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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Stimulation was delivered using a MagPro R30 stimulator equipped with a Cool DB-80 double-cone coil (MagVenture A/S, Farum, Denmark). The stimulation site was localized using the 25% nasion-inion scalp heuristic for dorsomedial prefrontal cortex (dmPFC) targeting. The intermittent theta-burst stimulation (iTBS) protocol consisted of triplet 50 Hz bursts repeated at 5 Hz, applied as 2-second trains with 8-second inter-train intervals. Each session delivered 600 pulses sequentially to the left and right dmPFC (1,200 pulses per session), at a target intensity of 120% of the hemisphere-specific resting motor threshold. Four sessions were delivered per day with approximately 50-minute inter-session intervals. The total treatment course was 20 sessions over 5 days, extended to 30 sessions over 8 days for partial responders.
Istanbul University-Cerrahpaşa Cerrahpaşa Medical Faculty Psychiatry Department
Istanbul, Bakırköy, Turkey (Türkiye)
Change in Hamilton Depression Rating Scale (HAMD-17) Score
Depression severity was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and within 1 week after completion of the accelerated iTBS course. The HAMD-17 is a clinician-administered scale; scores range from 0 to 52, with higher scores indicating more severe depression. Treatment response was defined as a 50% or greater reduction from baseline HAMD-17 score, and remission as a post-treatment HAMD-17 score of 7 or lower.
Time frame: Baseline, Day 5, and Day 8 for extended courses
Heart rate deceleration during stimulation
Heart rate was continuously sampled at 1-second intervals using a Polar H10 chest strap during every stimulation session. Heart rate deceleration (HRD) was calculated as the percentage reduction from the 1-minute pre-stimulation baseline heart rate to the mean stimulation heart rate, using the formula: HRD (%) = \[(HR\_baseline - HR\_stimulation) / HR\_baseline\] x 100. HRD was computed across four parameters (all left-sided sessions, all right-sided sessions, highest-intensity left-sided sessions, highest-intensity right-sided sessions) and averaged per participant. Higher values indicate greater stimulation-induced heart rate deceleration.
Time frame: Through completion of the treatment course, up to 8 days
Change in Beck Depression Inventory (BDI)
Beck Depression Inventory (BDI), a self-report scale; total scores range from 0 to 63, with higher scores indicating more severe depression.
Time frame: Baseline, Day 5, and Day 8 for extended courses
Change in Beck Anxiety Inventory (BAI)
Beck Anxiety Inventory (BAI), a self-report scale; total scores range from 0 to 63, with higher scores indicating more severe anxiety.
Time frame: Baseline, Day 5, and Day 8 for extended courses
Change in Beck Scale for Suicide Ideation (BSS)
Beck Scale for Suicide Ideation (BSS), a self-report scale; total scores range from 0 to 38, with higher scores indicating greater suicidal ideation.
Time frame: Baseline, Day 5, and Day 8 for extended courses
Change in Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR16) Total Score
Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR16); total scores range from 0 to 27, with higher scores indicating more severe depression.
Time frame: Baseline, Day 5, and Day 8 for extended courses
Change in Clinical Global Impression - Severity (CGI-S)
Clinical Global Impression - Severity (CGI-S); scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients), with higher scores indicating greater illness severity.
Time frame: Baseline, Day 5, and Day 8 for extended courses
Hamilton Depression Rating Scale (HAMD-17) Total Score at 30-Day Follow-up
17-item Hamilton Depression Rating Scale (HAMD-17) assessed 30 days after completion of treatment; total scores range from 0 to 52, with higher scores indicating more severe depression.
Time frame: 30 days post-treatment
Resting State Quantitative EEG (qEEG) Spectral Power and Theta Cordance
Absolute spectral power in the delta, theta, alpha, and beta frequency bands, derived from quantitative resting-state EEG (qEEG) analysis. Power was computed across standard electrode regions. Prefrontal theta cordance, a quantitative EEG measure combining absolute and relative theta-band power at prefrontal electrodes, derived from resting-state qEEG analysis.
Time frame: Baseline and completion of treatment (Day5 or Day8 for extended courses)
Heart-Brain Coupling (HBC): Heart Rate Oscillation Power at the Stimulation Frequency
Heart-brain coupling (HBC), a parameter quantifying the strength of stimulation-induced heart rate deceleration, computed as the mean oscillation power of cardiac rate at the frequency determined by the stimulation train interval (Dijkstra et al., 2023). HBC ranges from 0 to 1. Measurements were obtained in a dedicated session using a 10 Hz protocol (50 pulses per train, 5-second train duration, 15 trains, 11-second inter-train interval), recorded with a Polar H10 chest strap and the HeartBrainConnect application. HBC was assessed sequentially at four sites per participant: left dmPFC, left dorsolateral prefrontal cortex (DLPFC), right dmPFC and right DLPFC. For each site, stimulation began at 28% below target intensity and increased by 2% per train, yielding 15 HBC values that were averaged to produce a per-site HBC value.
Time frame: Single dedicated measurement session after the target dose was reached, up to Day 8
EEG Microstate Temporal Parameters
Temporal parameters of the canonical resting-state EEG microstate classes (A, B, C, and D), including mean duration (milliseconds), occurrence (mean appearances per second), time coverage (percentage of recording time), and transition probabilities between classes. Parameters were derived from microstate segmentation of resting-state EEG recordings.
Time frame: Baseline and completion of treatment (Day5 or Day8 for extended courses)
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