Matching Corticospinal and Cortical Excitability along the motor cortex: TMS-EMG-EEG study

There is still no consensus on how to choose intensities for transcranial magnetic stimulation (TMS). The resting motor threshold (RMT), the intensity needed to evoke muscle contractions in the contralateral limb muscles, is a robust muscle-specific index of corticospinal excitability. RMT from one of the hand muscles is commonly used as a reference for TMS neuromodulation interventions and TMS-electroencephalography (EEG) studies. However, it only provides an indirect measure of cortical excitability, and even for the primary motor cortex (M1), we do not understand how cortical and corticospinal excitability correspond to each other. Indeed, it remains unclear whether cortical responses to TMS follow similar location-dependent patterns along the M1, and whether subthreshold stimulation can reliably engage cortical circuits relevant to motor output. Combining TMS with electromyography (EMG) and EEG, TMS-EMG-EEG, enables simultaneous assessment of corticospinal and cortical excitability to answer these questions. We investigated how cortical excitability thresholds (CETs, measured with EEG), relate to corticospinal excitability thresholds (RMTs, measured with EMG) at the hand, arm, and leg hotspots along the M1 in 24 subjects. RMTs and CETs were strongly correlated, and both increased from hand to arm to leg. CETs were generally lower than RMTs, indicating that subthreshold stimulation was enough to evoke robust early TMS evoked potentials (TEPs). Within subjects, CETs differed from the corresponding RMTs at all three M1 hotspots, and this difference increased from hand to leg representations. The findings of the present study argue against using a default hand-muscle RMT to set cortical excitability dosage along the M1 and beyond. Online TMS-EEG can enable real-time dosing and could improve stimulation precision, efficiency, and generalizability, but the site-specific variability calls for adaptive control.