2025/07/15 by Martijn Arns, Nolan Williams, Jonathan Downar +3 · 1 voice · 1 citation
Medicine · Neuroscience · #Pain Management and Treatment #Transcranial Magnetic Stimulation Studies #Vagus Nerve Stimulation Research
paper · pdf · doi:10.1016/j.brs.2025.07.004
openalex created_date 2025/07/14 · openalex publication_date 2025/07/15 · openalex updated_date 2026/07/23
The inertness of sham controls in transcranial magnetic stimulation (TMS) studies, particularly those involving Transcutaneous Electrical Nerve Stimulation (TENS), remains controversial. Using heart-brain coupling (HBC) as a frontal-vagal engagement measure, we analyzed pilot data and data from two placebo-controlled accelerated intermittent theta burst stimulation (aiTBS) trials (combined N = 100). Active-TMS induced significantly stronger HBC compared to sham in both studies, with the effect size for TENS-sham considerably attenuated, and significantly stronger HBC for TENS-sham relative to SAINT-sham (d = 0.9). HBC in the TENS-sham group was associated with clinical improvement (d = 1.12), reflecting antidepressant effects of trigeminal nerve stimulation. These findings suggest TENS-sham should be seen as an active control condition, also controlling for trigeminal nerve stimulation, resulting in downstream vagal and cortical engagement and thus controlling for this non-specific effect of TMS. Future studies should be aware of this active effect and conduct power-analyses accordingly, modifying the expected effect size. Furthermore, HBC could be used to titrate the intensity of TENS-stimulation to minimize active effects.