Flexibility, Alcohol Misuse, and Excitation

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.

Eligibility Criteria:
Inclusion Criteria:

* • 22-50 years old

  * Have a high school diploma or equivalent
  * Medically healthy
  * Fluent in English

For RISK group only:

* High risk alcohol use in the past month \[World Health Organization (WHO ) risk level 2-4\]
* No history of adolescent binge drinking

For RISK+ Adolescent binge alcohol (AIE) group only:

* High risk alcohol use in the past month (WHO risk level 2-4)
* High levels of adolescent alcohol use (4 or more binge drinking episodes before age 18)

For Control (CON) group only:

* Low risk alcohol use throughout the lifetime (WHO risk level 0-1)
* No history of adolescent binge drinking
* No lifetime history of Alcohol Use Disorder (AUD)

Exclusion Criteria:

* Any individual who meets one or more of the following criteria will be excluded from participation \[excluding positive breath alcohol concentration (BAC), urine drug screen, psychiatric diagnoses, and color blindness, all will be self-reported\]:

  * Lifetime history of a substance use disorder (SUD; including nicotine) but participants will not be excluded for an AUD.
  * Neurological disease such as dementia, seizures or head trauma
  * History of psychosis or psychotic episodes
  * Diagnosis of attention deficit hyperactivity disorder (ADHD)
  * Any systemic or inflammatory disease that could affect cognitive functioning (e.g., cancer, cardiovascular disease)
  * Any motor or visual disturbances that could hinder task performance (e.g., color blindness)
  * Use of psychoactive recreational drugs in the past month (excluding caffeine and alcohol)
  * Use of psychotropic medications in the past month including antidepressants, mood stabilizers, antipsychotics, anxiolytics, stimulants, or hypnotics (excluding antidepressant use when dosage has been stable for 1 month or longer)
  * Use of therapeutic brain stimulation \[e.g. transcranial magnetic stimulation (TMS) or electroconvulsive therapy (ECT)\] in the past month
  * Any history of brain surgery
  * History of migraine headaches
  * Pregnancy
  * Any brain implants or devices
  * First degree relative with primary epilepsy
  * Claustrophobia
  * Any magnetic resonance imaging (MRI) contraindication based on the University of North Carolina Biomedical Research Imaging Center's MRI safety checklist
  * Breath alcohol above 0.0% at time of session
  * Positive urine drug screen at time of session

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).