Biophysical Modeling of Frontocentral ERP Generation Links Circuit-Level Mechanisms of Action-Stopping to a Behavioral Race Model.

Human frontocentral event-related potentials (FC-ERPs) are ubiquitous neural correlates of cognition and control, but their generating multiscale mechanisms remain mostly unknown. We used the Human Neocortical Neurosolver's biophysical model of a canonical neocortical circuit under exogenous thalamic and cortical drive to simulate the cell and circuit mechanisms underpinning the P2, N2, and P3 features of the FC-ERP observed after Stop-Signals in the Stop-Signal task (SST; N = 234 humans, 137 female). We demonstrate that a sequence of simulated external thalamocortical and corticocortical drives can produce the FC-ERP, similar to what has been shown for primary sensory cortices. We used this model of the FC-ERP to examine likely circuit-mechanisms underlying FC-ERP features that distinguish between successful and failed action-stopping. We also tested their adherence to the predictions of the horse-race model of the SST, with specific hypotheses motivated by theoretical links between the P3 and Stop process. These simulations revealed that a difference in P3 onset between successful and failed Stops is most likely due to a later arrival of thalamocortical drive in failed Stops, rather than, for example, a difference in the effective strength of the input. In contrast, the same model predicted that early thalamocortical drives underpinning the P2 and N2 differed in both strength and timing across stopping accuracy conditions. Overall, this model generates novel testable predictions of the thalamocortical dynamics underlying FC-ERP generation during action-stopping. Moreover, it provides a detailed cellular and circuit-level interpretation that supports links between these macroscale signatures and predictions of the behavioral race model.

Distinct Action Signals by Subregions in the Nucleus Accumbens during STOP-Change Performance.

The nucleus accumbens (NAc) is thought to contribute to motivated behavior by signaling the value of reward-predicting cues and the delivery of anticipated reward. The NAc is subdivided into core and shell, with each region containing different populations of neurons that increase or decrease firing to rewarding events. While there are numerous theories of functions pertaining to these subregions and cell types, most are in the context of reward processing, with fewer considering that the NAc might serve functions related to action selection more generally. We recorded from single neurons in the NAc as rats of both sexes performed a STOP-change task that is commonly used to study motor control and impulsivity. In this task, rats respond quickly to a spatial cue on 80% of trials (GO) and must stop and redirect planned movement on 20% of trials (STOP). We found that the activity of reward-excited neurons signaled accurate response direction on GO, but not STOP, trials and that these neurons exhibited higher precue firing after correct trials. In contrast, reward-inhibited neurons significantly represented response direction on STOP trials at the time of the instrumental response. Finally, the proportion of reward-excited to reward-inhibited neurons and the strength of precue firing decreased as the electrode traversed the NAc. We conclude that reward-excited cells (more common in core) promote proactive action selection, while reward-inhibited cells (more common in shell) contribute to accurate responding on STOP trials that require reactive suppression and redirection of behavior.

Decreased Beta Power and OFC-STN Phase Synchronization during Reactive Stopping in Freely Behaving Rats.

During natural behavior, an action often needs to be suddenly stopped in response to an unexpected sensory input-referred to as reactive stopping. Reactive stopping has been mostly investigated in humans, which led to hypotheses about the involvement of different brain structures, in particular the hyperdirect pathway. Here, we directly investigate the contribution and interaction of two key regions of the hyperdirect pathway, the orbitofrontal cortex (OFC) and subthalamic nucleus (STN), using dual-area, multielectrode recordings in male rats performing a stop-signal task. In this task, rats have to initiate movement to a go-signal, and occasionally stop their movement to the go-signal side after a stop-signal, presented at various stop-signal delays. Both the OFC and STN show near-simultaneous field potential reductions in the beta frequency range (12-30 Hz) compared with the period preceding the go-signal and the movement period. These transient reductions (∼200 ms) only happen during reactive stopping, which is when the stop-signal was received after action initiation, and are well timed after stop-signal onset and before the estimated time of stopping. Phase synchronization analysis also showed a transient attenuation of synchronization between the OFC and STN in the beta range during reactive stopping. The present results provide the first direct quantification of local neural oscillatory activity in the OFC and STN and interareal synchronization specifically timed during reactive stopping.

Low blood concentration of alcohol enhances activity related to stopping failure in the right inferior frontal cortex.

This study investigated the effects of low doses of alcohol, which are acceptable for driving a car, on inhibitory control and neural processing using the stop-signal task (SST) in 17 healthy right-handed social drinkers. The study employed simultaneous functional magnetic resonance imaging and electromyography (EMG) recordings to assess behavioral and neural responses under conditions of low-dose alcohol (breath-alcohol concentration of 0.15 mg/L) and placebo. The results demonstrated that even a small amount of alcohol consumption prolonged Go reaction times in the SST and modified stopping behavior, as evidenced by a decrease in the frequency and magnitude of partial response EMG that did not result in button pressing during successful inhibitory control. Furthermore, alcohol intake enhanced neural activity during failed inhibitory responses in the right inferior frontal cortex, suggesting its potential role in behavioral adaptation following stop-signal failure. These findings suggest that even low levels of alcohol consumption within legal driving limits can greatly impact both the cognitive performance and brain activity involved in inhibiting responses. This research provides important evidence on the neurobehavioral effects of low-dose alcohol consumption, with implications for understanding the biological basis of impaired motor control and decision-making and potentially informing legal guidelines on alcohol consumption.

The Neural Signature of Impaired Inhibitory Control in Individuals with Heroin Use Disorder.

Heroin addiction imposes a devastating toll on society, with little known about its neurobiology. Excessive salience attribution to drug over nondrug cues/reinforcers, with concomitant inhibitory control decreases, are common mechanisms underlying drug addiction. Although inhibitory control alterations generally culminate in prefrontal cortex (PFC) hypoactivations across drugs of abuse, patterns in individuals with heroin addiction (iHUDs) remain unknown. We used a stop-signal fMRI task designed to meet recent consensus guidelines in mapping inhibitory control in 41 iHUDs and 24 age- and sex-matched healthy controls (HCs). Despite group similarities in the stop-signal response time (SSRT; the classic inhibitory control measure), compared with HCs, iHUDs exhibited impaired target detection sensitivity (proportion of hits in go vs false alarms in stop trials; p = 0.003). Additionally, iHUDs exhibited lower right anterior PFC (aPFC) and dorsolateral PFC (dlPFC) activity during successful versus failed stops (the hallmark inhibitory control contrast). Lower left dlPFC/supplementary motor area (SMA) activity was associated with slower SSRT specifically in iHUDs and lower left aPFC activity with worse target sensitivity across all participants (p < 0.05 corrected). Importantly, in iHUDs, lower left SMA and aPFC activity during inhibitory control was associated with shorter time since last use and higher severity of dependence, respectively (p < 0.05 corrected). Together, results revealed lower perceptual sensitivity and hypoactivations during inhibitory control in cognitive control regions (e.g., aPFC, dlPFC, SMA) as associated with task performance and heroin use severity measures in iHUDs. Such neurobehavioral inhibitory control deficits may contribute to self-control lapses in heroin addiction, constituting targets for prevention and intervention efforts to enhance recovery.SIGNIFICANCE STATEMENT Heroin addiction continues its deadly impact, with little known about the neurobiology of this disorder. Although behavioral and prefrontal cortical impairments in inhibitory control characterize addiction across drugs of abuse, these patterns remain underexplored in heroin addiction. Here, we illustrate a significant behavioral impairment in target discrimination in individuals with heroin addiction compared with matched healthy controls. We further show lower engagement during inhibitory control in the anterior and dorsolateral prefrontal cortex (key regions that regulate cognitive control) as associated with slower stopping, worse discrimination, and heroin use measures. Mapping the neurobiology of inhibitory control in heroin addiction for the first time, we identify potential treatment targets inclusive of prefrontal cortex-mediated cognitive control amenable for neuromodulation en route to recovery.

On the interplay between state-dependent reconfigurations of global signal correlation and BOLD fluctuations: An fMRI study.

BACKGROUND: The dynamics of global, state-dependent reconfigurations in brain connectivity are yet unclear. We aimed at assessing reconfigurations of the global signal correlation coefficient (GSCORR), a measure of the connectivity between each voxel timeseries and the global signal, from resting-state to a stop-signal task. The secondary aim was to assess the relationship between GSCORR and blood-oxygen-level-dependent (BOLD) activations or deactivation across three different trial-conditions (GO, STOP-correct, and STOP-incorrect). METHODS: As primary analysis we computed whole-brain, voxel-wise GSCORR during resting-state (GSCORR-rest) and stop-signal task (GSCORR-task) in 107 healthy subjects aged 21-50, deriving GSCORR-shift as GSCORR-task minus GSCORR-rest. GSCORR-tr and trGSCORR-shift were also computed on the task residual time series to quantify the impact of the task-related activity during the trials. To test the secondary aim, brain regions were firstly divided in one cluster showing significant task-related activation and one showing significant deactivation across the three trial conditions. Then, correlations between GSCORR-rest/task/shift and activation/deactivation in the two clusters were computed. As sensitivity analysis, GSCORR-shift was computed on the same sample after performing a global signal regression and GSCORR-rest/task/shift were correlated with the task performance. RESULTS: Sensory and temporo-parietal regions exhibited a negative GSCORR-shift. Conversely, associative regions (ie. left lingual gyrus, bilateral dorsal posterior cingulate gyrus, cerebellum areas, thalamus, posterolateral parietal cortex) displayed a positive GSCORR-shift (FDR-corrected p < 0.05). GSCORR-shift showed similar patterns to trGSCORR-shift (magnitude increased) and after global signal regression (magnitude decreased). Concerning BOLD changes, Brodmann area 6 and inferior parietal lobule showed activation, while posterior parietal lobule, cuneus, precuneus, middle frontal gyrus showed deactivation (FDR-corrected p < 0.05). No correlations were found between GSCORR-rest/task/shift and beta-coefficients in the activation cluster, although negative correlations were observed between GSCORR-task and GO/STOP-correct deactivation (Pearson rho=-0.299/-0.273; Bonferroni-p < 0.05). Weak associations between GSCORR and task performance were observed (uncorrected p < 0.05). CONCLUSION: GSCORR state-dependent reconfiguration indicates a reallocation of functional resources to associative areas during stop-signal task. GSCORR, activation and deactivation may represent distinct proxies of brain states with specific neurofunctional relevance.

Action initiation and action inhibition follow the same time course when compared under matched experimental conditions.

The ability to initiate an action quickly when needed and the ability to cancel an impending action are both fundamental to action control. It is often presumed that they are qualitatively distinct processes, yet they have largely been studied in isolation and little is known about how they relate to one another. Comparing previous experimental results shows a similar time course for response initiation and response inhibition. However, the exact time course varies widely depending on experimental conditions, including the frequency of different trial types and the urgency to respond. For example, in the stop-signal task, where both action initiation and action inhibition are involved and could be compared, action inhibition is typically found to be much faster. However, this apparent difference is likely due to there being much greater urgency to inhibit an action than to initiate one in order to avoid failing at the task. This asymmetry in the urgency between action initiation and action inhibition makes it impossible to compare their relative time courses in a single task. Here, we demonstrate that when action initiation and action inhibition are measured separately under conditions that are matched as closely as possible, their speeds are not distinguishable and are positively correlated across participants. Our results raise the possibility that action initiation and action inhibition may not necessarily be qualitatively distinct processes but may instead reflect complementary outcomes of a single decision process determining whether or not to act.NEW & NOTEWORTHY The time courses of initiating an action and canceling an action have largely been studied in isolation, and little is known about their relationship. Here, we show that when measured under comparable conditions the speeds of action initiation and action inhibition are the same. This finding raises the possibility that these two functions may be more closely related than previously assumed, with potentially important implications for their underlying neural basis.

The relationship between frontal alpha asymmetry and behavioral and brain activity indices of reactive inhibitory control.

Reactive inhibitory control plays an important role in phenotype of different diseases/different phases of a disease. One candidate electrophysiological marker of inhibitory control is frontal alpha asymmetry (FAA). FAA reflects the relative difference in contralateral frontal brain activity. However, the relationship between FAA and potential behavioral/brain activity indices of reactive inhibitory control is not yet clear. We assessed the relationship between resting-state FAA and indicators of reactive inhibitory control. Additionally, we investigated the effect of modulation of FAA via transcranial direct current stimulation (tDCS). We implemented a randomized sham-controlled design with 65 healthy humans (Mage = 23.93, SDage = 6.08; 46 female). Before and after 2-mA anodal tDCS of the right frontal site (with the cathode at the contralateral site) for 20 min, we collected EEG data and reactive inhibitory performance in neutral and food-reward conditions, using the stop signal task (SST). There was no support for the effect of tDCS on FAA or any indices of reactive inhibitory control. Our correlation analysis revealed an association between inhibitory brain activity in the food-reward condition and (pre-tDCS) asymmetry. Higher right relative to left frontal brain activity was correlated with reduced early-onset inhibitory activity and, in contrast, linked with higher late-onset inhibitory control in the food-reward condition. Similarly, event-related potential analyses showed reduced early-onset and enhanced late-onset inhibitory brain activity over time, particularly in the food-reward condition. These results suggest that there can be a dissociation regarding the lateralization of frontal brain activity and early- and late-onset inhibitory brain activity.NEW & NOTEWORTHY This research reveals dissociation between baseline frontal alpha asymmetry and the timing of reactive inhibitory brain activities in food-reward contexts. Whereas inhibitory control performance decreases over time in a stop signal task, electrophysiological indices show reduced early- and heightened late-onset inhibitory brain activity, especially in the reward condition. Additionally, greater right frontal activity correlates with reduced early-onset and increased late-onset inhibitory brain activity.

A touching advantage: cross-modal stop-signals improve reactive response inhibition.

The ability to inhibit an already initiated response is crucial for navigating the environment. However, it is unclear which characteristics make stop-signals more likely to be processed efficiently. In three consecutive studies, we demonstrate that stop-signal modality and location are key factors that influence reactive response inhibition. Study 1 shows that tactile stop-signals lead to better performance compared to visual stop-signals in an otherwise visual choice-reaction task. Results of Study 2 reveal that the location of the stop-signal matters. Specifically, if a visual stop-signal is presented at a different location compared to the visual go-signal, then stopping performance is enhanced. Extending these results, study 3 suggests that tactile stop-signals and location-distinct visual stop-signals retain their performance enhancing effect when visual distractors are presented at the location of the go-signal. In sum, these results confirm that stop-signal modality and location influence reactive response inhibition, even in the face of concurrent distractors. Future research may extend and generalize these findings to other cross-modal setups.

Attentional spatial cueing of the stop-signal affects the ability to suppress behavioural responses.

The ability to adapt to the environment is linked to the possibility of inhibiting inappropriate behaviours, and this ability can be enhanced by attention. Despite this premise, the scientific literature that assesses how attention can influence inhibition is still limited. This study contributes to this topic by evaluating whether spatial and moving attentional cueing can influence inhibitory control. We employed a task in which subjects viewed a vertical bar on the screen that, from a central position, moved either left or right where two circles were positioned. Subjects were asked to respond by pressing a key when the motion of the bar was interrupted close to the circle (go signal). In about 40% of the trials, following the go signal and after a variable delay, a visual target appeared in either one of the circles, requiring response inhibition (stop signal). In most of the trials the stop signal appeared on the same side as the go signal (valid condition), while in the others, it appeared on the opposite side (invalid condition). We found that spatial and moving cueing facilitates inhibitory control in the valid condition. This facilitation was observed especially for stop signals that appeared within 250ms of the presentation of the go signal, thus suggesting an involvement of exogenous attentional orienting. This work demonstrates that spatial and moving cueing can influence inhibitory control, providing a contribution to the investigation of the relationship between spatial attention and inhibitory control.

Shared genetic etiology between ADHD, task-related behavioral measures and brain activation during response inhibition in a youth ADHD case-control study.

Impaired response inhibition is commonly present in individuals with attention-deficit/hyperactivity disorder (ADHD) and their unaffected relatives, suggesting impaired response inhibition as a candidate endophenotype in ADHD. Therefore, we explored whether behavioral and neural correlates of response inhibition are related to polygenic risk scores for ADHD (PRS-ADHD). We obtained functional magnetic resonance imaging of neural activity and behavioral measures during a stop-signal task in the NeuroIMAGE cohort, where inattention and hyperactivity-impulsivity symptoms were assessed with the Conners Parent Rating Scales. Our sample consisted of 178 ADHD cases, 103 unaffected siblings, and 173 controls (total N = 454; 8-29 years), for whom genome-wide genotyping was available. PRS-ADHD was constructed using the PRSice-2 software. We found PRS-ADHD to be associated with ADHD symptom severity, a slower and more variable response to Go-stimuli, and altered brain activation during response inhibition in several regions of the bilateral fronto-striatal network. Mean reaction time and intra-individual reaction time variability mediated the association of PRS-ADHD with ADHD symptoms (total, inattention, hyperactivity-impulsivity), and activity in the left temporal pole and anterior parahippocampal gyrus during failed inhibition mediated the relationship of PRS-ADHD with hyperactivity-impulsivity. Our findings indicate that PRS-ADHD are related to ADHD severity on a spectrum of clinical, sub-threshold, and normal levels; more importantly, we show a shared genetic etiology of ADHD and behavioral and neural correlates of response inhibition. Given the modest sample size of our study, future studies with higher power are warranted to explore mediation effects, suggesting that genetic liability to ADHD may adversely affect attention regulation on the behavioral level and point to a possible response inhibition-related mechanistic pathway from PRS-ADHD to hyperactivity-impulsivity.

Altered prefrontal signaling during inhibitory control in a salient drug context in cocaine use disorder.

INTRODUCTION: Drug addiction is characterized by impaired response inhibition and salience attribution (iRISA), where the salience of drug cues is postulated to overpower that of other reinforcers with a concomitant decrease in self-control. However, the neural underpinnings of the interaction between the salience of drug cues and inhibitory control in drug addiction remain unclear. METHODS: We developed a novel stop-signal functional magnetic resonance imaging task where the stop-signal reaction time (SSRT-a classical inhibitory control measure) was tested under different salience conditions (modulated by drug, food, threat, or neutral words) in individuals with cocaine use disorder (CUD; n = 26) versus demographically matched healthy control participants (n = 26). RESULTS: Despite similarities in drug cue-related SSRT and valence and arousal word ratings between groups, dorsolateral prefrontal cortex (dlPFC) activity was diminished during the successful inhibition of drug versus food cues in CUD and was correlated with lower frequency of recent use, lower craving, and longer abstinence (Z > 3.1, P < 0.05 corrected). DISCUSSION: Results suggest altered involvement of cognitive control regions (e.g. dlPFC) during inhibitory control under a drug context, relative to an alternative reinforcer, in CUD. Supporting the iRISA model, these results elucidate the direct impact of drug-related cue reactivity on the neural signature of inhibitory control in drug addiction.

Poorer inhibitory control was related to greater food intake across meals varying in portion size: A randomized crossover trial.

Individuals eat more food when larger portions are served, and this portion size effect could be influenced by inhibitory control (the ability to suppress an automatic response). Inhibitory control may also relate to obesogenic meal behaviors such as eating faster, taking larger bites, and frequent switching between meal components (such as bites of food and sips of water). In a randomized crossover design, 44 adults ate lunch four times in the laboratory. Lunch consisted of a pasta dish that was varied in portion size (400, 500, 600, or 700 g) along with 700 g of water. Meals were video-recorded to assess meal duration and bite and sip counts, which were used to determine mean eating rate (g/min), mean bite size (g/bite), and number of switches between bites and sips. Participants completed a food-specific stop-signal task, which was used to calculate Stop-Signal Reaction Time (SSRT). Across participants, SSRT values ranged from 143 to 306 msec, where greater SSRT indicates poorer inhibitory control. As expected, serving larger portions increased meal intake (p < 0.0001); compared to the smallest portion, intake of the largest increased by 121 ± 17 g (mean ± SEM). SSRT did not moderate the portion size effect (p = 0.34), but individuals with poorer inhibitory control ate more across all meals: 24 ± 11 g for each one SD unit increase in SSRT (p = 0.035). SSRT was not related to eating rate or bite size (both p > 0.13), but poorer inhibitory control predicted greater switching between bites and sips, such that 1.5 ± 0.7 more switches were made during meals for each one SD unit increase in SSRT (p = 0.03). These findings indicate that inhibitory control can contribute to overconsumption across meals varying in portion size, potentially in part by promoting switching behavior.

The effectiveness of Go/No-Go and Stop-Signal training in reducing food consumption and choice: A systematic review and meta-analysis.

The Go/No-Go and Stop-Signal tasks have been used to reduce excess food intake via repeated pairing of food cues with response inhibition. A meta analysis of 32 studies was conducted to determine whether, and under which conditions, the Go/No-Go and Stop-Signal training tasks are effective in reducing food consumption or choice. Moderators included task parameters (e.g., number of sessions, stop signal), sample differences (e.g., age, weight), and the measure of food consumption or choice. Overall, there was a small effect for Go/No-Go and Stop-Signal training in reducing food consumption or choice, g = -0.21, CI95 = [-0.31, -0.11], p < .001, with this holding individually only for a single session of the Go/No-Go Task, g = -0.31, CI95 = [-0.45, -0.18], p < .001. Comprehensive investigation of the impact of varying moderators indicated that the effect for Go/No-Go training was robust. Nevertheless, there was significant variation in the specific parameters of the task. Overall, the present meta-analysis extends previous findings by providing comprehensive evidence that the Go/No-Go Task is effective in reducing food consumption and choice, as well as providing optimal parameter recommendations for the task.

A proof-of-concept study testing the factor structure of the Stop Signal Task: overlap with substance use and mental health symptoms.

Background: Research utilizing experimental tasks usually does not report estimates of internal reliability of measurement. However, modern measurement theories conceptualize reliability as sample dependent indicating that reliability should be empirically demonstrated in the samples used to make inferences.Objectives: Test whether confirmatory factor analytic (CFA) estimates of reliability can be applied to a commonly used task measuring response inhibition (the Stop Signal Task) to predict substance use (alcohol and cannabis) and mental health symptoms.Methods: Thirty-seven participants between the ages of 18-20 (72% female; 16% Asian, 3% Native American, 11% Black or African American, 59% White; 32% Latino/a/x) were recruited via social media advertisement and attended a laboratory visit. The Stop Signal Reaction Time (SSRT) was calculated as the outcome for three experimental blocks and used as indicators in a CFA.Results: CFA suggests the task yields reliable scores; factor loadings were statistically significant (p < .05) and substantial (standardized loadings ranged from .74 to .94). However, reliability increased across experimental blocks and error was non-trivial (ranging from 50% to 12% of the variance). The inhibition factor predicted higher maximum number of drinks consumed (ß = .37, p < .05), higher frequency of cannabis use (ß = .39, p < .05), and more cannabis use occasions within using days (ß = .40, p < .05), as well as facets of mental health (anxious/depression, attention, and anxiety problems; all p's < .05).Conclusion: Results support the utility of CFA to test for reliability of measurement, with the ability to inhibit dominant responses serving as a transdiagnostic correlate of substance use and mental health problems.

Practice makes perfect: Restrained eaters' heightened control for food images.

OBJECTIVE: Restrained eaters (RE) show behaviourally unregulated food intake, which is often explained by a deficit in inhibitory control. Despite evidence for general inhibitory deficits in RE, it remains unclear how the variety of (food) cues in our environment can influence cognitive control. METHOD: In this re-analysis, we explored the inhibitory capacity of RE and unrestrained eaters (URE) on a stop-signal task with modal (pictures) and amodal (word) food and non-food stimuli. RESULTS: Although we did not find the expected inhibitory deficits in RE compared to URE, we found a significant Group × Modality × Stimulus Type interaction. This indicated that RE have relatively good inhibitory control for food, compared to non-food modal cues, and that this relationship is reversed for amodal cues. CONCLUSIONS: Hence, we showed differential processing of information based on food-specificity and presentation format in RE. The format of food cues is thus an important new avenue to understand how the food environment impedes those struggling with regulating their eating behaviour.

The effect of staircase stopping accuracy and testing environment on stop-signal reaction time.

The stop-signal task is widely used in experimental psychology and cognitive neuroscience research, as well as neuropsychological and clinical practice for assessing response inhibition. The task requires participants to make speeded responses on a majority of trials, but to inhibit responses when a stop signal appears after the imperative cue. The stop-signal delay after the onset of the imperative cue determines how difficult it is to cancel an initiated action. The delay is typically staircased to maintain a 50% stopping accuracy for an estimation of stopping speed to be calculated. However, the validity of this estimation is compromised when participants engage in strategic slowing, motivated by a desire to avoid stopping failures. We hypothesized that maintaining stopping accuracy at 66.67% reduces this bias, and that slowing may also be impacted by the level of experimenter supervision. We found that compared with 50%, using a 66.67% stopping accuracy staircase produced slower stop-signal reaction time estimations (≈7 ms), but resulted in fewer strategic slowing exclusions. Additionally, both staircase procedures had similar within-experiment test-retest reliability. We also found that while individual and group testing in a laboratory setting produced similar estimations of stopping speed, participants tested online produced slower estimates. Our findings indicate that maintaining stopping accuracy at 66.67% is a reliable method for estimating stopping speed and can have benefits over the standard 50% staircase procedure. Further, our results show that care should be taken when comparing between experiments using different staircases or conducted in different testing environments.

A hybrid approach to dynamic cognitive psychometrics : Dynamic cognitive psychometrics.

Dynamic cognitive psychometrics measures mental capacities based on the way behavior unfolds over time. It does so using models of psychological processes whose validity is grounded in research from experimental psychology and the neurosciences. However, these models can sometimes have undesirable measurement properties. We propose a "hybrid" modeling approach that achieves good measurement by blending process-based and descriptive components. We demonstrate the utility of this approach in the stop-signal paradigm, in which participants make a series of speeded choices, but occasionally are required to withhold their response when a "stop signal" occurs. The stop-signal paradigm is widely used to measure response inhibition based on a modeling framework that assumes a race between processes triggered by the choice and the stop stimuli. However, the key index of inhibition, the latency of the stop process (i.e., stop-signal reaction time), is not directly observable, and is poorly estimated when the choice and the stop runners are both modeled by psychologically realistic evidence-accumulation processes. We show that using a descriptive account of the stop process, while retaining a realistic account of the choice process, simultaneously enables good measurement of both stop-signal reaction time and the psychological factors that determine choice behavior. We show that this approach, when combined with hierarchical Bayesian estimation, is effective even in a complex choice task that requires participants to perform only a relatively modest number of test trials.

Prefrontal Cortical Connectivity Mediates Locus Coeruleus Noradrenergic Regulation of Inhibitory Control in Older Adults.

Response inhibition is a core executive function enabling adaptive behavior in dynamic environments. Human and animal models indicate that inhibitory control and control networks are modulated by noradrenaline, arising from the locus coeruleus. The integrity (i.e., cellular density) of the locus coeruleus noradrenergic system can be estimated from magnetization transfer (MT)-sensitive magnetic resonance imaging (MRI), in view of neuromelanin present in noradrenergic neurons of older adults. Noradrenergic psychopharmacological studies indicate noradrenergic modulation of prefrontal and frontostriatal stopping-circuits in association with behavioral change. Here, we test the noradrenergic hypothesis of inhibitory control, in healthy adults. We predicted that locus coeruleus integrity is associated with age-adjusted variance in response inhibition, mediated by changes in connectivity between frontal inhibitory control regions. In a preregistered analysis, we used MT MRI images from N = 63 healthy humans aged above 50 years (of either sex) who performed a Stop-Signal Task (SST), with atlas-based measurement of locus coeruleus contrast. We confirm that better response inhibition is correlated with locus coeruleus integrity and stronger connectivity between presupplementary motor area (preSMA) and right inferior frontal gyrus (rIFG), but not volumes of the prefrontal cortical regions. We confirmed a significant role of prefrontal connectivity in mediating the effect of individual differences in the locus coeruleus on behavior, where this effect was moderated by age, over and above adjustment for the mean effects of age. Our results support the hypothesis that in normal populations, as in clinical settings, the locus coeruleus noradrenergic system regulates inhibitory control.SIGNIFICANCE STATEMENT We show that the integrity of the locus coeruleus, the principal source of cortical noradrenaline, is related to the efficiency of response inhibition in healthy older adults. This effect is in part mediated by its effect on functional connectivity in a prefrontal cortical stopping-network. The behavioral effect, and its mediation by connectivity, are moderated by age. This supports the psychopharmacological and genetic evidence for the noradrenergic regulation of behavioral control, in a population-based normative cohort. Noradrenergic treatment strategies may be effective to improve behavioral control in impulsive clinical populations, but age, and locus coeruleus integrity, are likely to be important stratification factors.

Machine learning approaches linking brain function to behavior in the ABCD STOP task.

The stop-signal task (SST) is one of the most common fMRI tasks of response inhibition, and its performance measure, the stop-signal reaction-time (SSRT), is broadly used as a measure of cognitive control processes. The neurobiology underlying individual or clinical differences in response inhibition remain unclear, consistent with the general pattern of quite modest brain-behavior associations that have been recently reported in well-powered large-sample studies. Here, we investigated the potential of multivariate, machine learning (ML) methods to improve the estimation of individual differences in SSRT with multimodal structural and functional region of interest-level neuroimaging data from 9- to 11-year-olds children in the ABCD Study. Six ML algorithms were assessed across modalities and fMRI tasks. We verified that SST activation performed best in predicting SSRT among multiple modalities including morphological MRI (cortical surface area/thickness), diffusion tensor imaging, and fMRI task activations, and then showed that SST activation explained 12% of the variance in SSRT using cross-validation and out-of-sample lockbox data sets (n = 7298). Brain regions that were more active during the task and that showed more interindividual variation in activation were better at capturing individual differences in performance on the task, but this was only true for activations when successfully inhibiting. Cortical regions outperformed subcortical areas in explaining individual differences but the two hemispheres performed equally well. These results demonstrate that the detection of reproducible links between brain function and performance can be improved with multivariate approaches and give insight into a number of brain systems contributing to individual differences in this fundamental cognitive control process.