Dopamine and Cognition
Dopaminergic Mechanisms of Gating Working Memory, Learning and Motivation: a Pharmaco-fMRI Study
1 other identifier
interventional
47
1 country
1
Brief Summary
Rationale: To unravel the role of dopamine in gating of working memory, motivation and learning. Objective: The primary objective of this study is to isolate effects of blocking D2 receptor stimulation on gating of working memory, reinforcement learning and reward-based motivation, and their associated physiological changes (measured with fMRI and eye tracking). The secondary objective is to assess the degree to which the effects of D2 receptor action vary as a function of proxy measures of baseline dopamine levels. Study design: A double-blind placebo controlled within-subject design will be employed, in which young healthy participants are tested twice, once on placebo, and once on a low oral dose (400mg) of the D2 receptor antagonist sulpiride. This design and drug dose is commonly used in our lab without side effects (previously approved CMO protocols 2011/204, 2008/078 \& 2016/2646). Study population: Healthy human participants, 18 - 45 yr old. We will recruit 46 participants. Intervention: Participants will receive both 400 mg sulpiride and placebo, in separate sessions in a counterbalanced order. Main study parameters/endpoints: BOLD signal measured with fMRI, and behavioural performance on cognitive tasks. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participants will attend 3 study sessions: A screening session and 2 pharmaco-fMRI sessions (sulpiride and placebo). Participants will complete a baseline battery of tasks and questionnaires, a structural MRI scan, as well as a battery of tasks both in and outside the scanner. On the day preceding each pharmaco-fMRI session, participants will have to adhere to some simple restrictions with respect to medication, alcohol and drug intake. On the day of testing participants will have to refrain from smoking and stimulant-containing drinks. Sulpiride can be administered safely without any relevant risk of serious adverse events and has been approved for clinical use in the Netherlands.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Sep 2021
Shorter than P25 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 23, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 12, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
July 12, 2022
CompletedFirst Submitted
Initial submission to the registry
March 21, 2023
CompletedFirst Posted
Study publicly available on registry
June 1, 2023
CompletedSeptember 21, 2023
September 1, 2023
10 months
March 21, 2023
September 19, 2023
Conditions
Outcome Measures
Primary Outcomes (14)
Working memory gating task: Reaction time
Reaction time \[ms\] during selective vs. non-selective input- and output-gating to assess the ability (speed) to selectively input- and output-gate working memory representations at intervention (sulpiride) versus placebo.
Measured at intervention day 1, 115 min after the pharmacological intervention took place. Measurements are compared regarding intervention type (drug versus placebo).
Working memory gating task: Reaction time
Reaction time \[ms\] during selective vs. non-selective input- and output-gating to assess the ability (speed) to selectively input- and output-gate working memory representations at intervention (sulpiride) versus placebo.
Measured at intervention day 2, 115 min after the pharmacological intervention took place. Measurements are compared regarding intervention type (drug versus placebo).
Working memory gating task: Accuracy
Accuracy \[%\] during selective vs. non-selective input- and output-gating to assess the ability (correctness) to selectively input- and output-gate working memory representations at intervention (sulpiride) versus placebo.
Measured at intervention day 1, 115 min after the pharmacological intervention took place. Measurements are compared regarding intervention type (drug versus placebo).
Working memory gating task: Accuracy
Accuracy \[%\] during selective vs. non-selective input- and output-gating to assess the ability (correctness) to selectively input- and output-gate working memory representations at intervention (sulpiride) versus placebo.
Measured at intervention day 2, 115 min after the pharmacological intervention took place. Measurements are compared regarding intervention type (drug versus placebo).
Working memory gating task: BOLD-response
BOLD-response to selective vs. global cues, examined for both pre- and retro-cue conditions (i.e., input- and output-gating respectively) to assess the neural response to selective working memory gating at intervention (sulpiride) versus placebo.
Measured at intervention day 1, 115 min after the pharmacological intervention took place. Measurements are compared regarding intervention type (drug versus placebo).
Working memory gating task: BOLD-response
BOLD-response to selective vs. global cues, examined for both pre- and retro-cue conditions (i.e., input- and output-gating respectively) to assess the neural response to selective working memory gating at intervention (sulpiride) versus placebo.
Measured at intervention day 2, 115 min after the pharmacological intervention took place. Measurements are compared regarding intervention type (drug versus placebo).
Simon task: Accuracy
Accuracy \[%\] during high and low average reward rate congruent and incongruent trials to assess cognitive effort investment after intervention versus placebo.
Measured at intervention day 1, 250 min after the pharmacological intervention took place. Measurements are compared regarding intervention type (drug versus placebo).
Simon task: Accuracy
Accuracy \[%\] during high and low average reward rate congruent and incongruent trials to assess cognitive effort investment after intervention versus placebo.
Measured at intervention day 2, 250 min after the pharmacological intervention took place. Measurements are compared regarding intervention type (drug versus placebo).
Simon task: Reaction time
Reaction time \[ms\] during high and low average reward rate congruent and incongruent trials to assess cognitive effort investment after intervention versus placebo
Measured at intervention day 1, 250 min after the pharmacological intervention took place. Measurements are compared regarding intervention type (drug versus placebo).
Simon task: Reaction time
Reaction time \[ms\] during high and low average reward rate congruent and incongruent trials to assess cognitive effort investment after intervention versus placebo
Measured at intervention day 2, 250 min after the pharmacological intervention took place. Measurements are compared regarding intervention type (drug versus placebo).
Perceptual decision-making task: Accuracy
Accuracy \[%\] as a function of average reward rate to assess cognitive effort investment after intervention versus placebo.
Measured at intervention day 1, 215 min after the pharmacological intervention took place. Measurements are compared regarding intervention type (drug versus placebo).
Perceptual decision-making task: Accuracy
Accuracy \[%\] as a function of average reward rate to assess cognitive effort investment after intervention versus placebo.
Measured at intervention day 2, 215 min after the pharmacological intervention took place. Measurements are compared regarding intervention type (drug versus placebo).
Perceptual decision-making task: Reaction time
Reaction time \[ms\] as a function of average reward rate to assess cognitive effort investment after intervention versus placebo.
Measured at intervention day 1, 215 min after the pharmacological intervention took place. Measurements are compared regarding intervention type (drug versus placebo).
Perceptual decision-making task: Reaction time
Reaction time \[ms\] as a function of average reward rate to assess cognitive effort investment after intervention versus placebo.
Measured at intervention day 2, 215 min after the pharmacological intervention took place. Measurements are compared regarding intervention type (drug versus placebo).
Secondary Outcomes (11)
Eye-blink rate
Measured at baseline during intake session
Operation Span test
Measured at baseline during intake session
Digit Span test
Measured at baseline during intake session
Digit Span test
Measured during intervention day 1 (sessions at least 14 days apart), 290 min after the pharmacological intervention took place
Digit Span test
Measured during intervention day 2 (sessions at least 14 days apart), 290 min after the pharmacological intervention took place
- +6 more secondary outcomes
Other Outcomes (40)
Diastolic blood pressure
Measured at baseline on intervention day 1 (before pharmacological intervention took place)
Diastolic blood pressure
Measured at baseline on intervention day 2 (before pharmacological intervention took place)
Diastolic blood pressure
Measured 90 min post drug/placebo intake on intervention day 1
- +37 more other outcomes
Study Arms (2)
Sulpiride
ACTIVE COMPARATORAll study participants receive both placebo and the active medication (sulpiride 400mg), in a within-subjects , double-blind, randomized design.
Placebo
PLACEBO COMPARATORAll study participants receive both placebo and the active medication (sulpiride 400mg), in a within-subjects , double-blind, randomized design.
Interventions
All participants will receive one single dose of 400mg sulpiride. None of the participants will receive repeated doses. In order for the fMRI data acquisition to coincide with the time-window of maximal drug effects represented by a combination of plasma kinetics and physiological effects we will administer the drug 90 minutes prior to fMRI data acquisition.
Eligibility Criteria
You may qualify if:
- Healthy volunteers between 18 and 45 years of age
- Predominant right-handedness
You may not qualify if:
- Presence of prolactin-dependent tumors (e.g., pituitary prolactinoma or breast cancer)
- (History of) autonomic failure (e.g., vasovagal reflex syncope).
- (History of) clinically significant hepatic, cardiac, obstructive respiratory, renal, cerebrovascular, cardiovascular, metabolic, ocular or pulmonary disease/disorders
- (History of) epilepsy in adulthood (i.e. no insult after 18 years of age, no current medication for epilepsy and no insult in the last five years)
- Diagnosis (or history of) endocrine treatment
- Diagnosis (or history of) neuroendocrine treatment (e.g., phechromocytoma, hyperthyroidism, Cushing's syndrome)
- (History of) melanoma
- Hypersensitivity to sulpiride
- One first degree or two or more second degree family members with a history of sudden death or ventricular arrhythmia
- Abnormal QT interval (assessed via ECG)
- Uncontrolled hypertension, defined as diastolic blood pressure at rest \> 95 mmHg or systolic blood pressure at rest \> 180 mmHg
- Hypotension, defined as diastolic blood pressure \< 50 mm Hg or systolic \< 95 mm Hg
- or resting pulse rate \< 45 beats/min
- Diabetes
- History of prescribed medication within the last month prior to the start of the study.
- +26 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Donders Centre for Cognition, Radboud University
Nijmegen, Gelderland, Netherlands
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Prof. Dr.
Study Record Dates
First Submitted
March 21, 2023
First Posted
June 1, 2023
Study Start
September 23, 2021
Primary Completion
July 12, 2022
Study Completion
July 12, 2022
Last Updated
September 21, 2023
Record last verified: 2023-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- ANALYTIC CODE
- Time Frame
- After publication
- Access Criteria
- As described on the website of the Donders Repository, shared data can be accessed via a persistent identifier. This identifier can be obtained directly from the authors or via a link in the publication. Also see: https://data.donders.ru.nl/doc/help/user-manual/access-shared-data/request-access.html?4
Following publication, raw and processed data will be archived for scientific integrity. The data use agreement gives access to the data, provided that certain conditions set by the local institutional guidelines as well as (inter)national (EU) law are met. Data sharing will be done using the Donders Institute research data repository (http://data.donders.ru.nl) in accordance to institutional and EU guidelines.