Effects of quinpirole in the ventral tegmental area on impulsive behaviour during performance on the five-choice serial reaction time task.

Impulsive behaviour on the five-choice serial reaction time task (5CSRTT), a task measuring attention and impulsivity in rodents, is known to depend on dopamine (DA) neurotransmission in the mesolimbic DA pathway. Previous research in our lab reported that systemic administration of the D2/3 agonist quinpirole, which decreases DA release in the striatum, reduced premature responses in rats performing the 5CSRTT. It is unclear, however, whether this effect is mediated by the activation of inhibitory somatodendritic receptors in the ventral tegmental area (VTA), which in turn leads to a reduction in DA release in the nucleus accumbens, a major terminal region of the mesolimbic DA pathway. In the present study, we investigated this possibility by infusing quinpirole directly into the VTA of rats during performance on the 5CSRTT. We found that quinpirole, at the highest dose, significantly reduced the frequency of premature responses on the 5CSRTT. Thus, the effects of quinpirole and other D2/3 receptor agonists to reduce this form of impulsive behaviour appear to depend on the activation of somatodendritic D2/3 receptors in the VTA.

Time-Dependent Effects of Buspirone versus Desipramine on the 5-Choice Serial Reaction Time Task in Rats Reared in Social Isolation: Implication of Early Life Experience and Motoric Impulsivity.

BACKGROUND: Early life social experience and the function of the central serotonin (5-Hydroxytryptophan, 5-HT) system are involved in development of behavioral impulsivity in which individuals act without forethought or before all necessary information is available. However, most of the evidence has been obtained from acute 5-HT manipulation, whereas, the present study aimed to investigate the effects of subchronic regimen targeting of 5-HT1A receptors on motoric waiting impulsivity in socially isolated rats. METHODS: A two-week protocol of buspirone (0.5 mg/kg/day) and desipramine (2.5 mg/kg/day) was employed for rats following social isolation rearing (IR) to examine their behavioral performance in a 5-choice serial reaction time task (5-CSRTT) during the treatment regimen. Responses in any one of the apertures prior to an informative signal were recorded as a premature response. RESULTS: IR rats presented with more locomotor activity than socially reared (SR) rats. Buspirone progressively increased the baseline level of premature responding in a time-dependent manner that was not observed in IR rats. Both IR and SR rats exhibited less premature responding following acute buspirone challenge. For a subchronic desipramine regimen, IR rats followed the same trend of SR controls to increase the prematurity of baseline response. CONCLUSIONS: Buspirone but not desipramine-induced time-dependent effects of motoric waiting impulsivity can be reversed by IR, indicating a role for early life social experience on 5-HT1A receptor-associated ability to control impulsiveness.

Tailoring transcranial alternating current stimulation based on endogenous event-related P3 to modulate premature responses: a feasibility study.

Background: Transcranial alternating current stimulation (tACS) is a brain stimulation method for modulating ongoing endogenous oscillatory activity at specified frequency during sensory and cognitive processes. Given the overlap between event-related potentials (ERPs) and event-related oscillations (EROs), ERPs can be studied as putative biomarkers of the effects of tACS in the brain during cognitive/sensory task performance. Objective: This preliminary study aimed to test the feasibility of individually tailored tACS based on individual P3 (latency and frequency) elicited during a cued premature response task. Thus, tACS frequency was individually tailored to match target-P3 ERO for each participant. Likewise, the target onset in the task was adjusted to match the tACS phase and target-P3 latency. Methods: Twelve healthy volunteers underwent tACS in two separate sessions while performing a premature response task. Target-P3 latency and ERO were calculated in a baseline block during the first session to allow a posterior synchronization between the tACS and the endogenous oscillatory activity. The cue and target-P3 amplitudes, delta/theta ERO, and power spectral density (PSD) were evaluated pre and post-tACS blocks. Results: Target-P3 amplitude significantly increased after activetACS, when compared to sham. Evoked-delta during cue-P3 was decreased after tACS. No effects were found for delta ERO during target-P3 nor for the PSD and behavioral outcomes. Conclusion: The present findings highlight the possible effect of phase synchronization between individualized tACS parameters and endogenous oscillatory activity, which may result in an enhancement of the underlying process (i.e., an increase of target-P3). However, an unsuccessful synchronization between tACS and EEG activity might also result in a decrease in the evoked-delta activity during cue-P3. Further studies are needed to optimize the parameters of endogenous activity and tACS synchronization. The implications of the current results for future studies, including clinical studies, are further discussed since transcranial alternating current stimulation can be individually tailored based on endogenous event-related P3 to modulate responses.

Transcranial Direct Current Stimulation Decreases P3 Amplitude and Inherent Delta Activity during a Waiting Impulsivity Paradigm: Crossover Study.

The inability to wait for a target before initiating an action (i.e., waiting impulsivity) is one of the main features of addictive behaviors. Current interventions for addiction, such as transcranial Direct Current Stimulation (tDCS), have been suggested to improve this inability. Nonetheless, the effects of tDCS on waiting impulsivity and underlying electrophysiological (EEG) markers are still not clear. Therefore, this study aimed to evaluate the effects of neuromodulation over the right inferior frontal gyrus (rIFG) on the behavior and EEG markers of reward anticipation (i.e., cue and target-P3 and underlying delta/theta power) during a premature responding task. For that, forty healthy subjects participated in two experimental sessions, where they received active and sham tDCS over the rIFG combined with EEG recording during the task. To evaluate transfer effects, participants also performed two control tasks to assess delay discounting and motor inhibition. The active tDCS decreased the cue-P3 and target-P3 amplitudes, as well as delta power during target-P3. While no tDCS effects were found for motor inhibition, active tDCS increased the discounting of future rewards when compared to sham. These findings suggest a tDCS-induced modulation of the P3 component and underlying oscillatory activity during waiting impulsivity and the discounting of future rewards.

Waiting impulsivity in progressive supranuclear palsy-Richardson's syndrome.

Background: Waiting impulsivity in progressive supranuclear palsy-Richardson's syndrome (PSP-RS) is difficult to assess, and its regulation is known to involve nucleus accumbens (NAc) subregions. We investigated waiting impulsivity using the "jumping the gun" (JTG) sign, which is defined as premature initiation of clapping before the start signal in the three-clap test and compared clinical features of PSP-RS patients with and without the sign and analyzed neural connectivity and microstructural changes in NAc subregions. Materials and methods: A positive JTG sign was defined as the participant starting to clap before the start sign in the three-clap test. We classified participants into the JTG positive (JTG +) and JTG negative (JTG-) groups and compared their clinical features, microstructural changes, and connectivity between NAc subregions using diffusion tension imaging. The NAc was parcellated into core and shell subregions using data-driven connectivity-based methods. Results: Seventy-seven patients with PSP-RS were recruited, and the JTG + group had worse frontal lobe battery (FAB) scores, more frequent falls, and more occurrence of the applause sign than the JTG- group. A logistic regression analysis revealed that FAB scores were associated with a positive JTG sign. The mean fiber density between the right NAc core and right medial orbitofrontal gyrus was higher in the JTG + group than the JTG- group. Discussion: We show that the JTG sign is a surrogate marker of waiting impulsivity in PSP-RS patients. Our findings enrich the current literature by deepening our understanding of waiting impulsivity in PSP patients and introducing a novel method for its evaluation.

ImGo: A Novel Tool for Behavioral Impulsivity Assessment Based on Go/NoGo Tasks.

This manuscript aims to present a novel behavioral impulsivity test ImGo, which is suitable for impulsivity assessment in the general population. A series of three studies was conducted to validate its psychometric qualities. In Study 1 we describe the principles of ImGo and verify its test-retest and split-half reliability and its convergent validity with an impulsivity self-report scale and Stop Signal test. In Study 2 we re-analyze the convergent validity of ImGo with a Stop Signal test and examine the potential relationship between ImGo and oculomotor inhibition measured by an Anti-Saccades test. In Study 3 we present a robust research with a large sample size and investigate the discriminant validity of ImGo with tests of other related cognitive and executive processes. Backed by our findings from these studies we can safely claim ImGo is a powerful tool with a good level of reliability (both test-retest and split-half) and validity (convergent and discriminant). Its potential lies in its use in diagnostic and research practice of experts from various countries as the test has already been translated to 9 languages so far. The open-source Hypothesis platform, on which the ImGo test is running, provides the option of both individual and group testing in laboratory conditions as well as remotely through an internet browser.

Preconception paternal morphine exposure leads to an impulsive phenotype in male rat progeny.

RATIONALE: Identifying the long-term neurocognitive implications of opioid addiction may further our understanding of the compulsive nature of this brain disorder. The aim of this study was to examine the effects of paternal adolescent opiate exposure on cognitive performance (visual attention, impulsivity, and compulsivity) in the next generation. METHODS: Male Wistar rats received escalating doses of morphine (2.5-25 mg/kg, s.c.) or saline for 10 days during adolescence (P30-39). In adulthood (P70-80), these rats were allowed to mate with drug-naive females. Male offspring from morphine- and saline-exposed sires, once in adulthood, were trained and tested in the 5-choice serial reaction time test (5-CSRTT) to evaluate their cognitive abilities under baseline, drug-free conditions as well as following acute (1, 3, 5 mg/kg morphine) and subchronic morphine (5 mg/kg morphine for 5 days) treatment. Behavioral effects of the opioid receptor antagonist naloxone were also assessed. RESULTS: Morphine-sired offspring exhibited delayed learning when the shortest stimulus duration (1 s) was introduced, i.e., when cognitive load was highest. These subjects also exhibited a reduced ability to exert inhibitory control, as reflected by increased premature and perseverative responding under drug-free baseline conditions in comparison to saline-sired rats. These impairments could not be reversed by administration of naloxone. Moreover, impulsive behavior was further enhanced in morphine-sired rats following acute and subchronic morphine treatment. CONCLUSION: Paternal opiate exposure during adolescence was found to primarily impair inhibitory control in male progeny. These results further our understanding of the long-term costs and risk of opioid abuse, extending across generations.

Are hazardous drinkers more impulsive than light drinkers? A comprehensive assessment in young adults.

Those with alcohol dependence are characteristically impulsive. It is unclear whether the same is true of hazardous drinkers (i.e., women routinely drinking more than 14 units in a typical week but fewer than 35, and men drinking more than 14 units but fewer than 50). Yet, it is important to understand the mechanisms involved in such drinking, since it places the drinker at risk for future harm. The present study thus comprehensively assessed whether impulsivity was elevated in hazardous drinkers, compared to lighter drinkers. An opportunity sample of 57 light and 49 hazardous drinkers was assessed on the following impulsivity subdomains (via the measures in parentheses): (i) trait impulsivity (the Barratt Impulsiveness Scale, Version 11); (ii) temporal impulsivity (the Monetary Choice Questionnaire); (iii) stopping impulsivity (the Stop-Signal Task); (iv) waiting impulsivity (the Continuous Performance Task or CPT); (v) reward-sensitivity (the Behavioural Activation Scales); and (vi) risk-taking (the Balloon Analogue Risk Task). Alcohol- and other drug-dependent individuals were excluded from the study, while socio-demographics (age, gender, and socio-economic status), mood, binge drinking, and nicotine intake were all controlled for. The groups were compared via a series of Bonferroni-corrected, independent-measures t tests. The results revealed that hazardous drinkers were more impulsive than light drinkers on the CPT; there were no other statistically significant group differences. Consistent with the above, a logistic regression, with drinking group as the dependent variable and the impulsivity indices as independent variables, revealed that only CPT performance was a significant predictor of drinking status. Other than gender, none of the control variables significantly correlated with CPT performance. A sequential linear regression revealed that drinking status continued to predict CPT performance, after first accounting for gender. Thus, from a battery of impulsivity measures, only waiting impulsivity (i.e., CPT score) was elevated in hazardous drinkers, relative to lighter drinkers. Waiting impulsivity may thus be important in the maintenance of hazardous drinking.

Waiting impulsivity: a distinctive feature of ADHD neuropsychology?

Impulsivity is a core feature of attention-deficit hyperactivity disorder (ADHD). It has been conceptualized in a number of different ways. In the current article, we examine how the new concept of "waiting impulsivity", which refers to premature responding before a scheduled target appears, adds to our understanding of impulsivity in ADHD. Sixty children (8-12 years old; 30 ADHD; 30 typically developing controls) completed the 4-choice serial reaction time task, a measure of waiting impulsivity, alongside tasks measuring inhibitory control and temporal discounting and questionnaires measuring behavioral disorder symptoms, delay aversion, and various aspects of impulsivity. A multiple logistic regression model was used to explore the contribution of the primary task outcomes to predict group membership. Children with ADHD displayed more waiting impulsivity and less inhibitory control; they did not differ in temporal discounting. There was no correlation between waiting impulsivity and inhibitory control. Waiting impulsivity was correlated with parent-reported ratings of hyperactivity/impulsivity, inattention, oppositional defiant disorder (ODD), and conduct disorder (CD) and with self-reported delay aversion ratings. Only waiting impulsivity was a significant predictor of ADHD status. In conclusion, waiting impulsivity is distinct from inhibitory control deficits and predicts ADHD status independently of it. Future research needs to examine the relationship with delay aversion and ODD/CD more thoroughly.

Models of Impulsivity with a Focus on Waiting Impulsivity: Translational Potential for Neuropsychiatric Disorders.

Waiting impulsivity, also known as premature or anticipatory responding, is well established in preclinical studies through the 5-Choice Serial Reaction Time (5-CSRT) task. Waiting impulsivity is important in disorders of addiction. Preclinical studies suggest a role both as a predictor, and as a consequence, in disorders of addiction. Here we discuss the relationship between the preclinical 5-CSRT and translational fidelity in newly developed translational tasks. Preclinical and clinical literature relevant to premature responding and disorders of addiction are reviewed. Understanding which processes are critical to premature responding is important in understanding the nature of premature responding. Premature responding may also have overlaps with motivational processes, proactive response inhibition, tonic inhibitory processes, and delay discounting.