Anxiety, Stress Related Disorder
Conditions
Brief summary
The aim of this study is to examine the effects of transcranial electrical stimulation on processes associated with fear extinction in healthy humans.
Detailed description
Research links the processes of fear conditioning and extinction to the treatment of anxiety and stress-related disorders. Moreover, considerable translational research examines the neural correlates of these processes. However, virtually no research in humans manipulates neural correlates of these processes, which limits basic-clinical integration. The present study aimed to use transcranial electrical stimulation (tES) to modulate processes associated with fear extinction in order to assess the potential utility of tES in enhancing exposure-based treatment. To this end, healthy participants underwent a three-day fear conditioning and extinction paradigm. Participants were randomly assigned into 3 groups, differing in terms of tES applied during the extinction learning phase (Day 2) and targeting the medial prefrontal cortex: 1) direct current (DC) stimulation, aimed at enhancing extinction learning; 2) alternate current (AC) stimulation, aimed at interfering with reconsolidation of the fear memory activated during the extinction phase; and 3) sham stimulation. The outcome measures (outlined next) involve the assessment of extinction recall during a test phase (Day 3). Successful modulation of extinction learning by tES would be reflected in enhanced extinction recall.
Interventions
DEVICESham stimulation (1.5 milliampere,30 seconds)
DEVICEDC stimulation (1.5 milliampere, 20 minutes)
DEVICEAC stimulation (1.5 milliampere,1.5 Hertz frequency)
Sponsors
Tel Aviv University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Exclusion criteria
* Self-reported major psychiatric condition * Screening specific for electrical stimulation (psychotropic medication, metal implants in head, epilepsy or seizure history)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Galvanic Skin Response (GSR) | During three-day experimental task | GSR was measured throughout the task using 2 standard electrodes on the fingers. Measurement units were in micro-Siemens; scores were square-root-transformed (a common method in GSR studies). A higher level of GSR in response to stimuli is taken to reflect greater physiological fear response, and thus worse in the context of the relevance of the study conditions to the treatment of anxiety disorders. Scores were collected in response to presentation of the CS+ (the stimulus conditioned to be associated with an aversive outcome) and the CS- (the stimulus not conditioned to be associated with any outcome). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Self-reported Fear Rankings | During three-day experimental task | Participants marked how fearful they are of stimuli used in the task on a single 10-point scale (1=not afraid, 10=extremely afraid). Higher scores therefore reflect greater fear and are worse in the context of treatment for anxiety disorders. Scores were collected in response to presentation of the CS+ (the stimulus conditioned to be associated with an aversive outcome) and the CS- (the stimulus not conditioned to be associated with any outcome). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sham Sham electrical stimulation
Sham stimulation (1.5 milliampere,30 seconds) | 15 |
| DC: Direct Current Direct current electrical stimulation
DC stimulation (1.5 milliampere, 20 minutes) | 15 |
| AC: Alternating Current Alternating current electrical stimulation
AC stimulation (1.5 milliampere,1.5 Hertz frequency) | 15 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | DC: Direct Current | AC: Alternating Current | Sham | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 15 Participants | 15 Participants | 45 Participants |
| Age, Continuous | 23 years STANDARD_DEVIATION 3 | 25 years STANDARD_DEVIATION 5 | 27 years STANDARD_DEVIATION 7 | 25 years STANDARD_DEVIATION 6 |
| Region of Enrollment Israel | 15 Participants | 15 Participants | 15 Participants | 45 Participants |
| Sex: Female, Male Female | 9 Participants | 8 Participants | 5 Participants | 22 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 10 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Galvanic Skin Response (GSR)
GSR was measured throughout the task using 2 standard electrodes on the fingers. Measurement units were in micro-Siemens; scores were square-root-transformed (a common method in GSR studies). A higher level of GSR in response to stimuli is taken to reflect greater physiological fear response, and thus worse in the context of the relevance of the study conditions to the treatment of anxiety disorders. Scores were collected in response to presentation of the CS+ (the stimulus conditioned to be associated with an aversive outcome) and the CS- (the stimulus not conditioned to be associated with any outcome).
Time frame: During three-day experimental task
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham | Galvanic Skin Response (GSR) | CS (conditioned stimulus)+ | .45 micro-Siemens | Standard Deviation 0.38 |
| Sham | Galvanic Skin Response (GSR) | CS- | .23 micro-Siemens | Standard Deviation 0.25 |
| DC: Direct Current | Galvanic Skin Response (GSR) | CS (conditioned stimulus)+ | .56 micro-Siemens | Standard Deviation 0.57 |
| DC: Direct Current | Galvanic Skin Response (GSR) | CS- | .54 micro-Siemens | Standard Deviation 0.54 |
| AC: Alternating Current | Galvanic Skin Response (GSR) | CS (conditioned stimulus)+ | .65 micro-Siemens | Standard Deviation 0.46 |
| AC: Alternating Current | Galvanic Skin Response (GSR) | CS- | .24 micro-Siemens | Standard Deviation 0.38 |
Secondary
Self-reported Fear Rankings
Participants marked how fearful they are of stimuli used in the task on a single 10-point scale (1=not afraid, 10=extremely afraid). Higher scores therefore reflect greater fear and are worse in the context of treatment for anxiety disorders. Scores were collected in response to presentation of the CS+ (the stimulus conditioned to be associated with an aversive outcome) and the CS- (the stimulus not conditioned to be associated with any outcome).
Time frame: During three-day experimental task
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham | Self-reported Fear Rankings | CS+ | 3.8 units on a scale | Standard Deviation 2.5 |
| Sham | Self-reported Fear Rankings | CS- | 3.2 units on a scale | Standard Deviation 2 |
| DC: Direct Current | Self-reported Fear Rankings | CS+ | 4.7 units on a scale | Standard Deviation 2.1 |
| DC: Direct Current | Self-reported Fear Rankings | CS- | 2.5 units on a scale | Standard Deviation 1.2 |
| AC: Alternating Current | Self-reported Fear Rankings | CS+ | 5.3 units on a scale | Standard Deviation 2.5 |
| AC: Alternating Current | Self-reported Fear Rankings | CS- | 2.7 units on a scale | Standard Deviation 2.2 |