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.

TMS-Induced Modulation of EEG Functional Connectivity Is Affected by the E-Field Orientation

“…The authors showed that brain oscillatory response modulations in the theta–alpha range are higher when E-field points anteriorly compared to any other tested orientation, while the same and other coil orientations showed higher brain oscillatory response modulations in the beta band. These results for spectral perturbation do not strictly match ours in terms of the coil orientations at which maximal effects are observed, possibly because in [ 29 ], the observed spectral perturbation is calculated for channels close to the stimulation site, thus capturing TMS-induced modulation of local induced activity, whereas our results capture long-range phase coupling of oscillatory brain activity.…”

“…Conversely, when the coil was oriented along the −115° macro-orientation, the maximal increase in functional connectivity between the left pre-SMA and the left motor cortex was observed. Several studies showed that the direction of the TMS coil influences brain responses, and there is already ample evidence of the importance of coil orientation for the stimulation of the primary motor cortex [ 25 , 29 , 30 , 50 , 51 , 52 ]. Less is known for the stimulation of SMA.…”

“…Indeed, several lines of evidence pointed out the structural and excitability heterogeneity of pre-SMA [ 47 , 53 ], factors that might justify the different responses of the same region to different stimulus orientations. Indeed, a recent study by Casula et al [ 29 ] demonstrated that by stimulating pre-SMA, different populations of neurons could be activated by varying coil orientation and stimulation intensities. The authors showed that brain oscillatory response modulations in the theta–alpha range are higher when E-field points anteriorly compared to any other tested orientation, while the same and other coil orientations showed higher brain oscillatory response modulations in the beta band.…”

“…A recent approach using navigated multi-locus TMS (mTMS) [ 24 , 25 , 26 ], in which a transducer composed of several coils overcomes the slow manual coil adjustment, thus allowing a fast stimulation of different brain locations, enabling to automatically find the optimal position of the E-field in order to maximize peripheral [ 27 ] and cortical responses [ 28 ]. Indeed, previous studies using mTMS-EEG [ 28 ], together with other studies using nTMS–EEG [ 7 , 29 , 30 ], have shown that changing the E-field orientation causes a different brain response in terms of TEPs.…”

Real-time cortical dynamics during motor inhibition

“…Then, we further verified the correspondence with a well-known brain atlas 54 to define the SMA-ROI for source analysis. Our localization was also verified comparing a recent study in which we specifically optimized the targeting and stimulation of the SMA using TMS–EEG 55 . Another limitation lies in the relatively low spatial resolution of our EEG recording, which did not allow to discriminate specific portions of the SMA.…”