Examining the Effects of Neural Stimulation on Inhibitory Control and Cigarette Smoking

Examining the Effects of Theta Burst Stimulation on Corticothalamic Mediated Inhibitory Control and Smoking Relapse Vulnerability

The purpose of this research study is to examine the effects of theta-burst Transcranial Magnetic Stimulation on inhibitory control and smoking among adult cigarette smokers.

Study Overview

• Status: Completed
• Conditions: Tobacco Use Disorder
• Intervention / Treatment: Device: Continuous Theta-burst stimulation (cTBS); Device: Intermittent Theta-burst stimulation (iTBS)

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65211
      • University of Missouri - Columbia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Be between the ages of 18 and 65.
2. Be in stable mental and physical health.
3. Be willing to provide informed consent.
4. Be able to comply with protocol requirements and likely to complete all study procedures.
5. Be a current nicotine dependent cigarette smoker (smoke ≥10 cigs/day) with a minimum smoking history of smoking an average of ≥ 10 cigs/day over the past two years.

Exclusion Criteria:

• 1. Contraindication to MRI (e.g., presence of metal in the skull, orbits or intracranial cavity, claustrophobia).

  2. Contraindication to TMS (history of neurological disorder or seizure, increased intracranial pressure, brain surgery, or head trauma with loss of consciousness for > 15 minutes, implanted electronic device, metal in the head, or pregnancy, as indicated by a positive urine pregnancy test at screening).

  3. Any use of substances that lower seizure threshold (such as thyroid medications or cocaine).

  4. History of autoimmune, endocrine, viral, or vascular disorder affecting the brain.

  5. History or MRI evidence of neurological disorder that would lead to local or diffuse brain lesions or significant physical impairment.

  6. Unstable cardiac disease, uncontrolled hypertension, severe renal or liver insufficiency, or sleep apnea.

  7. BAC greater than 0.0. 8. Any other condition or concern that in the Investigator's opinion would impact participant safety, compliance with study instructions, or potentially confound the interpretation of the study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intermittent Theta-burst stimulation (iTBS); Cross-over design - participants will receive both experimental treatments.	Device: Continuous Theta-burst stimulation (cTBS); Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected. Continuous TBS (cTBS) which is thought to temporarily dampen brain activity in that specific area.; Device: Intermittent Theta-burst stimulation (iTBS); Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected. Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected.
Experimental: Continuous Theta-burst stimulation (cTBS); Cross-over design - participants will receive both experimental treatments.	Device: Continuous Theta-burst stimulation (cTBS); Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected. Continuous TBS (cTBS) which is thought to temporarily dampen brain activity in that specific area.; Device: Intermittent Theta-burst stimulation (iTBS); Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected. Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Change in Behavioral Inhibition Between Baseline and 1 Hour Post Treatment.	Changes in errors of omission on an inhibitory control task performed prior to and immediately after cTBS, and changes in errors of omission on an inhibitory control task performed prior to and immediately after iTBS. Outcomes will be measured as the mean change in behavioral performance percent correct on inhibition trials between baseline and 1 hour post treatment. Scores on the inhibitory control task range from 0% correct to 100% correct, and the change from pre-post TBS is expressed as a percent increase or decrease in performance. Positive values represent an improved outcome, whereas negative values represent a worse outcome.	1 hour
The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 1 Hour Post Treatment.	Changes in self-reported craving to smoke will be assessed using the Questionnaire on Smoking Urges brief (QSUb) at 1 hour post session on each of three conditions (Baseline, cTBS, iTBS). The values are calculated as the mean of the scores between conditions at 1 hour post session. Scores on the QSUb range from 10 to 70. The lower the score, the better the outcome.	1 hour
The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 24hrs Post Treatment Between Conditions.	Changes in self-reported craving to smoke will be assessed using the Questionnaire on Smoking Urges brief (QSUb) at 24hrs post session on each of three conditions (Baseline, cTBS, iTBS). The values are calculated as the mean of the scores between conditions at 24 hours post session. Scores on the QSUb range from 10 to 70. The lower the score, the better the outcome.	24 hours
The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 48hrs Post Treatment Between Conditions.	Changes in self-reported craving to smoke will be assessed using the Questionnaire on Smoking Urges brief (QSUb) at 48hrs post session on each of three conditions (Baseline, cTBS, iTBS). The values are calculated as the mean of the scores between conditions at 48 hours post session. Scores on the QSUb range from 10 to 70. The lower the score, the better the outcome.	48 hours
The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Hyperdirect Brain Circuit Function Between Pre and Post Session.	Changes in inhibitory control task functional connectivity between the r.IFG and nodes within the hyperdirect pathway (r.SMA, r.STN) prior to and immediately after cTBS, and changes in inhibitory control task functional connectivity between the r.IFG and nodes within the hyperdirect pathway (r.SMA, r.STN) prior to and immediately after iTBS. Outcomes will be measured as the transformed correlation (rZ value) of BOLD functional connectivity collected during the inhibitory task. The higher the rZ, the better the outcome.	1 hour

Collaborators and Investigators

• Sponsor: University of Missouri-Columbia

Publications and helpful links

General Publications

• Froeliger B, McConnell PA, Bell S, Sweitzer M, Kozink RV, Eichberg C, Hallyburton M, Kaiser N, Gray KM, McClernon FJ. Association Between Baseline Corticothalamic-Mediated Inhibitory Control and Smoking Relapse Vulnerability. JAMA Psychiatry. 2017 Apr 1;74(4):379-386. doi: 10.1001/jamapsychiatry.2017.0017.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2019
• Primary Completion (Actual): April 25, 2021
• Study Completion (Actual): April 25, 2021

Study Registration Dates

• First Submitted: May 10, 2019
• First Submitted That Met QC Criteria: May 21, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Estimate): March 10, 2023
• Last Update Submitted That Met QC Criteria: March 9, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder
• Other Study ID Numbers: 00074836

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No