Ricardo Salvador

The electric field in the cortex during transcranial current stimulation.

The electric field in the cortex during transcranial current stimulation was calculated based on a realistic head model derived from structural MR images. The aim of this study was to investigate the effect of tissue heterogeneity and of the complex cortical geometry on the electric field distribution. To this end, the surfaces separating the different tissues were represented as accurately as possible, particularly the cortical surfaces. Our main finding was that the complex cortical geometry combined with the high conductivity of the CSF which covers the cortex and fills its sulci gives rise to a very distinctive electric field distribution in the cortex, with a strong normal component confined to the bottom of sulci under or near the electrodes and a weaker tangential component that covers large areas of the gyri that lie near each electrode in the direction of the other electrode. These general features are shaped by the details of the sulcal and gyral geometry under and between the electrodes. Smaller electrodes resulted in a significant improvement in the focality of the tangential component but not of the normal component, when focality is defined in terms of percentages of the maximum values in the cortex. Experimental validation of these predictions could provide a better understanding of the mechanisms underlying the acute effects of tCS.

Determining which mechanisms lead to activation in the motor cortex: a modeling study of transcranial magnetic stimulation using realistic stimulus waveforms and sulcal geometry

OBJECTIVE To determine which mechanisms lead to activation of neurons in the motor cortex during transcranial magnetic stimulation (TMS) with different current directions and pulse waveforms. METHODS The total electric field induced in a simplified model of a cortical sulcus by a figure-eight coil was calculated using the finite element method (FEM). This electric field was then used as the input to determine the response of compartmental models of several types of neurons. RESULTS The modeled neurons were stimulated at different sites: fiber bends for pyramidal tract neurons, axonal terminations for cortical interneurons and axon collaterals, and a combination of both for pyramidal association fibers. All neurons were more easily stimulated by a PA - directed electric field, except association fibers. Additionally, the second phase of a biphasic pulse was found to be more efficient than the first phase of either monophasic or biphasic pulses. CONCLUSIONS The stimulation threshold for different types of neurons depends on the pulse waveform and relative current direction. The reported results might account for the range of responses obtained in TMS of the motor cortex when using different stimulation parameters. SIGNIFICANCE Modeling studies combining electric field calculations and neuronal models may lead to a deeper understanding of the effect of the TMS-induced electric field on cortical tissue, and may be used to improve TMS coil and waveform design.

Transcranial Current Brain Stimulation (tCS): Models and Technologies

In this paper, we provide a broad overview of models and technologies pertaining to transcranial current brain stimulation (tCS), a family of related noninvasive techniques including direct current (tDCS), alternating current (tACS), and random noise current stimulation (tRNS). These techniques are based on the delivery of weak currents through the scalp (with electrode current intensity to area ratios of about 0.3-5 A/m2) at low frequencies (typically <; 1 kHz) resulting in weak electric fields in the brain (with amplitudes of about 0.2-2 V/m). Here we review the biophysics and simulation of noninvasive, current-controlled generation of electric fields in the human brain and the models for the interaction of these electric fields with neurons, including a survey of in vitro and in vivo related studies. Finally, we outline directions for future fundamental and technological research.

Modeling the electric field induced in a high resolution realistic head model during transcranial current stimulation

Much of our knowledge about the electric field distribution in transcranial current stimulation (tCS) still relies on results obtained from layered spherical head models. In this work we created a high resolution finite element model of a human head by segmentation of MRI images, and paid particular attention to the representation of the cortical sheet. This model was then used to calculate the electric field induced by two electrodes: an anode placed above the left motor cortex, and a cathode placed over the right eyebrow. The results showed that the maxima of the current density appear located on localized hotspots in the bottom of sulci and not on the cortical surface as would be expected from spherical models. This also applies to the components of the current density normal and tangential to the cortical surface. These results show that such highly detailed head models are needed to correctly predict the effects of tCS on cortical neurons.

From Oscillatory Transcranial Current Stimulation to Scalp EEG Changes: A Biophysical and Physiological Modeling Study

Both biophysical and neurophysiological aspects need to be considered to assess the impact of electric fields induced by transcranial current stimulation (tCS) on the cerebral cortex and the subsequent effects occurring on scalp EEG. The objective of this work was to elaborate a global model allowing for the simulation of scalp EEG signals under tCS. In our integrated modeling approach, realistic meshes of the head tissues and of the stimulation electrodes were first built to map the generated electric field distribution on the cortical surface. Secondly, source activities at various cortical macro-regions were generated by means of a computational model of neuronal populations. The model parameters were adjusted so that populations generated an oscillating activity around 10 Hz resembling typical EEG alpha activity. In order to account for tCS effects and following current biophysical models, the calculated component of the electric field normal to the cortex was used to locally influence the activity of neuronal populations. Lastly, EEG under both spontaneous and tACS-stimulated (transcranial sinunoidal tCS from 4 to 16 Hz) brain activity was simulated at the level of scalp electrodes by solving the forward problem in the aforementioned realistic head model. Under the 10 Hz-tACS condition, a significant increase in alpha power occurred in simulated scalp EEG signals as compared to the no-stimulation condition. This increase involved most channels bilaterally, was more pronounced on posterior electrodes and was only significant for tACS frequencies from 8 to 12 Hz. The immediate effects of tACS in the model agreed with the post-tACS results previously reported in real subjects. Moreover, additional information was also brought by the model at other electrode positions or stimulation frequency. This suggests that our modeling approach can be used to compare, interpret and predict changes occurring on EEG with respect to parameters used in specific stimulation configurations.

The electric field distribution in the brain during TTFields therapy and its dependence on tissue dielectric properties and anatomy: a computational study

Tumor treating fields (TTFields) are a non-invasive, anti-mitotic and approved treatment for recurrent glioblastoma multiforme (GBM) patients. In vitro studies have shown that inhibition of cell division in glioma is achieved when the applied alternating electric field has a frequency in the range of 200 kHz and an amplitude of 1-3 V cm(-1). Our aim is to calculate the electric field distribution in the brain during TTFields therapy and to investigate the dependence of these predictions on the heterogeneous, anisotropic dielectric properties used in the computational model. A realistic head model was developed by segmenting MR images and by incorporating anisotropic conductivity values for the brain tissues. The finite element method (FEM) was used to solve for the electric potential within a volume mesh that consisted of the head tissues, a virtual lesion with an active tumour shell surrounding a necrotic core, and the transducer arrays. The induced electric field distribution is highly non-uniform. Average field strength values are slightly higher in the tumour when incorporating anisotropy, by about 10% or less. A sensitivity analysis with respect to the conductivity and permittivity of head tissues shows a variation in field strength of less than 42% in brain parenchyma and in the tumour, for values within the ranges reported in the literature. Comparing results to a previously developed head model suggests significant inter-subject variability. This modelling study predicts that during treatment with TTFields the electric field in the tumour exceeds 1 V cm(-1), independent of modelling assumptions. In the future, computational models may be useful to optimize delivery of TTFields.

Transcranial magnetic stimulation of small animals: A modeling study of the influence of coil geometry, size and orientation

Several recent studies have investigated the mechanisms of repetitive transcranial magnetic stimulation (rTMS) using small animals. However, there is still limited knowledge about the distribution of the induced electric field, and its dependence on coil size, geometry and orientation. In this work we calculate the electric field induced in a realistically shaped homogeneous mouse model by commercially available coils in several different orientations. The results show that the secondary field, resulting from charge accumulation at the skin - air interface, drastically changes the magnitude, decay and focality of the primary field induced by the coil. Accurate knowledge about the distribution of the field is invaluable in designing experimental protocols and new coils for small animal stimulation.

High-Permeability Core Coils for Transcranial Magnetic Stimulation of Deep Brain Regions

Stimulation of deep brain regions with transcranial magnetic stimulation (TMS) may have an important role as a therapy to treat chemical dependency and depression. The coils traditionally used in TMS, however, have a poor performance in stimulating deep neurons. In this work we study the usage of high permeability cores combined with coils specifically designed to induce fields that decay slowly with depth. By using the finite elements method we show that the use of such cores increases the fields magnitude, decreases its decay rate and improves its focality. Such improvements make these high permeability core coils more suited to stimulate deep brain regions.

Reduced Current Spread by Concentric Electrodes in Transcranial Electrical Stimulation (tES)

OBJECTIVE We propose the use of a new montage for transcranial direct current stimulation (tDCS), called concentric electrodes tDCS (CE-tDCS), involving two concentric round electrodes that may improve stimulation focality. METHODS To test efficacy and focality of CE-tDCS, we modelled the current distribution and tested physiological effects on cortical excitability. Motor evoked potentials (MEPs) from first dorsal interosseous (FDI) and abductor digiti minimi (ADM) were recorded before and after the delivery of anodal, cathodal and sham stimulation on the FDI hotspot for 10 minutes. RESULTS MEP amplitude of FDI increased after anodal-tDCS and decreased after cathodal-tDCS, supporting the efficacy of CE-tDCS in modulating cortical excitability. Moreover, modelled current distribution and no significant effects of stimulation on MEP amplitude of ADM suggest high focality of CE-tDCS. CONCLUSIONS CE-tDCS may allow a better control of current distribution and may represent a novel tool for applying tDCS and other transcranial current stimulation approaches.

High permeability cores to optimize the stimulation of deeply located brain regions using transcranial magnetic stimulation.

Efficient stimulation of deeply located brain regions with transcranial magnetic stimulation (TMS) poses many challenges, arising from the fact that the induced field decays rapidly and becomes less focal with depth. We propose a new method to improve the efficiency of TMS of deep brain regions that combines high permeability cores, to increase focality and field intensity, with a coil specifically designed to induce a field that decays slowly with increasing depth. The performance of the proposed design was investigated using the finite element method to determine the total electric field induced by this coil/core arrangement on a realistically shaped homogeneous head model. The calculations show that the inclusion of the cores increases the fields magnitude by as much as 25% while also decreasing the fields decay with depth along specific directions. The focality, as measured by the area where the fields norm is greater than 1/sq.rt.2 of its maximum value, is also improved by as much as 15% with some core arrangements. The coils inductance is not significantly increased by the cores. These results show that the presence of the cores might make this specially designed coil even more suited for the effective stimulation of deep brain regions.