Browsing by Subject "Delay discounting"

Now showing 1 - 5 of 5
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    Delay Discounting in At-Risk Preadolescents: Brain Mechanisms and Behavior
    (2021-12) Butcher, Tarah J; Oberlin, Brandon; Lapish, Christopher; Hulvershorn, Leslie
    It is well documented that adolescent substance use is associated with deficits in brain function and behavior. However, possible deficits that predate substance use initiation remain poorly characterized in preadolescents at-risk for developing substance use disorder (SUD). To characterize potential brain and behavioral differences that predate substance use, substance naïve preadolescents, ages 11–12, were recruited into three groups to complete functional magnetic resonance imaging delay discounting: (1) High-risk youth (n=35) with a family history of SUD and externalizing psychiatric disorders, (2) psychiatric controls (n=35) with no family history of SUD, but equivalent externalizing psychiatric disorders as high-risk youth, and (3) healthy controls (n=29) with no family history of SUD and minimal psychopathology. While no behavioral differences between groups were identified, there were group differences in posterior cingulate cortex (PCC) function during decision making. Specifically, the high-risk group showed stronger deactivation of the PCC than healthy controls. These results suggest that high-risk preadolescents may need to suppress activity of key nodes of the default mode network (a task negative network) to a greater extent to properly allocate attention to the task.
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    Guanfacine treatment improves ADHD phenotypes of impulsivity and hyperactivity in a neurofibromatosis type 1 mouse model
    (BMC, 2020-01-15) Lukkes, J. L.; Drozd, H. P.; Fitz, S. D.; Molosh, A. I.; Clapp, D. W.; Shekhar, A.; Psychiatry, School of Medicine
    BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a mutation in one copy of the neurofibromin gene (NF1+/-). Even though approximately 40-60% of children with NF1 meet the criteria for attention deficit hyperactivity disorder (ADHD), very few preclinical studies, if any, have investigated alterations in impulsivity and risk-taking behavior. Mice with deletion of a single NF1 gene (Nf1+/-) recapitulate many of the phenotypes of NF1 patients. METHODS: We compared wild-type (WT) and Nf1+/- mouse strains to investigate differences in impulsivity and hyperactivity using the delay discounting task (DDT), cliff avoidance reaction (CAR) test, and open field. We also investigated whether treatment with the clinically effective alpha-2A adrenergic receptor agonist, guanfacine (0.3 mg/kg, i.p.), would reverse deficits observed in behavioral inhibition. RESULTS: Nf1+/- mice chose a higher percentage of smaller rewards when both 10- and 20-s delays were administered compared to WT mice, suggesting Nf1+/- mice are more impulsive. When treated with guanfacine (0.3 mg/kg, i.p.), Nf1+/- mice exhibited decreased impulsive choice by waiting for the larger, delayed reward. Nf1+/- mice also exhibited deficits in behavioral inhibition compared to WT mice in the CAR test by repetitively entering the outer edge of the platform where they risk falling. Treatment with guanfacine ameliorated these deficits. In addition, Nf1+/- mice exhibited hyperactivity as increased distance was traveled compared to WT controls in the open field. This hyperactivity in Nf1+/- mice was reduced with guanfacine pre-treatment. CONCLUSIONS: Overall, our study confirms that Nf1+/- mice exhibit deficits in behavioral inhibition in multiple contexts, a key feature of ADHD, and can be used as a model system to identify alterations in neural circuitry associated with symptoms of ADHD in children with NF1.
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    Impulsivity in rodents with a genetic predisposition for excessive alcohol consumption is associated with a lack of a prospective strategy
    (Springer, 2017-04) Linsenbardt, David N.; Smoker, Michael P.; Janetsian-Fritz, Sarine S.; Lapish, Christopher C.; Psychology, School of Science
    Increasing evidence supports the hypothesis that impulsive decision-making is a heritable risk factor for an alcohol use disorder (AUD). Clearly identifying a link between impulsivity and AUD risk, however, is complicated by the fact that both AUDs and impulsivity are heterogeneous constructs. Understanding the link between the two requires identifying the underlying cognitive factors that lead to impulsive choices. Rodent models have established that a family history of excessive drinking can lead to the expression of a transgenerational impulsive phenotype, suggesting heritable alterations in the decision-making process. In the present study, we explored the cognitive processes underlying impulsive choice in a validated, selectively bred rodent model of excessive drinking-the alcohol-preferring ("P") rat. Impulsivity was measured via delay discounting (DD), and P rats exhibited an impulsive phenotype as compared to their outbred foundation strain-Wistar rats. Steeper discounting in P rats was associated with a lack of a prospective behavioral strategy, which was observed in Wistar rats and was directly related to DD. To further explore the underlying cognitive factors mediating these observations, a drift diffusion model of DD was constructed. These simulations supported the hypothesis that prospective memory of the delayed reward guided choice decisions, slowed discounting, and optimized the fit of the model to the experimental data. Collectively, these data suggest that a deficit in forming or maintaining a prospective behavioral plan is a critical intermediary to delaying reward, and by extension, may underlie the inability to delay reward in those with increased AUD risk.
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    Integrating Preclinical and Clinical Models of Negative Urgency
    (Frontiers, 2019-05-23) Halcomb, Meredith; Argyriou, Evangelia; Cyders, Melissa A.; Radiology and Imaging Sciences, School of Medicine
    Overwhelming evidence suggests that negative urgency is robustly associated with rash, ill-advised behavior, and this trait may hamper attempts to treat patients with substance use disorder. Research applying negative urgency to clinical treatment settings has been limited, in part, due to the absence of an objective, behavioral, and translational model of negative urgency. We suggest that development of such a model will allow for determination of prime neurological and physiological treatment targets, the testing of treatment effectiveness in the preclinical and the clinical laboratory, and, ultimately, improvement in negative-urgency-related treatment response and effectiveness. In the current paper, we review the literature on measurement of negative urgency and discuss limitations of current attempts to assess this trait in human models. Then, we review the limited research on animal models of negative urgency and make suggestions for some promising models that could lead to a translational measurement model. Finally, we discuss the importance of applying objective, behavioral, and translational models of negative urgency, especially those that are easily administered in both animals and humans, to treatment development and testing and make suggestions on necessary future work in this field. Given that negative urgency is a transdiagnostic risk factor that impedes treatment success, the impact of this work could be large in reducing client suffering and societal costs.
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    Resting-state EEG, impulsiveness, and personality in daily and nondaily smokers
    (Elsevier, 2016-01) Rass, Olga; Ahn, Woo-Young; O'Donnell, Brian F.; Department of Psychiatry, IU School of Medicine
    OBJECTIVES: Resting EEG is sensitive to transient, acute effects of nicotine administration and abstinence, but the chronic effects of smoking on EEG are poorly characterized. This study measures the resting EEG profile of chronic smokers in a non-deprived, non-peak state to test whether differences in smoking behavior and personality traits affect pharmaco-EEG response. METHODS: Resting EEG, impulsiveness, and personality measures were collected from daily smokers (n=22), nondaily smokers (n=31), and non-smokers (n=30). RESULTS: Daily smokers had reduced resting delta and alpha EEG power and higher impulsiveness (Barratt Impulsiveness Scale) compared to nondaily smokers and non-smokers. Both daily and nondaily smokers discounted delayed rewards more steeply, reported lower conscientiousness (NEO-FFI), and reported greater disinhibition and experience seeking (Sensation Seeking Scale) than non-smokers. Nondaily smokers reported greater sensory hedonia than nonsmokers. CONCLUSIONS: Altered resting EEG power in daily smokers demonstrates differences in neural signaling that correlated with greater smoking behavior and dependence. Although nondaily smokers share some characteristics with daily smokers that may predict smoking initiation and maintenance, they differ on measures of impulsiveness and resting EEG power. SIGNIFICANCE: Resting EEG in non-deprived chronic smokers provides a standard for comparison to peak and trough nicotine states and may serve as a biomarker for nicotine dependence, relapse risk, and recovery.