On the (un)reliability of common behavioral and electrophysiological measures from the stop signal task: Measures of inhibition lack stability over time.

Response inhibition, the intentional stopping of planned or initiated actions, is often considered a key facet of control, impulsivity, and self-regulation. The stop signal task is argued to be the purest inhibition task we have, and it is thus central to much work investigating the role of inhibition in areas like development and psychopathology. Most of this work quantifies stopping behavior by calculating the stop signal reaction time as a measure of individual stopping latency. Individual difference studies aiming to investigate why and how stopping latencies differ between people often do this under the assumption that the stop signal reaction time indexes a stable, dispositional trait. However, empirical support for this assumption is lacking, as common measures of inhibition and control tend to show low test-retest reliability and thus appear unstable over time. The reasons for this could be methodological, where low stability is driven by measurement noise, or substantive, where low stability is driven by a larger influence of state-like and situational factors. To investigate this, we characterized the split-half and test-retest reliability of a range of common behavioral and electrophysiological measures derived from the stop signal task. Across three independent studies, different measurement modalities, and a systematic review of the literature, we found a pattern of low temporal stability for inhibition measures and higher stability for measures of manifest behavior and non-inhibitory processing. This pattern could not be explained by measurement noise and low internal consistency. Consequently, response inhibition appears to have mostly state-like and situational determinants, and there is little support for the validity of conceptualizing common inhibition measures as reflecting stable traits.

Corticospinal excitability reductions during action preparation and action stopping in humans: Different sides of the same inhibitory coin?

Motor functions and cognitive processes are closely associated with each other. In humans, this linkage is reflected in motor system state changes both when an action must be prepared and stopped. Single-pulse transcranial magnetic stimulation showed that both action preparation and action stopping are accompanied by a reduction of corticospinal excitability, referred to as preparatory and response inhibition, respectively. While previous efforts have been made to describe both phenomena extensively, an updated and comprehensive comparison of the two phenomena is lacking. To ameliorate such deficit, this review focuses on the role and interpretation of single-coil (single-pulse and paired-pulse) and dual-coil TMS outcome measures during action preparation and action stopping in humans. To that effect, it aims to identify commonalities and differences, detailing how TMS-based outcome measures are affected by states, traits, and psychopathologies in both processes. Eventually, findings will be compared, and open questions will be addressed to aid future research.

Assessing the Longitudinal Associations Between Decision-Making Processes and Attention Problems in Early Adolescence.

Cognitive functions and psychopathology develop in parallel in childhood and adolescence, but the temporal dynamics of their associations are poorly understood. The present study sought to elucidate the intertwined development of decision-making processes and attention problems using longitudinal data from late childhood (9-10 years) to mid-adolescence (11-13 years) from the Adolescent Brain Cognitive Development (ABCD) Study (n = 8918). We utilised hierarchical drift-diffusion modelling of behavioural data from the stop-signal task, parent-reported attention problems from the Child Behavior Checklist (CBCL), and multigroup univariate and bivariate latent change score models. The results showed faster drift rate was associated with lower levels of inattention at baseline, as well as a greater reduction of inattention over time. Moreover, baseline drift rate negatively predicted change in attention problems in females, and baseline attention problems negatively predicted change in drift rate. Neither response caution (decision threshold) nor encoding- and responding processes (non-decision time) were significantly associated with attention problems. There were no significant sex differences in the associations between decision-making processes and attention problems. The study supports previous findings of reduced evidence accumulation in attention problems and additionally shows that development of this aspect of decision-making plays a role in developmental changes in attention problems in youth.

Long-term improvements in executive functions after frontal-midline theta neurofeedback in a (sub)clinical group.

Impairments in executive functions (EFs) are common across disorders and can greatly affect daily functioning. Frontal-midline (FM) theta neurofeedback (NF) has been shown effective in enhancing EFs in healthy adults, prompting interest in exploring its potential as an alternative treatment for EFs in (sub)clinical samples. This study aims to determine the effects of FM theta NF on EFs in a sample of 58 adults (aged 20-60 years) with pronounced subjective EF complaints in daily life. Using a pre/post/follow-up design with a sham NF group, the present study assessed upregulation of FM theta in an eight-session individualized FM theta NF training and its immediate and long-term transfer effects on objective and subjective measures of EFs. These included behavioral performance on EF tasks assessing working memory updating (N-back task), set-shifting (Switching task), conflict monitoring (Stroop task), and response inhibition (Stop-signal task), as well as FM theta power during these tasks, and subjective EFs in daily life (BRIEF-A). The results indicate that there are only differences in FM theta self-upregulation between the NF group and sham group when non-responders are excluded from the analysis. Regarding behavioral transfer effects, NF-specific improvements are found in working memory updating reaction time (RT) and conflict monitoring RT variability at 6-month follow-up, but not immediately after the NF training. The effects on FM theta power during the EF tasks and subjective changes in EFs in daily life were not specific to the NF training. As a next step, research should identify the best predictors to stratify NF training, as well as explore ways to improve NF responsiveness, for instance by increasing neuroplasticity.

Reaction Time Variability in Children Is Specifically Associated With Attention Problems and Regional White Matter Microstructure.

BACKGROUND: Increased intraindividual variability (IIV) in reaction times (RTs) has been suggested as a key cognitive and behavioral marker of attention problems, but findings for other dimensions of psychopathology are less consistent. Moreover, while studies have linked IIV to brain white matter microstructure, large studies testing the robustness of these associations are needed. METHODS: We used data from the Adolescent Brain Cognitive Development (ABCD) Study baseline assessment to test the associations between IIV and psychopathology (n = 8622, age = 8.9-11.1 years) and IIV and white matter microstructure (n = 7958, age = 8.9-11.1 years). IIV was investigated using an ex-Gaussian distribution analysis of RTs in correct response go trials in the stop signal task. Psychopathology was measured by the Child Behavior Checklist and a bifactor structural equation model was performed to extract a general p factor and specific factors reflecting internalizing, externalizing, and attention problems. To investigate white matter microstructure, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were examined in 23 atlas-based tracts. RESULTS: Increased IIV in both short and long RTs was positively associated with the specific attention problems factor (Cohen's d = 0.13 and d = 0.15, respectively). Increased IIV in long RTs was also positively associated with radial diffusivity in the left and right corticospinal tract (both tracts, d = 0.12). CONCLUSIONS: Using a large sample and a data-driven dimensional approach to psychopathology, the results provide novel evidence for a small but specific association between IIV and attention problems in children and support previous findings on the relevance of white matter microstructure for IIV.

Working memory in pre-school children with autism spectrum disorder: An eye-tracking study.

Working memory (WM) was examined in pre-school children with Autism spectrum disorder (ASD) and children with typical development using eye-tracking technology. The children were presented with a digital A-not-B task (with a short and a long waiting condition) where they passively viewed animations of a moving train. Moreover, the current study investigated the relationship between non-verbal mental age (NVMA) and the performance on the task. No group differences were found in the average looking durations between the ASD and typically developing (TD) groups on either the short or long waiting conditions. Although the NVMA of the ASD group was lower than that of the TD group there were no correlations between NVMA and task performance in either group. The results suggest that WM in young children with ASD might not be different from that of TD children. However, the results might be due to ceiling effects of the task and thus needs to be further investigated.

Partial response electromyography as a marker of action stopping.

Response inhibition is among the core constructs of cognitive control. It is notoriously difficult to quantify from overt behavior, since the outcome of successful inhibition is the lack of a behavioral response. Currently, the most common measure of action stopping, and by proxy response inhibition, is the model-based stop signal reaction time (SSRT) derived from the stop signal task. Recently, partial response electromyography (prEMG) has been introduced as a complementary physiological measure to capture individual stopping latencies. PrEMG refers to muscle activity initiated by the go signal that plummets after the stop signal before its accumulation to a full response. Whereas neither the SSRT nor the prEMG is an unambiguous marker for neural processes underlying response inhibition, our analysis indicates that the prEMG peak latency is better suited to investigate brain mechanisms of action stopping. This study is a methodological resource with a comprehensive overview of the psychometric properties of the prEMG in a stop signal task, and further provides practical tips for data collection and analysis.

Inhibitory Control and the Structural Parcelation of the Right Inferior Frontal Gyrus.

The right inferior frontal gyrus (rIFG) has most strongly, although not exclusively, been associated with response inhibition, not least based on covariations of behavioral performance measures and local gray matter characteristics. However, the white matter microstructure of the rIFG as well as its connectivity has been less in focus, especially when it comes to the consideration of potential subdivisions within this area. The present study reconstructed the structural connections of the three main subregions of the rIFG (i.e., pars opercularis, pars triangularis, and pars orbitalis) using diffusion tensor imaging, and further assessed their associations with behavioral measures of inhibitory control. The results revealed a marked heterogeneity of the three subregions with respect to the pattern and extent of their connections, with the pars orbitalis showing the most widespread inter-regional connectivity, while the pars opercularis showed the lowest number of interconnected regions. When relating behavioral performance measures of a stop signal task to brain structure, the data indicated an association between the dorsal opercular connectivity and the go reaction time and the stopping accuracy.

Investigating Cognitive Flexibility in Preschool Children With Autism Spectrum Disorder.

The current study investigated cognitive flexibility in preschool children with Autism Spectrum Disorder (ASD) and those with typical development using the Reverse Categorization (RC) task and the Dimensional Change Card Sort (DCCS) task. We further examined the relationship between non-verbal mental age (NVMA) and the performance on the two tasks. While no significant difference in performance on the RC task between the two groups was found, significantly more children in the typical developing group passed the DCCS task than children in the ASD group. NVMA was found to correlate with performance in both tasks in the typical developing group but not in the ASD group. When the children were matched on NVMA, no differences in task performance between the two groups were found. The current study found the disparity in performance in two groups on the RC and the DCCS tasks, hence illuminating the importance related to the selection of tasks when studying cognitive flexibility in preschool children with ASD. The study also cast some light on the involvement of NVMA in the performance on the RC and DCCS tasks.

Frontal-midline theta reflects different mechanisms associated with proactive and reactive control of inhibition.

Reactive control of response inhibition is associated with a right-lateralised cortical network, as well as frontal-midline theta (FM-theta) activity measured at the scalp. However, response inhibition is also governed by proactive control processes, and how such proactive control is reflected in FM-theta activity and associated neural source activity remains unclear. To investigate this, simultaneous recordings of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data was performed while participants performed a cued stop-signal task. The cues (0%, 25% or 66%) indicated the likelihood of an upcoming stop-signal in the following trial. Results indicated that participants adjusted their behaviour proactively, with increasing go-trial reaction times following increasing stop-signal probability, as well as modulations of both go-trial and stop-trial accuracies. Target-locked theta activity was higher in stop-trials than go-trials and modulated by probability. At the single-trial level, cue-locked theta was associated with shorter reaction-times, while target-locked theta was associated with both faster reaction times and higher probability of an unsuccessful stop-trial. This dissociation was also evident at the neural source level, where a joint ICA revealed independent components related to going, stopping and proactive preparation. Overall, the results indicate that FM-theta activity can be dissociated into several mechanisms associated with proactive control, response initiation and response inhibition processes. We propose that FM-theta activity reflects both heightened preparation of the motor control network, as well as stopping-related processes associated with a right lateralized cortical network.

Electrophysiological and behavioral indices of cognitive conflict processing across adolescence.

Cognitive control enables goal-oriented adaptation to a fast-changing environment and has a protracted development spanning into young adulthood. The neurocognitive processes underlying this development are poorly understood. In a cross-sectional sample of participants 8-19 years old (n = 108), we used blind source separation of EEG data recorded in a Flanker task to derive electrophysiological measures of attention and conflict processing, including a N2-like frontal negative component and a P3-like parietal positive component. Outside the recording session, we examined multiple behavioral measures of interference control derived from the Flanker, Stroop, and Anti-saccade tasks. We found a positive association between age and P3 amplitude, but no relationship between age and N2 amplitude. A stronger N2 was age-independently related to better performance on Stroop and Anti-saccade measures of interference control. A Gratton effect was found on the Flanker task, with slower reaction times on current congruent and better accuracy on current incongruent trials when preceded by incongruent as opposed to congruent trials. The Gratton effect on accuracy was positively associated with age. Together, the findings suggest a multifaceted developmental pattern of the neurocognitive processes involved in conflict processing across adolescence, with a more protracted development of the P3 compared to the N2.

Probing the neural signature of mind wandering with simultaneous fMRI-EEG and pupillometry.

Mind wandering reflects the shift in attentional focus from task-related cognition driven by external stimuli toward self-generated and internally-oriented thought processes. Although such task-unrelated thoughts (TUTs) are pervasive and detrimental to task performance, their underlying neural mechanisms are only modestly understood. To investigate TUTs with high spatial and temporal precision, we simultaneously measured fMRI, EEG, and pupillometry in healthy adults while they performed a sustained attention task with experience sampling probes. Features of interest were extracted from each modality at the single-trial level and fed to a support vector machine that was trained on the probe responses. Compared to task-focused attention, the neural signature of TUTs was characterized by weaker activity in the default mode network but elevated activity in its anticorrelated network, stronger functional coupling between these networks, widespread increase in alpha, theta, delta, but not beta, frequency power, predominantly reduced amplitudes of late, but not early, event-related potentials, and larger baseline pupil size. Particularly, information contained in dynamic interactions between large-scale cortical networks was predictive of transient changes in attentional focus above other modalities. Together, our results provide insight into the spatiotemporal dynamics of TUTs and the neural markers that may facilitate their detection.

The P300 as marker of inhibitory control - Fact or fiction?

Inhibitory control, i.e., the ability to stop or suppress actions, thoughts, or memories, represents a prevalent and popular concept in basic and clinical neuroscience as well as psychology. At the same time, it is notoriously difficult to study as successful inhibition is characterized by the absence of a continuously quantifiable direct behavioral marker. It has been suggested that the P3 latency, and here especially its onset latency, may serve as neurophysiological marker of inhibitory control as it correlates with the stop signal reaction time (SSRT). The SSRT estimates the average stopping latency, which itself is unobservable since no overt response is elicited in successful stop trials, based on differences in the distribution of go reaction times and the delay of the stop-relative to the go-signal in stop trials. In a meta-analysis and an independent electroencephalography (EEG) experiment, we found that correlations between the P3 latency and the SSRT are indeed replicable, but also unspecific. Not only does the SSRT also correlate with the N2 latency, but both P3 and N2 latency measures show similar or even higher correlations with other behavioral parameters such as the go reaction time or stopping accuracy. The missing specificity of P3-SSRT correlations, together with the general pattern of associations, suggests that these manifest effects are driven by underlying latent processes other than inhibition, such as behavioral adaptations in context of performance monitoring operations.

A Single Mechanism for Global and Selective Response Inhibition under the Influence of Motor Preparation.

In our everyday behavior, we frequently cancel one movement while continuing others. Two competing models have been suggested for the cancellation of such specific actions: (1) the abrupt engagement of a unitary global inhibitory mechanism followed by reinitiation of the continuing actions; or (2) a balance between distinct global and selective inhibitory mechanisms. To evaluate these models, we examined behavioral and physiological markers of proactive control, motor preparation, and response inhibition using a combination of behavioral task performance measures, electromyography, electroencephalography, and motor evoked potentials elicited with transcranial magnetic stimulation. Healthy human participants of either sex performed two versions of a stop signal task with cues incorporating proactive control: a unimanual task involving the initiation and inhibition of a single response, and a bimanual task involving the selective stopping of one of two prepared responses. Stopping latencies, motor evoked potentials, and frontal ß power (13-20 Hz) did not differ between the unimanual and bimanual tasks. However, evidence for selective proactive control before stopping was manifest in the bimanual condition as changes in corticomotor excitability, µ (9-14 Hz), and ß (15-25 Hz) oscillations over sensorimotor cortex. Together, our results favor the recruitment of a single inhibitory stopping mechanism with the net behavioral output depending on the levels of action-specific motor preparation.SIGNIFICANCE STATEMENT Response inhibition is a core function of cognitive flexibility and movement control. Previous research has suggested separate mechanisms for selective and global inhibition, yet the evidence is inconclusive. Another line of research has examined the influence of preparation for action stopping, or what is called proactive control, on stopping performance, yet the neural mechanisms underlying this interaction are unknown. We combined transcranial magnetic stimulation, electroencephalography, electromyography, and behavioral measures to compare selective and global inhibition models and to investigate markers of proactive control. The results favor a single inhibitory mechanism over separate selective and global mechanisms but indicate a vital role for preceding motor activity in determining whether and which actions will be stopped.

Neuropsychological functions, sleep, and mental health in adults with Klinefelter syndrome.

A few studies have examined neuropsychological functions, sleep, and mental health combined in Klinefelter syndrome (KS; 47,XXY). We investigated neuropsychological functions with standard tests, sleep with actigraphy, and self-reported mental health in 30 men with KS (Mean age = 36.7 years) compared to 21 controls (Mean age = 36.8 years). Men with KS scored significantly lower on mental speed, attention span, working memory, inhibition, and set-shifting tests, as well as overall IQ (mean effect size difference Cohen's d = 0.79). Men with KS had significantly longer night wakes, with no differences in other sleep variables (mean d = 0.34). Men with KS reported poorer mental health than controls (mean d = 1.16). Regression analyses showed neuropsychological functions explained variance in some sleep domains for men with KS but not for controls. Neuropsychological functions explained variance in some mental health domains for controls. For men with KS, however, verbal IQ was the only significant predictor of mental health. Altogether, men with KS display problems in neuropsychological functions and mental health but do not appear different from controls on most sleep parameters. Our findings indicate that relations between neuropsychological functions, sleep, and mental health differ between men with KS and controls.

tDCS over the inferior frontal gyri and visual cortices did not improve response inhibition.

The ability to cancel an already initiated response is central to flexible behavior. While several different behavioral and neural markers have been suggested to quantify the latency of the stopping process, it remains unclear if they quantify the stopping process itself, or other supporting mechanisms such as visual and/or attentional processing. The present study sought to investigate the contributions of inhibitory and sensory processes to stopping latency markers by combining transcranial direct current stimulation (tDCS), electroencephalography (EEG) and electromyography (EMG) recordings in a within-participant design. Active and sham tDCS were applied over the inferior frontal gyri (IFG) and visual cortices (VC), combined with both online and offline EEG and EMG recordings. We found evidence that neither of the active tDCS condition affected stopping latencies relative to sham stimulation. Our results challenge previous findings suggesting that anodal tDCS over the IFG can reduce stopping latency and demonstrates the necessity of adequate control conditions in tDCS research. Additionally, while the different putative markers of stopping latency showed generally positive correlations with each other, they also showed substantial variation in the estimated latency of inhibition, making it unlikely that they all capture the same construct exclusively.

Differences in unity: The go/no-go and stop signal tasks rely on different mechanisms.

Response inhibition refers to the suppression of prepared or initiated actions. Typically, the go/no-go task (GNGT) or the stop signal task (SST) are used interchangeably to capture individual differences in response inhibition. On the one hand, factor analytic and conjunction neuroimaging studies support the association of both tasks with a single inhibition construct. On the other hand, studies that directly compare the two tasks indicate distinct mechanisms, corresponding to action restraint and cancellation in the GNGT and SST, respectively. We addressed these contradictory findings with the aim to identify the core differences in the temporal dynamics of the functional networks that are recruited in both tasks. We extracted the time-courses of sensory, motor, attentional, and cognitive control networks by group independent component (G-ICA) analysis of electroencephalography (EEG) data from both tasks. Additionally, electromyography (EMG) from the responding effector muscles was recorded to detect the timing of response inhibition. The results indicated that inhibitory performance in the GNGT may be comparable to response selection mechanisms, reaching peripheral muscles at around 316 â€‹ms. In contrast, inhibitory performance in the SST is achieved via biasing of the sensorimotor system in preparation for stopping, followed by fast sensory, motor and frontal integration during outright stopping. Inhibition can be detected at the peripheral level at 140 â€‹ms after stop stimulus presentation. The GNGT and the SST therefore seem to recruit widely different neural dynamics, implying that the interchangeable use of superficially similar inhibition tasks in both basic and clinical research is unwarranted.

Strategy switches in proactive inhibitory control and their association with task-general and stopping-specific networks.

Prior information about the likelihood of a stop-signal pre-activates networks associated with response inhibition in both go- and stop-trials. How such prior information modulates the neural mechanisms enacting response inhibition is only poorly understood. To investigate this, a cued stop-signal task (with cues indicating stopping probabilities of 0%, 25% or 66%) was implemented in combination with functional magnetic resonance imaging (fMRI) data acquisition. Specifically, we focused on the effect of proactive inhibitory control as reflected in the activity of regions known to regulate response inhibition. Further, modulatory activity profiles in three different sub-regions of the right inferior frontal area were investigated. Behavioural results revealed an adaptation of task strategies through proactive control, with a possible gain for efficient inhibition at high stopping probabilities. The imaging data indicate that this adaption was supported by different regions traditionally involved in the stopping network. While the right inferior parietal cortex (IPC), right middle frontal gyrus (MFG), right inferior frontal gyrus (rIFG) pars triangularis, and left anterior insula all showed increased go-trial activity in the 0% condition compared to the 25% condition, the pre-supplementary motor area (pre-SMA), anterior midcingulate cortex (aMCC), right anterior insula, and the rIFG pars opercularis showed a more stopping-specific pattern, with stronger stop-trial activity in the 66% condition than in the 25% condition. Furthermore, activity in inferior frontal sub-regions correlated with behavioural changes, where more pronounced response slowing was associated with stronger activity increases from low to high stopping probabilities. Notably, the different right inferior frontal sub-regions showed different activity patterns in response to proactive inhibitory control modulations, supporting the idea of a functional dissociation within this area. Specifically, while the pars opercularis and the right insula showed stopping-related modulations of activity, the rIFG pars triangularis exhibited modulations only in go-trials with strong adaptions to fast responding or proactive slowing. Overall, the results indicate that proactive inhibitory control results in the switching of task or strategy modes, either favouring fast responding or stopping, and that these strategical adaptations are governed by an interplay of different regions of the stopping network.

Error processing in the adolescent brain: Age-related differences in electrophysiology, behavioral adaptation, and brain morphology.

Detecting errors and adjusting behaviour appropriately are fundamental cognitive abilities that are known to improve through adolescence. The cognitive and neural processes underlying this development, however, are still poorly understood. To address this knowledge gap, we performed a thorough investigation of error processing in a Flanker task in a cross-sectional sample of participants 8 to 19 years of age (n = 98). We examined age-related differences in event-related potentials known to be associated with error processing, namely the error-related negativity (ERN) and the error positivity (Pe), as well as their relationships with task performance, post-error adjustments and regional cingulate cortex thickness and surface area. We found that ERN amplitude increased with age, while Pe amplitude remained constant. A more negative ERN was associated with higher task accuracy and faster reaction times, while a more positive Pe was associated with higher accuracy, independently of age. When estimating post-error adjustments from trials following both incongruent and congruent trials, post-error slowing and post-error improvement in accuracy both increased with age, but this was only found for post-error slowing when analysing trials following incongruent trials. There were no age-independent associations between either ERN or Pe amplitude and cingulate cortex thickness or area measures.