Test-retest reliability of the effects of continuous theta-burst stimulation

Objectives: The utility of continuous theta-burst stimulation (cTBS) as index of cortical plasticity is limited by inadequate characterization of its test-retest reliability. We thus evaluated the reliability of cTBS aftereffects, and explored the roles of age and common single-nucleotide polymorphisms in the brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) genes. Methods: Twenty-eight healthy adults (age range 21-65) underwent two identical cTBS sessions (median interval = 9.5 days) targeting the motor cortex. Intraclass correlation coefficients (ICCs) of the log-transformed, baseline-corrected amplitude of motor evoked potentials (ΔMEP) at 5-60 min post-cTBS (T5-T60) were calculated. Adjusted effect sizes for cTBS aftereffects were then calculated by taking into account the reliability of each cTBS measure. Results: ΔMEP at T50 was the most-reliable cTBS measure in the whole sample (ICC = 0.53). Area under-the-curve (AUC) of ΔMEPs was most reliable when calculated over the full 60 min post-cTBS (ICC = 0.40). cTBS measures were substantially more reliable in younger participants (< 35 years) and in those with BDNF Val66Val and APOE ϵ4-genotypes. Conclusion: CTBS aftereffects are most reliable when assessed 50 min post-cTBS, or when cumulative ΔMEP measures are calculated over 30-60 min post-cTBS. Reliability of cTBS aftereffects is influenced by age, and BDNF and APOE polymorphisms. Reliability coefficients are used to adjust effect-size calculations for interpretation and planning of cTBS studies.