Effects of Concurrent and Consecutive Repetitive Transcranial Magnetic Stimulation (rTMS) and Cognitive Bias Modification (CBM) (TMS CBM)

The goal of this study is to learn whether combining repetitive transcranial magnetic stimulation (rTMS) with a computerized behavioral intervention (imagery cognitive bias modification, CBM-I) reduces negative interpretation bias and mild-to-moderate depressive symptoms. The study will also examine neural changes in the dorsolateral prefrontal cortex (DLPFC) and whether timing of interventions affects outcomes.

The main questions it aims to answer are:

Does active TMS reduce negative interpretation bias and depressive symptoms more than sham TMS? Is delivering CBM-I concurrently with TMS more effective than delivering it consecutively (separate sessions) at reducing negative bias and depressive symptoms? Do combined rTMS + CBM-I approaches produce greater neural changes and improved cognitive control over self-referential interpretation than controls? Researchers will compare active TMS versus sham TMS, and concurrent versus consecutive delivery of CBM-I, to test effects on negative bias and depressive symptoms.

Participants will:

Receive either active rTMS or sham TMS targeting the DLPFC Complete imagery CBM-I sessions either concurrently with TMS or in separate (consecutive) sessions Undergo assessments of negative interpretation bias, depressive symptoms, and neural measures before and after the intervention

Study Overview

• Status: Recruiting
• Conditions: Depression - Major Depressive Disorder
• Intervention / Treatment: Device: TMS; Behavioral: Cognitive Bias Modification; Device: Sham TMS

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Richard Liu Mr. Liu; Phone Number: +85290971398; Email: richliu18@connect.hku.hk

Study Locations

• Hong Kong
  • Hong Kong Island
    • Quarry Bay, Hong Kong Island, Hong Kong
      • Recruiting
      • InnoCentre of Clinical Neuropsychology, The University of Hong Kong
      • Contact: Richard Mr. Liu; Phone Number: +85290971398; Email: richliu18@connect.hku.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18 years or above
• Right-handed
• Normal or corrected hearing and vision
• Obtained primary education or above
• Able to fluently read and understand Chinese
• Beck's Depression Inventory-II (BDI-II) score ranging from 14-28

Exclusion Criteria:

• History of severe physical disease, brain organic diseases, and neurological disorders (e.g., dementia, brain injury, stroke, epilepsy, Parkinson's disease)
• History of substance use/ dependence/ withdrawal
• Participants with intellectual disability based on IQ scores
• Participants with contraindications for rTMS such as foreign metal bodies, implant devices (cochlear implants) or history (personal or family) of seizure
• Participants who are not suitable to be scanned by magnetic resonance imaging (MRI) machine (e.g., claustrophobic, pregnant, metal in the body, hearing aids)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CC-R-CBM; Concurrent, Real TMS, CBM	Device: TMS; The rTMS group will receive 10 Hz stimulation to the left DLPFC at an intensity of 120% of the resting motor threshold of the right abductor pollicis brevis (APB) muscle with 4 sec trains and 11 sec intertrain intervals for 3000 pulses.Specifically in our study, we combine both intervention, but applying them concurrently and consecutively between groups.; Behavioral: Cognitive Bias Modification; Imagery CBM-I focuses on 2 cognitive aspects, mental imagery and interpretation. Participants will be presented with scenarios in which they have to imagine themselves to be in and practice constructing positive endings or interpretations for them.
Sham Comparator: CC-S-CBM; Concurrent, Sham TMS, CBM	Behavioral: Cognitive Bias Modification; Imagery CBM-I focuses on 2 cognitive aspects, mental imagery and interpretation. Participants will be presented with scenarios in which they have to imagine themselves to be in and practice constructing positive endings or interpretations for them.; Device: Sham TMS; The TMS coil will be rotated 90 degrees, and will not be delivering active stimulation to the participant. The intensity will be set to 30 and the TMS device will be active, generating enough sound effect but no real stimulation for sham control.
Active Comparator: CS-R-CBM; Consecutive, Real TMS, CBM	Device: TMS; The rTMS group will receive 10 Hz stimulation to the left DLPFC at an intensity of 120% of the resting motor threshold of the right abductor pollicis brevis (APB) muscle with 4 sec trains and 11 sec intertrain intervals for 3000 pulses.Specifically in our study, we combine both intervention, but applying them concurrently and consecutively between groups.; Behavioral: Cognitive Bias Modification; Imagery CBM-I focuses on 2 cognitive aspects, mental imagery and interpretation. Participants will be presented with scenarios in which they have to imagine themselves to be in and practice constructing positive endings or interpretations for them.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Bias	Measurement: Self-Referent Encoding Task Tool: PsychoPy Unit:Self-Referential Bias Index measured by positive and negative self-description affirmation	"From enrollment to the end of treatment at 4 weeks"
Depressive Symptoms	Measurement: Beck's Depressive Inventory-II Tool: Qualtrics Questionnaire Unit:Beck's Depressive Inventory-II Index	"From enrollment to the end of treatment at 4 weeks"
Resting State functional MRI	Measurement: resting-state functional MRI Image Tool: SIGNA Premier 3T wide-bore MRI scanner Unit: functional dicom images	"From enrollment to the end of treatment at 4 weeks"

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective Well Being	Measurement: Subjective Well-Being Scale Tool: Qualtrics Questionnaire Unit: Subjective Well-Being Index	"From enrollment to the end of treatment at 4 weeks"
Sleep Quality	Measurement: Pittsburgh Sleep Quality Index (PSQI) Tool: Qualtrics Questionnaire Unit: Sleep Quality Index	"From enrollment to the end of treatment at 4 weeks"
Anxiety Symptoms	Measurement: Beck Anxiety Inventory Task Tool: Qualtrics Questionnaire Unit: Anxiety Index	"From enrollment to the end of treatment at 4 weeks"
Structural MRI	Measurement: T1 Structural MRI Brain Image Tool: SIGNA Premier 3T wide-bore MRI scanner Unit: structural dicom images	"From enrollment to the end of treatment at 4 weeks"
Rumination Symptoms	Measurement: Rumination Response Scale (RRS) Task Tool: Qualtrics Questionnaire Unit: Rumination Index	"From enrollment to the end of treatment at 4 weeks"
Anhedonia Symptoms	Measurement: Dimensional Anhedonia Rating Scale Tool: Qualtrics Questionnaire Unit: Anhedonia Index	"From enrollment to the end of treatment at 4 weeks"
Cognitive Measures-Attention	Measurement: Conners Continuous Performance Tests - III Tool: CPT-III (Computer Task) Unit: Reaction Time	"From enrollment to the end of treatment at 4 weeks"
Cognitive Measures-Attention	Measurement: Conners Continuous Performance Tests - III Tool: CPT-III (Computer Task) Unit: Correct Responses and Error responses will be used to calculate a performance index of sustained attention	"From enrollment to the end of treatment at 4 weeks"

Collaborators and Investigators

• Sponsor: The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: EA230645

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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