Related Experiment Video
Updated: Oct 31, 2025
Assessing Primary Motor Cortex Excitability and Excitability Modulation by Pairing Transcranial Magnetic Stimulation with Electromyography
Published on: October 7, 2025
Subthreshold stimulation intensity is associated with greater clinical efficacy of intermittent theta-burst
Jonathan C Lee1, Juliana Corlier1, Andrew C Wilson1
1TMS Clinical and Research Service, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior, And the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, 760 Westwood Plaza, Los Angeles, CA, 90024, USA.
Background:
Intermittent theta-burst stimulation priming (iTBS-P) can improve clinical outcome of patients with Major Depressive Disorder (MDD) who do not show early benefit from 10 Hz stimulation of left dorsolateral prefrontal cortex (DLPFC), also known as high-frequency left-sided (HFL) stimulation. The intensity and pulse number for iTBS-P needed to induce clinical benefit have not been systematically examined.
Objective:
To study the effect of intensity and pulse number on the clinical efficacy of iTBS-P.
Methods:
We conducted a retrospective review of 71 participants who received at least five sessions of HFL with limited clinical benefit and received iTBS-P augmentation for between 5 and 25 sessions. Intensity of iTBS-P priming stimuli ranged from 75 to 120% of motor threshold (MT) and pulse number ranged from 600 to 1800. Associations among intensity, pulse number, and clinical outcome were analyzed using a mixed methods linear model with change in IDS-SR as the primary outcome variable, priming stimulation intensity (subthreshold or suprathreshold), pulse number (<1200 or >1200 pulses), and gender as fixed factors, and number of iTBS-P treatments and age as continuous covariates.
Results:
Subjects who received subthreshold intensity iTBS-P experienced greater reduction in depressive symptoms than those who received suprathreshold iTBS-P (p = 0.011) with no effect of pulse number after controlling for stimulus intensity.
Conclusions:
Subthreshold intensity iTBS-P was associated with greater clinical improvement than suprathreshold stimulation. This finding is consistent with iTBS-P acting through homeostatic plasticity mechanisms.
