Effect of Transcranial Alternative Current Stimulation at Alpha Frequency (α-tACS) on Stressed Healthy Subjects (CAF-TAS)

Biological, Neuropsychological and Electrophysiological Effect of Transcranial Alternative Current Stimulation at Alpha Frequency (α-tACS) on Stressed Healthy Subjects

stress. Notably, several studies reported that stress could alter impulsivity, source monitoring, and time perception.

Several mechanisms are involved in the response to a stress factor, among them the hypothalamic-pituitary-adrenal (HPA) axis. The cortisol reactivity (it means the cortisol secretion after the exposure to a standardized stress factor) is a reliable tool to assess the function of HPA. Cortisol secretion is bidirectionally influenced by the prefrontal cortex (PFC), which is involved in the expression and regulation of stress as well. The asymmetry of the alpha band (AFα) is a well known electrophysiological parameter to assess the function of PFC. More precisely, AFα is arising a growing interest, as it is believed to be correlated with the cortisol reactivity. Modifying this asymmetry could influence the stress response.

Transcranial Alternating Current Stimulation (tACS) consists in delivering a sinusoidal alternating current between two electrodes placed on the scalp at a predefined frequency. Previous studious reported that tACS, if delivered at the alpha frequency, increased the alpha band in the stimulated areas

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Procedure: Transcranial alternative current stimulation (tACS) at alpha frequency; Procedure: Sham stimulation

Detailed Description

The study will focus on the effect of tACS at alpha frequency (α-tACS), delivered on the dorsolateral prefrontal cortex, on the response to a stress factor.

In this study, while receiving a single α-tACS session, the participants will complete a standardized stress test combining cognitive stress (mental calculation) and physical stress (cold pressure): the Maastricht Acute Stress Test. The main objective aims at assessing the effect of a single session of tACS at alpha frequency, delivered on the dorsolateral prefrontal cortex, on the cortisol reactivity in healthy stressed subjects. In that study, the influence of α-tACS on other biological ; electrophysiological, neuropsychological parameters relevant for the stress response will be assessed also.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Aura
    • Bron, Aura, France, 69678 CEDEX
      • Recruiting
      • Centre Hospitalier le Vinatier
      • Contact: POULET EMMANUEL, PUPH; Phone Number: +33 0033437915120; Email: emmanuel.poulet@chu-lyon.fr
      • Contact: SARTELET Lydie; Phone Number: 0033437915531; Email: lydie.sartelet@ch-le-vinatier.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Right-handed Men and Women aged between 18 and 45
• If woman, hormonal contraception required
• Having given their written informed consent
• Affiliated with a social security scheme
• French speakers and readers

Exclusion Criteria:

• Contraindication to the exposure to exposure to tACS
• Current psychiatric disorder as classified in the DSM-5
• Regular intake of any psychotropic drug or Beta Blocker
• Recent exposure to a traumatic event
• Any debilitating condition making the experimental procedure not feasible
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active tACS stimulation; Transcranial alternative current stimulation (tACS) at alpha frequency Single session of tACS : 30 minutes, 2mA, frequency = 10Hz, both electrodes located on the dorsolateral prefrontal cortex (left and right)	Procedure: Transcranial alternative current stimulation (tACS) at alpha frequency; Single session of tACS
Placebo Comparator: Sham stimulation; Single session of tACS sham stimulation : both electrodes located on the dorsolateral prefrontal cortex (left and right) ; real current delivered for the first and last 30s of the total stimulation time (ramp-in and ramp-out)	Procedure: Sham stimulation; Single session of tACS sham stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) of the cortisol secretion after the stress task.	Samples of salivary cortisol will be repeatedly (10 occurences) collected during the experiment. The collection will take place before, during and after the stress task.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of α-tACS on the cortisol awakening response in stressed healthy subjects	Samples of morning salivary cortisol will be collected repeatedly (3 times) before experimental session (including the stress task and the tACS session). A last sample of morning salivary cortisol will be collected the following day	4 days
Effect of α-tACS on the molecular reactivity to stress	The expression level of different proteins implicated in the intracellular communication channel after the couple cortisol-glucocorticoid receptor was formed (namely : NR3C1) will be assessed. A blood sample will be collected and the expression level of the relevant genes will be assessed by qPCR	1 day
Effect of α-tACS on the molecular reactivity to stress	The expression level of different proteins implicated in the intracellular communication channel after the couple cortisol-glucocorticoid receptor was formed (namely : FKBP4) will be assessed. A blood sample will be collected and the expression level of the relevant genes will be assessed by qPCR	1 day
Effect of α-tACS on the molecular reactivity to stress	The expression level of different proteins implicated in the intracellular communication channel after the couple cortisol-glucocorticoid receptor was formed (namely : FKBP5) will be assessed. A blood sample will be collected and the expression level of the relevant genes will be assessed by qPCR	1 day
Effect of α-tACS on the molecular reactivity to stress	The expression level of different proteins implicated in the intracellular communication channel after the couple cortisol-glucocorticoid receptor was formed (namely : BAG1) will be assessed. A blood sample will be collected and the expression level of the relevant genes will be assessed by qPCR	1 day
Effect of α-tACS on the molecular reactivity to stress	The expression level of different proteins implicated in the intracellular communication channel after the couple cortisol-glucocorticoid receptor was formed (namely : PTGES3) will be assessed. A blood sample will be collected and the expression level of the relevant genes will be assessed by qPCR	1 day
Effect of α-tACS on the molecular reactivity to stress	The expression level of different proteins implicated in the intracellular communication channel after the couple cortisol-glucocorticoid receptor was formed (namely : HSP90AA1) will be assessed. A blood sample will be collected and the expression level of the relevant genes will be assessed by qPCR	1 day
Effect of α-tACS on the molecular reactivity to stress	The expression level of different proteins implicated in the intracellular communication channel after the couple cortisol-glucocorticoid receptor was formed (namely : HSPA1A) will be assessed. A blood sample will be collected and the expression level of the relevant genes will be assessed by qPCR	1 day
Effect of α-tACS on the asymmetry of the alpha band (AFα) in stressed healthy subjects	AFα refers to the average difference in alpha-band activity (typically8-13 Hz) between the left and right frontal areas (F3- F7 versus F4-F8, respectively). For a 5-minute block, AFα will be assessed by EEG recording while the participant is at resting state and only requested to alternatively open and close the eyes, according to a standardized procedure	1 day
Effect of α-tACS on the beta band in stressed healthy subjects	The participant will have to complete the Kirby Delay Discounting Task (DDT). Subjects are presented with a series of hypothetical choices of amount of reinforcer to be had instantaneously, and a larger reinforcer available after a fixed delay. (For example : "Would you prefer 37€ today or 80€ in 60 days?" The outcome will be the change in the number of immediate choices between before and after the stress period (ΔDDT) express in percent	1 day
Effect of α-tACS on source monitoring in stressed healthy subjects	Source monitoring refers to the cognitive processes involved in making attributions about the origins of mental experiences (for example : was this mental experience dreamt?, imagined?, really perceived? If this was perceived, was it produced by myself or by anybody else?". Two subtypes of source monitoring will be tested : the reality monitoring (RM) and the internal monitoring (IM). In each task the participant will be confronted with a list of words he/she will have to determine the source of. The outcome will be the proportion of false attributions, expressed in percent	1 day
Effect of α-tACS on impulsivity in stressed healthy subjects	The participant will have to complete the Kirby Delay Discounting Task (DDT). Subjects are presented with a series of hypothetical choices of amount of reinforcer to be had instantaneously, and a larger reinforcer available after a fixed delay. (For example : "Would you prefer 37€ today or 80€ in 60 days?") The outcome will be the change in the number of immediate choices between before and after the stress period (ΔDDT) express in percent	1 day
Effect of α-tACS on time perception in stressed healthy subjects	time perception refers to how the brain represents the temporal structure of events and of our environment. This ability can be assessed through different experimental designs. In this protocol, the participants will complete a time reproduction task, consisting in tapping at a defined frequency (1Hz) with a push-button. After a training phase (pressing the push-button while being guided), the participant will have to produce the same rhythm on his own. The outcome will be the mean difference between the reference interval (1s) and the time intervals executed by the participant, express in milliseconds	1 day

Collaborators and Investigators

• Sponsor: Hôpital le Vinatier

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: December 20, 2023
• First Submitted That Met QC Criteria: January 25, 2024
• First Posted (Actual): January 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 2023-A01368-37

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No