title: Safety of different inter-train intervals for repetitive transcranial magnetic stimulation and recommendations for safe ranges of stimulation parameters.
abstract: Induction of a seizure in a normal subject with trains of repetitive transcranial magnetic stimulation (rTMS) applied in close succession suggested that short inter-train intervals, a parameter not considered in our previous safety studies, may not be safe. Here, we evaluate the safety of different inter-train intervals for rTMS in 10 healthy volunteers. Ten rTMS trains at 20 Hz for 1.6 s and a stimulus intensity of 110% of motor threshold (MT) were found to be safe at the inter-train interval of 5 s. However, inter-train intervals of 1 s or less were unsafe for trains of 20 Hz for 1.6 s and stimulus intensities higher than 100% of MT. Based on these results, we propose safety guidelines for inter-train intervals at different stimulus intensities. We also analyzed the stimulus parameters, used in 3 studies, that led to seizures in normal subjects. One seizure was due to short inter-train intervals, one was likely related to intense individual rTMS trains close to the limit of our previous safety recommendations, and one was likely due to a combination of these two factors. To provide an additional safety margin, we suggest reducing the duration for individual rTMS trains by 25% from our previous recommendations. Updated safety tables currently in use at our institution are provided.
authors.affiliation: Human Cortical Physiology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1428, USA.
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.forename: C
authors.initials: C
authors.lastname: Gerloff
authors.forename: J
authors.initials: J
authors.lastname: Classen
authors.forename: E M
authors.initials: EM
authors.lastname: Wassermann
authors.forename: M
authors.initials: M
authors.lastname: Hallett
authors.forename: L G
authors.initials: LG
authors.lastname: Cohen
mesh_terms: D000328:Adult; D004574:Electromagnetic Fields / Q000009:adverse effects; D004576:Electromyography; D019054:Evoked Potentials, Motor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000502:physiology*; D010812:Physical Stimulation / Q000009:adverse effects* / Q000379:methods; D012016:Reference Values; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects*