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"Choice Behavior."
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Role of Dopamine D2 Receptors in Human Reinforcement Learning
Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well.
Journal Article
Baseline impulsivity may moderate L-DOPA effects on value-based decision-making
Research has indicated a major role of dopamine in decision-making processes, but the underlying mechanisms remain largely unknown due to inconsistency in effects of dopaminergic drugs. To clarify the impact of dopamine on impulsive choice, we administered 150 mg L-DOPA to 87 healthy adults in a randomized, placebo-controlled, double-blind, crossover study, evaluating performance in four value-based decision-making tasks. We predicted that baseline impulsivity would moderate L-DOPA effects. In support of our hypothesis, L-DOPA had no main effect on impulsive choice, but reduced risk-seeking for gains in more-impulsive subjects. Because L-DOPA effects may be influenced by body weight, we repeated our analyses on data from half of the sample (n = 44) with lower weight, anticipating a stronger effect. In addition to the effect on risk-seeking for gains, low-weight participants also exhibited baseline-dependent effects of L-DOPA on loss aversion and delay discounting. Our results are consistent with the hypothesis of an inverted U-shaped dopamine function in which both low and high extremes of dopamine signaling are associated with high-impulsive choice. Consideration of differential baseline impulsivity and body weight may resolve previous seemingly paradoxical pharmacological results and might deepen our understanding of dopaminergic mechanisms underlying impulsivity.
Journal Article
Making smart choices
\"Discusses making good life choices, including eating healthy foods, staying active, and learning to deal with stress\"--Amazon.com.
Book
The catechol-O-methyltransferase inhibitor tolcapone modulates alcohol consumption and impulsive choice in alcohol use disorder
RationaleIndividuals suffering from alcohol use disorder (AUD) demonstrate difficulty with decision-making and impulsivity that may be associated with impaired frontal cortical function. Therapeutics that enhance frontal dopamine tone could decrease impulsivity and in turn reduce alcohol consumption in individuals with AUD.ObjectivesTo determine if the catechol-O-methyltransferase (COMT) inhibitor tolcapone can attenuate alcohol consumption in individuals with AUD and whether this attenuation correlates with tolcapone-induced changes in laboratory-based decision-making tasks.MethodsWe used daily self-report and a novel group laboratory bar task to assess the effects of randomized double-blind crossover administration of tolcapone (100 mg TID for 5 days) on alcohol consumption and laboratory tasks assessing impulsivity in 55 non-treatment-seeking subjects with AUD.ResultsTolcapone significantly reduced self-reported alcohol consumption (t (54) = 2.05, p = 0.045). The effects of tolcapone on drinking significantly correlated with changes in impulsive decision-making, such that subjects with the greatest decrease in impulsive choice on tolcapone also reported the greatest decrease in alcohol consumption (r (45) = 0.40, p = 0.0053). We did not see effects of tolcapone on laboratory bar consumption. Adverse event (AE) reporting was low, with no significant difference in frequency or severity of AEs on tolcapone versus placebo.ConclusionsThese data demonstrate that COMT inhibitors such as tolcapone may be useful therapeutics for AUD.Trial registrationClinicalTrials.gov Identifier: NCT 02740582
Journal Article
On freedom
\"In this pathbreaking book, New York Times bestselling author Cass Sunstein asks us to rethink freedom. He shows that freedom of choice isn't nearly enough. To be free, we must also be able to navigate life. People often need something like a GPS device to help them get where they want to go--whether the issue involves health, money, jobs, children, or relationships. In both rich and poor countries, citizens often have no idea how to get to their desired destination. That is why they are unfree. People also face serious problems of self-control, as many of them make decisions today that can make their lives worse tomorrow. And in some cases, we would be just as happy with other choices, whether a different partner, career, or place to live--which raises the difficult question of which outcome best promotes our well-being. Accessible and lively, and drawing on perspectives from the humanities, religion, and the arts, as well as social science and the law, On Freedom explores a crucial dimension of the human condition that philosophers and economists have long missed--and shows what it would take to make freedom real.\"--Page [2] of cover.
Book
The effect of atomoxetine on random and directed exploration in humans
The adaptive regulation of the trade-off between pursuing a known reward (exploitation) and sampling lesser-known options in search of something better (exploration) is critical for optimal performance. Theory and recent empirical work suggest that humans use at least two strategies for solving this dilemma: a directed strategy in which choices are explicitly biased toward information seeking, and a random strategy in which decision noise leads to exploration by chance. Here we examined the hypothesis that random exploration is governed by the neuromodulatory locus coeruleus-norepinephrine system. We administered atomoxetine, a norepinephrine transporter blocker that increases extracellular levels of norepinephrine throughout the cortex, to 22 healthy human participants in a double-blind crossover design. We examined the effect of treatment on performance in a gambling task designed to produce distinct measures of directed exploration and random exploration. In line with our hypothesis we found an effect of atomoxetine on random, but not directed exploration. However, contrary to expectation, atomoxetine reduced rather than increased random exploration. We offer three potential explanations of our findings, involving the non-linear relationship between tonic NE and cognitive performance, the interaction of atomoxetine with other neuromodulators, and the possibility that atomoxetine affected phasic norepinephrine activity more so than tonic norepinephrine activity.
Journal Article
Lipopolysaccharide Alters Motivated Behavior in a Monetary Reward Task: a Randomized Trial
Inflammation-induced sickness is associated with a large set of behavioral alterations; however, its motivational aspects remain poorly explored in humans. The present study assessed the effect of lipopolysaccharide (LPS) administration at a dose of 2 ng/kg of body weight on motivation in 21 healthy human subjects in a double-blinded, placebo (saline)-controlled, cross-over design. Incentive motivation and reward sensitivity were measured using the Effort Expenditure for Rewards Task (EEfRT), in which motivation for high-effort/high-reward trials vs low-effort/low-reward trials are manipulated by variations in reward magnitude and probability to win. Because of the strong interactions between sleepiness and motivation, the role of sleepiness was also determined. As expected, the probability to win predicted the choice to engage in high-effort/high-reward trials; however, this occurred at a greater extent after LPS than after saline administration. This effect was related to the level of sleepiness. Sleepiness increased motivation to choose the high-effort/high-reward mode of response, but only when the probability to win was the highest. LPS had no effect on reward sensitivity either directly or via sleepiness. These results indicate that systemic inflammation induced by LPS administration causes motivational changes in young healthy subjects, which are associated with sleepiness. Thus, despite its association with energy-saving behaviors, sickness allows increased incentive motivation when the effort is deemed worthwhile.
Journal Article