Inhibitory Control in Children with Tourette Syndrome Is Impaired in Everyday Life but Intact during a Stop Signal Task

Tourette Syndrome (TS) has previously been associated with deficits in inhibitory control (IC). However, studies on IC in individuals with TS have produced conflicting results. In the present study, we investigated IC, comparing the Stop Signal Reaction Time (SSRT) measure with parent and teacher ratings of daily life IC in 169 children aged 8–12 (60 with TS, 60 typically developing controls, 27 with attention-deficit/hyperactivity disorder (ADHD), and 22 with TS + ADHD). We further investigated associations of IC with TS and ADHD symptom severity. Children with TS showed intact SSRT performance, but impairments in daily life IC, as reported by parents and teachers. For the latter, we observed a staircase distribution of groups, with the healthy controls presenting with the best IC, followed by TS, TS + ADHD, and finally ADHD. Dimensional analyses indicated a strong association between ADHD severity and both measures of IC. Our results indicate that children with TS are not impaired in a laboratory-based measure of IC, although some difficulties were evident from measures of everyday behaviour, which may in part be due to parents and teachers interpreting tics as disinhibited behaviour. Comorbid ADHD or the severity of subthreshold ADHD symptomatology appeared to account for IC deficits.

Investigating the modulation of methylphenidate’s effects on impulsivity by fluoxetine

<p>The co-prescribing of methylphenidate (MPH) and a selective serotonin reuptake inhibitor for patients presenting co-morbidly with both attention deficit/hyperactivity disorder and depression or anxiety is in some cases recommended. Little research has been conducted on the specific cognitive and behavioural outcomes of this. Studies with rats have shown that SSRI’s potentiate MPH-induced dopamine release in the pre-frontal cortex, hippocampus and nucleus accumbens, as well as enhancing MPH-induced hyper-locomotion (Borycz, Zapata, Quiroz, Volkow, & Ferré, 2008; Weikop, Yoshitake, & Kehr, 2007b). Impulsivity is a behavioural construct with dissociable sub-types, of which one, ‘action restraint’, has been consistently shown to be associated with increased dopamine activity in the mesolimbic system, including the nucleus accumbens. It was hypothesised that rats would make more ‘no-go’ errors in a Go/No-Go task, indicative of an increase in ‘action restraint’ type impulsivity, when co-administered fluoxetine (FLX) and MPH compared to either drug administered alone. Although this was not shown in the current study, tentative evidence was found to suggest that the combination of these drugs may negatively impact on attention, based on a decrease in ‘go’ accuracy. A second subtype of impulsivity, “action cancellation”, was tested using a new variant of the Stop-Signal Reaction Time (SSRT) task that we have developed for rats. Studies show that this subtype of impulsivity seems to be unaffected by changes in dopamine activity, but is improved by increases in norepinephrine. In the Weikop study mentioned above, the SSRI citalopram enhanced not only MPH-induced dopamine release, but also norepinephrine release in the nucleus accumbens. Thus it was hypothesised that FLX may potentiate MPH’s impulsivity-reducing effects as measured by stopping latency in the SSRT. We were not able to show this in the current study, however the demonstration that lower doses of MPH reduced stopping latency, consistent with previous versions of the SSRT, validated the new version developed for the current study. A final experiment revealed a rapid, short-term increase in locomotor activity when rats were co-administered FLX and MPH, an effect not present when either drug was administered singly. This synergistic effect replicates previous findings, and indicates a potentiation of dopamine release in the nucleus accumbens, as was found in previous studies. Although FLX was not found to moderate MPH’s effects on impulsivity in the current study, synergistic effects of the two drugs were effects were found on motor activity and potentially on attention also. This is an indication of the value of further research into specific behavioural and cognitive process that may be affected by co-administration of MPH and an SSRI.</p>

Investigating the modulation of methylphenidate’s effects on impulsivity by fluoxetine

<p>The co-prescribing of methylphenidate (MPH) and a selective serotonin reuptake inhibitor for patients presenting co-morbidly with both attention deficit/hyperactivity disorder and depression or anxiety is in some cases recommended. Little research has been conducted on the specific cognitive and behavioural outcomes of this. Studies with rats have shown that SSRI’s potentiate MPH-induced dopamine release in the pre-frontal cortex, hippocampus and nucleus accumbens, as well as enhancing MPH-induced hyper-locomotion (Borycz, Zapata, Quiroz, Volkow, & Ferré, 2008; Weikop, Yoshitake, & Kehr, 2007b). Impulsivity is a behavioural construct with dissociable sub-types, of which one, ‘action restraint’, has been consistently shown to be associated with increased dopamine activity in the mesolimbic system, including the nucleus accumbens. It was hypothesised that rats would make more ‘no-go’ errors in a Go/No-Go task, indicative of an increase in ‘action restraint’ type impulsivity, when co-administered fluoxetine (FLX) and MPH compared to either drug administered alone. Although this was not shown in the current study, tentative evidence was found to suggest that the combination of these drugs may negatively impact on attention, based on a decrease in ‘go’ accuracy. A second subtype of impulsivity, “action cancellation”, was tested using a new variant of the Stop-Signal Reaction Time (SSRT) task that we have developed for rats. Studies show that this subtype of impulsivity seems to be unaffected by changes in dopamine activity, but is improved by increases in norepinephrine. In the Weikop study mentioned above, the SSRI citalopram enhanced not only MPH-induced dopamine release, but also norepinephrine release in the nucleus accumbens. Thus it was hypothesised that FLX may potentiate MPH’s impulsivity-reducing effects as measured by stopping latency in the SSRT. We were not able to show this in the current study, however the demonstration that lower doses of MPH reduced stopping latency, consistent with previous versions of the SSRT, validated the new version developed for the current study. A final experiment revealed a rapid, short-term increase in locomotor activity when rats were co-administered FLX and MPH, an effect not present when either drug was administered singly. This synergistic effect replicates previous findings, and indicates a potentiation of dopamine release in the nucleus accumbens, as was found in previous studies. Although FLX was not found to moderate MPH’s effects on impulsivity in the current study, synergistic effects of the two drugs were effects were found on motor activity and potentially on attention also. This is an indication of the value of further research into specific behavioural and cognitive process that may be affected by co-administration of MPH and an SSRI.</p>

Ahead of the (ROC) Curve: A Statistical Approach to Utilizing Ex-Gaussian Parameters of Reaction Time in Diagnosing ADHD Across Three Developmental Periods

Introduction: Performance on executive function (EF) tasks is only modestly predictive of a diagnosis of Attention Deficit Hyperactivity Disorder (ADHD), despite the common assumption that EF deficits are ubiquitous to the disorder. The current study sought to determine whether ex-Gaussian parameters of simple reaction time are better able to discriminate between children and adults with and without ADHD, compared with traditional measures of inhibitory control. Methods: Receiver Operating Characteristic (ROC) analyses and the area under the curve (AUC) were used to examine the ability of performance on two commonly used tasks of inhibitory control (i.e. stop signal reaction time (SSRT) and go-no-go tasks) to predict ADHD status in preschool (N = 108), middle childhood (N = 309), and young adulthood (N = 133). Results: Across all samples, SSRT, go-no-go percentage of failed inhibits, and standard deviation of reaction (SDRT) time to “go” trials, all successfully discriminated between individuals with and without ADHD. Ex-Gaussian decomposition of the RT distribution indicated that both larger tau and larger sigma drove findings for SDRT. Contrary to predictions, traditional measures of inhibitory control were equal if not better predictors of ADHD status than ex-Gaussian parameters. Conclusions: Findings support ongoing work to quantify the separate contributions of cognitive subprocesses that drive task performance, which in turn is critical to developing and improving process-based approaches in clinical assessment.

Towards a taxonomy of inhibition-related processes: A dual-task approach

The ability to inhibit responses is key to controlled behavior and is commonly investigated with the stop-signal paradigm. The authors investigated how response inhibition is situated within a taxonomy of control processes by combining multiple forms of control within novel dual tasks. Response inhibition, as measured by stop-signal reaction time (SSRT), was impaired when combined with shape matching, but not the flanker task, and when combined with cued task switching, but not predictable task switching, suggesting that response inhibition may be weakly or variably impaired when combined with selective attention and set switching demands, respectively. Response inhibition was consistently impaired when combined with the N-back or directed forgetting tasks, putative measures of working memory. Impairments of response inhibition by other control demands appeared to be driven by task context rather than evoked control demands, as SSRT slowing was similar for trials where control demands were either present (e.g., task switch) or absent (e.g., task stay). These results were initially identified in a discovery sample and subsequently validated in a pre-registered analysis of a held-out sample of subjects (N = 33 and 33, respectively). Taken together, these results show that response inhibition processes are often impaired in the context of other control demands, even on trials where direct engagement of those other control processes is not required. This suggests a taxonomy of control in which response inhibition overlaps with related control processes, especially working memory.

A Bayesian Mixture Modelling of Stop Signal Reaction Time Distributions: The Second Contextual Solution for the Problem of Aftereffects of Inhibition on SSRT Estimations

The distribution of single Stop Signal Reaction Times (SSRT) in the stop signal task (SST) has been modelled with two general methods: a nonparametric method by Hans Colonius (1990) and a Bayesian parametric method by Dora Matzke, Gordon Logan and colleagues (2013). These methods assume an equal impact of the preceding trial type (go/stop) in the SST trials on the SSRT distributional estimation without addressing the relaxed assumption. This study presents the required model by considering a two-state mixture model for the SSRT distribution. It then compares the Bayesian parametric single SSRT and mixture SSRT distributions in the usual stochastic order at the individual and the population level under ex-Gaussian (ExG) distributional format. It shows that compared to a single SSRT distribution, the mixture SSRT distribution is more varied, more positively skewed, more leptokurtic and larger in stochastic order. The size of the results’ disparities also depends on the choice of weights in the mixture SSRT distribution. This study confirms that mixture SSRT indices as a constant or distribution are significantly larger than their single SSRT counterparts in the related order. This result offers a vital improvement in the SSRT estimations.

Investigating the sex-dependent effects of prefrontal cortex stimulation on response execution and inhibition

Context-dependent execution or inhibition of a response is an important aspect of executive control, which is impaired in neuropsychological and addiction disorders. Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) has been considered a remedial approach to address deficits in response control; however, considerable variability has been observed in tDCS effects. These variabilities might be related to contextual differences such as background visual-auditory stimuli or subjects' sex. In this study, we examined the interaction of two contextual factors, participants' sex and background acoustic stimuli, in modulating the effects of tDCS on response inhibition and execution. In a sham-controlled and cross-over (repeated-measure) design, 73 participants (37 females) performed a Stop-Signal Task in different background acoustic conditions before and after tDCS (anodal or sham) was applied over the DLPFC. Participants had to execute a speeded response in Go trials but inhibit their response in Stop trials. Participants' sex was fully counterbalanced across all experimental conditions (acoustic and tDCS). We found significant practice-related learning that appeared as changes in indices of response inhibition (stop-signal reaction time and percentage of successful inhibition) and action execution (response time and percentage correct). The tDCS and acoustic stimuli interactively influenced practice-related changes in response inhibition and these effects were uniformly seen in both males and females. However, the effects of tDCS on response execution (percentage of correct responses) were sex-dependent in that practice-related changes diminished in females but heightened in males. Our findings indicate that participants' sex influenced the effects of tDCS on the execution, but not inhibition, of responses.

The comparisons of inhibitory control and post-error behaviors between different types of athletes and physically inactive adults

To properly behave and correct mistakes, individuals must inhibit inappropriate actions and detect errors for future behavioral adjustment. Increasing evidence has demonstrated that athletes are superior in cognitive functions and this benefit varied dependent on the types of sport that individuals involved in, but less is known on whether athletes have a different error-related behavioral pattern. The purpose of this study was to compare the behavioral performance of inhibition and error monitoring between individuals who participated in an open-skill sport (n = 12), a closed-skill sport (n = 12), and a sedentary lifestyle (n = 16). A combined flanker/stop signal task was presented and the derived stop signal reaction time (SSRT), post-correct accuracy and reaction time (RT), as well as post-error accuracy and RT were compared across groups. Our findings indicated there was no difference in SSRT between groups. Surprisingly, significant post-error slowing (PES) was observed only in controls but not in sport groups, the controls also exhibited significantly longer post-error RT compared with the open-skill group. However, there was no difference in the post-error accuracy between groups, indicating a higher efficiency in the post-error processing among open- and closed-skill groups by requiring comparatively less time for behavioral adjustments. The present study is the first to disclose the discrepancies in PES between different types of athletes and controls. The findings suggest that sport training along with higher amounts of physical activity is associated with a more efficient behavioral pattern for error processing especially when the sport requires open skills in nature.

Cognitive process modeling addresses context independence violations in the ABCD Study stop-signal task

The Adolescent Brain Cognitive Development (ABCD) Study is a longitudinal neuroimaging study of unprecedented scale that is in the process of following over 11,000 youth from middle childhood though age 20. However, a design feature of the study's stop-signal task violates "context independence", an assumption critical to current non-parametric methods for estimating stop-signal reaction time (SSRT), a key measure of inhibitory ability in the study. This has led some experts to call for the task to be changed and for previously collected data to be used with caution. We present a formal cognitive process model, the BEESTS-ABCD model, that provides a mechanistic explanation for the impact of this design feature, describes key behavioral trends in the ABCD data, and allows biases in SSRT estimates resulting from context independence violations to be quantified. We use the model to demonstrate that, although non-parametric SSRT estimates generally preserve the rank ordering of participants' SSRT values, failing to account for context independence violations can lead to erroneous inferences in several realistic scenarios. Nonetheless, as the BEESTS-ABCD model can be used to accurately recover estimates of SSRT and other mechanistic parameters of interest from ABCD data, the impact of such violations can be effectively mitigated.

Cortical silent period reflects individual differences in action stopping performance

Inhibitory control is the ability to suppress inappropriate movements and unwanted actions, allowing to regulate impulses and responses. This ability can be measured via the Stop Signal Task, which provides a temporal index of response inhibition, namely the stop signal reaction time (SSRT). At the neural level, Transcranial Magnetic Stimulation (TMS) allows to investigate motor inhibition within the primary motor cortex (M1), such as the cortical silent period (CSP) which is an index of GABAB-mediated intracortical inhibition within M1. Although there is strong evidence that intracortical inhibition varies during action stopping, it is still not clear whether differences in the neurophysiological markers of intracortical inhibition contribute to behavioral differences in actual inhibitory capacities. Hence, here we explored the relationship between intracortical inhibition within M1 and behavioral response inhibition. GABABergic-mediated inhibition in M1 was determined by the duration of CSP, while behavioral inhibition was assessed by the SSRT. We found a significant positive correlation between CSP’s duration and SSRT, namely that individuals with greater levels of GABABergic-mediated inhibition seem to perform overall worse in inhibiting behavioral responses. These results support the assumption that individual differences in intracortical inhibition are mirrored by individual differences in action stopping abilities.