Theta Phase-specific TMS to Modulate Prefrontal Activity

The Effects of Closed-loop TMS-EEG on Immediate Prefrontal Activity and Approach/Avoidance Behavior

The purpose of this study is to evaluate the causal link between the phase of ongoing theta oscillations in the prefrontal cortex and approach/avoidance (Ap/Av) behavior in adults using theta phase-specific transcranial magnetic stimulation (TMS).

Study Overview

• Status: Recruiting
• Conditions: Approach/Avoidance Behavior
• Intervention / Treatment: Device: Transcranial magnetic stimulation (TMS)

Detailed Description

Approach/avoidance (Ap/Av) behavior is a reliable marker of the emotional processes in the human brain and a robust predictor of mood disorders. Although existing scientific studies found a correlation between the approach/avoidance behavior and ongoing theta activity (3-7 Hz) in the left dorsolateral prefrontal cortex, the causal evidence of the phase-dependent role and strength of association between the prefrontal theta oscillations and approach/avoidance behavior are still unclear. Here, we will monitor brain oscillations in real-time non-invasively using electroencephalography during the approach/avoidance test and modulate theta peaks or troughs with transcranial magnetic stimulation. These data will provide novel understanding of the mechanisms of emotional processing in human brain.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alexander Opitz, PhD; Phone Number: 612-624-1118; Email: aopitz@umn.edu
• Study Contact Backup: Name: Ivan Alekseichuk, PhD; Phone Number: 612-624-1118; Email: ialeksei@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
      • Contact: Alexander Opitz, PhD; Phone Number: 612-624-1118; Email: aopitz@umn.edu
      • Contact: Ivan Alekseichuk, PhD; Phone Number: 612-624-1118; Email: ialeksei@umn.edu
      • Principal Investigator: Alexander Opitz, PhD
      • Sub-Investigator: Ivan Alekseichuk, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age between 18 and 65 years old.
2. Confident level of English language.

Exclusion Criteria:

1. Chronic condition that requires pharmacological treatment over the course of study participation.
2. Metallic or electric implant in the head, neck, or chest area or otherwise MRI-noncompatible implants.
3. History or evidence of seizures, head injuries with loss of consciousness, chronic neurological or mental disorder.
4. Pregnancy or breast-feeding.
5. History or evidence of alcohol or drug addiction.

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: TMS over the left prefrontal cortex; Transcranial magnetic stimulation (TMS) will be administrated with a figure-8 coil over the left dorsolateral prefrontal cortex (DLPFC) at the intensity of up to 120% of the individualized resting motor threshold (rMT). Stimulation will be performed during and for the duration of the cognitive test. Up to three TMS pulses will be delivered at the beginning of every test trial (each trial duration is 2-6 seconds). The total duration of the cognitive testing and stimulation per session is approximately 40 minutes (in 4 blocks with breaks in-between).	Device: Transcranial magnetic stimulation (TMS); TMS will be performed at either peaks or troughs of ongoing prefrontal theta oscillations (3-7 Hz) concurrently with the cognitive test at the beginning of every test trial. Theta oscillations will be monitored in real-time at the left dorsolateral prefrontal cortex using electroencephalography (EEG).
Sham Comparator: TMS over the head vertex; Transcranial magnetic stimulation (TMS) will be administrated with a figure-8 coil over the head vertex at the intensity of up to 120% of the individualized resting motor threshold (rMT). Stimulation will be performed during and for the duration of the cognitive test. Up to three TMS pulses will be delivered at the beginning of every test trial (each trial duration is 2-6 seconds). The total duration of the cognitive testing per session is approximately 40 minutes (in 4 blocks with breaks in-between).	Device: Transcranial magnetic stimulation (TMS); TMS will be performed at either peaks or troughs of ongoing prefrontal theta oscillations (3-7 Hz) concurrently with the cognitive test at the beginning of every test trial. Theta oscillations will be monitored in real-time at the left dorsolateral prefrontal cortex using electroencephalography (EEG).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reaction times in the Approach/Avoidance test	Reaction times (in milliseconds) in the Approach/Avoidance test during transcranial magnetic stimulation (TMS) at the peak vs. trough phases of ongoing prefrontal theta activity.	Immediate effect during stimulation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amplitude of TMS evoked potentials	Amplitude of transcranial magnetic stimulation (TMS)-evoked potentials (in microvolts) in ongoing electroencephalography (EEG) in the left prefrontal cortex during the stimulation at the peak vs. trough phases of ongoing prefrontal theta activity.	Immediate effect during stimulation

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Alexander Opitz, PhD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: June 8, 2022
• First Submitted That Met QC Criteria: June 8, 2022
• First Posted (Actual): June 13, 2022

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: July 17, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: STUDY00016214

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Full or partial access to the preprocessed data will be provided upon the request to the faculty / research staff of recognized research, medical, and educational institutions for educational and scientific purposes. The request should be sent via an institutional email and will be stored with the study materials. The request should include a short description of the scientific or educational aims.
• IPD Sharing Time Frame: Data will be shared only upon request after the study has ended (within 6 months).
• IPD Sharing Access Criteria: To receive access, the study investigators need to be contacted via an institutional e-mail including a short description of the scientific or educational aims.

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