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

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.

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.