TranSlationChip

TRANSCRANIAL STIMULATION ON A CHIP

Summary

Over the past decade, non-invasive stimulation paradigms, such as Transcranial Direct CurrentStimulation (TDCS), Alternating Current Stimulation (ACS) and Transcranial Magnetic Stimulation(TMS), have become part of the therapeutic portfolio. Various neurological conditions includingepilepsy, phantom limb pain and depressions, are potential targets, just to name a few. For'classical' pulsed neurostimulation the full chain of events, from injected current to voltage-gatedion channels, is textbook knowledge. The temporal characteristics of DC and ACS is different, andthe slow changes in voltage are far from the rapid fluctuations needed to excite a neuron. On theone hand, a large body of literature supports the beneficial effects of transcranial stimulation. Onthe other, there is enormous variability in the reported effectiveness. We can neither explain whyit works, nor why other patients, seemingly receiving identical treatment, report no effect at all.This lack of consistency goes across all application fields.

We know that DC, ACS and TMS can influence brain circuits in a clinically relevant way,for instance promoting plasticity. Nevertheless, we lack a thorough understanding of the physicaland biological fundaments over which such stimulation acts on the brain. We have some links, butnot yet a chain. In order to reach more patients, it is of the utmost importance to link this chain,from the single cell to the circuit and brain level.

To address this, I propose that technology, modelling, and experiments in vitro and in vivo,are brought together with the common goal to map the different pathways by which stimulationmay influence neural circuits. The experimental work would include stimulation with varioustemporal characteristics, from slow sinusoidal signals (0.1-10 Hz) to direct current and TMS. Oncemore light is shed on the mechanisms, this information would be translated to modelling platforms,both computational and in vitro disease models. Strong electrical fields may, in fact, not only betherapeutic but can, over certain thresholds also harm tissue. Understanding how field strengths,e.g. generated during a seizure, may disrupt organization in a tissue slice, would be a first steptowards understanding how seizures drive the progressive neuro-degeneration associated withepilepsy. Furthermore, with a sound theoretical understanding, future patients could be offeredpersonalized stimulation, accounting for their individual anatomy and condition and synchronizedwith the optimal brain state.