Publications
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.
Deciphering the dynamics of neuronal activity evoked by transcranial magnetic stimulation.
Transcranial magnetic stimulation (TMS), a non-invasive method for stimulating the brain, has been used for more than 35 years. Since then, there have been many human studies using sophisticated methods to infer how TMS interacts with the brain. However, these methods have their limitations, e.g. recording of EEG potentials, which are summation potentials from many cells and generated across many cortical layers, make it very difficult to localize the origin of the potentials and relate it to TMS induced effects. However, this is necessary to build accurate models that predict TMS action in the human brain. In recent years, we have developed a method that allows us to demonstrate nearly the direct effect of a TMS pulse at the cellular level. We transferred a TMS stimulation protocol from humans to a rat model. In this way, we were able to gain direct access to neurons activated by TMS, thereby reducing the parameter space by many factors. Our data show that a single TMS pulse affects cortical neurons for more than 300 ms. In addition to temporal dynamics, there are also spatial effects. These effects arise at both local and global scale after a single TMS pulse. The local effect occurs in the motor cortex and is very short-lived. It is characterized by a high-frequency neuronal discharge and is reminiscent of the I-wave patterns described in humans at the level of the spinal cord. The global effect occurs in many cortical and subcortical areas in both hemispheres and is characterized by an alternation of excitation and inhibition. Both effects either occur together or only the global effect is present. Next, we are planning to correlate these neurometric data with induced electric field modeling to create detailed TMS-triggered neuronal excitation models that could help us better understand cortical TMS interference.