on cardiac arrest in pregnancy, implemented at 11 acute care facilities. The program's toolkit included no-go considerations for in situ simulation safety: situations prompting a need to cancel, reschedule, or postpone a simulation to ensure patient and/or staff safety. Data were collected from June 2018 through December 2019. The simulation sites reviewed the 13 established no-go considerations before each simulation event to assess if the simulation was safe to "go". After the conclusion of the initiative, all data related to no-go considerations were analyzed.Two hundred seventy-four in situ simulations were scheduled and 223 simulations (81%) were completed. Fifty-one no-go events were reported, with 78% identifying a reason by category. Twenty-two percent did not report a reason or category. Four of the 13 suggested no-go considerations were not reported. The no-go considerations framework promotes standardized and strategic scheduling of in situ simulation. Analysis of no-go consideration application during this system-wide initiative provides a model for the usage of tracking no-go data to enhance safety and inform future simulation planning.

Effects of subtype of attention-deficit/hyperactivity disorder in adults on lateralized readiness potentials during a go/no-go choice reaction time task.

We studied 40 young adults with attention-deficit/hyperactivity disorder (ADHD; 18 predominantly inattentive type, 22 combined type) and 38 demographically comparable controls in a go/no-go choice reaction time task with 2 levels of difficulty. The ADHD/combined group was less accurate and had more variable reactions than controls. The ADHD/inattentive sample was slower than controls and had smaller early lateralized readiness potentials (LRPs). Compared with controls, both subtypes had (a) smaller early LRPs for no-go stimuli and (b) relatively earlier LRP onsets for difficult no-go events. The ADHD/combined sample also had smaller late LRP waves than controls. The results suggest that adults with ADHD, particularly those with the combined subtype, exhibit weaker central preparation to respond to both stimuli requiring a motor response and those prompting response inhibition.

Citalopram enhances action inhibition systems in Parkinson's disease

Impulsivity in Parkinson’s disease (PD) is highlighted by the severity of impulse control disorders (ICDs). However, subtler impulsivity is common even in the absence of ICDs and is likely to be multifactorial. In addition to dopaminergic ‘overdose’1,2 and structural changes3 in the frontostriatal circuits for motor control, we propose that changes in serotonergic projections to the forebrain also exacerbate the impairment of response inhibition. Enhancing central serotonin transmission with selective serotonin reuptake inhibitors (SSRIs) might therefore provide adjunctive treatment for behavioural impulsivity in Parkinson’s disease. We investigated whether the SSRI citalopram reduces impulsivity and enhances the neural systems mediating response inhibition in Parkinson’s disease. We studied two forms of inhibition: (1) restraint, using NoGo events; and (2) cancellation, in terms of the Stop-Signal Reaction Time (SSRT). There is strong preclinical evidence from animal and human studies that serotonin plays an important role in regulating action restraint4. In contrast, the link between serotonin and action cancellation is less well established. We tested three specific hypotheses. Hypothesis1: PD impairs both action restraint and cancellation. Hypothesis2: The effect of citalopram on behavioural performance depends on patients’ disease severity. Hypothesis3: The behavioural effect relates to the enhancement of inferior frontal cortical activation following citalopram.

Penetrating the fog of the decoupled mind: The effects of visual salience in the sustained attention to response task.

An absence of coupling between cognition and perception can mean that the mind neglects the careful processing of information relevant to the task at hand and errors can ensue. Given that highly salient perceptual events can automatically capture attention, the current study explored whether the same neglect of task-relevant information was possible for stimuli with high levels of perceptual saliency (e.g., identifiable by colour). In four experiments, participants performed a go/no-go task with a low frequency of no-go events. Across all experiments, response inhibition was more successful for coloured no-go targets than for stimuli that shared the same colour as the go targets. In addition, the response time (reaction time [RT]) for rare, coloured go targets was slower than when the same events were noncolored. Together, these results suggest that in relatively simple go/no-go tasks, highly salient perceptual events capture attention in an automatic fashion. Increased visual salience is argued to be beneficial when associated with no-go targets because it momentarily enforces coupling between attention and perception, disrupting ongoing behaviour at the precise moment when not responding is the correct action to take. These results suggest that although the mind may at times neglect events in the environment, salient perceptual events cannot be ignored in the same way.

Theta power as a marker for cognitive interference

Objective The present study aimed at investigating whether theta activity within medio-frontal cortex (MFC) serves as a marker for increased cognitive control demands such as performance monitoring. Methods We confronted participants with at least two incompatible sources of information in a Simon task, a flanker task, and a NoGo task to assess whether changes in EEG theta activity correspond to executive control demands across different sources of cognitive interference. Results Overall, increases of theta power were to a different extent observed in all interference situations: (1) differences in theta power were largest between successful response inhibition in NoGo events compared to Go responses, (2) incongruent and congruent events in the flanker task differed to a lesser extent, and (3) differences in theta power were smallest comparing incompatible and compatible Simon events. Scalp-topographies and dipole modeling of theta activity pointed to different sources across interference conditions that encompassed various MFC areas within anterior cingulate cortex and (pre-) supplementary motor areas. Conclusions Our results indicate that theta power amplitude is sensitive to the recruitment of executive control in interference situations, whereas the MFC sources of theta power varied across different interference situations. Significance This study shows for the first time theta power enhancement related to the recruitment of cognitive control across different types of conflicts in the stream of information processing.

FMRI of Intrasubject Variability in ADHD: Anomalous Premotor Activity With Prefrontal Compensation

Objective Children 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. Method Event-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. Results For 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. Conclusions These 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.

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.

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.

When ‘go’ and ‘nogo’ are equally frequent: ERP components and cortical tomography

In human electrophysiology, a considerable corpus of studies using event-related potentials have investigated inhibitory processes by employing the 'go-nogo' paradigm, which requires responding to one type of event while withholding the response to another type of event. Two event-related potential waveform features (N2 and P3) have been associated with larger amplitude in nogo trials than in go trials. Traditionally, these differences were thought to reflect response inhibition. Recently, the source localization of N2 to the anterior cingulate cortex, as well as the colocalization of N2 with error-related negativity, has been interpreted in terms of conflict monitoring. In order to isolate the contribution of inhibitory processes, we matched the frequency of the go and nogo events, thus minimizing differences in response conflict between event types. A data-driven analytical procedure contrasted go with nogo events across the entire event-related potential segment and found that N2 reliably differentiated between the two conditions while P3 did not. Tomographical analyses of the N2 difference observed in conditions of equal go and nogo trial frequency localized N2 to the right ventral and dorsolateral prefrontal cortex. Because a growing body of evidence implicates these brain regions in inhibitory processes, we conclude that N2 does, at least in part, reflect inhibition.

A supramodal limbic‐paralimbic‐neocortical network supports goal‐directed stimulus processing

Limited processing resources are allocated preferentially to events that are relevant for behavior. Research using the novelty "oddball" paradigm suggests that a widespread network of limbic, paralimbic, and association areas supports the goal-directed processing of task-relevant target events. In that paradigm, greater activity in diverse brain areas is elicited by rare task-relevant events that require a subsequent motor response than by rare task-irrelevant novel events that require no response. Both stimulus infrequency (unexpectedness) and novelty, however, may contribute to the pattern of activity observed using that paradigm. The goal of the present study was to examine the supramodal neural activity elicited by regularly occurring, equiprobable, and non-novel stimuli that differed in the subsequent behavior they prescribed. We employed event-related functional magnetic resonance imaging (fMRI) during auditory and visual versions of a Go/NoGo task. Participants made a motor response to the designated "Go" (target) stimulus, and no motor response to the equiprobable "NoGo" (nontarget) stimulus. We hypothesized that task-relevant Go events would elicit relatively greater hemodynamic activity than would NoGo events throughout a network of limbic, paralimbic, and association areas. Indeed, Go events elicited greater activity than did NoGo events in the amygdala-hippocampus, paralimbic cortex at the anterior superior temporal sulcus, insula, posterior orbitofrontal cortex, and anterior and posterior cingulate cortex, as well as in heteromodal association areas located at the temporoparietal junction, anterior intraparietal sulcus and precuneus, and premotor cortex. Paralimbic cortex offers an important site for the convergence of motivational/goal-directed influences from limbic cortex with stimulus processing and response selection mediated within the frontoparietal areas.

A topography of executive functions and their interactions revealed by functional magnetic resonance imaging

We used fMRI to study the brain processes involved in the executive control of behavior. The Sustained Attention to Response Task (SART), which allows unpredictable and predictable NOGO events to be contrasted, was imaged using a mixed (block and event-related) fMRI design to examine tonic and phasic processes involved in response inhibition, error detection, conflict monitoring and sustained attention. A network of regions, including right ventral prefrontal cortex (PFC), left dorsolateral PFC (DLPFC) and right inferior parietal cortex, was activated for successful unpredictable inhibitions, while rostral anterior cingulate was implicated in error processing and the pre-SMA in conflict monitoring. Furthermore, the pattern of correlations between left dorsolateral PFC, implicated in task-set maintenance, and the pre-SMA were indicative of a tight coupling between prefrontally mediated control and conflict levels monitored more posteriorly. The results reveal that the executive control of behavior can be separated into distinct functions performed by discrete cortical regions.

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≤0.05). For both tasks, Go responses were associated with signal change in the left primary sensorimotor cortex, supplementary motor area (SMA) proper, and anterior cerebellum (right>left). For the simple task, No-go events were associated with activation in the pre-SMA; the working memory-loaded ‘counting’ task elicited additional No-go activation in the right dorsolateral prefrontal cortex. The findings suggest that neural contributions to response inhibition may be task dependent; the pre-SMA appears necessary for inhibition of unwanted movements, while the dorsolateral prefrontal cortex is recruited for tasks involving increased working memory load.

Event-related fMRI study of response inhibition.

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