Abstracts

Rationale: Neural activity can be induced or modulated by an exogenous electric field, which can be generated non-invasively by transcranial electrical stimulation (TES). The physiological effects of TES are determined by the spatial distribution and temporal pattern of the induced intracerebral currents. In most cases in human patients there is no direct data accessible about the local neuronal entrainment by TES, but still the a priori knowledge on the expectable local intracerebral effects of given stimulation parameters may allow to design targeted treatment plans. In principle, TES can be also spatially selective (similarly to deep brain stimulation) by modulating the distribution of the electric fields.Methods: In our experiments, we set out to measure the TES generated electric fields in human brains and to test the viability of a spatially focused TES protocol. Our assumption is that the effect of repetitively delivered high frequency (>1 kHz) Gaussian pulses on multiple bilateral electrode pairs may be temporally integrated by the neuronal membranes, leading to a stronger neuronal entrainment around the overlapping region of the diagonal fields than at the periphery. We recorded TES-generated field potentials in human cadavers and anesthetized rats. Stimulation was applied by placing Ag/AgCl EEG electrodes over the external surface of the skull. We used independently isolated stimulation pairs to deliver sinusoidally modulated TES with various parameters and repetitive high-frequency Gaussian stimulus trains in various arrangements. Custom made multiple-site electrodes (>200 contact points) and 32-channel silicon probes were used to thoroughly sample the field potentials in the brain. We also measured the shunting effect of the skin during transcutaneous stimulation.Results: In addition to our earlier results, we found that the skin dramatically reduced the generated intracranial electric fields, and alters its geometry. We recorded the unit activity during the high-frequency pulsed TES, and estimated its effects on neuronal activity. We found that the high-frequency stimulation generates a relatively small diameter axial voltage gradient in the geometrical axis of the stimulator electrodes (<50% gradient strength off-axis vs in-axis). The multiple crossing stimulation pairs protocol resulted in a spatially focal effect after temporal integration (>30% larger electric field magnitude at the crosspoint than at the periphery). We also suggest a protocol to selectively and unilaterally stimulate the frontal cortex via TES.Conclusions: According to our knowledge the results of these measurements are going to be useful to determine the most efficient parameters of TES in clinical studies.