Self-activation in Individuals With and Without Nicotine Dependence

Self-activation of Reward-related Brain Regions in Individuals With and Without Nicotine Dependence

The purpose of this study is to see if a non-medication intervention can increase motivation and reward processing to non-drug reward cues (for example, a picture of one's favorite food) in individuals with and without nicotine dependence by observing brain activity using electroencephalography (EEG) and/or functional magnetic resonance imaging (fMRI). The investigators hypothesize that learning to increase brain activity to non-drug cues may improve reward responses and motivation to non-drug cues, and for individuals who smoke, may eventually result in improved smoking cessation outcomes.

Study Overview

• Status: Terminated
• Conditions: Addiction Nicotine
• Intervention / Treatment: Device: Neurofeedback (from fMRI and/or EEG)

Detailed Description

The purpose of this study is to:

1. Assess the ability of adults with and without nicotine dependence (ND) to activate reward-related brain regions (e.g., ventral tegmental area (VTA), striatum, prefrontal cortex).
2. Evaluate whether fMRI and/or EEG neurofeedback improves the ability to increase reward-related brain activation in individuals with and without ND.
3. Examine the relationship between activation of reward-related regions via neurofeedback and dopamine availability (as assessed genetically).
4. Examine the effects of neurofeedback on clinically relevant outcomes, including reward responsivity and smoking related behaviors.

Procedure:

Prior to coming to a screening visit, all potential participants will undergo a phone pre-screening using an IRB approved phone script to pre-identify potentially eligible participants and to potentially decrease screen fail rate. These interested potential participants call or email the site in response to advertisements. The pre-screening will take place via phone. Participants who pass the pre-screening will complete some or all of the following visits: Screening, Camera Return Visit, Real-Time Neurofeedback Visit, Follow-up Phone Call/Debriefing.

Screening Visit:

Participants with nicotine dependence who pass the pre-screen will come to the lab at Duke to complete additional screening. All participants will undergo informed consent and those with ND will complete a urine drug screen. Participants who pass the urine drug screen (results are provided immediately) will complete questionnaires assessing mood, reward processing, and smoking behaviors.

Some participants may also be given a camera to use to capture pictures of personalized rewarding objects (e.g., picture of their pet, favorite book, favorite food). Participants may be loaned the camera for a period of 1-2 weeks to capture pictures of rewarding objects. We will instruct participants that the camera is to be used exclusively for capturing pictures for the study and not for personal use. Some participants may not be asked to take their own pictures for the study protocol and may simply be shown neutral or positive pictures/images/objects provided by the experimenters (e.g., shapes, pictures, etc.). Note, no aversive images will be shown to participants.

Camera Return Visit:

Participants who were loaned a camera will be asked to come to the lab at Duke to return the camera. The experimenters will ensure that enough pictures have been acquired to use during the experiment. Participants will be given guidelines about what types of pictures are required for the study. Participants are also free to provide photos they already have by uploading them to a secure website or brining them in on a device (e.g., thumbdrive).

Participants may also be asked to view and rate the pictures they provide along with neutral and positive images we provide (e.g., puppy, flower) on dimensions such as valence and arousal.

Real-Time Neurofeedback Visit:

Eligible participants will be scheduled for an fMRI and/or EEG session to assess and measure the ability to self-activate reward-related regions. The fMRI session will be conducted at the Duke Brain Imaging and Analysis Center (BIAC) and/or the UNC Biomedical Research Imaging Center (BRIC). Female participants will have a urine pregnancy test prior to fMRI scanning; the test will be verified to be negative in order to proceed with the scanning session. The EEG sessions will take place in private testing space in the Levine Science Research Center or the BIAC.

Participants may complete some or all of the following tasks: Reward Activation Task, Passive Viewing Task, and Reward Learning Task. All of these tasks aim to assess how adults can learn to interact with neurofeedback provided from an fMRI or EEG system. The tasks vary slightly from each other in terms of stimuli used (personalized pictures, images provided by the experimenters, feedback display, etc.). It may be possible that we will not be able to get a good EEG signal for some participants, based on equipment error or head size. If this occurs, participants will be debriefed. We will be sure to emphasize there was no error on the participant's part, and that sometime the signal is difficult to acquire for a variety of reasons.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kathryn Dickerson, PhD; Phone Number: 919-668-6091; Email: kathryn.dickerson@duke.edu
• Study Contact Backup: Name: R. Alison Adcock, MD, PhD; Phone Number: 919-681-7486; Email: alison.adcock@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Center for Cognitive Neuroscience

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. 18-45 years of age
2. Right handed
3. In good general health
4. Male or Female
5. For ND individuals: Self-reported smoking ≥ 5 combustible cigarettes per day
6. For ND individuals: Afternoon expired CO concentration of ≥ 8 ppm
7. For ND individuals: Is willing and able to abstain from smoking for a few hours

Exclusion Criteria:

1. History of chronic/significant medical condition
2. Current or past 6 month use of prescription medications for psychiatric conditions (e.g., depression, anxiety)
3. Current or past 6 month diagnosis of anxiety, bipolar disorder, depression, OCD, schizophrenia, psychosis, or personality disorder.
4. Current substance abuse or dependence or history within the last 6 months (other than nicotine for ND individuals)
5. For ND individuals: Positive drug test for anything other than marijuana
6. For ND individuals: Currently on nicotine replacement therapy
7. For ND individuals: Individuals who role their own cigarettes
8. For ND individuals: Daily cannabis use
9. For ND individuals: Consume more than 21 alcoholic drinks per week
10. For ND individuals: Use harder drugs (e.g., cocaine, methamphetamine) more than 10 times per year
11. For ND individuals: Currently taking medication that directly acts on the dopamine system (e.g., L-DOPA).
12. Inability to understand written and/or spoken English language
13. For MRI subjects: Claustrophobia or other contraindications to MRI scanning
14. For MRI subjects: If female, pregnancy as determined by urine pregnancy test on the day of MRI scanning
15. For MRI subjects: Presence of any metal in the body (e.g., implant, non-removable piercing, metal IUD)
16. For MRI subjects: Head injury resulting in loss of consciousness
17. For MRI subjects: Worked with metal (e.g., welding) or had an injury to the eye involving metal
18. For MRI subjects: Weigh more than 250 pounds

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reward-related Brain Region Feedback; Participants in this group will receive neurofeedback from a reward-related brain area (e.g., VTA, PFC) using EEG and/or fMRI during the experiment.	Device: Neurofeedback (from fMRI and/or EEG); During part of the task, a feedback display (e.g., thermometer stimulus) will be used to display the average brain activity for each participant. This signal will be acquired ~ every 1 second during the neurofeedback session and will dynamically update to reflect ongoing changes in brain activity. This continuously updated display is the primary feedback mechanism provided to the participant.
Sham Comparator: Noise Control; Participants in this group will receive sham neurofeedback. Participants will be debriefed at the end of the study.	Device: Neurofeedback (from fMRI and/or EEG); During part of the task, a feedback display (e.g., thermometer stimulus) will be used to display the average brain activity for each participant. This signal will be acquired ~ every 1 second during the neurofeedback session and will dynamically update to reflect ongoing changes in brain activity. This continuously updated display is the primary feedback mechanism provided to the participant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in reward-related brain activation	The investigators will examine the change in brain activation in the target region (e.g., VTA) during the task. This includes prior to, during, and following real-time neurofeedback.	Changes will be assessed across the task (~30 minutes) during the neurofeedback visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dopamine availability	Dopamine availability as assessed by genetic saliva samples	Collected once during the screening visit
Onset to smoking a cigarette	We will measure the time (in minutes) to when participants smoke their first cigarette following the MRI session	To occur following the neurofeedback session, up to 30 minutes following the session

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institutes of Health (NIH); National Center for Advancing Translational Sciences (NCATS); Brain & Behavior Research Foundation
• Investigators: Principal Investigator: R. Alison Adcock, MD, PhD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2018
• Primary Completion (Actual): June 28, 2022
• Study Completion (Actual): July 5, 2022

Study Registration Dates

• First Submitted: May 26, 2017
• First Submitted That Met QC Criteria: May 26, 2017
• First Posted (Actual): May 31, 2017

Study Record Updates

• Last Update Posted (Actual): July 21, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: EEG; reward; dopamine; motivation; real-time fMRI
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder
• Other Study ID Numbers: Pro00081458; UL1TR001117 (U.S. NIH Grant/Contract); 24393 (Other Grant/Funding Number: Brain & Behavior Research Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We plan to upload the fMRI statistical image maps on NeuroVault. We will do so after data collection is complete.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes