Intra- and Interindividual Moderators of Prefrontal Excitability Investigated Using Simultaneous TMS With Neuroimaging

The simultaneous application of brain stimulation and neuroimaging offers significant potential for advancing basic neuroscience research and developing objective diagnostic and prognostic markers for mental disorders. The University Research Facility in Behavioral and Systems Neuroscience (UBSN), in collaboration with Principal Investigator Dr. Georg Kranz, recently acquired a TMS-compatible Magnetic Resonance Imaging (MRI) radio-frequency head coil. This cutting-edge equipment, developed by Dr. Martin Tik's research lab in Vienna, enables detailed mapping of both local and remote neural effects of intermittent theta-burst stimulation (iTBS)-a non-pharmacological treatment with proven efficacy for mental disorders. The upgraded setup addresses limitations of older concurrent TMS-fMRI systems, which struggled with image quality and practical applicability. The new system incorporates a multi-channel receiver array, allowing for high-resolution imaging at a fast rate. In this design, the TMS coil is positioned outside the imaging coil, with stimulation pulses passing through the thin imaging coil to reach the participant's brain and induce targeted neural changes. This advanced system enables the investigation of therapeutic network changes induced by iTBS by capturing acute brain responses during stimulation. Additionally, its sensitivity allows for dose-response assessments at the individual subject level. To leverage these advancements, pilot studies utilizing concurrent rTMS/fMRI are proposed to investigate intra- and interindividual moderators of therapeutic brain stimulation. The iTBS/fMRI study will focus on stimulation-induced hemodynamic changes in key subcortical structures and networks that mediate therapeutic responses to iTBS. Specifically, the study aims to examine changes in central limbic regions, including the subgenual anterior cingulate cortex (sgACC), anterior insula, amygdala, ventromedial prefrontal cortex, and orbitofrontal cortex. By exploring these regions, the mechanisms underlying the therapeutic effects of rTMS can be elucidated, providing a comprehensive understanding of how acute brain responses translate into clinical outcomes. This approach represents a significant step forward in advancing the understanding of iTBS, with the potential to refine and optimize this treatment for mental disorders.

Study Overview

• Status: Recruiting
• Conditions: Healthy Adults

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Georg S Kranz, PhD; Phone Number: 27664838; Email: georg.kranz@polyu.edu.hk

Study Locations

• China
  • Hong Kong, China
    • Recruiting
    • The Hong Kong Polytechnic University
    • Contact: Georg S Kranz, PhD; Phone Number: 27664838; Email: georg.kranz@polyu.edu.hk
    • Principal Investigator: Georg S Kranz, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Healthy adults

Description

Inclusion Criteria:

• consider yourself healthy in general and aged 18-60

Exclusion Criteria:

• current internal illness;
• current or former psychiatric or neurological illness;
• current or former alcohol or substance abuse;
• current or previous use of any psychotropic medication;
• current or previous use of any illicit drug;
• any ferromagnetic metal in your body;
• known or possible pregnancy, including the situation when the first day of a
• female's last menstrual period was more than 28 days ago; or
• any contraindication to TMS as assessed by Rossi et al.'s (2011) screening questionnaire.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Healthy experimental group; A group of healthy adults shall undergo concurrent 5 Hz iTBS/fMRI measurements
Active control group; A group of healthy adults shall undergo concurrent 2.5 Hz iTBS/fMRI measurements

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOLD signals	This repeated-measures study involves two participant groups. Each participant will attend one screening (visit 1) and two experimental visits (visits 2 and 3), with at least a 48-hour washout period between experimental visits. One group will receive active iTBS and the other active control iTBS during both experimental visits. We will assess iTBS-induced BOLD signal changes in the DLPFC and other brain regions (before, during, and after stimulation) and investigate modulation by interpersonal and day-to-day intrapersonal factors.	Before stimulation (3-5 minutes), during stimulation (3-5 minutes), and post-stimulation (up to 15 minutes after iTBS completion) on visit 2 and visit 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age	Participant's age in years.	visit 1
Gender	Participant's self-reported gender (e.g., male, female).	visit 1
Caffeine consumption	Self-reported caffeine consumption (e.g., number of cups of coffee) prior to the experiment	Before stimulation on visit 2 and visit 3
Mood states	Mood states will be assessed using the International Positive and Negative Affect Schedule - Short Form (I-PANAS-SF). Scale Description: The I-PANAS-SF is a self-report questionnaire consisting of two 5-item subscales: Positive Affect (PA) subscale: Score ranges from 5 (minimum) to 25 (maximum). Higher scores indicate a better outcome (i.e., greater positive affect). Negative Affect (NA) subscale: Score ranges from 5 (minimum) to 25 (maximum). Higher scores indicate a worse outcome (i.e., greater negative affect).	Before stimulation on visit 2 and visit 3
Physical activity	Assessment of self-reported physical activity level over the last 7 days, measured using the International Physical Activity Questionnaire (IPAQ). The IPAQ asks about the frequency (days) and duration (minutes) of walking, moderate-intensity activities, and vigorous-intensity activities.Self-reported physical activity (e.g., went to the gym or engaged in strenuous exercise before the experiment).	Before stimulation on visit 2 and visit 3
Sleep quality	Assessment of self-reported subjective sleep quality experienced "the previous night," measured using the Groningen Sleep Quality Scale (GSQS). The GSQS is a 15-item questionnaire (typically 14 items scored) where participants respond "yes" or "no" to questions about their sleep.	Before stimulation on visit 2 and visit 3
Time of the experiment	The time of day when the experiment was conducted (e.g., morning or afternoon)	Before stimulation on visit 2 and visit 3
Working Memory	Working memory performance as measured with 3-back task	After stimulation on visit 2 and visit 3
Vigilance	Vigilance levels as measured with the Sustained Attention to Response Task (SART)	After stimulation on visit 2 and visit 3
Attention	Attention levels as measured with Flanker task	After stimulation on visit 2 and visit 3
Childhood maltreatment	Assessment of self-reported history and severity of childhood maltreatment using a 33-item version of the Childhood Trauma Questionnaire (CTQ-33). The CTQ retrospectively measures experiences of emotional, physical, and sexual abuse, and emotional and physical neglect during childhood and adolescence.	Visit 1
Family history in first-degree relatives	Self-reported family history of mental disorders in first-degree relatives	Visit 1
Marital status	Participant's self-reported marital status (e.g., single, married, divorced, widowed)	Visit 1
Handedness	Participant's handedness assessed using the Edinburgh Handedness Inventory (EHI). The EHI is a self-report questionnaire measuring preference for hand use in a series of common activities.	Visit 1
Education years	Total number of years of formal education completed by the participant	Visit 1

Collaborators and Investigators

• Sponsor: The Hong Kong Polytechnic University
• Investigators: Principal Investigator: Georg S Kranz, PhD, The Hong Kong Polytechnic University

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: April 15, 2025
• First Submitted That Met QC Criteria: May 9, 2025
• First Posted (Actual): May 16, 2025

Study Record Updates

• Last Update Posted (Actual): May 16, 2025
• Last Update Submitted That Met QC Criteria: May 9, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: HSEARS20231218001

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: No