Stop-signal Reaction Time Task Research Articles

Differential effects of sertraline and cognitive behavioural therapy on behavioural inhibition in patients with obsessive compulsive disorder.

Patients with obsessive compulsive disorder (OCD) randomised to sertraline, manualised cognitive behavioural therapy (CBT), or combination (sertraline + CBT), underwent cognitive assessment. Cognitive testing was conducted at baseline and at week 16. The stop signal reaction time task (SSRT) was used to evaluate motor impulsivity and attentional flexibility was evaluated using the intra/extra-dimensional set shifting task. Paired-samples t -tests or nonparametric variants were used to compare baseline and posttreatment scores within each treatment group. Forty-five patients were tested at baseline (sertraline n = 14; CBT n = 14; sertraline + CBT n = 17) and 23 patients at week 16 (sertraline n = 6; CBT n = 7; sertraline + CBT n = 10). The mean dosage of sertraline was numerically higher in those taking sertraline as a monotherapy (166.67 mg) compared with those taking sertraline in combination with CBT (100 mg). Analysis of pre-post treatment scores using an intent-to-treat-analysis found a significant reduction in the SSRT in those treated with sertraline, whilst there was no significant change on this task for those treated with CBT or the combination. This study found that motor inhibition improved significantly following sertraline monotherapy. Suboptimal sertraline dosing might explain the failure to detect an effect on motor inhibition in the group receiving combination of sertraline + CBT. Higher dose sertraline may have broader cognitive effects than CBT for OCD, motor impulsivity may have value as a measure of treatment outcome and, by extension, the SSRT could serve as a biomarker for personalising care.

Stop it! Relationship between sport expertise and response inhibition in elite athletes.

The dynamic structure of sport games forces players to make time-sensitive decisions and to initiate actions that may then have to be canceled in response to sudden changes in the game situation. Whether and up to which time already initiated movements can still be inhibited is an important criterion for game performance in elite sport. Research indicates that elite athletes show superior motor inhibition performance compared to recreational athletes. However, no study has examined whether differences also emerge among professional elite athletes themselves. Therefore, this study aimed to investigate whether motor inhibition performance is a differential feature among elite athletes, and whether inhibition performance increases with greater expertise. In total of 106 elite athletes (ice hockey, basketball, volleyball, American football, handball, and soccer) completed a PC-based procedure to determine motor inhibition performance using the stop-signal reaction time (SSRT) task for hands and feet. In addition, an expertise score was determined for each elite athlete. Multiple linear regression was used to calculate the relationship between expertise and SSRT. Results showed that the expertise score of the elite athletes was between 3.7 and 11.7 out of 16 possible points (MExpertise = 6.8 points, SD = 1.76). The average SSRT of the hands was 224.0 ms (SD = 35.0); of the feet, 257.9 ms (SD = 48.5). Regression results showed a significant relationship between expertise and SSRT (F(2,101) = 9.38, p = 0.04, R2 = 0.06). SSRTs of the hands were significant predictors of expertise (b = -0.23, t = -2.1, p = 0.04). Taken together, results suggest that elite athletes with higher expertise outperform elite athletes with lower expertise, indicating that it is possible to differentiate within elite athletes with respect to inhibition performance of the hands. However, whether expertise affects inhibition performance or vice versa cannot be answered at present.

511 Eliminating System xc- Signaling Between Astrocytes and Neurons Selectively Impairs Complex Cognition

OBJECTIVES/GOALS: We aim to discover safer and more effective therapeutics for CNS disorders. Current therapeutic development is hindered by dosing out drugs for safe consumption. By identifying proteins with narrow functional roles in the brain (i.e., behavioral control), we can develop drugs targeting these proteins for improved treatment safety and efficacy. METHODS/STUDY POPULATION: We focused on an evolutionarily new, non-neuronal, non-synaptic glutamate signaling mechanism, system xc- (Sxc). Sxc activity was eliminated by mutating the gene Slc7a11 through pronuclear injection of zinc-finger nucleases into Sprague Dawley rat embryos to create a line of rats lacking Sxc (MSxc). To confirm Sxc mutation, we verified that tissue from MSxc rats had a complete lack of xCT, which is the regulatory subunit of Sxc that is encoded by Slc7a11. We also verified that astrocyte cultures generated from MSxc tissue lacked cystine-evoked glutamate release. Next, we measured development (body weight), CNS regulation of metabolism, and other indicators of generalized, non-specific brain function as well as behaviors that are reliant on behavioral control, such as impulse control and response inhibition. RESULTS/ANTICIPATED RESULTS: Eliminating Sxc was not lethal and did not impair development or produce widespread changes in brain function as is commonly observed when deleting other glutamate mechanisms. MSxc rats did not differ from wildtype in growth rate, central regulation of metabolism as reflected by absolute or diurnal changes in core body temperature, locomotor activity in a familiar or novel environment, or simple forms of cognition such as novel object recognition, or operant responding (food and cocaine-reinforced). In contrast, behaviors that rely on behavioral control were impaired. MSxc rats displayed deficits in impulse control and behavioral flexibility. We hypothesize that MSxc rats will also show deficits in response inhibition using the stop signal reaction time task, a common metric used in clinical populations. DISCUSSION/SIGNIFICANCE: Eliminating Sxc activity in rats produced deficits in behaviors reliant on impulse control, without impacting development or simple brain function. These results show the potential of targeting Sxc to restore behavioral control without generating therapeutically limiting adverse effects resulting from non-specific changes in brain function.

Excessive response to provocation rather than disinhibition mediates irritable behaviour in Huntington's disease.

Irritable and impulsive behaviour are common in Huntington's disease (HD: an autosomal dominant disorder causing degeneration in cortico-striatal networks). However, the cognitive mechanisms underlying these symptoms remain unclear, and previous research has not determined if common mechanisms underpin both symptoms. Here we used established and novel tasks to probe different aspects of irritable and impulsive behaviour to determine the neural mechanisms involved. We recruited a cohort of 53 gene positive HD participants and 26 controls from non-affected family members and local volunteers. We used established questionnaire measures of irritability in HD (Snaith Irritability Scale, Problem Behaviours Assessment) and impulsivity [Urgency, Premeditation Perseverance, Sensation-seeking, Positive urgency scale (UPPSP), Barratt Impulsivity Scale], in addition to cognitive tasks of provocation, motor inhibition, delay discounting and decision making under uncertainty. We used generalised linear models to determine differences between cases and controls, and associations with irritability in the HD group. We found differences between cases and controls on the negative urgency subscale of the UPPSP, which was associated with irritability in HD. The frustrative non-reward provocation task also showed differences between cases and controls, in addition to predicting irritability in HD. The stop signal reaction time task showed case-control differences but was not associated with irritability in HD. None of the other measures showed group differences or predicted irritability in HD after correcting for confounding variables. Irritability in HD is mediated by excessive response to provocation, rather than a failure of motor inhibition.

401 Eliminating System xc- Signaling Between Astrocytes and Neurons Selectively Impairs Complex Cognition

OBJECTIVES/GOALS: We aim to determine whether non-neuronal, non-synaptic glutamate signaling mechanisms can be targeted to produce highly specific, narrow changes in brain function that would benefit CNS disorders. To do this, we investigated cognitive changes produced through manipulating the activity of the astrocytic glutamate release mechanism system xc-. METHODS/STUDY POPULATION: System xc- (Sxc) activity was eliminated by mutating the gene Slc7a11 through pronuclear injection of zinc-finger nucleases into Sprague Dawley rat embryos to create a line of rats lacking Sxc (MSxc rats). To confirm a lack of Sxc activity, we verified that tissue from MSxc rats had a complete lack of xCT, which is the regulatory subunit of Sxc that is encoded by Slc7a11. We also verified that astrocyte cultures generated from MSxc tissue lacked cystine-evoked glutamate release. Next, we measured development (body weight), CNS regulation of metabolism, and other indicators of generalized, non-specific brain function as well as behaviors that are reliant on executive function, such as cognitive flexibility, impulse control, decision-making, and response inhibition. RESULTS/ANTICIPATED RESULTS: Eliminating Sxc was not lethal and did not impair development or produce widespread changes in brain function as is commonly observed when deleting other glutamate mechanisms. MSxc rats did not differ from wildtype in growth rate, central regulation of metabolism as reflected by absolute or diurnal changes in core body temperature, locomotor activity in a familiar or novel environment, or simple forms of cognition such as novel object recognition, or operant responding (food and cocaine-reinforced). In contrast, behaviors that rely on executive function were impaired. MSxc rats displayed deficits in cocaine reinstatement and attentional set-shifting. We anticipate MSxc rats to also show impairments in decision-making in the rat gambling task and response inhibition in the stop-signal reaction time task. DISCUSSION/SIGNIFICANCE: Eliminating Sxc activity in rats produced deficits in behaviors reliant on executive function without impacting development or simple brain function. These results highlight the potential of targeting Sxc to enhance cognition without generating therapeutically limiting adverse effects resulting from non-specific changes in brain function.

Deep brain stimulation effect on anterior pallidum reduces motor impulsivity in Parkinson's disease

BackgroundDeep Brain Stimulation (DBS) of the subthalamic nucleus or globus pallidus internus is used to treat the motor symptoms of Parkinson's disease. The former can worsen impulsive and compulsive behaviors after controlling for the reduction of dopaminergic medications. However, the effect of pallidal DBS on such behaviors in PD patients is less clear.Objective/Hypothesis: We hypothesized that greater stimulation spread to the pallidum with prefrontal connectivity would reduce motor impulsivity. MethodsSeven Parkinson's patients with stable globus pallidus internus DBS settings for 3 months, disease duration of 13 ± 1.3 years, and Montreal Cognitive Assessment of 26.8 ± 1.1 each had two stimulation settings defined based on reconstructions of lead placement and volume of tissue activation targeting either a dorsal or ventral position along the DBS electrode but still within the globus pallidus internus. Subjects performed a stop signal reaction time task with the DBS turned off vs. on in each of the defined stimulation settings, which was correlated with the degree of stimulation effect on pallidal subregions. ResultsA shorter distance between the volume of tissue activation and the right prefrontally-connected GPi correlated with less impulsivity on the stop signal reaction time task (r = 0.69, p < 0.05). Greater volume of tissue activation overlap with the non-prefrontally-connected globus pallidus internus was associated with increased impulsivity. ConclusionThese data can be leveraged to optimize DBS programming in PD patients with problematic impulsivity or in other disorders involving impulsive behaviors such as substance use disorders.

Changes in functional connectivity in people with HIV switching antiretroviral therapy

We assessed changes in functional connectivity by fMRI (functional magnetic resonance imaging) and cognitive measures in otherwise neurologically asymptomatic people with HIV (PWH) switching combination antiretroviral therapy (cART). In a prospective study (baseline and follow-up after at least 4 months), virologically suppressed PWH switched non-nuclease reverse-transcriptase inhibitors (NNRTI; tenofovir-DF/emtricitabine with efavirenz to rilpivirine) and integrase-strand-transfer inhibitors (INSTI; tenofovir-DF/emtricitabine with raltegravir to dolutegravir). PWH were assessed by resting-state fMRI and stop-signal reaction time (SSRT) task fMRI as well as with a cognitive battery (CogState™) at baseline and follow-up. Switching from efavirenz to rilpivirine (n = 10) was associated with increased functional connectivity in the dorsal attention network (DAN) and a reduction in SSRTs (p = 0.025) that positively correlated with the time previously on efavirenz (mean = 4.8 years, p = 0.02). Switching from raltegravir to dolutegravir (n = 12) was associated with increased connectivity in the left DAN and bilateral sensory-motor and associative visual networks. In the NNRTI study, significant improvements in the cognitive domains of executive function, working memory and speed of visual processing were observed, whereas no significant changes in cognitive function were observed in the INSTI study. Changes in fMRI are evident in PWH without perceived neuropsychiatric complaints switching cART. fMRI may be a useful tool in assisting to elucidate the underlying pathogenic mechanisms of cART-related neuropsychiatric effects.

The rise and fall of executive functions in high-level football players

IntroductionExecutive functions are higher-level cognitive functions. Despite being relevant to many aspects of everyday life, it is contentious whether executive functions are important for high performing athletes. Executive functions increase throughout the career of an athlete, yet it remains unknown what are the main contributors. Therefore, this study examined the effect of age and experience on executive functions in a cohort of high performing football players. MethodsData were collected over three seasons, resulting in a mixed longitudinal sample of 1018 observations in 343 male players (1–5 observations/player, age: 10.34–34.72 years; playing experience: 5–22 years) from the U12-Senior age groups of a professional German football club. Players participated in four cognitive tasks aimed at measuring higher-level cognitive functioning: a precued choice reaction-time task, a stop-signal reaction-time task, a sustained attention task, and a multiple-object tracking task, from which a total of eight dependent variables related to response time and/or accuracy were derived. ResultsLinear and non-linear mixed effects regressions were used to investigate the relationship between age, experience and executive functions. A second order polynomial revealed that, generally, a negatively accelerated curve best described the relationship between age, experience and executive functions. An increasingly smaller difference in executive functioning was generally observed between subsequent age groups, with a performance plateau evident around adulthood (~21 years old). Age and experience only explained a very low to moderate proportion of the variance in executive functions (marginal explained variance ranged between 2 and 57%). A significant age by field position interaction effect was only observed for the sustained attention task’s accuracy and response time components (p < 0.001). ConclusionsBoth age and experience showed a negatively accelerated relationship with executive functions in youth football players, and this relationship was generally field position-independent. These negatively accelerated curves seem to reflect those observed in general populations, where a plateau phase in the development of higher-level cognitive functioning is also observed around 21 years, reflecting the maturation of the central nervous system in normally developing individuals. Therefore, this study challenges the assumption surrounding the use and validity of executive functions as a measure of football performance potential in high performing athletes.

The therapeutic effect of progranulin derived Pcgin on neuronopathic Gaucher disease

Executive functions are higher-level cognitive functions. Despite being relevant to many aspects of everyday life, it is contentious whether executive functions are important for high performing athletes. Executive functions increase throughout the career of an athlete, yet it remains unknown what are the main contributors. Therefore, this study examined the effect of age and experience on executive functions in a cohort of high performing football players.Data were collected over three seasons, resulting in a mixed longitudinal sample of 1018 observations in 343 male players (1–5 observations/player, age: 10.34–34.72 years; playing experience: 5–22 years) from the U12-Senior age groups of a professional German football club. Players participated in four cognitive tasks aimed at measuring higher-level cognitive functioning: a precued choice reaction-time task, a stop-signal reaction-time task, a sustained attention task, and a multiple-object tracking task, from which a total of eight dependent variables related to response time and/or accuracy were derived.Linear and non-linear mixed effects regressions were used to investigate the relationship between age, experience and executive functions. A second order polynomial revealed that, generally, a negatively accelerated curve best described the relationship between age, experience and executive functions. An increasingly smaller difference in executive functioning was generally observed between subsequent age groups, with a performance plateau evident around adulthood (~21 years old). Age and experience only explained a very low to moderate proportion of the variance in executive functions (marginal explained variance ranged between 2 and 57%). A significant age by field position interaction effect was only observed for the sustained attention task’s accuracy and response time components (p < 0.001).Both age and experience showed a negatively accelerated relationship with executive functions in youth football players, and this relationship was generally field position-independent. These negatively accelerated curves seem to reflect those observed in general populations, where a plateau phase in the development of higher-level cognitive functioning is also observed around 21 years, reflecting the maturation of the central nervous system in normally developing individuals. Therefore, this study challenges the assumption surrounding the use and validity of executive functions as a measure of football performance potential in high performing athletes.

Age-Related Differences in Executive Functions Within High-Level Youth Soccer Players

Background: When measuring executive functions (EF), it is common for athletes to be assessed on their ability to detect and process explicit sources of information. Yet not all of the information is perceived explicitly in an environment. Aim: This study aimed to include a new assessment that measures the impact of implicitly perceived congruent and incongruent visual precues on response times. Method: Seventy-four male soccer players: U12 (n=15), U13 (n=17), U17 (n=21) and U19 (n=21) representing a German 1st league club were assessed on four cognitive tasks. Results: The MANOVAs revealed a multivariate effect of age group on a reactive stress tolerance task (F(6,140)=11.670, p&lt;0.001, ES=0.38) and a Stop Signal Reaction Time task (F(6,144)=6.142, p&lt;0.001, ES=0.20). A one-way ANOVA revealed an age group effect for response accuracy in a multiple-object-tracking task (F(3,74)=4.05, p=0.01, ES=0.14). Lastly, a within-subjects effect of congruency on the implicit precued task (F(1,74)=51.32, p&lt;0.001, ES=0.41) and a between-subjects effect of age group (F(3,74)=4.30, p=0.008, ES=0.15) was observed. Interpretation: The results provided support for including an implicit precueing task, while the overall testing demonstrated that the magnitude of the increase in EF performance between ages was greater across the younger age groups compared to the older age groups.&#x0D;

L-theanine and Caffeine Improve Sustained Attention, Impulsivity and Cognition in Children with Attention Deficit Hyperactivity Disorders by Decreasing Mind Wandering (OR29-04-19)

ObjectivesOur previous research corroborate the work of others to indicate that L-theanine and caffeine are known to improve sustained attention in healthy adults. The effects of these substances have not been studied in relation to attention deficit hyperactivity disorders (ADHD). We aimed to examine the effects of L-theanine, caffeine and their combination on sustained attention, impulse control and overall cognition in male children with ADHD in a four-way, placebo-controlled repeated measures crossover study. MethodsFive male children (8–17) years with ADHD, who have responded to stimulants were recruited via advertisement. L-theanine (2.5 mg/kg body weight), caffeine (2.0 mg/kg body weight), their combination and a placebo were administered in a randomized crossover design on four separate days. Functional magnetic resonance imaging (fMRI) was performed 55 minutes post-dose, while the subjects engaged in a Go/NoGo continuous performance task (CPT) and a stop-signal reaction time (SSRT) task. NIH Cognition Toolbox was administered 110 minutes post-dose. Data were analyzed using two-level regression models constructed using R and FSL software to compare the three treatments vs. the placebo on all measured outcomes. ResultsL-theanine, caffeine and their combination improved hit rate in CPT (p < 0.001) and total cognition composite in NIH Cognition Toolbox (p < 0.05) compared to placebo. L-theanine and caffeine, when administered alone, increased SSRT (p = 0.007 and p = 0.018 respectively), while the combination decreased SSRT compared to placebo (p = 0.012). L-theanine, caffeine and the combination decreased task-related fMRI reactivity of the default mode network in the brain, which is known to show increased activity during mind wandering. ConclusionsL-theanine, caffeine and their combination seem to improve sustained attention and overall cognitive performance in children with ADHD, possibly via decreasing mind wandering during exertion of attention. While L-theanine alone and caffeine alone seem to increase impulsivity, the combination seems to decrease (i.e., improve) impulsivity in children with ADHD. As such, the combination of L-theanine and caffeine may have the potential to be used as a therapeutic and/or dose sparing agent to manage symptoms in children with ADHD. Funding SourcesTexas Tech Neuroimaging Institute.

Prader-Willi syndrome imprinting centre deletion mice have impaired baseline and 5-HT2CR-mediated response inhibition.

Prader–Willi syndrome (PWS) is a neurodevelopmental disorder caused by deletion or inactivation of paternally expressed imprinted genes on human chromosome 15q11–q13. In addition to endocrine and developmental issues, PWS presents with behavioural problems including stereotyped behaviour, impulsiveness and cognitive deficits. The PWS genetic interval contains several brain-expressed small nucleolar (sno) RNA species that are subject to genomic imprinting, including snord115 that negatively regulates post-transcriptional modification of the serotonin 2C receptor (5-HT2CR) pre-mRNA potentially leading to a reduction in 5-HT2CR function. Using the imprinting centre deletion mouse model for PWS (PWSICdel) we have previously shown impairments in a number of behaviours, some of which are abnormally sensitive to 5-HT2CR-selective drugs. In the stop-signal reaction time task test of impulsivity, PWSICdel mice showed increased impulsivity relative to wild-type (WT) littermates. Challenge with the selective 5-HT2CR agonist WAY163909 reduced impulsivity in PWSICdel mice but had no effect on WT behaviour. This behavioural dissociation in was also reflected in differential patterns of immunoreactivity of the immediate early gene c-Fos, with a blunted response to the drug in the orbitofrontal cortex of PWSICdel mice, but no difference in c-Fos activation in the nucleus accumbens. These findings suggest specific facets of response inhibition are impaired in PWSICdel mice and that abnormal 5-HT2CR function may mediate this dissociation. These data have implications for our understanding of the aetiology of PWS-related behavioural traits and translational relevance for individuals with PWS who may seek to control appetite with the new obesity treatment 5-HT2CR agonist lorcaserin.

Mindfulness-Based Relapse Prevention and Transcranial Direct Current Stimulation to Reduce Heavy Drinking: A Double-Blind Sham-Controlled Randomized Trial.

Mindfulness-based relapse prevention (MBRP) and transcranial direct current stimulation (tDCS) have independently shown benefits for treating alcohol use disorder (AUD). Recent work suggests tDCS may enhance mindfulness. The combination of MBRP and tDCS may provide synergistic benefits and may target both behavioral and neurobiological dysfunctions in AUD. The goal of this double-blind sham-controlled randomized trial was to examine the efficacy of a rolling group MBRP treatment combined with tDCS among individuals interested in reducing their drinking. Individuals who were interested in reducing their alcohol use (n=84; 40.5% female; mean age=52.3; 98.9% with current AUD) were randomized to receive active (2.0 milliamps) or sham (0.0 milliamps) anodal tDCS (5cm×3cm electrode) of the right inferior frontal gyrus with the 5cm×3cm cathodal electrode applied to the left upper arm, combined with 8weeks of outpatient MBRP rolling group treatment. Assessments were conducted at baseline, posttreatment, and 2months following treatment. The primary outcome was drinks per drinking day, and secondary outcomes were percent heavy drinking days, self-reported craving, alcohol cue reactivity in an alcohol cue task, and response inhibition in a stop signal reaction time task. Results indicated significant reductions in drinks per drinking day over time, B(SE)=-0.535 (0.16), p=0.001, and a significant dose effect for number of groups attended, B(SE)=-0.259 (0.11), p=0.01. There were also significant effects of time and dose for number of groups attended on secondary outcomes of percent heavy drinking days and alcohol cue reactivity. There were no effects of active versus sham tDCS on primary or secondary outcomes. Findings from the current study provide initial support for the effectiveness of rolling group MBRP as an outpatient treatment for drinking reduction. The current study did not find additive effects of this tDCS protocol in enhancing MBRP among individuals with drinking reduction goals.

The orexin-1 receptor antagonist SB-334867 reduces motivation, but not inhibitory control, in a rat stop signal task

There is considerable clinical interest in the neuropeptide orexin/hypocretin for its ability to regulate motivation and reward as well as arousal and wakefulness. For instance, antagonists for the orexin-1 receptor (OxR1) are thought to hold great promise for treating drug addiction and disorders associated with overeating, as these compounds repeatedly have been found to suppress seeking of various drugs of abuse as well as highly palatable foods in preclinical models. Given the hypothesized role of OxR1 signaling in cue-driven motivation, an outstanding question is whether pharmacologically blocking this receptor affects cognitive functioning. Response inhibition – the ability to cancel ongoing behavior – is one aspect of cognitive control that may be particularly relevant. Response inhibition deficits are commonly associated with a range of psychiatric disorders and neurological diseases, including substance use disorders and obesity. Moreover, OxR1 signaling recently has been implicated in waiting impulsivity, another aspect of inhibitory control. Here, we investigated the effects of the OxR1 antagonist SB-334867 on response inhibition in a rat version of the stop-signal reaction time task. Results show that acutely blocking OxR1 had minimal effects on response inhibition or attentional functioning. In contrast, this manipulation reduced motivation to perform the task and earn food rewards, consistent with other recent findings. These results add to the growing body of literature implicating OxR1 in the regulation of motivation and suggest that effects of pharmacological compounds such as SB-334867 on drug-seeking behavior are not related to effects on response inhibition.

Effects of amphetamine, methylphenidate, atomoxetine, and morphine in rats responding under an adjusting stop signal reaction time task

Stop signal reaction time procedures are used to investigate behavioral and neurobiological processes that contribute to behavioral inhibition and to evaluate potential therapeutics for disorders characterized by disinhibition and impulsivity. The current study examined effects of amphetamine, methylphenidate, atomoxetine, and morphine in rats responding under an adjusting stop signal reaction time task that measures behavioral inhibition, as well as motor impulsivity. Rats (n = 8) completed a two-response sequence to earn food. During most trials, responses following presentation of a visual stimulus (go signal) delivered food. Occasionally, a tone (stop signal) was presented signifying that food would be presented only if the second response was withheld. Responding after the stop signal measured inhibition and responding prior to the start of the trial (premature) measured motor impulsivity. Delay to presentation of the stop signal was adjusted for individual subjects based on performance. Amphetamine and methylphenidate increased responding after presentation of the stop signal and markedly increased premature responding. Atomoxetine modestly improved accuracy on stop trials and decreased premature responding. Morphine did not alter stop trial accuracy or premature responding up to doses that decreased the number of trials initiated. These data demonstrate the sensitivity of an adjusting stop signal reaction time task to a range of drug effects and shows that some drugs that enhance dopaminergic transmission, such as amphetamine, can differentially alter various types of impulsive behavior.

Effects of daily morphine treatment on impulsivity in rats responding under an adjusting stop-signal reaction time task.

Opioids can enhance delay discounting and premature responding under attentional tasks that might reflect increased impulsivity; although it is not clear whether repeated opioid administration alters behavioral inhibition. Effects of morphine and amphetamine were determined before, during, and after daily morphine administration in rats responding under a stop-signal reaction time task, measuring behavioral inhibition and motor impulsivity. Rats (n=5) completed a two-response sequence to earn food. Occasionally, a tone (stop signal) was presented signifying that food would only be presented if the second response was withheld. Responding after the stop signal measured inhibition, and responding before the start of the trial (premature) measured motor impulsivity. Before daily treatment, morphine (0.32-17.8 mg/kg, intraperitoneally) decreased premature responding but did not increase responding on stop trials, whereas amphetamine (0.1-3.2 mg/kg, intraperitoneally) increased premature responding. Daily morphine administration (3.2 mg/kg/day) enhanced its effects on premature responding but did not impact other effects. Daily morphine treatment diminished the effects of amphetamine on premature and timeout responding. Repeated morphine treatment increased motor impulsivity but did not enhance behavioral inhibition. These data add to studies elucidating the relationship between impulsivity and opioid treatment and suggest that opioids differentially impact impulsive behaviors.

Response inhibition in patients with functional neurological symptom disorder

Abnormal response inhibition has been demonstrated in psychogenic movement disorders (PMD) and is a plausible mechanism for other forms of functional neurological symptom disorder (FNSD), in which response inhibition has not yet been investigated. Response inhibition was therefore studied in patients with FNSD, including patients with psychogenic non-epileptic seizures (PNES), functional weakness (FW) or both. Twenty-nine patients with FNSD and 29 age and sex-matched healthy volunteers underwent a go-nogo task, a stop-signal reaction time (SSRT) task, and a negative priming flanker task. The Attentional Resource Allocation Scale, the Beck Depression Inventory and the Spielberger State and Trait Anxiety Inventory were also administered. Mean hit rates on nogo trials, miss rates on go signals and discriminability index were higher and go signal reaction times were significantly longer in the FNSD group than in healthy controls. The presence of FW was associated with increased hit rates on nogo trials, suggesting a bias toward responding to nogo signals rather than missed go signals. SSRT and negative priming were not significantly different from healthy controls. It is unclear whether impaired performance on the go-nogo task reflects dysfunctional inhibitory processes, disordered attention, or impaired ability to discriminate between stimuli.

Electrophysiological indicators of inhibitory control deficits in depression

Ample evidence from behavioral and brain imaging studies suggests that inhibitory control is impaired in depression, though the precise nature of this impairment is unclear. The purpose of the present study was to examine potential deficits in three aspects of inhibitory control – conflict monitoring, conflict resolution, and overt behavioral inhibition – in the context of depressive symptoms. Depressed (n=15) and non-depressed (n=15) participants completed a stop-signal reaction time (SSRT) task while electroencephalography (EEG) data were recorded. EEG results indicate that depression impacts only the conflict resolution phase of inhibitory control, with higher levels of depressive and reflective pondering symptoms associated with poorer conflict resolution. Findings have clear implications for treatments of depression, many of which do not currently target the inhibitory control deficits present in this disorder.

Impairment of manual but not saccadic response inhibition following acute alcohol intoxication

BackgroundAlcohol impairs response inhibition; however, it remains contested whether such impairments affect a general inhibition system, or whether affected inhibition systems are embedded in, and specific to, each response modality. Further, alcohol-induced impairments have not been disambiguated between proactive and reactive inhibition mechanisms, and nor have the contributions of action-updating impairments to behavioural ‘inhibition’ deficits been investigated. MethodsForty Participants (25 female) completed both a manual and a saccadic stop-signal reaction time (SSRT) task before and after a 0.8g/kg dose of alcohol and, on a separate day, before and after a placebo. Blocks in which participants were required to ignore the signal to stop or make an additional ‘dual' response were included to obtain measures of proactive inhibition as well as updating of attention and action. ResultsAlcohol increased manual but not saccadic SSRT. Proactive inhibition was weakly reduced by alcohol, but increases in the reaction times used to baseline this contrast prevent clear conclusions regarding response caution. Finally, alcohol also increased secondary dual response times of the dual task uniformly as a function of the delay between tasks, indicating an effect of alcohol on action-updating or execution. ConclusionsThe modality-specific effects of alcohol favour the theory that response inhibition systems are embedded within response modalities, rather than there existing a general inhibition system. Concerning alcohol, saccadic control appears relatively more immune to disruption than manual control, even though alcohol affects saccadic latency and velocity. Within the manual domain, alcohol affects multiple types of action updating, not just inhibition.

Cross-species studies of cognition relevant to drug discovery: a translational approach.

This review advances the case that bidirectional, cross-species translation of findings from experimental animals to and from humans is an important strategy for drug discovery. Animal models of mental disorders require appropriate behavioural or cognitive outcome variables that can be generalized cross-species. One example is the treatment of impulsive behaviour in attention deficit hyperactivity disorder (ADHD) with stimulant drugs. Performance on the stop signal reaction task as an index of impulsivity is improved both in healthy human volunteers and in patients with adult ADHD by stimulant drugs and also by the selective noradrenaline reuptake blocker atomoxetine. Functional neuroimaging evidence suggests a modulation of circuitry including the inferior prefrontal cortex by this drug. Parallel work in rats had shown that atomoxetine improves stop signal performance by affecting possibly homologous regions of the rodent prefrontal cortex. This parallel effect of atomoxetine in rodents and humans could potentially be exploited in other disorders in which impulsivity plays a role, such as stimulant abuse and Parkinson's disease. A contrasting relative lack of involvement of 5-HT mechanisms in the stop signal reaction time task will also be described. Research in humans and experimental animals that demonstrate effects of serotoninergic agents such as the selective serotonin (5-HT) reuptake inhibitor citalopram on probabilistic learning and reversal (upon which atomoxetine has little effect) will also be reviewed, possibly relevant to the treatment of clinical depression, Finally, other promising examples of parallel studies of behavioural effects of CNS-active drugs in animals and humans will also be described. Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc.