Recognizing EEG responses to active TMS vs. sham stimulations in different TMS-EEG datasets: A machine learning approach

Transcranial Magnetic Stimulation with simultaneous Electroencephalogram (TMS-EEG) allows for the assessment of neurophysiological properties of cortical neurons. However, TMS-evoked EEG potentials (TEPs) can be affected by components unrelated to TMS direct neuronal activation. Accurate, automatic tools are therefore needed to establish the quality of TEPs. We defined innovative comparisons, including effects of both baseline and post-TMS responses, while employing a sequence-to-sequence machine learning model to objectively ascertain active TMS vs. sham stimulation responses. Two independent TMS-EEG datasets including TMS and several sham stimulation conditions were obtained from the left motor area of 33 healthy individuals (total: 27,590 trials across datasets). A Bi-directional Long Short-Term Memory (BiLSTM) machine learning network was used to label each time point of the EEG signals as pertaining to TMS or sham conditions. For TMS conditions, post-stimulus vs. baseline/pre-stimulus EEG comparisons yielded moderate (60 %-75 %) single-trial accuracy and high-accuracy ('75 %) for 20 trials across datasets. For sham conditions, post- vs. baseline/pre-stimulus EEG comparisons yielded lower accuracy rates than for TMS conditions, except for unmasked auditory stimulation. Baseline/pre-stimulus TMS vs. baseline/pre-stimulus sham EEG comparisons showed chance-level accuracy. Conversely, post-stimulus TMS vs. post-stimulus sham EEG comparisons had moderate (single trial) to high (20 trial) accuracy, except for TMS with and without the click noise masking. Consistently across datasets, TEPs after active TMS are discernible from various sham stimulations after few trials and at the single-subject level using a BiLSTM ML model. This approach offers objective criteria to support TEP authenticity, which may help address ongoing discussions about TEP characteristics in TMS-EEG studies.