This study investigates whether physiological signals recorded during transcranial magnetic stimulation (TMS) can predict which patients with major depression respond to treatment. Thirty-two adults with major depressive disorder receive an accelerated TMS protocol targeting the dorsomedial prefrontal cortex using a double-cone coil, delivered as four sessions per day over five to eight days. Heart rate is continuously monitored throughout every stimulation session using a chest-strap sensor, and electroencephalography (EEG) is recorded before and after treatment. Heart-brain coupling was assessed in a separate dedicated session after the target stimulation dose was reached.The primary clinical outcome is the change in depression severity measured by the Hamilton Depression Rating Scale (HAMD-17) from baseline to post-treatment. Prespecified physiological outcomes include stimulation-evoked heart rate deceleration, resting-state EEG parameters, and heart-brain coupling metrics. The aim is to evaluate whether these electrophysiological measures index target engagement and predict antidepressant response, potentially supporting their use as functional biomarkers for personalizing accelerated TMS in depression.

Inclusion Criteria:

• Adults aged 18 to 65 years
• Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of major depressive disorder, of at least moderate severity, confirmed by structured psychiatric interview
• Insufficient response to at least one adequate trials of antidepressant pharmacotherapy during the current episode
• Stable psychotropic medication regimen for at least 4 weeks prior to enrollment
• Ability to provide written informed consent

Exclusion Criteria:

• Cardiac arrhythmia or use of antiarrhythmic medication
• Benzodiazepine use exceeding the equivalent of 1 mg/day lorazepam
• Active suicidal ideation
• Comorbid psychiatric disorders other than anxiety disorders (including bipolar disorder, psychotic disorders, substance use disorders, and primary obsessive-compulsive disorder)
• Standard contraindications to transcranial magnetic stimulation, including history of seizure, intracranial metal implants, cochlear implants, or implanted neurostimulators
• Pregnancy
• Severe or unstable medical illness

De-identified individual-level data are not publicly available due to privacy and ethical restrictions on sensitive clinical data, but may be available from the corresponding author upon reasonable request and with appropriate ethics committee approval.