Is it possible to separate intra-cortical evoked neural dynamics from peripheral evoked potentials during transcranial magnetic stimulation?
When TMS is applied over motor cortex, it elicits movements that can be recorded in humans as motor-evoked muscle potentials, as well as in patterns in EEG. A discussion has been started recently in the community that TMS may not only excite neuronal structures in the central nervous system, but also cause peripheral co-stimulation of sensory and motor axons of the meninges, blood vessels, skin, and muscle. These structures may also excite the same cortical site that TMS was meant to stimulate in the first place, resulting in contamination of the TMS-induced cortical response. Therefore, many efforts are made to identify and isolate peripheral evoked potentials (PEPs) from TMS-induced cortical responses in EEG-Data. However, it is very difficult to develop an appropriate sham stimulation for humans that closely reflects auditory, somatosensory, and motor responses accompanying TMS. An obvious route to clarify the issue is the blockade of cranial nerves, which requires animal models where invasive experiments to discover putative areas of origin can be done. In recent years, we have developed a method to demonstrate the direct effect of a TMS pulse at the cellular level. We have transferred single pulse and repeated stimulation protocols from humans to a rat model. With selective blockade of PEP, we were able to show that the trigeminal nerve is a major contributor to TMS-evoked neuronal signals in motor cortex, represented by a prominent excitatory peak at around 20 ms after stimulation. TEPs starts much earlier and lasts up to 6 ms after the stimulus pulse. Both inputs then merge into a canonical inhibition-excitation pattern lasting more than 350 ms.