Investigating high- and low-frequency neuro-cardiac-guided TMS for probing the frontal vagal pathway

Manreena Kaur, Jessica A. Michael, Kate E. Hoy, Bernadette M. Fitzgibbon, Megan S. Ross, Tabitha A. Iseger, Martijn Arns, Abdul-Rahman Hudaib, Paul B. Fitzgerald

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20 Citations (Scopus)


Background: Investigating approaches for determining a functionally meaningful dorsolateral prefrontal cortex (DLPFC) stimulation site is imperative for optimising repetitive transcranial magnetic stimulation (rTMS) response rates for treatment-resistant depression. One proposed approach is neuro-cardiac-guided rTMS (NCG-TMS) in which high frequency rTMS is applied to the DLPFC to determine the site of greatest heart rate deceleration. This site is thought to index a frontal-vagal autonomic pathway that intersects a key pathway believed to underlie rTMS response. Objective: We aimed to independently replicate previous findings of high-frequency NCG-TMS and extend it to evaluate the use of low-frequency rTMS for NCG-TMS. Methods: Twenty healthy participants (13 female; aged 38.6 ± 13.9) underwent NCG-TMS on frontal, fronto-central (active) and central (control) sites. For high-frequency NCG-TMS, three 5 s trains of 10 Hz were provided at each left hemisphere site. For low-frequency NCG-TMS, 60 s trains of 1 Hz were applied to left and right hemispheres and heart rate and heart rate variability outcome measures were analysed. Results: For high-frequency NCG-TMS, heart rate deceleration was observed at the left frontal compared with the central site. For low-frequency NCG-TMS, accelerated heart rate was found at the right frontal compared with central sites. No other site differences were observed. Conclusion: Opposite patterns of heart rate activity were found for high- and low-frequency NCG-TMS. The high-frequency NCG-TMS data replicate previous findings and support further investigations on the clinical utility of NCG-TMS for optimising rTMS site localisation. Further work assessing the value of low-frequency NCG-TMS for rTMS site localisation is warranted.

Original languageEnglish
Pages (from-to)931-938
Number of pages8
JournalBrain Stimulation
Issue number3
Publication statusPublished - May 2020


  • Heart rate
  • Heart rate variability
  • High-frequency
  • Low-frequency
  • Neuro-cardiac-guided rTMS

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