Vasovagal syncope as a specific side effect of rTMS: A frontal-vagal dose-finding study

Abstract

Abstract In the treatment of depression using repetitive Transcranial Magnetic Stimulation (rTMS), the intensity of stimulation is established based on the motor threshold (MT). Neuro-Cardiac-Guided TMS (NCG-TMS) is a newly developed method to optimize and individualize target location and to determine the intensity of treatment. In this method, the frontal threshold is established by evaluating the effect of stimulation of the DLPFC on heart rate variability and may be a better proxy for frontal excitability thresholds. In our pilot study (n=10), aimed at further optimizing NCG-TMS, one of the subjects experienced a syncope during the stimulation. In this case 10Hz stimulation (ITI 11 sec) was applied to the left Beam-F3 site in increasing intensities. Intensity was started at a low intensity and was increased in 5% points of machine output in 7 consequent steps, where the 5th intensity corresponded to 100% of the MT. ECG was measured simultaneously using a Brainquiry PET EEG device and BioExplorer software. ECG data were analyzed offline using Kubios software. During the assessment the resting heart rate dropped from 80BPM to 60BPM and HRV increased. The first cardiac effects already appeared at a stimulation intensity of 45% machine output, which represented 75% of the individual MT. The subject experienced feelings of dizziness and lightheadedness during the stimulation. The HR-data of the subject’s Fitbit collected over the prior month demonstrated an average HR of 67.6 BPM and a minimum HR of 65 BPM. This suggests that the DLPFC-rTMS specifically induced a HR-deceleration below the subject’s minimum HR. Presumably, the syncope was caused by overstimulation relative to the frontal excitability threshold. This may suggest that vasovagal syncope is a specific side effect of applying rTMS over the DLPFC. To avoid unwanted side effects of over stimulation, future studies should focus on frontal thresholding when applying rTMS. Keywords: Frontal Thresholding, Syncope, NCG-TMS, rTMS