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

Official title

Study on the Regulation of Heart-Brain Coupling in Individuals With Depressive Tendencies Using Transcranial Magnetic Stimulation (TMS) Based on Personalized Functional Connectivity

Overview

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.

Detailed description

This is an exploratory, randomized, single-blind, sham-controlled, within-subject crossover study designed to investigate the regulatory effects-and underlying mechanisms-of TMS (based on individualized functional connectivity targeting) on heart-brain coupling in individuals with depressive tendencies.

Participants will undergo structural and functional neuroimaging using a 3T MRI scanner. The imaging protocol includes a structural T1-weighted scan and a functional blood-oxygen-level-dependent (BOLD) scan, used for structural image registration and functional connectivity analysis to identify TMS stimulation targets.

In this study targeting individuals with depressive tendencies, each participant will undergo four distinct stimulation conditions: individualized DLPFC-sgACC functional connectivity targeting, individualized DLPFC-insula functional connectivity targeting, standard F3 targeting, and sham stimulation. The order of these four conditions will be balanced using a Latin square design to minimize sequence effects, learning effects, and carry-over effects between conditions; a minimum interval of 5 days will be maintained between experimental sessions. High-frequency Repetitive transcranial magnetic stimulation (rTMS) will be used for the intervention, with the following parameters: stimulation frequency of 10 Hz, intensity at 90% of resting motor threshold (RMT), 2-second stimulation duration, 8-second inter-train interval, 20 pulses per train, and 45 repetitions (totaling 900 pulses), resulting in a total session duration of approximately 7.5 minutes.

Primary measures include: Phase-Amplitude Coupling (PAC), which reflects real-time information exchange between the central and autonomic nervous systems and serves as a key biomarker for the functional status of the "brain-heart axis"; TMS-induced Heart-Brain Coupling (HBC), which quantifies the rhythmic effects of TMS and provides direct evidence regarding the engagement of the prefrontal-vagal pathway; Heartbeat-Evoked Potentials (HEP), an EEG component extracted via time-locking to the ECG R-peak, which precisely reflects cortical processing of cardiac afferent signals and interoceptive function; and Heart Rate Variability (HRV), which reflects the balance of sympathetic and parasympathetic regulation. Secondary measures include EEG power spectra, fMRI data, heart rate (HR), and clinical assessment scales.

Interventions

• Device DLPFC-insula TMS
  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
• Device DLPFC-sgACC TMS
  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 sequence
• Device 10-20 F3 TMS
  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.
• Device sham TMS
  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.

Primary outcome measures

• TMS-induced heart-brain coupling [Time frame: Perioperative. During the 7-minute-22-second treatment period under each stimulation condition.]
• Phase-amplitude coupling [Time frame: Perioperative period. Specifically, within 10 minutes before and after each stimulus condition.]
• Heartbeat-evoked potentials [Time frame: Perioperative period. Specifically, within 10 minutes before and after each stimulus condition.]

Secondary outcome measures (3)

• EEG power spectrum [Time frame: Perioperative period. Specifically, within 10 minutes before and after each stimulus condition.]
• Functional connectivity of brain networks [Time frame: Baseline. During the 6-minute-30-second fMRI scan.]
• Transient Assessment Scale [Time frame: Baseline and Perioperative.]

Eligibility criteria

Inclusion criteria

一、Inclusion criteria for the depressed group:

• 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;
• Able and willing to cooperate with the completion of scale assessments. 二、Inclusion criteria for healthy participants:

(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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Basic science

Study locations

China · 1 center

• Xidian University — Xi'an

Identifiers

NCT: NCT07753473 · 20260721

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗