Modulatory Effects of Personalized Transcranial Magnetic Stimulation (TMS) on Heart-Brain Coupling in Individuals With Depressive Tendencies

NCT07753473 | Recruiting

• 1 other identifier: 20260721
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study focuses on individuals with depressive tendencies and investigates the regulatory effects of Transcranial Magnetic Stimulation (TMS)-guided by personalized functional connectivity mapping-on heart-brain coupling in this population, while also exploring the underlying mechanisms.Participants will undergo 3T functional magnetic resonance imaging (fMRI) scans, followed by four different types of neurostimulation: stimulation targeting individualized Dorsolateral Prefrontal Cortex (DLPFC) -Subgenual Anterior Cingulate Cortex (sgACC) functional connectivity, stimulation targeting individualized DLPFC-insula functional connectivity, standard F3 targeting, and sham stimulation. The order of these stimulation sessions will be randomized. Researchers will simultaneously record the participants' electroencephalogram (EEG) and electrocardiography (ECG) signals before and after stimulation, and will record ECG in real-time during the stimulation. The primary objective of this study is to investigate the effects of DLPFC targeting specificity on metrics such as heart-brain coupling in individuals with depressive tendencies, thereby providing a basis for future research on objective assessment and personalized interventions for depression.

Conditions

fMRI Research; Heart-Brain Coupling; Depression Disorder

Keywords

Functional Connectivity; Individualized treatment; Transcranial magnetic stimulation

Outcome Measures

Primary Outcomes (3)

• TMS-induced heart-brain coupling

  By linking the stimulation rhythm to the inter-beat interval and quantifying the rhythmic effects of TMS, direct evidence is provided regarding the engagement of the prefrontal-vagal pathway.

  Perioperative. During the 7-minute-22-second treatment period under each stimulation condition.

• Phase-amplitude coupling

  It reflects the real-time exchange of information between the central nervous system and the autonomic nervous system, serving as an important biomarker of the functional status of the "brain-heart axis."

  Perioperative period. Specifically, within 10 minutes before and after each stimulus condition.

• Heartbeat-evoked potentials

  An EEG component extracted via time-locking to the cardiac R-peak. It precisely reflects the cerebral cortex's processing of cardiac afferent signals and interoceptive function.

  Perioperative period. Specifically, within 10 minutes before and after each stimulus condition.

Secondary Outcomes (3)

• EEG power spectrum

  Perioperative period. Specifically, within 10 minutes before and after each stimulus condition.

• Functional connectivity of brain networks

  Baseline. During the 6-minute-30-second fMRI scan.

• Transient Assessment Scale

  Baseline and Perioperative.

Study Arms (4)

Personalized stimulation targeting the functional connectivity between the DLPFC-sgACC.

EXPERIMENTAL

At this stage, participants will receive transcranial magnetic stimulation with a frequency of 10Hz and a stimulation intensity of 90% of the resting exercise threshold; Each stimulation lasts for 2 seconds, with a stimulation interval of 8 seconds; A total of 45 repeated stimuli were performed, each containing 20 pulses, for a total of 900 pulses. And the stimulation targets are located through a transcranial magnetic stimulation laser navigation system. The entire stimulation process lasts approximately 7.5 minutes.

Device: DLPFC-sgACC TMS

Personalized stimulation targeting DLPFC-insula functional connectivity

EXPERIMENTAL

At this stage, participants will receive transcranial magnetic stimulation with a frequency of 10Hz and a stimulation intensity of 90% of the resting exercise threshold; Each stimulation lasts for 2 seconds, with a stimulation interval of 8 seconds; A total of 45 repeated stimuli were performed, each containing 20 pulses, for a total of 900 pulses. And the stimulation targets are located through a transcranial magnetic stimulation laser navigation system. The entire stimulation process lasts approximately 7.5 minutes.

Device: DLPFC-insula TMS

Standard F3 Target Stimulation

EXPERIMENTAL

At this stage, participants will receive transcranial magnetic stimulation with a frequency of 10Hz and a stimulation intensity of 90% of the resting exercise threshold; Each stimulation lasts for 2 seconds, with a stimulation interval of 8 seconds; A total of 45 repeated stimuli were performed, each containing 20 pulses, for a total of 900 pulses. And the stimulation targets are located through 10-20 international standard lead EEG positioning caps. The entire stimulation process lasts approximately 7.5 minutes.

Device: 10-20 F3 TMS

sham stimulation

SHAM COMPARATOR

At this stage, participants will receive transcranial magnetic stimulation with a frequency of 10Hz and a stimulation intensity of 90% of the resting exercise threshold; Each stimulation lasts for 2 seconds with an interval of 8 seconds. Using a transcranial magnetic stimulation laser navigation system to locate stimulation targets, rotate the stimulation coil 90 degrees to apply false stimulation. The entire stimulation process lasts approximately 7.5 minutes.

Device: sham TMS

Interventions

DLPFC-insula TMS DEVICE

Transcranial magnetic stimulation was applied to the dorsolateral prefrontal cortex (DLPFC); the specific insular subregion exerting the greatest negative influence on the left DLPFC was identified based on Granger causality connectivity. Stimulation parameters were as follows: frequency of 10 Hz, intensity of 90% of the resting motor threshold (RMT), a 2-second stimulation duration followed by an 8-second inter-stimulus interval, and 45 repeated sequences (each comprising 20 pulses) for a total of 900 pulses, resulting in a total session duration of approximately 7.5 minutes.

Personalized stimulation targeting DLPFC-insula functional connectivity

DLPFC-sgACC TMS DEVICE

Transcranial magnetic stimulation was applied to the dorsolateral prefrontal cortex, with individualized targeting of the region in the left dorsolateral prefrontal cortex showing the strongest negative functional correlation with the subgenual anterior cingulate cortex. The stimulation parameters were: frequency of 10 Hz, intensity of 90% of the resting motor threshold (RMT), 2-second stimulation duration, and 8-second inter-stimulus interval; each sequence comprised 20 pulses, with 45 sequences repeated for a total of 900 pulses, resulting in a total session duration of approximately 7.5 minutes.

Personalized stimulation targeting the functional connectivity between the DLPFC-sgACC.

10-20 F3 TMS DEVICE

Transcranial magnetic stimulation was applied to the dorsolateral prefrontal cortex, targeting the F3 site based on the international 10-20 system. The stimulation parameters were as follows: frequency of 10 Hz, intensity of 90% RMT, 2-second stimulation duration, 8-second inter-train interval, and 20 pulses per train; a total of 45 trains were delivered (900 pulses in total), with a single session lasting approximately 7.5 minutes.

Standard F3 Target Stimulation

sham TMS DEVICE

A form of sham transcranial magnetic stimulation-either inactive or sensory-matched-designed to simulate the sensation of stimulation associated with device activation without delivering therapeutic frequencies.

sham stimulation

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18-30 years;
• Recent feelings of low mood and presence of depressive symptoms;
• Physically healthy, with no history of neurological disorders;
• No participation in other neuromodulation experiments within the past month;
• Normal hearing and normal (or corrected-to-normal) vision;
• PHQ-9 score \> 5 and BDI-II score \> 13;
• Avoidance of staying up late, alcohol consumption, and excessive caffeine intake prior to the experiment;
• (1) Aged 18-30 years; (2) No significant symptoms of depression and no history of neuropsychiatric disorders; (3) Physically healthy with no history of neurological disorders; (4) No participation in other neuromodulation experiments within the past month; (5) Normal hearing and normal (or corrected-to-normal) vision; (6) PHQ-9 score \< 5 and BDI-II score \< 13; (7) Avoidance of staying up late, alcohol consumption, and excessive caffeine intake prior to the experiment; (8) Able and willing to cooperate with the completion of scale assessments.

You may not qualify if:

• History of head trauma (including neurosurgery), stroke, elevated intracranial pressure, or other brain-related disorders;
• History of epileptic seizures or family history of epilepsy;
• Receipt of TMS or other neuromodulation stimulation within the past month;
• Presence of intracranial or internal metallic foreign bodies, electrodes made of silver or gold, or metal prostheses;
• Presence of devices potentially affected by TMS, such as pacemakers, drug pumps, cochlear implants, or implanted brain stimulators;
• Severe or recent cardiac, pulmonary, or hematopoietic system disorders, or other neurological diseases;
• Clinically diagnosed moderate-to-severe depressive disorder;
• Substance abuse, alcohol dependence, etc.;
• Current active suicidal ideation or suicidal behavior; Refusal to sign the informed consent form.

Sponsors & Collaborators

• Xidian University: lead

Study Sites (1)

Xidian University

Xi'an, Shaanxi, 71000, China

RECRUITING

Central Study Contacts

Xue-Juan, Yang

CONTACT

13227038185; xjyang@xidian.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2026
• First Posted: August 7, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: August 7, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)