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| ID | Type | Description | Link |
|---|---|---|---|
| P60AA011605 | U.S. NIH Grant/Contract | View source |
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The study was terminated due to the death of the Principal Investigator.
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| Name | Class |
|---|---|
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | NIH |
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The goal of this study is to learn whether a single non-invasive brain stimulation alpha-transcranial alternating current stimulation (alpha-tACS) session changes measures of excitability in the prefrontal cortex. It will also learn whether these changes predict differences in habitual action selection in a laboratory task and whether the effects depend on alcohol use history. The main questions it aims to answer are:
Does alpha-tACS reduce habitual action selection by reducing excitability in the prefrontal cortex? Is alpha-tACS most effective in reducing habitual action selection in hazardous drinkers who engaged in binge-drinking during adolescence?
Researchers will compare alpha-tACS to sham stimulation to see if alpha-tACS changes habitual action selection by changing prefrontal excitability.
Participants will:
Visit the lab for behavioral training Visit the imaging center for an MRI session Visit the lab to receive alpha-tACS or sham stimulation during behavioral testing and undergo EEG recordings before and after stimulation Visit the imaging center for a repeat MRI session Provide a small sample of blood from a finger-prick in the first and last visits.
This study is designed to probe the role of the balance between excitatory (E) and inhibitory (I) signaling (E/I) in key nodes of control circuitry in mediating the relationship between alcohol misuse and inflexible behavior. In addition, the investigators aim to determine whether adolescent binge alcohol exposure amplifies the effects of binge exposure in adulthood. The investigators will accomplish this goal via a single multi-session study. Participants (n=66) will comprise three groups: adults self-reporting high risk drinking [World Health Organization (WHO) risk levels 2, 3, or 4], with (n=22) or without (n=22) a history of adolescent alcohol misuse (AIE), and lifetime low risk drinking adults (WHO risk levels 0 or 1; n=22).
Design: a 3-session study that includes an initial screening session and behavioral training (Session 1), behavioral testing and a magnetic resonance imaging (MRI) scan session (Session 2), bifrontal 10Hz-transcranial alternating current stimulation (tACS; true or sham) during behavioral testing with pre- and post-electroencephalogram (EEG) recording in a resting-state, followed by a second MRI scan session (Session 3). The investigators predict that adolescent and adult binge history will have interacting effects on E/I balance indices derived from EEG and magnetic resonance spectroscopy (MRS) and on behavioral flexibility measured in the Hidden Association between Images Task (HABIT) Test and that E/I balance indices will mediate the relationship between alcohol misuse and behavioral flexibility. The investigators also propose to test a causal relationship between E/I balance and behavioral flexibility by testing whether 10Hz-tACS to bilateral dorsolateral prefrontal cortex (dlPFC) alters habitual action selection in the HABIT Test in proportion to its effects on the dlPFC 1/f EEG slope and/or the MRS-derived gamma-amino-butyric acid (GABA)/glutamate+glutamine (Glx) ratio. The investigators predict that changes in indices of E/I balance induced by tACS will inversely associate with changes in habitual response selection. The investigators will collect a small amount of blood from a finger prick in Sessions 1 and 3 will use the collected dried blood spots to measure inflammatory markers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 10Hz bi-frontal tACS | Experimental | For Session 3, participants will complete a Habitual Association between Images Task (HABIT) Test Session in the Howell Hall Neurostimulation Core Lab or electroencephalogram (EEG) Core Lab, which is located one floor below the Boettiger Lab. Participants will receive either 10Hz bi-frontal transcranial alternating current stimulation (tACS) or sham tACS. 10 Hz bi-frontal tACS: Alternating current stimulation is delivered by an XCSITE 100 device (Pulvinar Neuro, Chapel Hill, NC), through three conductive carbon-rubber electrodes. Electrodes are placed over the apex of the head (Cz) and the prefrontal cortex bilaterally (F3 and F4). Stimulation is delivered during the second half of the HABIT Test session. Stimulation parameters: 2mA peak-to-peak 10Hz sine-wave flanked by 10 second linear envelope ramps in and out for a total duration of 30 min and 20 seconds. |
|
| sham tACS | Sham Comparator | Sham transcranial alternating current stimulation (tACS): The procedure for sham stimulation will be identical, but the actual stimulation will last for 2 minutes instead of 30 minutes. Participants generally report that stimulation is felt most strongly at the beginning of active stimulation, before they adjust to the sensation. Sham stimulation is meant to mimic this progression in terms of tactile salience. Stimulation is delivered for 2 minutes at the beginning of the HABIT reversal task, flanked by 10 second linear envelope ramps. The stimulating electrodes are left on the head until completion of the HABIT task, as is the case in active stimulation. There is no visual or auditory indication to the participant or researcher when the 2-minute sham stimulation period has ended, allowing the sham stimulation condition to feel similar to active stimulation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 10 Hz transcranial alternating current stimulation (tACS) | Other | 10 Hz bi-frontal tACS: Alternating current stimulation is delivered by an XCSITE 100 device (Pulvinar Neuro, Chapel Hill, NC), through three conductive carbon-rubber electrodes. Electrodes are placed over the apex of the head (Cz) and the prefrontal cortex bilaterally (F3 and F4). Stimulation is delivered during the second half of the HABIT Test session. Stimulation parameters: 2mA peak-to-peak 10Hz sine-wave flanked by 10 second linear envelope ramps in and out for a total duration of 30 min and 20 seconds. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Proportion of Errors | In the HABIT task participants are trained to associate abstract images on the computer screen with specific responses (button presses). They initially learn two stimulus-response pairings and then practice these two pairings at the beginning of each session; these are referred to as the familiar (FAM) sets. At sessions 2 and 3 they also learn two new stimulus-response pairings, which are referred to as the novel (NOV) sets and which they do not encounter at later sessions. During sessions 2 and 3 they undergo a reversal test, during which the correct responses for one familiar set and one novel set are changed, and they must learn the new correct responses by trial and error. The outcome measure here is the proportion of total errors made in response to the devalued familiar set during the reversal test that are perseverative errors, or errors in which they respond with a button press that was previously correct but is no longer correct. | Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after |
| Change in Prefrontal GABA:Glutamate/Glutamine Ratio | The researchers will evaluate the difference in the gamma-aminobutyric acid (GABA):glutamate/glutamine ratios in the left dorsolateral prefrontal cortex, measured via single voxel magnetic resonance spectroscopy (MRS) at rest. | Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after |
| Measure | Description | Time Frame |
|---|---|---|
| Change in C-reactive Protein | The researchers will measure the effect of transcranial alternating current stimulation (tACS) of bilateral dorsolateral prefrontal cortex on C-reactive protein. | Baseline, study completion (an average of 2 weeks) |
| Change in Interleukin-6 (IL-6) |
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Inclusion Criteria:
• 22-50 years old
For RISK group only:
For RISK+ Adolescent binge alcohol (AIE) group only:
For Control (CON) group only:
Exclusion Criteria:
Any individual who meets one or more of the following criteria will be excluded from participation [excluding positive breath alcohol concentration (BAC), urine drug screen, psychiatric diagnoses, and color blindness, all will be self-reported]:
If a participant should have an exclusion criterion arise in the course of their participation (e.g. pregnancy or psychotic episode), their participation in the study will end unless the circumstances are transitory in nature (e.g. positive breath alcohol or urine drug screen).
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| Name | Affiliation | Role |
|---|---|---|
| Charlotte A Boettiger, PhD | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina, Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21072168 | Background | Zaehle T, Rach S, Herrmann CS. Transcranial alternating current stimulation enhances individual alpha activity in human EEG. PLoS One. 2010 Nov 1;5(11):e13766. doi: 10.1371/journal.pone.0013766. | |
| 26361052 | Background | Wood W, Runger D. Psychology of Habit. Annu Rev Psychol. 2016;67:289-314. doi: 10.1146/annurev-psych-122414-033417. Epub 2015 Sep 10. |
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Brief summary of the assessment schedule for data that will eventually be shared with the NIAAADA:
In this 3-visit study, eligibility is first determined at the screening and randomization visit; dried blood spot measures of inflammatory markers will also be collected. In visit 2, measures of baseline habitual action selection in the HABIT, structural MRI, baseline resting-state fMRI, and single-voxel MRS measuring GABA and glutamate/glutamine will be collected. At visit 3, resting-state EEG before and after 10Hz- or sham-tACS, as well as habitual action selection in the HABIT during 10Hz- or sham-tACS, as well as repeat structural and functional MRI and MRS, and dried blood spot collection following 10Hz- or sham-tACS will be collected. Demographic, psychometric, and substance-related information will be collected via REDCap at the participant's convenience. Data will be uploaded to the PI's NIMH Data Archive (NDA) account by established deadlines.
Upon approval of the study data structure by the NIMH Data Archive (NDA), data will be uploaded every six months.
For each manuscript based on findings from this project, investigators will submit to the NDA: data, list of variables, analytic plan, and results.
The researchers will determine who will have access to which aspects of the project data based on NIH's data access principles. The researchers will provide access to person-level data for research purposes only, based on Data Use Certifications. Data on UNC servers will be made available to investigators with appropriate IRB approval and Data Use Agreements.
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| ID | Title | Description |
|---|---|---|
| FG000 | 10Hz Active tACS in Controls | Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants complete a Habitual Association between Images Task (HABIT) while receiving 10Hz bi-frontal transcranial alternating current stimulation (tACS) delivered via an XCSITE 100 device through electrodes placed over Cz, F3, and F4. Stimulation parameters consist of 2mA peak-to-peak 10Hz sine-wave with 10-second ramps in and out, lasting 30 minutes and 20 seconds during the second half of the HABIT task. |
| FG001 | Sham tACS in Controls | Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants complete a HABIT task while receiving sham tACS. Electrodes are placed identically to active stimulation (Cz, F3, F4), but actual stimulation lasts only 2 minutes at the task beginning with 10-second ramps. Electrodes remain on the head throughout the task to maintain blinding. |
| FG002 | 10Hz Active tACS in Current High-Risk Drinkers | Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants complete a HABIT task while receiving 10Hz bi-frontal tACS delivered via an XCSITE 100 device through electrodes placed over Cz, F3, and F4. Stimulation parameters consist of 2mA peak-to-peak 10Hz sine-wave with 10-second ramps in and out, lasting 30 minutes and 20 seconds during the second half of the HABIT task. |
| FG003 | Sham tACS in Current High-Risk Drinkers | Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants complete a HABIT task while receiving sham tACS. Electrodes are placed identically to active stimulation (Cz, F3, F4), but actual stimulation lasts only 2 minutes at the task beginning with 10-second ramps. Electrodes remain on the head throughout the task to maintain blinding. |
| FG004 | 10Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking | Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants complete a HABIT task while receiving 10Hz bi-frontal tACS delivered via an XCSITE 100 device through electrodes placed over Cz, F3, and F4. Stimulation parameters consist of 2mA peak-to-peak 10Hz sine-wave with 10-second ramps in and out, lasting 30 minutes and 20 seconds during the second half of the HABIT task. |
| FG005 | Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking | Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants complete a HABIT task while receiving sham tACS. Electrodes are placed identically to active stimulation (Cz, F3, F4), but actual stimulation lasts only 2 minutes at the task beginning with 10-second ramps. Electrodes remain on the head throughout the task to maintain blinding. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Study terminated prior to enrollment of participants into the "10 Hz Active tACS in Current High-Risk Drinkers," "10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking," or "Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking" Arms.
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| ID | Title | Description |
|---|---|---|
| BG000 | 10Hz Active tACS in Controls | Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants received active 10Hz bi-frontal tACS. |
| BG001 | Sham tACS in Controls |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Proportion of Errors | In the HABIT task participants are trained to associate abstract images on the computer screen with specific responses (button presses). They initially learn two stimulus-response pairings and then practice these two pairings at the beginning of each session; these are referred to as the familiar (FAM) sets. At sessions 2 and 3 they also learn two new stimulus-response pairings, which are referred to as the novel (NOV) sets and which they do not encounter at later sessions. During sessions 2 and 3 they undergo a reversal test, during which the correct responses for one familiar set and one novel set are changed, and they must learn the new correct responses by trial and error. The outcome measure here is the proportion of total errors made in response to the devalued familiar set during the reversal test that are perseverative errors, or errors in which they respond with a button press that was previously correct but is no longer correct. | Study terminated prior to enrollment of participants into the "10 Hz Active tACS in Current High-Risk Drinkers," "10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking," or "Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking" Arms. | Posted | Mean | Standard Deviation | proportion of perseverative errors | Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after |
From the time of signing informed consent through study completion, up to two weeks.
Study terminated prior to enrollment of participants into the "10 Hz Active tACS in Current High-Risk Drinkers," "10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking," or "Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking" Arms.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 10Hz Active tACS in Controls | Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants received active 10Hz bi-frontal tACS. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Grace Elliott, MA | University of North Carolina at Chapel Hill | 919-843-9193 | gelliott@unc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 2, 2024 | Jan 9, 2026 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 19, 2024 | Jan 9, 2026 | ICF_001.pdf |
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Study design consists of 3 groups of participants:
Within each group (n=22), participants will be randomly assigned to either the 10Hz tACS (stim) group or the sham tACS (sham) group.
Study design requires randomly assigning individuals to a stimulation group after completing Session 1. Prior to study onset, Dr. Boettiger will create a randomization table in which stimulation type (true or sham) is pseudo randomly ordered within groups, stratified by sex. Dr. Boettiger will provide assignment to the study team based on this predefined randomization table in order to ensure balanced sex and group for each stimulation type.
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The study team will be provided a numeric code to enter into the XCSITE 100 tACS system, which will conceal the stimulation parameters from the study team, ensuring double blinding. The XSCITE 100 device allows for the programming of stimulation codes corresponding to sham or active stimulation, both of which are set to a total duration of 30 minutes, allowing for reliable double-blinding.
|
| sham transcranial alternating current stimulation (tACS) | Other | Sham tACS: The procedure for sham stimulation will be identical, but it will last for 2 minutes instead of 30 minutes. |
|
The researchers will measure the effect of transcranial alternating current stimulation (tACS) of bilateral dorsolateral prefrontal cortex on interleukin-6 (IL-6). |
| Baseline, study completion (an average of 2 weeks) |
| Change in Tumor Necrosis Factor-alpha (TNF-alpha) | The researchers will measure the effect of transcranial alternating current stimulation (tACS) of bilateral dorsolateral prefrontal cortex on tumor necrosis factor-alpha (TNF-alpha). | Baseline, study completion (an average of 2 weeks) |
| Change in Functional Connectivity Between the Bilateral dlPFC and the aIC | The effect of 10Hz-tACS on resting-state functional connectivity between the bilateral dorsolateral prefrontal cortex (dlPFC) and anterior insular cortex (aIC) was quantified as the Fisher Z-transformed Pearson correlation coefficient. The BOLD timeseries for regions of interest were first extracted and then transformed into Z-scores using the Fisher r-to-z transformation. The Z-score represents the number of standard deviations away from the mean of the functional connectivity distribution. A Z-score of 0 represents the mean connectivity in the sample, with positive values indicating greater connectivity after stimulation, and a negative Z-score indicating less connectivity after stimulation. | Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after |
| Change in Functional Connectivity Between the dlPFC and Limbic Striatum | The effect of 10Hz-tACS on resting-state functional connectivity between the bilateral dorsolateral prefrontal cortex (dlPFC) and limbic striatum was quantified as the Fisher Z-transformed Pearson correlation coefficient. The BOLD timeseries for regions of interest were first extracted and then transformed into Z-scores using the Fisher r-to-z transformation. The Z-score represents the number of standard deviations away from the mean of the functional connectivity distribution. A Z-score of 0 represents the mean connectivity in the sample, with positive values indicating greater connectivity after stimulation, and a negative Z-score indicating less connectivity after stimulation. | Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after |
| Change in Functional Connectivity Between aIC and Limbic Striatum | The effect of 10Hz-tACS on resting-state functional connectivity between the aIC and limbic striatum was quantified as the Fisher Z-transformed Pearson correlation coefficient. The BOLD timeseries for regions of interest were first extracted and then transformed into Z-scores using the Fisher r-to-z transformation. The Z-score represents the number of standard deviations away from the mean of the functional connectivity distribution. A Z-score of 0 represents the mean connectivity in the sample, with positive values indicating greater connectivity after stimulation, and a negative Z-score indicating less connectivity after stimulation. | Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after |
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Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants received sham bi-frontal tACS. |
| BG002 | 10 Hz Active tACS in Current High-Risk Drinkers | Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received active 10Hz bi-frontal tACS. |
| BG003 | Sham tACS in Current High-Risk Drinkers | Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received sham bi-frontal tACS. |
| BG004 | 10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking | Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received active 10Hz bi-frontal tACS. |
| BG005 | Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking | Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received sham bi-frontal tACS. |
| BG006 | Total | Total of all reporting groups |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Primary | Change in Prefrontal GABA:Glutamate/Glutamine Ratio | The researchers will evaluate the difference in the gamma-aminobutyric acid (GABA):glutamate/glutamine ratios in the left dorsolateral prefrontal cortex, measured via single voxel magnetic resonance spectroscopy (MRS) at rest. | Study terminated prior to enrollment of participants into the "10 Hz Active tACS in Current High-Risk Drinkers," "10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking," or "Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking" Arms. | Posted | Mean | Standard Deviation | ratio | Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after |
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| Secondary | Change in C-reactive Protein | The researchers will measure the effect of transcranial alternating current stimulation (tACS) of bilateral dorsolateral prefrontal cortex on C-reactive protein. | While the protocol was not modified, no post-stimulation blood samples were obtained due to session 3 time constraints. As a result, change-from-baseline values for the planned biomarker outcomes could not be generated. In addition, the baseline samples were not analyzed because the study team no longer had the required laboratory expertise or funding to conduct the assays following the death of the Principal Investigator. | Posted | Baseline, study completion (an average of 2 weeks) |
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| Secondary | Change in Interleukin-6 (IL-6) | The researchers will measure the effect of transcranial alternating current stimulation (tACS) of bilateral dorsolateral prefrontal cortex on interleukin-6 (IL-6). | While the protocol was not modified, no post-stimulation blood samples were obtained due to session 3 time constraints. As a result, change-from-baseline values for the planned biomarker outcomes could not be generated. In addition, the baseline samples were not analyzed because the study team no longer had the required laboratory expertise or funding to conduct the assays following the death of the Principal Investigator. | Posted | Baseline, study completion (an average of 2 weeks) |
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| Secondary | Change in Tumor Necrosis Factor-alpha (TNF-alpha) | The researchers will measure the effect of transcranial alternating current stimulation (tACS) of bilateral dorsolateral prefrontal cortex on tumor necrosis factor-alpha (TNF-alpha). | While the protocol was not modified, no post-stimulation blood samples were obtained due to session 3 time constraints. As a result, change-from-baseline values for the planned biomarker outcomes could not be generated. In addition, the baseline samples were not analyzed because the study team no longer had the required laboratory expertise or funding to conduct the assays following the death of the Principal Investigator. | Posted | Baseline, study completion (an average of 2 weeks) |
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| Secondary | Change in Functional Connectivity Between the Bilateral dlPFC and the aIC | The effect of 10Hz-tACS on resting-state functional connectivity between the bilateral dorsolateral prefrontal cortex (dlPFC) and anterior insular cortex (aIC) was quantified as the Fisher Z-transformed Pearson correlation coefficient. The BOLD timeseries for regions of interest were first extracted and then transformed into Z-scores using the Fisher r-to-z transformation. The Z-score represents the number of standard deviations away from the mean of the functional connectivity distribution. A Z-score of 0 represents the mean connectivity in the sample, with positive values indicating greater connectivity after stimulation, and a negative Z-score indicating less connectivity after stimulation. | Study terminated prior to enrollment of participants into the "10 Hz Active tACS in Current High-Risk Drinkers," "10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking," or "Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking" Arms. | Posted | Mean | Standard Deviation | Z-transformed correlation coefficient | Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after |
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| Secondary | Change in Functional Connectivity Between the dlPFC and Limbic Striatum | The effect of 10Hz-tACS on resting-state functional connectivity between the bilateral dorsolateral prefrontal cortex (dlPFC) and limbic striatum was quantified as the Fisher Z-transformed Pearson correlation coefficient. The BOLD timeseries for regions of interest were first extracted and then transformed into Z-scores using the Fisher r-to-z transformation. The Z-score represents the number of standard deviations away from the mean of the functional connectivity distribution. A Z-score of 0 represents the mean connectivity in the sample, with positive values indicating greater connectivity after stimulation, and a negative Z-score indicating less connectivity after stimulation. | Study terminated prior to enrollment of participants into the "10 Hz Active tACS in Current High-Risk Drinkers," "10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking," or "Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking" Arms. | Posted | Mean | Standard Deviation | Z-transformed correlation coefficient | Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after |
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| Secondary | Change in Functional Connectivity Between aIC and Limbic Striatum | The effect of 10Hz-tACS on resting-state functional connectivity between the aIC and limbic striatum was quantified as the Fisher Z-transformed Pearson correlation coefficient. The BOLD timeseries for regions of interest were first extracted and then transformed into Z-scores using the Fisher r-to-z transformation. The Z-score represents the number of standard deviations away from the mean of the functional connectivity distribution. A Z-score of 0 represents the mean connectivity in the sample, with positive values indicating greater connectivity after stimulation, and a negative Z-score indicating less connectivity after stimulation. | Study terminated prior to enrollment of participants into the "10 Hz Active tACS in Current High-Risk Drinkers," "10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking," or "Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking" Arms. | Posted | Mean | Standard Deviation | Z-transformed correlation coefficient | Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after |
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| 0 |
| 3 |
| 0 |
| 3 |
| 0 |
| 3 |
| EG001 | Sham tACS in Controls | Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants received sham bi-frontal tACS. | 0 | 3 | 0 | 3 | 0 | 3 |
| EG002 | 10 Hz Active tACS in Current High-Risk Drinkers | Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received active 10Hz bi-frontal tACS. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG003 | Sham tACS in Current High-Risk Drinkers | Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received sham bi-frontal tACS. | 0 | 1 | 0 | 1 | 0 | 1 |
| EG004 | 10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking | Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received active 10Hz bi-frontal tACS. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG005 | Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking | Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received sham bi-frontal tACS. | 0 | 0 | 0 | 0 | 0 | 0 |
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