Depression, Depressive Episode, Major Depressive Disorder, Premenstrual Dysphoric Disorder
Conditions
Keywords
tACS, transcranial alternating current stimulation, stimulation, heart rate variability, electroencephalogram, EEG
Brief summary
Purpose: Investigating the effects of non-invasive transcranial alternating current stimulation (tACS) on healthy participants and participants with mood disorders. Participants: 40 males and females, ages 18-65, with depressed mood; 40 healthy males and females, ages 18-65, free of neurological or psychiatric conditions. Procedures: This is a single visit study with two stimulation conditions (tACS and sham tACS). The session will begin with clinical assessments (including confirmation of diagnosis), followed by an interactive EEG task, then a 7 minute resting state EEG (2 minutes eyes closed, 5 minutes eyes open), followed by the stimulation session (40 minutes of tACS or sham tACS), followed by an additional 5 minute resting state EEG. The stimulation will involved 40 minutes of transcranial alternating current stimulation, 2 mA in amplitude and at individualized alpha frequency (determined by the 2 minutes eyes closed EEG recording; between 8 and 12Hz).
Detailed description
Participants will report for a study visit and will review and sign a consent form. Participants will complete several clinical assessments and also take a urine drug test and urine pregnancy test (if applicable). Eligibility will be re-assessed by the investigators before the participant moves on to the next phase. If the participant still qualifies, the participant will first be fitted with two 5x5cm electrodes placed over F3/F4 (10-20 measurement system) and one 5x7cm electrode placed over Cz. In addition, the participant will have a 128-channel EEG net placed on their head. Participants will provide a saliva sample to assess for brain-derived neurotrophic factor (BDNF), which may affect how the participant's brain responds to stimulation. Once the participant is fitted with this equipment, the participant will complete two interactive EEG tasks, then 2-minute resting state EEG with the participant's eyes closed, then a 5-minute resting state EEG with the participant's eyes open. Following these recordings, participants will respond to additional questionnaires. Immediately following this, the participant will receive 40 minutes of stimulation (tACS or sham tACS). During this stimulation, participants will sit comfortably upright and awake. After stimulation has completed, participants will respond to additional questionnaires. Once completed, participants will then complete an additional 5-minute resting state EEG with the participant's eyes open, as well as complete one of the additional interactive EEG tasks. Finally, participants will respond to a blinding questionnaire to assess if the participant thought that the participant received stimulation. Once complete, the participant will leave. This session is estimated to last about 4 hours.
Interventions
The participant will receive up to one minute of tACS stimulation until the stimulation fades. Sham stimulation mimics the skin sensations a participant would experience during a tACS session.
Transcranial alternating current stimulation (tACS) is a method of noninvasive brain stimulation in which weak electrical current are applied to the scalp in a sine wave pattern to induce cortical oscillations at the frequency at which they are applied.
Sponsors
National Institute of Mental Health (NIMH)
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
This is a double-blind study, meaning that neither the participant nor the experimenter knows what kind of stimulation the participant is receiving. An unblinded monitor (separate from the staff that interacts with the participant) is responsible for creating the stimulation codes that run each session and for ensuring that these codes worked correctly.
Intervention model description
This study recruits both participants currently experiencing a depressive episode (regardless of diagnosis) and those with no history of neurological or psychiatric illness. Randomization will occur in a 1:1 ratio for both of these groups, with half of each group receiving transcranial alternating current stimulation (tACS) at 10 Hz and the other half receiving placebo (or sham) stimulation.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
for individuals with depressed mood: * Ages 18-65 years * Hamilton Depression Rating Scale score \>8 * Capacity to understand all relevant risks and potential benefits of the study (informed consent) * Low suicide risk which will be determined through the use of both the Structured Clinical Interview for the DSM-5 and by scoring less than 3 (0,1, or 2) in the Hamilton rating depression scale. * Negative pregnancy test for female participants
Exclusion criteria
for individuals with depressed mood: * DSM-5 diagnosis of alcohol of substance abuse (other than nicotine) within the 12 months * DSM-5 diagnosis of alcohol or substance dependence (other than nicotine) within the last 12 months * DSM-5 diagnosis of personality disorder * Eating disorder (current or within the past 3 months) * Anything that, in the opinion of the investigator, would place the participant at increased risk or preclude the participant's full compliance with or completion of the study * Neurological disorders, including but not limited to history of seizures (except childhood febrile seizures and electro-convulsive therapy (ECT) induced seizures), dementia, history of stroke, Parkinson's disease, multiple sclerosis, cerebral aneurysm. * Medical or neurological illness (unstable cardiac disease, AIDS, malignancy, liver or renal impairment) or treatment for a medical disorder that could interfere with study participation * History of traumatic brain injury, reoccurring seizures or later cognitive rehabilitation or causing cognitive sequelae * History of childhood trauma (determined by the Childhood Trauma Questionnaire) * Prior brain surgery * Any brain devices/implants, including cochlear implants and aneurysm clips * Co-morbid neurological condition (i.e. seizure disorder, brain tumor) * Use of illicit drugs, confirmed by a drug test * Non English speakers * Pregnant or nursing females * Current use of benzodiazepines or anti-epileptic drugs Inclusion Criteria for healthy controls: * Ages 18-65 years * Hamilton Depression Rating Scale score ≤8 * Capacity to understand all relevant risks and potential benefits of the study (informed consent) * Negative pregnancy test for female participants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Alpha Frequency Electrical Activity in Left Frontal Cortex From Stimulation | 5 minute recording before and after intervention | Fast Fourier transform is applied to 5 minutes of EEG data before and after intervention. Primary outcome is the difference in alpha frequency amplitude (8-12 Hz) in the left frontal cortex from baseline as a result of intervention. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alpha Stimulation in Participants in a Depressive Episode Participants in a depressive episode will receive 2 mA of alternating current stimulation at individualized alpha stimulation (between 8 and 12 Hz; determined by an EEG recording prior to stimulation) for 40 minutes. tACS stimulation is delivered using the XCSITE100 Stimulator tACS.
XCSITE100 Stimulator tACS: Transcranial alternating current stimulation (tACS) is a method of noninvasive brain stimulation in which weak electrical current are applied to the scalp in a sine wave pattern to induce cortical oscillations at the frequency at which they are applied. | 21 |
| Sham Stimulation in Participants in a Depressive Episode Sham Stimulation mimics the physical effects of stimulation, with up to one minute of stimulation during the session. Sham stimulation to participants in a depressive episode is delivered using the XCSITE100 Stimulator Sham.
XCSITE100 Stimulator Sham: The participant will receive up to one minute of tACS stimulation until the stimulation fades. Sham stimulation mimics the skin sensations a participant would experience during a tACS session. | 20 |
| Alpha Stimulation in Healthy Participants Healthy participants will receive 2 mA of alternating current stimulation at individualized alpha stimulation (between 8 and 12 Hz; determined by an EEG recording prior to stimulation) for 40 minutes. tACS stimulation is delivered using the XCSITE100 Stimulator tACS.
XCSITE100 Stimulator tACS: Transcranial alternating current stimulation (tACS) is a method of noninvasive brain stimulation in which weak electrical current are applied to the scalp in a sine wave pattern to induce cortical oscillations at the frequency at which they are applied. | 21 |
| Sham Stimulation in Healthy Participants Sham Stimulation mimics the physical effects of stimulation, with up to one minute of stimulation during the session. Sham stimulation to healthy participants is delivered using the XCSITE100 Stimulator Sham.
XCSITE100 Stimulator Sham: The participant will receive up to one minute of tACS stimulation until the stimulation fades. Sham stimulation mimics the skin sensations a participant would experience during a tACS session. | 22 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Technical difficulty | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Alpha Stimulation in Participants in a Depressive Episode | Sham Stimulation in Participants in a Depressive Episode | Alpha Stimulation in Healthy Participants | Sham Stimulation in Healthy Participants |
|---|---|---|---|---|---|
| Age, Continuous | 27.796 years STANDARD_DEVIATION 11.831 | 28.429 years STANDARD_DEVIATION 11.902 | 27.65 years STANDARD_DEVIATION 12.227 | 28.095 years STANDARD_DEVIATION 11.432 | 27.182 years STANDARD_DEVIATION 12.133 |
| Alpha oscillations in left frontal cortex before stimulation | 0.818 microvolts STANDARD_DEVIATION 0.081 | 0.789 microvolts STANDARD_DEVIATION 0.088 | 0.812 microvolts STANDARD_DEVIATION 0.056 | 0.826 microvolts STANDARD_DEVIATION 0.076 | 0.845 microvolts STANDARD_DEVIATION 0.095 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 0 Participants | 1 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 70 Participants | 20 Participants | 19 Participants | 14 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 1 Participants | 1 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 4 Participants | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 54 Participants | 15 Participants | 16 Participants | 13 Participants | 10 Participants |
| Region of Enrollment United States | 84 Participants | 21 Participants | 20 Participants | 21 Participants | 22 Participants |
| Sex: Female, Male Female | 67 Participants | 17 Participants | 16 Participants | 17 Participants | 17 Participants |
| Sex: Female, Male Male | 17 Participants | 4 Participants | 4 Participants | 4 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 20 | 0 / 21 | 0 / 22 |
| other Total, other adverse events | 12 / 21 | 7 / 20 | 9 / 21 | 5 / 22 |
| serious Total, serious adverse events | 0 / 21 | 0 / 20 | 0 / 21 | 0 / 22 |
Outcome results
Primary
Change in Alpha Frequency Electrical Activity in Left Frontal Cortex From Stimulation
Fast Fourier transform is applied to 5 minutes of EEG data before and after intervention. Primary outcome is the difference in alpha frequency amplitude (8-12 Hz) in the left frontal cortex from baseline as a result of intervention.
Time frame: 5 minute recording before and after intervention
Population: One of the healthy participants that received sham stimulation could not be age and sex matched, therefore, we did not analyze this participant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alpha Stimulation in Participants in a Depressive Episode | Change in Alpha Frequency Electrical Activity in Left Frontal Cortex From Stimulation | -0.005 microvolts | Standard Deviation 0.022 |
| Sham Stimulation in Participants in a Depressive Episode | Change in Alpha Frequency Electrical Activity in Left Frontal Cortex From Stimulation | 0.008 microvolts | Standard Deviation 0.023 |
| Alpha Stimulation in Healthy Participants | Change in Alpha Frequency Electrical Activity in Left Frontal Cortex From Stimulation | 0.004 microvolts | Standard Deviation 0.017 |
| Sham Stimulation in Healthy Participants | Change in Alpha Frequency Electrical Activity in Left Frontal Cortex From Stimulation | 0.007 microvolts | Standard Deviation 0.022 |
Comparison: Interaction in the effect of tACS on left frontal alpha oscillation in the healthy group. Two-way interaction of within-participant factor of before/after tACS and between-participant factor of alpha-tACS/placebo.p-value: 0.6676ANOVA
Comparison: Interaction in the effect of tACS on left frontal alpha oscillation in the depressed group. Two-way interaction of within-participant factor of before/after tACS and between-participant factor of alpha-tACS/placebo.p-value: 0.0852ANOVA
Comparison: Main effect of alpha-tACS on session (before and after) on left frontal alpha oscillations across both groups (healthy and patient).p-value: 0.929ANOVA
Comparison: Difference in alpha oscillations after versus before in the depressed cohort (one-tailed Student's t-test) with the hypothesis to decrease pathologically elevate left frontal alpha oscillationsp-value: 0.195t-test, 1 sided
Comparison: Difference in alpha oscillations after versus before in the healthy cohort (one-tailed Student's t-test) run as a control analysisp-value: 0.8603t-test, 1 sided