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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
7
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: The procedure for sham stimulation will be identical, but it will last for 2 minutes instead of 30 minutes.
University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, United States
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.
Time frame: 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.
Time frame: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after
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.
Time frame: Baseline, study completion (an average of 2 weeks)
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).
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after
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