This study investigates how increasing noradrenaline levels with atomoxetine affects motivation and information processing relevant to apathy. Apathy, characterised by low motivation and reduced goal-directed behaviour, is common across neuropsychiatric disorders and is associated with poorer outcomes. Atomoxetine, a noradrenaline reuptake inhibitor, has been shown to influence effort, reward learning, and decision-making; however, its effects on cognitive processes relevant to apathy remain unclear. This study will investigate how pharmacologically increasing noradrenaline levels with atomoxetine affects different components of motivation altered in apathy, including reward processing, effort-based decision-making, goal-directed behaviour, and learning. In a within-subject, double-blind, placebo-controlled, randomised study, forty healthy participants with varying levels of apathy will complete a computerised task battery after receiving a single dose of atomoxetine (40 mg) and placebo. Validated tasks assessing motivation, reward learning, decision-making, goal-directed behaviour, and information processing will be used to examine whether and how atomoxetine influences motivation-related cognitive processes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
TRIPLE
Enrollment
40
Acute (single dose) of Atomoxetine (40mg). Oral administration. Atomoxetine is FDA approved for the treatment of ADHD in adults and children.
Sucrose pillules will be encapsulated in an opaque capsule (identical to the experimental drug).
Department of Psychiatry, University of Oxford
Oxford, United Kingdom
Effort-based choice behaviour during the Apple Gathering Task
Change in the acceptance rate of offers requiring varying levels of physical effort for reward, measured during the Apple Gathering Task. Higher acceptance rates indicate greater willingness to exert effort for reward.
Time frame: During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo.
Effort-based choice behaviour during the Mental Effort Task
Change in the acceptance rate of offers requiring varying levels of cognitive effort for reward, measured during the Mental Effort Task. Higher acceptance rates indicate greater willingness to exert cognitive effort for reward.
Time frame: During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo
Prior goal precision on the Goal Priors Assay Task
Estimated prior goal precision derived from the relationship between estimation error (difference between estimated and actual ball landing position) and performance error (difference between actual ball landing position and target position). Higher values indicate greater weighting of prior beliefs relative to sensory evidence.
Time frame: During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo.
Reinforcement learning under working memory load task behavioural performance
Change in behavioural performance, measured as the proportion of optimal choices across low and high working memory load conditions.
Time frame: During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo.
Reinforcement learning under working memory load task parameter estimate
Change in participant-specific learning rate parameter estimate derived from computational modelling of learning and working memory task performance across low and high working memory load conditions.
Time frame: During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo.
Affective Go/No-Go Task Behavioural Performance
Change in behavioural performance, (response time; accuracy) on the Affective Go/No-Go Task.
Time frame: During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo.
Reward sensitivity computational parameter estimates from effort-based decision-making tasks.
Change in participant-specific parameter estimates of reward sensitivity derived from computational modelling of performance on the Apple Gathering Task and Mental Effort Task.
Time frame: During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo.
Effort sensitivity computational parameter estimates from effort-based decision-making tasks.
Change in participant-specific effort sensitivity parameter derived from computational modelling of performance on the Apple Gathering Task and Mental Effort Task.
Time frame: During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo.
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