Consciousness Transcranial Alternative Electric STimulation

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to investigate the effect of transcranial Alternating Current Stimulation (tACS) at theta frequency and the the effect of transcranial Direct Current Stimulation (tDCS) on the conscious access to visual stimuli. tACS and tDCS are non-invasive stimulation techniques that are used to induce brain oscillations at certain frequency or to increase the brain activity in applied region. Healthy participants will perform a behavioral task measuring conscious access (visual backward metacontrast masking task) before, during and after fronto-parietal tACS or tDCS stimulation which will increase neural activity in the two sites. This will allow us to examine online and remaining effects of the stimulation and the causal role of fronto-parietal activity on conscious access.

Detailed Description
-----------------
Behavioral task The behavioral task consists in presentation of a para-foveal numerical target on a screen for 16 ms either right or left of a central fixation point, followed by a visual mask, made of letters surrounding the target, presented for 250 ms. The delay between the target and the mask (Stimulus Onset Asynchrony - SOA) will be variable (16 ms, 33 ms, 50 ms, 66 ms or 83 ms). Participants will then be asked to perform two tasks. First (objective task), participants will be asked to indicate as quickly as possible whether the target was bigger or smaller than the digit 5. Second (subjective task), they will be requested to judge the visibility of the presented target by indicating whether they had seen the target or not. tACS Study design The study design is composed of three experimental sessions. In these sessions, participants will first complete the behavioral paradigm as presented above while having their brain activity recorded with EEG. Afterwards, they will re-perform the task during and after tACS stimulation. tACS stimulation type will differ in each session : in-phase, anti-phase or sham (see below for further details). Stimulation sessions will occur in a double-blind randomized crossover design (neither the participant nor the experimenter knows which session includes which stimulation type), with at least 2 days of interval between them. Stimulation During tACS sessions, 6 Hz stimulation (1000 μA) will be applied simultaneously over the left prefrontal dorso-lateral cortex (F3 of the 10-20 international scalp EEG system) and the left parietal cortex (P3) using an 8-channels stimulator (Starstim NE, Neuroelectrics, Barcelona, Spain) with small round sponge electrodes (25 cm2 surface, maximal current density of 0.06 μA/cm2), controlled via Bluetooth. In the in-phase condition, the phase difference between the two stimulation sites will be 0° which will entrain synchronization between sites. In the anti-phase condition on the other hand, the phase difference will be 180°, which should desynchronize the activity in the two cortices. In the sham condition, the stimulation (also anti-phase) will start with a current intensity of 2000 μA lasting for 30 seconds. Afterwards, the intensity will progressively decrease over 20 seconds until cessation. Each stimulation session will take 20 minutes and the positions of stimulation electrodes and the duration of the stimulation will be kept identical for all conditions. tDCS Study design The study is composed of two experimental sessions: one tDCS session and one sham session. In the tDCS session, participants will do the behavioral task (with an EEG recording) during and after 20 minutes of 1000 μA tDCS stimulation. As a control, participants will do the behavioral task in a second session (sham session) during which they will have a sham stimulation instead of tDCS stimulation. The two sessions will occur in a double-blind randomized crossover design (neither the participant nor the experimenter knows which session includes which stimulation type), with at least 2 days of interval between them. Stimulation During tDCS session, 1000 μA stimulation will be applied simultaneously over the left prefrontal dorso-lateral cortex (F3 of the 10-20 international scalp EEG system) and the left parietal cortex (P3) using an 8-channels stimulator (Starstim NE, Neuroelectrics, Barcelona, Spain) with small round sponge electrodes (25 cm2 surface, maximal current density of 0.06 μA/cm2), controlled via Bluetooth. In the sham condition, the stimulation will start with a current intensity of 1000 μA lasting for 30 seconds. Afterwards, the intensity will progressively decrease over 20 seconds until cessation. The reason for this subtle manipulation is to make sure that participants will be unable to notice the difference between active tDCS and sham tDCS stimulation. Each stimulation session will take 20 minutes and the positions of stimulation electrodes and the duration of the stimulation will be kept identical for all conditions.

Official Title
-----------------
Effects of the Transcranial Alternative Electric Stimulation on the Consciousness Access in Healthy Subjects

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Device: tACS
* Device: tDCS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: French social security affiliation Absence of neurological and psychiatric disorders Absence of antiepileptic treatment Normal vision (with or without correction) Age between 18 and 60 years Right-handedness Signed informed consent to participate Exclusion Criteria: Person under legal protection (legal guardian, tutor, curator) Past medical history of epilepsy Past medical history of neurological or psychiatric disorders Electrical stimulation contraindication (metallic intra-cranial implants, pacemaker or implantable cardioverter-defibrillator, cranial prosthesis) Antiepileptic and other psychotropes treatment Pregnant, parturient or breastfeeding women Left-handedness

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 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: This study is composed of two independent sub-studies, one exploring the effects of tACS and the other the effects of tDCS, with different participants assigned to the two sub-studies. There will be 3 arms in tACS group and 2 arms in tDCS group. Among each sub-study, all participants will participate in all arms (hence the cross-over design).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: In-phase tACS<br>6 Hz stimulation (1000 μA) will be applied simultaneously over the left prefrontal dorso-lateral cortex (F3 of the 10-20 international scalp EEG system) and the left parietal cortex (P3) for 20 minutes using an 8-channels stimulator. The phase difference between the two stimulation sites will be 0°. | Device: tACS<br>* tACS is a non-invasive stimulation technique that works by delivering a weak sinusoidally oscillating electrical current to the surface of the skull to entrain oscillations in the brain.<br>|
| Active Comparator: Anti-phase tACS<br>6 Hz stimulation (1000 μA) will be applied simultaneously over the left prefrontal dorso-lateral cortex (F3 of the 10-20 international scalp EEG system) and the left parietal cortex (P3) for 20 minutes using an 8-channels stimulator. The phase difference will be 180°, | Device: tACS<br>* tACS is a non-invasive stimulation technique that works by delivering a weak sinusoidally oscillating electrical current to the surface of the skull to entrain oscillations in the brain.<br>|
| Sham Comparator: Sham tACS<br>The stimulation (anti-phase) will start with a current intensity of 1000 μA lasting for 30 seconds. Afterwards, the intensity will progressively decrease over 20 seconds until cessation. | Device: tACS<br>* tACS is a non-invasive stimulation technique that works by delivering a weak sinusoidally oscillating electrical current to the surface of the skull to entrain oscillations in the brain.<br>|
| Experimental: Active tDCS<br>1000 μA tDCS stimulation will be applied simultaneously over the left prefrontal dorso-lateral cortex (F3 of the 10-20 international scalp EEG system) and the left parietal cortex (P3) for 20 minutes using an 8-channels stimulator | Device: tDCS<br>* tDCS is a form of neuromodulation method where very low levels of constant current are delivered to specifically targeted areas of the brain<br>|
| Sham Comparator: Sham tDCS<br>The stimulation will start with a current intensity of 1000 μA lasting for 30 seconds. Afterwards, the intensity will progressively decrease over 20 seconds until cessation. | Device: tDCS<br>* tDCS is a form of neuromodulation method where very low levels of constant current are delivered to specifically targeted areas of the brain<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in subjective performance on the behavioral task (% of seen masked target) between before and after stimulation. | Change in the percentage of the correct responses on the subjective evaluation, that is the percentage of seen masked target at each SOA over all masked target presented, between before and after stimulation, for each stimulation modality (inphase theta, antiphase theta, sham). | Measured at each stimulation sessions (three sessions in a randomized cross-over order) for each participant. The three sessions will span in an average of two weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in visual evoked potentials between before and after stimulation. | Change in amplitudes and delays of event related potentials evoked by the target at different SOA and according to the visibility (P1, N1, N2, P300) between before and after stimulation for each stimulation modality. | Measured at each stimulation sessions (three sessions in a randomized cross-over order) for each participant. The three sessions will span in an average of two weeks. | 
| Change in quantitative EEG measures between before and after stimulation. | Changes in quantitative EEG measures (spectral power, complexity, connectivity) between before and after stimulation for each stimulation modality. | Measured at each stimulation sessions (three sessions in a randomized cross-over order) for each participant. The three sessions will span in an average of two weeks. | 
| Change in objective performance on the behavioral task (% of correct response on the number comparison task for masked target) between before and after stimulation. | Change in the percentage of the correct responses on the objective comparison task, that is the percentage of correct response on the number comparison task for masked target at each SOA, between before and after stimulation, for each stimulation modality (inphase theta, antiphase theta, sham). | Measured at each stimulation sessions (three sessions in a randomized cross-over order) for each participant. The three sessions will span in an average of two weeks. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Global neuronal workspace, Masking paradigm, tDCS, Conscious access, transcranial electric stimulation, tACS