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RATIONALE: Motivation and inhibitory control are dominantly regulated by the dopaminergic (DA) and noradrenergic (NA) systems, respectively. Hypothalamic hypocretin (orexin) neurons provide afferent inputs to DA and NA nuclei and hypocretin-1 receptors (HcrtR1) are implicated in reward and addiction. However, the role of the HcrtR1 in inhibitory control is not well understood. OBJECTIVES: To determine the effects of HcrtR1 antagonism and motivational state in inhibitory control using the go/no-go task in mice. METHODS: n = 23 male C57Bl/6JArc mice were trained in a go/no-go task. Decision tree dendrogram analysis of training data identified more and less impulsive clusters of animals. A HcrtR1 antagonist (BI001, 12.5 mg/kg, per os) or vehicle were then administered 30 min before go/no-go testing, once daily for 5 days, under high (food-restricted) and low (free-feeding) motivational states in a latin-square crossover design. Compound exposure levels were assessed in a satellite group of animals. RESULTS: HcrtR1 antagonism increased go accuracy and decreased no-go accuracy in free-feeding animals overall, whereas it decreased go accuracy and increased no-go accuracy only in more impulsive, food restricted mice. HcrtR1 antagonism also showed differential effects in premature responding, which was increased in response to the antagonist in free-feeding, less impulsive animals, and decreased in food restricted, more impulsive animals. HcrtR1 receptor occupancy by BI001 was estimated at ~ 66% during the task. CONCLUSIONS: These data indicate that hypocretin signalling plays roles in goal-directed behaviour and inhibitory control in a motivational state-dependant manner. While likely not useful in all settings, HcrtR1 antagonism may be beneficial in improving inhibitory control in impulsive subpopulations.
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Temporal discounting refers to the tendency to discount future rewards as a function of time until receipt of rewards. The discount rate can be reduced by experimentally manipulating time framing, an example being the date/delay effect: Specifically, if time until receipt of the reward is presented as a date (e.g., August 21, 2022) rather than as a delay (e.g., 136 days), temporal discounting is reduced. While this effect has been replicated several times, its underlying cognitive mechanisms are not well understood. Therefore, we used eye tracking to examine the role of attention in the date/delay effect. Participants completed both a delay and date condition of the Monetary Choice Questionnaire, while eye movements were recorded (N = 54). Results revealed a successful replication of the date/delay effect (p < .001, gav = 0.48). Eye tracking showed that participants compared time attributes (relative to reward attributes) more and fixated them longer in the date compared to the delay condition. Moreover, the absolute difference in reward values of choice options was more predictive of choosing the delayed reward in the date compared to the delay condition. Finally, explorative correlations revealed a stronger date/delay effect in participants who paid more attention to time than reward attributes in the delay condition and who used a more integrative search strategy. Our findings suggest that the date manipulation causes participants to weight rewards more strongly in their decision process than in the delay condition, ultimately reducing temporal discounting. Computation of time intervals in the date condition could possibly reflect an adaptation lowering the date/delay effect. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Temporal discounting (TD), the tendency to devalue future rewards as a function of delay until receipt, is aberrant in many mental disorders. Identifying symptom patterns and transdiagnostic dimensions associated with TD could elucidate mechanisms responsible for clinically impaired decision-making and facilitate identifying intervention targets. Here, we tested in a general population sample (N = 731) the extent to which TD was related to different symptom patterns and whether effects of time framing (dates/delay units) and monetary magnitude (large/small) had particularly strong effects in people scoring higher on specific symptom patterns. Analyses revealed that TD was related to symptom patterns loading on anxious-depression and inattention-impulsivity-overactivity dimensions. Moreover, TD was lower in the date than the delay version and with higher magnitudes, especially in people scoring higher on the inattention-impulsivity-overactivity dimension. Overall, this study provides evidence for TD as a transdiagnostic process across affective and impulsivity-related dimensions. Future studies should test framing interventions in clinical populations characterized by impulsivity.Preregistration: This research was preregistered at https://osf.io/fg9sc .
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Temporal discounting, the tendency to devalue future rewards as a function of delay until receipt, is influenced by time framing. Specifically, discount rates are shallower when the time at which the reward is received is presented as a date (date condition; e.g., June 8, 2023) rather than in delay units (delay condition; e.g., 30 days), which is commonly referred to as the date/delay effect. However, the cognitive and neural mechanisms of this effect are not well understood. Here, we examined the date/delay effect by analysing combined fMRI and eye-tracking data of N = 31 participants completing a temporal discounting task in both a delay and a date condition. The results confirmed the date/delay effect and revealed that the date condition led to higher fixation durations on time attributes and to higher activity in precuneus/PCC and angular gyrus, that is, areas previously associated with episodic thinking. Additionally, participants made more comparative eye movements in the date compared to the delay condition. A lower date/delay effect was associated with higher prefrontal activity in the date > delay contrast, suggesting that higher control or arithmetic operations may reduce the date/delay effect. Our findings are in line with hypotheses positing that the date condition is associated with differential time estimation and the use of more comparative as opposed to integrative choice strategies. Specifically, higher activity in memory-related brain areas suggests that the date condition leads to higher perceived proximity of delayed rewards, while higher frontal activity (middle/superior frontal gyrus, posterior medial frontal cortex, cingulate) in participants with a lower date/delay effect suggests that the effect is particularly pronounced in participants avoiding complex arithmetic operations in the date condition.