REALITY MONITORING

Study Overview
=================
Brief Summary
-----------------
Reality-monitoring characterizes the ability to determine whether information was perceived in the environment or only imagined . Impaired reality-monitoring abilities have been associated with hallucinations in patients with schizophrenia and patients with Parkinson's disease. The investigators hypothesize a link between dopaminergic (DA) transmission and reality-monitoring.

Detailed Description
-----------------
This hypothesis is based on several studies in the literature: 1) DA transmission anomalies are observed in both schizophrenia and Parkinson's disease; 2) DA agonists may induce hallucination; 3) DA antagonists reduce hallucinations and improve reality-monitoring abilities in patients with schizophrenia. In addition, also suggesting a link between mesocorticolimbic connectivity, subcortical DA transmission and reality-monitoring, The investigators have shown that fronto-temporal transcranial Direct Current Stimulation (tDCS) leads: on the one hand, to modulate reality-monitoring performance in healthy volunteers and patients; on the other hand, to induce subcortical DA release. However, to date, no study has yet explored the direct link between DA transmission and reality-monitoring.

Official Title
-----------------
MONITORING OF REALITY AND DOPAMINE: A PHARMACOLOGICAL RESEARCH

Conditions
-----------------
Neurosciences

Intervention / Treatment
-----------------
* Other: Précurseur de la dopamine
* Other: antagoniste D2
* Other: PLACEBO


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy volunteers who have given their written informed consent Men and women from 18 to 45 years old Normal or corrected vision Being fluent in French or French for native language Being affiliated with health insurance Exclusion Criteria: Healthy volunteers who have given their written informed consent Men and women from 18 to 45 years old Normal or corrected vision Being fluent in French or French for native language Being affiliated with health insurance Inadmissibility of the subject's consent or refusal Working-memory deficit (as controlled with MMSE score< 23) Any past or current psychiatric or somatic condition(as controlled with the Mini International Neuropsychiatric Interview, MINI) Any past or current neurological condition History of cranio-cerebral trauma, arterial hypotension or hypertension, cardiological or serious medical condition Abnormal potassium dosage (below 3.1 mmol/L or above 4.9 mmol/L) Anormal ECG History of schizophrenia or bipolar disorder in first-degree relatives Alcohol-drinking and caffeine intake at least during 24 hours before each session Drug therapy excepting contraceptives Cardiologic or severe medical conditio Pregnancy(checked with a pregnancy autotest), lactation, or insufficient contraceptive measure (precautionary measure) Consumption of recreational drugs during the last 6 months Known sensitivity to any of the study medication and their excipients Lactose intolerance Porphyria Hepatic insufficiency

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: MORDOR study will use a randomized, double dummy, placebo-controlled, three-arm crossover design.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dopamine precursor<br>In the first condition, volunteers will receive a dopamine (DA) precursor (L-dopa, 100mg). L-dopa will be combined with a dose of an Aromatic amino acid decarboxylase inhibitor (Benserazide) 25mg to multiplicate its bioavailability and with a dose of domperidone 10mg (peripheral antagonist of DA) to minimize the risk of side effects. | Other: Précurseur de la dopamine<br>* In the first condition, volunteers will receive a 100mg dose of L-dopa, 25mg dose of Aromatic amino acid decarboxylase inhibitors (Benserazide) and 10mg dose of Domperidone. In the second condition, volunteers will receive Sulpiride 800mg. In the third condition, volunteers will receive placebo Reality-monitoring performances will be evaluated with a standardized task. Working-memory will be evaluated with the n-back task. Self-monitoring performances will be observed during a speech production experiment in which speakers monitor their auditory feedback while speaking. Speech Bayesian reasoning: This task is a home-made task investigating the influence of prior on speech processing. Subjects will be required to identify speech in ambiguous auditory stimuli. Visual Bayesian reasoning: This task investigates the influence of prior on visual processing. Subjects will be required to recognize morph between faces and house.<br>|
| Active Comparator: D2 antagonist<br>In the second condition, volunteers will receive a D2 antagonist (Sulpiride, 800mg) | Other: antagoniste D2<br>* In the second condition, volunteers will receive Sulpiride 800 mg<br>|
| Placebo Comparator: PLACEBO<br>In the third condition, volunteers will receive a placebo (lactose) | Other: PLACEBO<br>* In the third condition, volunteers will receive placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reality-monitoring performance | Measured with a behavioral task developed, validated and used in investigators lab. During the memory retrieval phase, 48 words will be presented, including the 32 words presented during encoding as well as 16 new words. Subjects will be required to identify whether each word was previously heard, imagined or new. Three words lists will be used and assigned randomly depending on the substance condition (L-dopa, Sulpiride, placebo). Each verbal list will include 16 items with the imagine hear encoding condition and 16 items with the listen encoding condition. A single measure including two variables of interest will account for the main evaluation criteria: The average conditional source-identification measure (ACSIM) which represents the overall ability to correctly retrieve the source, conditional on that item was recognized as already presented. The source misattributions,the number of confusions between heard and imagined events. | One month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reaction times at the reality-monitoring task and scores of subjective confidence rating for reality-monitoring responses | Regarding reality-monitoring, a single test in which investigators will also measure the reaction times at the reality-monitoring task and scores of subjective confidence rating for reality-monitoring responses. The variable of interest will be the number of high-confident incorrect source-recognition responses. Investigators finally measure the vividness of each imagined or listened word with Visual Analogue Scales (VAS) from 0 to 100. | One month | 
| Other cognitive tasks | In the same test investigators will measure the number of correct/incorrect responses and reaction times at the n-back working memory task. The effect of dopamine modulation on the ability the ability to determine our speech as self-generated will be measured with a self-monitoring task. Investigators measure the magnitude of a voice peak response reflecting the feeling of agency. The effect of dopamine modulation on perception will be evaluated with the performances measured during 2 home-made Bayesian reasoning tasks, evaluating speech processing and visual processing, respectively. | One month |