Test-retest reliability of TMS-evoked potentials over fMRI-based definitions of non-motor cortical targets

ObjectiveThis study assessed the test-retest reliability of TMS-evoked potentials (TEPs) across two cortical regions--dorsolateral prefrontal cortex (DLPFC), and angular gyrus-- in comparison to motor cortex (M1), using individualized and literature-based targeting approaches. The study compared the reliability of single-pulse TMS, short-interval intracortical inhibition (SICI), and long-interval intracortical inhibition (LICI) protocols to evaluate TEP consistency in these regions. MethodsSeventeen healthy participants underwent two TMS-EEG sessions spaced by at least one week, with targets for DLPFC and angular gyrus identified using resting-state functional connectivity (RS) and Neurosynth-based functional overlays. Motor cortex was targeted using resting motor threshold (RMT). Early TEPs were quantified as peak-to-peak amplitude, in dBV. Test-retest reliability of early TEPs was calculated using the concordance correlation coefficient (CCC) for each region and protocol. ResultsM1 demonstrated the highest TEP reliability (CCCmean = 0.59), while DLPFC (CCCmean = 0.40) and angular gyrus (CCCmean = 0.45) showed lower reliability, particularly for anterior DLPFC targets. Neurosynth-based DLPFC targets exhibited slightly higher CCC values (mean CCC = 0.57) compared to RS-based targets (mean CCC = 0.30), but the difference was not statistically significant. No significant differences in reliability were found across single pulse and paired pulse protocols. Lateral targets, DLPFC and angular gyrus, showed lower reliability in comparison to motor cortex which might have been caused by muscle artifacts. ConclusionWhile individualized functional targeting methods provide advantages in engaging specific brain networks, their reliability for TEP measurements remains lower than the RMT-based approach for motor cortex. Future studies should integrate neuroimaging-based targeting with real-time TEP monitoring to enhance reliability in non-motor regions. This approach could enhance the precision of TMS-EEG protocols, especially for clinical applications targeting cortical regions like the DLPFC and angular gyrus.