THE EFFECT OF ROPINIROLE ON FUNCTIONAL CONNECTIVITY AND METACOGNITION IN HEALTHY SUBJECTS

Trial details

Who runs it

Universita' Degli Studi Di Modena E Reggio Emilia

Trial code

EU 2025-520800-81-00

Record updated

2026. szeptember 3.

Original description

The primary objective is to determine whether a single oral dose of the dopamine agonist ropinirole modulates metacognitive performance in healthy adults. Metacognition refers to the ability to reflect on and accurately judge one’s own cognitive performance. By studying metacognition in healthy volunteers, we can probe how neuromodulation might enhance or impair self-monitoring abilities, providing insight relevant to disorders characterized by anosognosia or unawareness of neurological disturbances. Pharmacological studies in healthy people have only recently begun to demonstrate that metacognitive ability is indeed susceptible to drug manipulation. Notably, Hauser et al. (2017) provided the first evidence that a drug can selectively improve metacognitive performance: in a placebo-controlled trial, blocking noradrenergic β-receptors with propranolol significantly increased subjects’ metacognitive accuracy (measured as type-II ROC area) without improving basic task performance. We aim to extend this line of research by testing a dopaminergic agent’s impact on metacognitive abilities. In particular, we hypothesize that increasing dopaminergic tone will transiently alter an individual’s insight into their performance by inducing overconfidence. This hypothesis is supported by preliminary evidence that inducing a transient hyper-dopaminergic state in healthy people can change both brain network dynamics and one’s capacity to judge personal errors. Through a controlled pharmacological challenge, our study will assess whether a single oral dose of the dopamine-agonist ropinirole can measurably improve or impair metacognitive performance on cognitive tasks requiring self-evaluation of accuracy. More precisely, we will use metacognitive measures from experimental psychology (Fleming & Lau, 2014; Ernst et al, 2017) to test the hypothesis that, relative to placebo, a single dose of ropinirole given to healthy volunteers transiently increases metacognitive bias (i.e., the difference between confidence rating and actual performance) and decreases metacognitive relative accuracy (measured as metacognitive efficiency, i.e., the ratio between performance and metacognitive performance, and Goodman–Kruskal Gamma correlation, i.e., the ability to identify with higher confidence correct answers and with lower confidence errors), without affecting the level of the actual cognitive performance. In other words, the primary objective is to test if a single dose of ropinirole makes the subject over-confident about their cognitive performance and decreases how well that participant’s confidence in their answers discriminates correct responses from incorrect ones and predicts whether those answers are correct on a trial-by-trial basis. Demonstrating drug-induced changes in metacognition will contribute to clarify the neurotransmitter systems involved in self-awareness and point toward novel pro-metacognitive interventions for patients with anosognosia or impaired insight.Read full original descriptionShow less

The primary objective is to determine whether a single oral dose of the dopamine agonist ropinirole modulates metacognitive performance in healthy adults. Metacognition refers to the ability to reflect on and accurately judge one’s own cognitive performance. By studying metacognition in healthy volunteers, we can probe how neuromodulation might enhance or impair self-monitoring abilities, providing insight relevant to disorders characterized by anosognosia or unawareness of neurological disturbances. Pharmacological studies in healthy people have only recently begun to demonstrate that metacognitive ability is indeed susceptible to drug manipulation. Notably, Hauser et al. (2017) provided the first evidence that a drug can selectively improve metacognitive performance: in a placebo-controlled trial, blocking noradrenergic β-receptors with propranolol significantly increased subjects’ metacognitive accuracy (measured as type-II ROC area) without improving basic task performance. We aim to extend this line of research by testing a dopaminergic agent’s impact on metacognitive abilities. In particular, we hypothesize that increasing dopaminergic tone will transiently alter an individual’s insight into their performance by inducing overconfidence. This hypothesis is supported by preliminary evidence that inducing a transient hyper-dopaminergic state in healthy people can change both brain network dynamics and one’s capacity to judge personal errors. Through a controlled pharmacological challenge, our study will assess whether a single oral dose of the dopamine-agonist ropinirole can measurably improve or impair metacognitive performance on cognitive tasks requiring self-evaluation of accuracy. More precisely, we will use metacognitive measures from experimental psychology (Fleming & Lau, 2014; Ernst et al, 2017) to test the hypothesis that, relative to placebo, a single dose of ropinirole given to healthy volunteers transiently increases metacognitive bias (i.e., the difference between confidence rating and actual performance) and decreases metacognitive relative accuracy (measured as metacognitive efficiency, i.e., the ratio between performance and metacognitive performance, and Goodman–Kruskal Gamma correlation, i.e., the ability to identify with higher confidence correct answers and with lower confidence errors), without affecting the level of the actual cognitive performance. In other words, the primary objective is to test if a single dose of ropinirole makes the subject over-confident about their cognitive performance and decreases how well that participant’s confidence in their answers discriminates correct responses from incorrect ones and predicts whether those answers are correct on a trial-by-trial basis. Demonstrating drug-induced changes in metacognition will contribute to clarify the neurotransmitter systems involved in self-awareness and point toward novel pro-metacognitive interventions for patients with anosognosia or impaired insight.

Inclusion: Male; Nonsmoker; Cognitively healthy (Mini-Mental State Examination, MMSE=30); Age 20-35; Able to understand and write in Italian; Years of Education > 13 years; Participants are required to ensure no alcohol or any psychotropic substance intake for all the duration of the study; Consent to refrain from driving until midnight in the day of the session; Required to fast 3 hours before drug/placebo administration; On no medical treatment.

Exclusion: Controindication to MRI (e.g. claustrophobia, metallic implants or foreign bodies, pacemaker); Known allergy to ropinirole and to eccipients; History of neurological or psychiatric conditions at screening visit or from past history; Significant or severe medical conditions including pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, cardiovascular or oncologic disease, or any other condition that, in the opinion of the Investigator, could jeopardize the safety of the subject, ability to complete or comply with the study procedures or validity of the study results; History of substance abuse; Evidence of renal (creatinine clearance < 60 mL/min) or hepatic dysfunction (GOT/GPT > 31 U/L) on blood testing at screening or from past clinical history; On medical treatment at screening.

EU CTIS 2025-520800-81-00