The Effect of Coil Orientation on the Stimulation of the Pre-Supplementary Motor Area: A Combined TMS and EEG Study

Abstract

Studies using transcranial magnetic stimulation (TMS) have demonstrated the importance of direction and intensity of the applied current when the primary motor cortex (M1) is targeted. By varying these, it is possible to stimulate different subsets of neural elements, as demonstrated by modulation of motor evoked potentials (MEPs) and motor behaviour. The latter involves premotor areas as well, and among them, the presupplementary motor area (pre-SMA) has recently received significant attention in the study of motor inhibition. It is possible that, similar to M1, different neuronal populations can be activated by varying the direction and intensity of TMS; however, the absence of a direct electrophysiological outcome has limited this investigation. The problem can be solved by quantifying direct cortical responses by means of combined TMS and electroencephalography (TMS-EEG). We investigated the effect of variable coil orientations (0°, 90°, 180° and 270°) and stimulation intensities (100%, 120% and 140% of resting motor threshold) on local mean field potential (LMFP), transcranial evoked potential (TEP) peaks and TMS-related spectral perturbation (TRSP) from pre-SMA stimulation. As a result, early and late LMFP and peaks were larger, with the coil handle pointing posteriorly (0°) and laterally (90°). This was true also for TRSP in the β-γ range, but, surprisingly, θ-α TRSP was larger with the coil pointing at 180°. A 90° orientation activated the right M1, as shown by MEPs elicitation, thus limiting the spatial specificity of the stimulation. These results suggest that coil orientation and stimulation intensity are critical when stimulating the pre-SMA.

Keywords: TMS–EEG; coil direction; electroencephalography; motor evoked potentials; presupplementary motor area; transcranial magnetic stimulation.

Figure 1

Panel (A): Experimental protocol. Single–pulse TMS was applied on the right pre–SMA using four different coil orientations (0°, 90°, 180°, 270°), starting with the coil handle pointing posteriorly on the transverse plane and proceeding counterclockwise). For each coil orientation, three stimulation intensities were used (100%, 120% and 140% of the RMT). Panel (B): Example of TEP obtained by averaging signals from all subjects in the 0° CO and 140% SI condition. Each line represents a signal from one electrode; all 62 recording electrodes are plotted. Panel (C): Example of LMFP obtained by averaging signals from all subjects in the 0° CO and 140% SI condition. Panel (D): Example of TRSP obtained by averaging signals from all subjects in the 0° CO and 140% SI condition.

Figure 2

Grande average TEP across subjects and conditions. Each red line depicts the TEP from one electrode. The thick black line indicates the TEP averaged across the four electrodes from which the LMFP was calculated (Fz, F2, FCz, FC2). The yellow panels indicate the time windows from which maximum/minimum values of TEP peak amplitudes were extracted (see text for details).

Figure 3

Pictorial representation of the E–field induced by TMS in the 12 conditions explored (see text for details).

Figure 4

Summary of results on LMFP and TRSP. Panel (A): Early LMFP (10–70 ms) was larger at 0° and 90° compared with 180° and 270°. Although this was true for all the tested SIs, the effect reached statistical significance only at 140% RMT. Panel (B): Late LMFP (70–250 ms) evoked by 0° CO was larger than 180° and 270°, and again, this occurred only when an SI of 140% RMT was used. Panel (C): For TRSP in the β–γ frequency range, 0° CO induced a higher TRSP than 180° and 270° at 100% SI. At higher intensities, both 0° and 90° COs induced a higher TRSP compared with 180° and 270°. Panel (D): TRSP in the θ–α frequency range showed higher values for 180° compared with the other CO, both at 120% and 140% RMT SIs. Panel (E): MEP recorded from the left FDI were larger with 90° CO when using 120% and 140% RMT SIs compared with all other conditions. Panel (F): MEP recorded from the right FDI showed no difference across different CO and SI. Note: TRSP is expressed as the relative change compared with baseline. Error bars indicate the standard error of the mean. Asterisks indicate statistical significance (* p < 0.05).

Figure 5

Summary of results on TEP peaks: panel (A), PI; panel (B), PII; panel (C), PIII; panel (D), PIV; panel (E), PV. Error bars indicate standard error of the mean. Asterisks indicate statistical significance (* p < 0.05).