Theta Phase-specific TMS to Modulate Prefrontal Activity

November 24, 2025 updated by: University of Minnesota

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • 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
        • University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Reaction Times in the Approach/Avoidance Test
Time Frame: During the stimulation/task for each condition (approximately 6 minutes per run, 4 runs per condition).
Reaction time (in milliseconds) in the Approach/Avoidance task during transcranial magnetic stimulation (TMS). TMS was synchronized to either the peaks or troughs of the participant's left prefrontal theta waves, in a randomized and counterbalanced order. The preregistered primary outcome measure is the average difference in reaction times between peak- and trough-synchronized stimulation stimuli. This statistical contrast specifically highlights the role of theta phase in phase-aligned stimulation.
During the stimulation/task for each condition (approximately 6 minutes per run, 4 runs per condition).

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Amplitude of TMS Evoked Potentials
Time Frame: During the stimulation/task for each condition (approximately 6 minutes per run, 4 runs per condition).
Amplitude of transcranial magnetic stimulation (TMS)-evoked potentials (in microvolts) in ongoing electroencephalography (EEG) in the left prefrontal cortex during the TMS synchronized to either peaks or troughs of the participant's left prefrontal theta waves. The preregistered secondary outcome measure is the average difference in early absolute evoked potentials between peak- and trough-synchronized stimulation epochs. This statistical contrast specifically highlights the phase-specific effect of theta phase-aligned stimulation.
During the stimulation/task for each condition (approximately 6 minutes per run, 4 runs per condition).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Minnesota

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Mental Health (NIMH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Alexander Opitz, PhD, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 31, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 8, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 8, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 13, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 10, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 24, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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