Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Prof. Dr. Robbert-Jan Verkes, Radboud University Medical Centre Department of Psychiatry | UNKNOWN |
| Funding: NWO + KNAW | UNKNOWN |
Not provided
Not provided
Not provided
Not provided
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.
A more detailed description can be found in the approved research protocol as well as the pre-registrations. The links to the pre-registrations will be made available upon publication.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sulpiride | Active Comparator | All study participants receive both placebo and the active medication (sulpiride 400mg), in a within-subjects , double-blind, randomized design. |
|
| Placebo | Placebo Comparator | All study participants receive both placebo and the active medication (sulpiride 400mg), in a within-subjects , double-blind, randomized design. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sulpiride 400 MG | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Eye-blink rate | Number of spontaneous eye blinks per minute, as a clinically relevant biomarker of striatal dopamine function | Measured at baseline during intake session |
| Operation Span test | Number of letters remembered while performing math problems, as a parameter for working memory capacity |
| Measure | Description | Time Frame |
|---|---|---|
| Diastolic blood pressure | Unit of measurement: mmHG | Measured at baseline on intervention day 1 (before pharmacological intervention took place) |
| Diastolic blood pressure | Unit of measurement: mmHG |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Donders Centre for Cognition, Radboud University | Nijmegen | Gelderland | Netherlands |
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.
After publication
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
Not provided
| ID | Term |
|---|---|
| D013469 | Sulpiride |
| ID | Term |
|---|---|
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 |
Not provided
Not provided
This is a within-subjects (i.e., crossover), double-blind, randomized placebo-controlled study.
Not provided
Not provided
Not provided
|
|
| Placebo | Drug | All participants will receive placebo during one of the sessions. |
|
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). |
| Measured at baseline during intake session |
| Digit Span test | Accuracy score [nr of correct responses] on forward span and backward span, as a parameter for working memory capacity | Measured at baseline during intake session |
| Digit Span test | Accuracy score [nr of correct responses] on forward span and backward span, as a parameter for working memory capacity | Measured during intervention day 1 (sessions at least 14 days apart), 290 min after the pharmacological intervention took place |
| Digit Span test | Accuracy score [nr of correct responses] on forward span and backward span, as a parameter for working memory capacity | Measured during intervention day 2 (sessions at least 14 days apart), 290 min after the pharmacological intervention took place |
| Beck Depression Inventory | Average score as indicator of depressive symptoms | Baseline measure via online questionnaire in between first and second intervention session (these take place at least 14 days apart) |
| Barratt Impulsiveness Scale | Average score as indicator of impulsivity (personality trait) | Baseline measure via online questionnaire in between first and second intervention session (these take place at least 14 days apart) |
| Behavioural Inhibition Scale/Behavioural Activation Scale | Average score as indicator of behavioural activation and inhibition | Baseline measure via online questionnaire in between first and second intervention session (these take place at least 14 days apart) |
| State and Trait Anxiety Inventory | Average score as indicator of state and trait anxiety | Baseline measure via online questionnaire in between first and second intervention session (these take place at least 14 days apart) |
| Utrechtse Burnout Schaal/Maslach Burnout Inventory | Average score as indicator of burn out | Baseline measure via online questionnaire in between first and second intervention session (these take place at least 14 days apart) |
| Covid-19 Stress Scales | Average score as indicator of COVID-related stress and anxiety | Baseline measure via online questionnaire in between first and second intervention session (these take place at least 14 days apart) |
| Measured at baseline on intervention day 2 (before pharmacological intervention took place) |
| Diastolic blood pressure | Unit of measurement: mmHG | Measured 90 min post drug/placebo intake on intervention day 1 |
| Diastolic blood pressure | Unit of measurement: mmHG | Measured 90 min post drug/placebo intake on intervention day 2 |
| Diastolic blood pressure | Unit of measurement: mmHG | Measured 300 min post drug/placebo intake on intervention day 1 |
| Diastolic blood pressure | Unit of measurement: mmHG | Measured 300 min post drug/placebo intake on intervention day 2 |
| Systolic blood pressure | Unit of measurement: mmHG | Measured at baseline on intervention day 1 (before pharmacological intervention took place) |
| Systolic blood pressure | Unit of measurement: mmHG | Measured at baseline on intervention day 2 (before pharmacological intervention took place) |
| Systolic blood pressure | Unit of measurement: mmHG | Measured 90 min post drug/placebo intake on intervention day 1 |
| Systolic blood pressure | Unit of measurement: mmHG | Measured 90 min post drug/placebo intake on intervention day 2 |
| Systolic blood pressure | Unit of measurement: mmHG | Measured 300 min post drug/placebo intake on intervention day 1 |
| Systolic blood pressure | Unit of measurement: mmHG | Measured 300 min post drug/placebo intake on intervention day 2 |
| Heart rate | Unit of measurement: beats per minute (bpm) | Measured at baseline on intervention day 1 (before pharmacological intervention took place) |
| Heart rate | Unit of measurement: beats per minute (bpm) | Measured at baseline on intervention day 2 (before pharmacological intervention took place) |
| Heart rate | Unit of measurement: beats per minute (bpm) | Measured 90 min post drug/placebo intake on intervention day 1 |
| Heart rate | Unit of measurement: beats per minute (bpm) | Measured 90 min post drug/placebo intake on intervention day 2 |
| Heart rate | Unit of measurement: beats per minute (bpm) | Measured 300 min post drug/placebo intake on intervention day 1 |
| Heart rate | Unit of measurement: beats per minute (bpm) | Measured 300 min post drug/placebo intake on intervention day 2 |
| Body temperature | Measured in degree Celsius by an in-ear thermometer | Measured at baseline on intervention day 1 (before pharmacological intervention took place) |
| Body temperature | Measured in degree Celsius by an in-ear thermometer | Measured at baseline on intervention day 2 (before pharmacological intervention took place) |
| Body temperature | Measured in degree Celsius by an in-ear thermometer | Measured 90 min post drug/placebo intake on intervention day 1 |
| Body temperature | Measured in degree Celsius by an in-ear thermometer | Measured 90 min post drug/placebo intake on intervention day 2 |
| Body temperature | Measured in degree Celsius by an in-ear thermometer | Measured 300 min post drug/placebo intake on intervention day 1 |
| Body temperature | Measured in degree Celsius by an in-ear thermometer | Measured 300 min post drug/placebo intake on intervention day 2 |
| Respiration movements | Voltage change over time measured by a respiration belt around participants' abdomen during MRI scanning | Measured during the MRI scan (115 min post drug/placebo) on intervention day 1. The pharmacological intervention sessions take place at least 14 days apart) |
| Respiration movements | Voltage change over time measured by a respiration belt around participants' abdomen during MRI scanning | Measured during the MRI scan (115 min post drug/placebo) on intervention day 2. The pharmacological intervention sessions take place at least 14 days apart) |
| Visual Analogue Scale (VAS) | Measured with 16 mood rating items measured on a continuous scale from 1 to 10 by self-report | Measured at baseline on intervention day 1 (before pharmacological intervention took place) |
| Visual Analogue Scale (VAS) | Measured with 16 mood rating items measured on a continuous scale from 1 to 10 by self-report | Measured at baseline on intervention day 2 (before pharmacological intervention took place) |
| Visual Analogue Scale (VAS) | Measured with 16 mood rating items measured on a continuous scale from 1 to 10 by self-report | Measured 90 min post drug/placebo intake on intervention day 1 |
| Visual Analogue Scale (VAS) | Measured with 16 mood rating items measured on a continuous scale from 1 to 10 by self-report | Measured 90 min post drug/placebo intake on intervention day 2 |
| Visual Analogue Scale (VAS) | Measured with 16 mood rating items measured on a continuous scale from 1 to 10 by self-report | Measured 300 min post drug/placebo intake on intervention day 1 |
| Visual Analogue Scale (VAS) | Measured with 16 mood rating items measured on a continuous scale from 1 to 10 by self-report | Measured 300 min post drug/placebo intake on intervention day 2 |
| Positive and Negative Affect Scale (PANAS) | Measured with 20 statements regarding feelings and emotions measured on a 5-point Likert scale by self-report | Measured at baseline on intervention day 1 (before pharmacological intervention took place) |
| Positive and Negative Affect Scale (PANAS) | Measured with 20 statements regarding feelings and emotions measured on a 5-point Likert scale by self-report | Measured at baseline on intervention day 2 (before pharmacological intervention took place) |
| Positive and Negative Affect Scale (PANAS) | Measured with 20 statements regarding feelings and emotions measured on a 5-point Likert scale by self-report | Measured 90 min post drug/placebo intake on intervention day 1 |
| Positive and Negative Affect Scale (PANAS) | Measured with 20 statements regarding feelings and emotions measured on a 5-point Likert scale by self-report | Measured 90 min post drug/placebo intake on intervention day 2 |
| Positive and Negative Affect Scale (PANAS) | Measured with 20 statements regarding feelings and emotions measured on a 5-point Likert scale by self-report | Measured 300 min post drug/placebo intake on intervention day 1 |
| Positive and Negative Affect Scale (PANAS) | Measured with 20 statements regarding feelings and emotions measured on a 5-point Likert scale by self-report | Measured 300 min post drug/placebo intake on intervention day 2 |
| Menstrual cycle stage (for female participants) | Day of onset of last menstrual bleeding measured by self-report | Measured within the first 10 min of the intervention day 1 (i.e., 10 min pre drug/placebo) |
| Menstrual cycle stage (for female participants) | Day of onset of last menstrual bleeding measured by self-report | Measured within the first 10 min of the intervention day 2 (i.e., 10 min pre drug/placebo) |
| Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |