NCT05732207 · Johns Hopkins University
Cerebellar Involvement in Alcohol Use Disorder (AUD)
What this study is about
The goal of this observational and interventional study is to better understand the involvement of the cerebellum in the brain reward system in persons with alcohol use disorder (AUD). The main questions it aims to answer are: 1. What is the nature of cerebellar input to the ventral tegmental area (VTA) in the brain reward system, and how is it perturbed in AUD? 2.
View original scientific description
The goal of this observational and interventional study is to better understand the involvement of the cerebellum in the brain reward system in persons with alcohol use disorder (AUD). The main questions it aims to answer are: 1. What is the nature of cerebellar input to the ventral tegmental area (VTA) in the brain reward system, and how is it perturbed in AUD? 2. What is the relationship between measures of cerebellar integrity and magnitude of reward activation to alcohol-related cues in cerebellar, VTA and other brain reward structures? 3. What is the therapeutic potential of cerebellar transcranial direct current stimulation (tDCS) for modulating alcohol cue reactivity, associated alcohol craving, and cerebellar - VTA functional connectivity in the brain reward system? Persons with AUD will be compared with healthy control participants.
Interventions
PROCEDURE
cerebellar transcranial direct current stimulation
TDCS is a safe and non-invasive technique for modulating cortical excitability and behavior. TDCS, delivered via surface electrodes, induces an intracerebral current flow sufficient to achieve changes in cortical excitability. Anodal stimulation up-regulates cortical excitability, while cathodal stimulation decreases excitability.
Primary outcome measures
Craving for alcohol during the cue reactivity task as assessed by a rating scale
Time frame: 28 minutes
Participants will view blocks of pictures of alcohol and non-alcohol beverages, as well as control pictures and periods of rest. Participant rating of alcohol craving are obtained during the picture presentations using one of 5 buttons placed under their fingers, where 5 (thumb) = Extreme, 4=Severe, 3=Moderate, 2=Mild, 1=None
Resting state functional connectivity during tDCS
Time frame: 28 minutes
Participants will rest quietly during tDCS administration
Brain activation to alcohol cues
Time frame: 28 minutes
Participants will view blocks of pictures of alcohol and non-alcohol beverages, as well as control pictures and periods of rest. Brain activation will be measured from the fMRI signal on alcohol minus non-alcohol conditions.
Brain functional connectivity to alcohol vs non-alcohol cues
Time frame: 28 minutes
A psychophysiological interaction (PPI) analysis will be used to determine if brain connectivity between the cerebellum and reward areas changes when viewing alcohol versus non-alcohol pictures
Brain activation related to reward prediction during the monetary incentive task
Time frame: 18 minutes
The monetary incentive task is performed during fMRI scanning. Two different cue symbols (dollar sign vs circle) will cue participants to expect a $1 or $0 reward shortly after they press a button in response to seeing an "X" on the screen. These expectations will be learned in an initial Learning phase, where one symbol is always rewarded with $1 and the other with $0, and participants will be tested to ensure that they have learned the appropriate expectations. This Learning phase will be followed by a Testing phase in which the amount of reward (on reward trials) can be greater than, less than, or equal to expectation. Brain activation during reward prediction will be measured by the post-cue activation on dollar sign versus circle trials.
Brain functional connectivity related to reward prediction during the monetary incentive task
Time frame: 18 minutes
The monetary incentive task is performed during fMRI scanning. Two different cue symbols (dollar sign vs circle) will cue participants to expect a $1 or $0 reward shortly after they press a button in response to seeing an "X" on the screen. These expectations will be learned in an initial Learning phase, where one symbol is always rewarded with $1 and the other with $0, and participants will be tested to ensure that they have learned the appropriate expectations. This Learning phase will be followed by a Testing phase in which the amount of reward (on reward trials) can be greater than, less than, or equal to expectation. Functional connectivity between the cerebellum and reward structures during reward prediction will be measured by a PPI analysis that measures post-cue functional connectivity on dollar sign versus circle trials.
Brain activation to reward prediction error during the monetary incentive task
Time frame: 18 minutes
Two different symbols (circle vs triangle) will cue participants to expect a $1 or $0 reward shortly after they press a button in response to seeing an "X" on the screen. These expectations will be learned in an initial Learning phase, where one symbol is always rewarded with $1 and the other with $0, and participants will be tested to ensure that they have learned the appropriate expectations. This Learning phase will be followed by a Testing phase in which the amount of reward (on reward trials) can be greater than, less than, or equal to expectation. Brain activation to reward prediction error will be measured from the activation observed after the participant receives feedback on his/her winnings, by contrasting trials in which reward obtained is equal to the amount expected versus not equal to the amount expected.
brain functional connectivity to reward prediction error during the monetary incentive task
Time frame: 18 minutes
Two different symbols (circle vs triangle) will cue participants to expect a $1 or $0 reward shortly after they press a button in response to seeing an "X" on the screen. These expectations will be learned in an initial Learning phase, where one symbol is always rewarded with $1 and the other with $0, and participants will be tested to ensure that they have learned the appropriate expectations. This Learning phase will be followed by a Testing phase in which the amount of reward (on reward trials) can be greater than, less than, or equal to expectation. Functional connectivity between the cerebellum and reward structures to reward prediction error will be measured using a PPI on the connectivity that is observed after the participant receives feedback on his/her winnings, by contrasting trials in which reward obtained is equal to the amount expected versus not equal to the amount expected.
Percentage of trials with a conditioned response during the classical eyeblink conditional task
Time frame: 21 minutes
Eyeblink conditioning involves pairing a neutral stimulus, e.g. an auditory conditioned stimulus (CS), with an air puff to the eye region. This unconditioned stimulus (US) evokes an unconditioned response (UR) that is detected by measuring the eyeblink. After repeated pairings of the CS and US, participants learn to blink in response to the conditioned stimulus and before air puff onset. The CS-US pairing dependent eyeblink that anticipates the onset of the US is referred to as the conditioned response (CR).
Mean time (in milliseconds) at which peak of conditioned response occurs during the classical eyeblink conditional task
Time frame: 21 minutes
Eyeblink conditioning involves pairing a neutral stimulus, e.g. an auditory conditioned stimulus (CS), with an air puff to the eye region. This unconditioned stimulus (US) evokes an unconditioned response (UR) that is detected by measuring the eyeblink. After repeated pairings of the CS and US, participants learn to blink in response to the conditioned stimulus and before air puff onset. The CS-US pairing dependent eyeblink that anticipates the onset of the US is referred to as the conditioned response (CR).
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- completed at least 8 years of education
Exclusion criteria
- Estimated Intelligence Quotient (IQ) \< 90
- less than 5th grade reading level
- Left handed
- Non-fluent in English
- current drug use disorder other than alcohol (except nicotine and caffeine) and or recent drug use in the last 90 days
- Positive breath alcohol level at time of MRI scan or discrepancies between alcohol biomarker and self-report that cannot be resolved
- Exhibiting symptoms of alcohol withdrawal on visit 1 assessment
- Significant current psychiatric distress and or treatment
- History of any central nervous system disorder, presence of a seizure disorder, or use of anticonvulsant medication in the past 3 months
- any serious medical condition detected on assessment or by medical record review; or have liver function tests more than three times normal at screening
- History of metal implantation that would preclude MRI scanning; or other implants, pumps, pacemakers that would be contraindications for MRI scanning
- Abnormal MRI scan or history of significant closed head trauma
- Evidence of dementia
- For women, pregnancy
Where
- Baltimore, Maryland
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
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Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
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Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
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Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 11, 2026 · Source of record for eligibility and locations