Threshold Tracked Short-Interval Intracortical Inhibition More Closely Predicts the Cortical Response to Transcranial Magnetic Stimulation

Abstract

Objectives: Short-interval intracortical inhibition (SICI) is a paired-pulse transcranial magnetic stimulation (TMS) technique that is commonly used to quantify intracortical inhibitory tone in the primary motor cortex. Whereas conventional measures of SICI (CSICI) quantify inhibition by the amplitude of the motor evoked potential (MEP), alternative measures involving threshold tracked SICI (TT-SICI) instead record the TMS intensity required to maintain a consistent MEP amplitude. Although both C-SICI and TT-SICI are thought to reflect inhibition mediated by γ-aminobutyric acid type A (GABAA) receptors, recent evidence suggests that the mechanisms involved with each measure may not be equivalent. This study aimed to use combined TMSelectroencephalography (TMS-EEG) to investigate the cortical mechanisms contributing to C-SICI and TT-SICI. Materials and Methods: In 20 young adults (30.6 ± 8.1 years), C-SICI and TT-SICI were recorded with multiple conditioning intensities, using both posterior-to-anterior (PA) and anterior-to-posterior (AP) induced currents, and this was compared with the TMS-evoked EEG potential (TEP). Results: We found no relationship between the magnitude of C-SICI and TT-SICI within each current direction. However, there was a positive relationship between the slope (derived from multiple conditioning intensities) of inhibition recorded with C-SICI and TT-SICI, but only with a PA current. Furthermore, irrespective of conditioning intensity or current direction, measures of C-SICI were unrelated to TEP amplitude. In contrast, TT-SICI was predicted by the P30 generated with AP stimulation. Conclusions: Our findings further demonstrate that C-SICI and TT-SICI likely reflect different facets of GABAA-mediated processes, with inhibition produced by TT-SICI appearing to align more closely with TMS-EEG measures of cortical excitability.