Investigating the effects of TMS-related somatosensory inputs on TMS-evoked potentials provides evidence against significant interaction

Why zapping the brain is harder than it looks

Doctors and neuroscientists increasingly use brief magnetic pulses to "ping" the brain and record its electrical echoes, hoping to measure how healthy or responsive different regions are. But there is a big catch: each pulse also produces loud clicks and tingling on the scalp, which themselves trigger brain activity. This study asked a simple but crucial question: do those side sensations actually change the brain response we care about, or can we reliably subtract them away?

Probing the brain with magnets and electrodes

The technique at the heart of this work combines transcranial magnetic stimulation (TMS) with electroencephalography (EEG). TMS sends a very brief magnetic pulse through the skull to nudge brain cells in a chosen area; EEG records the brains response as a series of tiny voltage changes over time. Ideally, these traces would reflect only the direct effect of the magnetic pulse on the cortexthe so-called TMS-evoked potentials. In reality, the same pulse also causes a sharp click and a skin jolt that activate the ears, skin, and muscles, generating their own "peripherally evoked" potentials. These overlapping signals are a headache for anyone who wants to use TMS-EEG as a precise test of brain function in health and disease.

Real versus sham: two ways to fake the pulse

To untangle direct brain responses from those triggered by sound and touch, the researchers compared real TMS with carefully designed sham conditions in 20 healthy volunteers. Real TMS was applied over two regions: the primary motor cortex, which controls hand movements, and the supplementary motor area, involved in planning and coordinating actions. At the same time, participants received masking noise in their ears to soften the click. For sham trials, the TMS coil was turned so that it mimicked the noise and vibration without effectively stimulating the brain. Short electrical pulses were delivered to the scalp or shoulder to reproduce the skin sensations of real TMS.

Two rival strategies for handling sensory noise

The team tested two main sham strategies. In the first, called "PEP saturation," the electrical stimulation on the scalp was made very strong in both real and sham trials. The idea was to push the brains sensory response to a ceiling level so that any extra input from real TMS barely mattered, making the sensory component virtually identical in both conditions. In the second strategy, the "PIMSIC" method, the intensity of the electrical pulses during sham was individually adjusted until the resulting sensory response in the EEG exactly matched that seen after real TMS, but without adding extra stimulation during real TMS. In both approaches, if the sensory-only signal from sham matched that in real trials, subtracting sham from real should reveal the true brain response to TMS.

Early brain responses stay stable

Across thousands of trials, the researchers compared the cleaned-up TMS responses obtained under the different sham procedures. They focused on the first 110 milliseconds after each pulse, when direct cortical responses are expected to dominate. Within this time window, they found no meaningful differences between conditions, whether they stimulated motor cortex or supplementary motor area. Statistical tests designed not only to detect differences but also to confirm similarity showed that early responses were effectively equivalent across all sham designs. Only at later timesbeyond about 150 to 200 millisecondsdid some differences appear, and these were best explained by imperfect matching of the sensory responses rather than true changes in the direct TMS effect.

What this means for future brain tests

The studys main message for non-specialists is reassuring: the earliest waves in the brains electrical echo after a magnetic pulse seem remarkably robust to the distracting sensations that accompany TMS. This suggests that, at least in the first hundred milliseconds, researchers can safely remove sensory contributions by subtracting a well-designed sham condition, without worrying that they are also erasing or distorting the signal of interest. Both the high-intensity saturation method and the individually calibrated matching method proved suitable, with the latter offering a potentially more comfortable option because it can avoid very strong scalp shocks. Together, these findings strengthen the case for using TMS-EEG as a precise, non-invasive probe of how different brain regions respond, which may ultimately aid in diagnosing and tracking neurological and psychiatric disorders.

Citation: Gordon, P.C., Metsomaa, J., Belardinelli, P. et al. Investigating the effects of TMS-related somatosensory inputs on TMS-evoked potentials provides evidence against significant interaction. Sci Rep 16, 4317 (2026). https://doi.org/10.1038/s41598-026-37418-w

Keywords: transcranial magnetic stimulation, EEG, brain responses, sensory artifacts, sham stimulation