Biology subjects

Winstanley, C. A.

Publications and source records attributed to Winstanley, C. A..

9 recordsLinked to original sources

bioRxiv2026

Dopamine Agonists in Parkinson's Disease Decouple Risk-Taking from Reward-Paired Cues by Enhancing Risky Choice in Their Absence

Background: Common side effects of dopamine replacement therapy (DRT) for Parkinson's Disease (PD) are addiction-like impulse control disorders, including compulsive gambling. Gambling products such as slot machines prominently feature reward-paired audiovisual stimuli, which can promote riskier choices on laboratory gambling tasks in both humans and rodents. In rats, risky decision making in the presence of reward-paired cues is dependent on dopamine D3 receptor activity and is increased by ropinirole, a D2/3 receptor agonist with a higher affinity for D3 receptors. In humans, it remains uncertain whether cue-induced risky choice is amplified by dopamine agonism. Methods: We tested effects of DRT on cue-induced risky choice in 62 patients with PD (34 on levodopa monotherapy, 27 on levodopa and dopamine agonists). Patients performed two versions of a risky decision-making task: one with and one without reward-paired sensory cues, both ON and OFF DRT. A group of 36 age-matched controls completed the same task versions without DRT. Results: Across all groups, participants made riskier choices when the task included reward-paired sensory cues. Levodopa monotherapy did not affect risky decision-making. However, a combination of levodopa and dopamine agonists increased risky choices specifically in the uncued version of the task, making performance indistinguishable from that on the cued task. Conclusions: Dopamine agonists combined with levodopa promote risk-taking even in the absence of reward-paired cues. This could translate into risky reward-seeking behaviors that are decoupled from contextual factors.

neuroscience↗

bioRxiv2026

Applying drift diffusion models to rat gambling task data reveals divergent cognitive mechanisms underlying risky choice

The rat gambling task (rGT) has been widely used to investigate the neural mechanisms underlying risky choice and motor impulsivity. Here, rats sample between four options (P1-P4) that vary in the size and probability of reward and time-out penalties. The optimal strategy is to avoid risky options that may yield higher per-trial gains, but deliver longer and more frequent time-outs. Previous reports suggest pairing wins with salient audiovisual cues increases risky decision making, but behavioural variation is high, and it is unclear whether motor impulsivity is also affected. Here we leveraged rGT data from over 750 rats to characterize behavioural performance across sex and cue condition. We compared different methods of classifying rats as optimal or risk-preferring, using either a unitary decision score variable or specific P-choice preference, and applied drift diffusion modeling (DDM) to explore whether divergent cognitive mechanisms underlie risky decision making across subgroups. We confirmed that risky choice is higher on the cued rGT, partly due to a greater proportion of risk-preferring rats, but also because net optimal decision-makers chose the risky options more often. Risk-preferring rats made more impulsive, premature responses regardless of cue condition, as did males. Optimal decision-makers made more premature responses when cues were present, such that premature response rates were higher overall on the cued rGT. DDM and response latency data suggest divergent cognitive processes underpinning risky decisions across sex. Wider decision boundaries were associated with both highly optimal and highly risky choice patterns, indicating risky choices are made deliberatively by highly risk-preferring individuals. Similar results were obtained regardless of classification method.

neuroscience↗

bioRxiv2026

Anterior insula activity increased by cued risky wins in healthy volunteers

Audiovisual cues ( bells and whistles) are ubiquitous in commercial gambling products. Pairing wins with sound and light cues in laboratory-based gambling paradigms increases risky choice, but the neurocognitive basis of this effect is unclear. Here we compared patterns of neural activation using functional MRI in healthy volunteers (n = 31) while they performed a two-choice lottery task. Reward-paired cues were either present or absent in a mixed-block, event-related design. As predicted, participants made riskier choices on cued trials. Choice latencies were also longer when cues were present, particularly on trials following a win. Activity within the nucleus accumbens and orbitofrontal cortex was greater during the decision phase when participants made risky choices. Nucleus accumbens signal was also greater when participants were anticipating risky outcomes, and in response to risky wins. Contrary to our pre-registered hypotheses, cue condition did not alter patterns of activity across any task phase, in either of these a priori regions of interest. As such, cue-induced risky choice does not appear to be driven by altered representation of risk or value within this canonically reward-sensitive circuitry. Instead, exploratory analyses revealed that the anterior insula was selectively activated by cued, risky wins. Such activation may signal the saliency of these events, or their emotional impact, and may reflect one mechanism through which cue-induced craving develops in vulnerable individuals.

neuroscience↗

bioRxiv2026

Chemogenetic inhibition of the noradrenergic locus coeruleus promotes the development of risk-taking decisional strategies and selectively enhances motor impulsivity in females

The locus coeruleus noradrenaline (LC-NA) system is a key regulator of arousal, attention, and reward learning. Noradrenaline plays a critical role in impulse control, and recent evidence indicates the importance of noradrenaline signaling in cost-benefit decision making once choice strategies are established. However, whether the LC causally shapes the acquisition of decision strategies, and how this contribution may differ across sexes, remains unclear. We addressed these questions by chemogenetically inhibiting catecholaminergic neurons within the LC of adult tyrosine-hydroxylase Cre (TH::Cre) rats (n=69; 35 females) throughout acquisition of the cued rat gambling task (crGT), a probabilistic decision making paradigm that incorporates salient audiovisual reward-paired cues and simultaneously measures motor impulsivity. LC inhibition accelerated the development of risky choice strategies early in training in both males and females, reflected by impaired adoption of the most advantageous option and increased preference for risky options. Trial-by-trial analyses reveal that LC inhibition promoted switches in choice strategy following safe wins, while reducing switches away from risky options after both wins and losses. LC inhibition therefore seemed to encourage the repetition of actions that resulted in more uncertain outcomes. LC inhibition also selectively enhanced motor impulsivity in females, particularly early in training. These results provide causal evidence that the LC system guides the formation of optimal decisional strategies, while exerting sex-specific control over impulsive action. Abbreviated summaryChernoff et al. demonstrate that noradrenergic locus coeruleus (LC) neurons are required to develop optimal decisional strategies, as their inhibition hastens the adoption of risk-preferring choice tendencies. This may be underpinned by reduced behavioural sensitivity to likely outcomes. They also show that the LC regulates impulse control, specifically in females.

neuroscience↗

bioRxiv2025

Short-term memory capacity and chronic stress levels predict cognitive effort choice as a function of reward level and effort demand

Every day, we make choices about how much effort we are willing and able to use to achieve the outcomes we desire against the backdrop of constantly shifting effort demands and available rewards. While factors like visual short-term memory and chronic stress levels can predict responses to stable cognitive effort demands, we do not yet know whether they constrain ones choices of higher effort trials for larger rewards when task demands and potential outcomes shift over time. Here, we examined whether these factors predicted the choice to deploy cognitive effort given increasing effort demands and the tendency to deploy effort given shifting reward availability. Undergraduate participants first performed an online visual short-term memory task to assess capacity for visuospatial short-term memory. They then completed a series of choice trials where they could choose between high-effort, high-reward or low-effort, low-reward trials. In two blocks, we varied either the effort required on high-effort trials or the reward offered on both trial types. We found that visual short-term memory predicted the likelihood of choosing high-effort trials given shifting rewards, while chronic stress and everyday preferences for cognitively effortful strategies predicted the tendency to deploy increasing amounts of effort for a stable reward. Furthermore, participants subjective reports show a strong focus on attentional processes, and balancing rewards and losses, when making decisions about how much effort to deploy. These findings shed light on distinct trait-level factors associated with cognitive effort choices given shifting demands and outcomes. Significance statementWe must often choose how much work to put in to complete everyday tasks. However, we do not know what behavioural factors drive these choices in humans when the effort required to complete a task - or potential rewards - shifts over time. In a visual short-term memory task adapted from rodent work, we found that those with higher visual short-term memory ability chose more high effort trials as effort demands increased, while chronic stress and everyday preferences for effortful strategies predicted more effort for a reward. Furthermore, participants described prioritizing sustaining attention in order to successfully complete the task. These findings shed light on distinct trait-level factors associated with cognitive effort choices given shifting demands and outcomes.

neuroscience↗

bioRxiv2024

Short-term memory capacity predicts willingness to expend cognitive effort for reward

We must often decide whether the effort required for a task is worth the reward. Past rodent work suggests that willingness to deploy cognitive effort can be driven by individual differences in perceived reward value, depression, or chronic stress. However, many factors driving cognitive effort deployment - such as short-term memory ability - cannot easily be captured in rodents. Furthermore, we do not fully understand how individual differences in short-term memory ability, depression, chronic stress, and reward anticipation impact cognitive effort deployment for reward. Here, we examined whether these factors predict cognitive effort deployment for higher reward in an online visual short-term memory task. Undergraduate participants were grouped into high and low effort groups (nHighEffort = 348, nLowEffort = 81; nFemale = 332, nMale = 92, MAge = 20.37, RangeAge = 16-42) based on decisions in this task. After completing a monetary incentive task to measure reward anticipation, participants completed short-term memory task trials where they could choose to encode either fewer (low effort/reward) or more (high effort/reward) squares before reporting whether or not the colour of a target square matched the square previously in that location. We found that only greater short-term memory ability predicted whether participants chose a much higher proportion of high vs. low effort trials. Drift diffusion modeling showed that high effort group participants were more biased than low effort group participants towards selecting high effort trials. Our findings highlight the role of individual differences in cognitive effort ability in explaining cognitive effort deployment choices. Significance statementWe must often make decisions about when cognitive effort is worth the potential reward. Reward value, depression, and chronic stress in rodents can impact cognitive effort deployment decisions for reward, but factors like short-term memory ability can only be easily characterized in humans. We examined whether short-term memory ability, depression, chronic stress, and reward anticipation predict cognitive effort decisions for reward. In a short-term visual memory task with a choice of easier or harder trials for low vs. high reward, we found that only short-term memory ability predicted more choices of high vs. low effort trials. This research suggests that cognitive effort decisions could be driven by cognitive effort ability more than motivational factors like depression or chronic stress.

neuroscience↗

bioRxiv2023

Insight into differing decision-making strategies that underlie cognitively effort-based decision making using computational modeling in rats

RationaleThe rat Cognitive Effort Task (rCET), a rodent model of cognitive rather than physical effort, requires animals to choose between an easy or hard visuospatial discrimination, with a correct hard choice more highly rewarded. Like in humans, there is stable individual variation in choice behavior. In previous reports, animals were divided into two groups - workers and slackers - based on their mean preference for the harder option. Although these groups differed in their response to pharmacological challenges, the rationale for using this criterion for grouping was not robust. MethodsWe collated experimental data from multiple cohorts of male and female rats performing the rCET, and used a model-based framework combining drift diffusion modeling with cluster analysis to identify the decision-making processes underlying variation in choice behavior. ResultsWe verified that workers and slackers are statistically different groups, but also found distinct intra-group profiles. These subgroups exhibited dissociable performance during the attentional phase, linked to distinct decision-making profiles during choice. Reanalysis of previous pharmacology data using this model-based framework showed that serotonergic drug effects were explained by changes in decision boundaries and non-decision times, whilst scopolamines effects were driven by changes in decision starting points and rates of evidence accumulation. ConclusionsModeling revealed the decision-making processes that are associated with cognitive effort costs, and how these differ across individuals. Reanalysis of drug data provided insight into the mechanisms through which different neurotransmitter systems impact cognitively effortful attention and decision-making processes, with relevance to multiple psychiatric disorders.

neuroscience↗

bioRxiv2022

Audiovisual cues must be predictable and win-paired to drive risky choice

Risky or maladaptive decision making is thought to be central to the etiology of both drug and gambling addiction. Salient audiovisual cues paired with rewarding outcomes, such as the jackpot sound on a win, can enhance disadvantageous, risky choice in both rats and humans, yet it is unclear which aspects of the cue-reward contingencies drive this effect. Here, we implemented six variants of the rat Gambling Task (rGT), in which animals can maximise their total sugar pellet profits by avoiding options paired with higher per-trial gains but disproportionately longer and more frequent time-out penalties. When audiovisual cues were delivered concurrently with wins, and scaled in salience with reward size, significantly more rats preferred the risky options as compared to the uncued rGT. Similar results were observed when the relationship between reward size and cue complexity was inverted, and when cues were delivered concurrently with all outcomes. Conversely, risky choice did not increase when cues occurred randomly on 50% of trials, and decision making actually improved when cues were coincident with losses alone. As such, cues do not increase risky choice by simply elevating arousal, or amplifying the difference between wins and losses. It is instead important that the cues are reliably associated with wins; presenting the cues on losing outcomes as well as wins does not diminish their ability to drive risky choice. Computational analyses indicate reductions in the impact of losses on decision making in all rGT variants in which win-paired cues increased risky choice. These results may help us understand how sensory stimulation can increase the addictive nature of gambling and gaming products.

animal behavior and cognition↗

bioRxiv2018

Win-concurrent sensory cues can bias decision making towards less favourable odds

Reward-related stimuli can potently influence behaviour; for example, exposure to drug-paired cues can trigger drug use and relapse in people with addictions. Psychological mechanisms that generate such outcomes likely include cue-induced cravings and attentional biases. Recent animal data suggest another candidate mechanism: reward-paired cues can enhance risky decision making, yet whether this translates to humans is unknown. Here, we examined whether sensory reward-paired cues alter decision making under uncertainty and risk, as measured respectively by the Iowa Gambling Task and a two-choice lottery task. In the cued version of both tasks, gain feedback was augmented with reward-concurrent audiovisual stimuli. Healthy human volunteers (53 males, 78 females) performed each task once, one with and the other without cues (cued IGT/uncued VGT: n = 63; uncued IGT/cued VGT: n = 68), with concurrent eye-tracking. Reward-paired cues did not affect choice on the Iowa Gambling Task. On the two-choice lottery task, the cued group displayed riskier choice and reduced sensitivity to probability information. The cued condition was associated with reduced eye fixations on probability information shown on the screen and greater pupil dilation related to decision and reward anticipation. This pupil effect was unrelated to the risk-promoting effects of cues: the degree of pupil dilation for risky versus risk-averse choices did not differ as a function of cues. Taken together, our data show that sensory reward cues can promote riskier decisions and have additional and distinct effects on arousal.\n\nSIGNIFICANCE STATEMENTAnimal data suggest that reward-paired cues can promote maladaptive reward-seeking by biasing cost-benefit decision making. Whether this finding translates to humans is unknown. We examined the effects of salient reward-paired audio-visual cues on decision making under risk and uncertainty in human volunteers. Cues had risk-promoting effects on a risky choice task and independently increased task-related arousal as measured by pupil dilation. By demonstrating risk-promoting effects of cues in human participants, our data identify a mechanism whereby cue reactivity could translate into maladaptive behavioural outcomes in people with addictions.

neuroscience↗