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.
Brain Stimulation: From Basic Research to Clinical Use
Originating in basic research, as a basis for understanding the function of brain areas, brain stimulation is currently employed for the treatment of many brain disorders including Parkinson's Disease, Epilepsy, and Depression. However, the available techniques for brain stimulation can differ, in the degree of surgical intervention: Invasive Brain Stimulation (IBS) techniques such as Deep Brain Stimulation (DBS) and Intracortical Microstimulation (ICMS) that require extensive surgical intervention for placement of electrodes, or Non-Invasive Brain Stimulation (NIBS) techniques, for example, Transcranial Magnetic Stimulation (TMS) and Transcranial Electrical Current Stimulation (tES) that require minimal or no intervention. With the development of thin movable electrodes having superior biocompatibility, some of the side effects related to the invasive procedure of IBS will very likely to be overcome. Likewise, advances in NIBS techniques related to spatial and temporal precision have closed the gap to its invasive counterparts. In parallel, considerable progress is being made in research laboratories using brain stimulation techniques to gain deeper insights into brain functions, and underlying neural and glial mechanisms, which in turn increase the efficacy of brain stimulation in treatments. Therefore, the therapeutic potential of stimulation techniques is not yet completed exhausted. However, the question remains, can the results from basic research be transferred easily to treatment of patients? By looking at the successes achieved in the past years, the answer to this question should be yes. Well-described animal models, good theoretical and anatomical models are essential for such translations. The proposed research topic aims to gather more evidence on the role of BS as a tool to better understand the physiological mechanisms of the brain, by studying the temporal and spatial dynamics of cortical and subcortical activations, and to discuss challenges and develop strategies for innovative therapeutic procedures. This Research Topic welcomes Original Research, Perspectives, Systematic Reviews, and Meta-Analyses covering the following topics: - Basic research models, theoretical models, preclinical or clinical applications of cortical and subcortical stimulation using TMS, tES, ICMS, and DBS in animal models and humans - Translational articles dealing with the effects of neuromodulation on the biochemistry of brain tissues, as well as those focusing on modeling strategies and closed-loop technologies - Neurophysiological studies in animal models and humans focusing on the mechanisms leading to altered cortical excitability, plasticity, and connectivity, or new experimental models aimed at understanding changes in cellular processes induced by electrical or inductive stimulation of neurons.
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.
Could non-invasive brain-stimulation prevent neuronal degeneration upon ion channel re-distribution and ion accumulation after demyelination?
Fast and efficient transmission of electrical signals in the nervous system is mediated through myelinated nerve fibers. In neuronal diseases such as multiple sclerosis, the conduction properties of axons are disturbed by the removal of the myelin sheath, leaving nerve cells at a higher risk of degenerating. In some cases, the protective myelin sheath of axons can be rebuilt by remyelination through oligodendroglial cells. In any case, however, changes in the ion channel organization occur and may help to restore impulse conduction after demyelination. On the other hand, changes in ion channel distribution may increase the energy demand of axons, thereby increasing the probability of axonal degeneration. Many attempts have been made or discussed in recent years to increase remyelination of affected axons in demyelinating diseases such as multiple sclerosis. These approaches range from pharmacological treatments that reduce inflammatory processes or block ion channels to the modulation of neuronal activity through electrical cortical stimulation. However, these treatments either affect the entire organism (pharmacological) or exert a very local effect (electrodes). Current results show that neuronal activity is a strong regulator of oligodendroglial development. To bridge the gap between global and very local treatments, non-invasive transcranial magnetic stimulation could be considered. Transcranial magnetic stimulation is externally applied to brain areas and experiments with repetitive transcranial magnetic stimulation show that the neuronal activity can be modulated depending on the stimulation parameters in both humans and animals. In this review, we discuss the possibilities of influencing ion channel distribution and increasing neuronal activity by transcranial magnetic stimulation as well as the effect of this modulation on oligodendroglial cells and their capacity to remyelinate previously demyelinated axons. Although the physiological mechanisms underlying the effects of transcranial magnetic stimulation clearly need further investigations, repetitive transcranial magnetic stimulation may be a promising approach for non-invasive neuronal modulation aiming at enhancing remyelination and thus reducing neurodegeneration