Pedro Cavaleiro Miranda

A technical guide to tDCS, and related non-invasive brain stimulation tools.

Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain.

The electric field induced in the brain by magnetic stimulation: a 3-D finite-element analysis of the effect of tissue heterogeneity and anisotropy

We investigate the effect of tissue heterogeneity and anisotropy on the electric field and current density distribution induced in the brain during magnetic stimulation. Validation of the finite-element (FE) calculations in a homogeneous isotropic sphere showed that the magnitude of the total electric field can be calculated to within an error of approximately 5% in the region of interest, even in the presence of a significant surface charge contribution. We used a high conductivity inclusion within a sphere of lower conductivity to simulate a lesion due to an infarct. Its effect is to increase the electric field induced in the surrounding low conductivity region. This boost is greatest in the vicinity of interfaces that lie perpendicular to the current flow. For physiological values of the conductivity distribution, it can reach a factor of 1.6 and extend many millimeters from the interface. We also show that anisotropy can significantly alter the electric field and current density distributions. Either heterogeneity or anisotropy can introduce a radial electric field component, not present in a homogeneous isotropic conductor. Heterogeneity and anisotropy are predicted to significantly affect the distribution of the electric field induced in the brain. It is, therefore, expected that anatomically faithful FE models of individual brains which incorporate conductivity tensor data derived from diffusion tensor measurements, will provide a better understanding of the location of possible stimulation sites in the brain.

Fundamentals of Transcranial Electric and Magnetic Stimulation Dose: Definition, Selection, and Reporting Practices

BACKGROUND The growing use of transcranial electric and magnetic (EM) brain stimulation in basic research and in clinical applications necessitates a clear understanding of what constitutes the dose of EM stimulation and how it should be reported. METHODS This paper provides fundamental definitions and principles for reporting of dose that encompass any transcranial EM brain stimulation protocol. RESULTS The biologic effects of EM stimulation are mediated through an electromagnetic field injected (via electric stimulation) or induced (via magnetic stimulation) in the body. Therefore, transcranial EM stimulation dose ought to be defined by all parameters of the stimulation device that affect the electromagnetic field generated in the body, including the stimulation electrode or coil configuration parameters: shape, size, position, and electrical properties, as well as the electrode or coil current (or voltage) waveform parameters: pulse shape, amplitude, width, polarity, and repetition frequency; duration of and interval between bursts or trains of pulses; total number of pulses; and interval between stimulation sessions and total number of sessions. Knowledge of the electromagnetic field generated in the body may not be sufficient but is necessary to understand the biologic effects of EM stimulation. CONCLUSIONS We believe that reporting of EM stimulation dose should be guided by the principle of reproducibility: sufficient information about the stimulation parameters should be provided so that the dose can be replicated.

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.

What does the ratio of injected current to electrode area tell us about current density in the brain during tDCS

OBJECTIVE To examine the relationship between the ratio of injected current to electrode area (I/A) and the current density at a fixed target point in the brain under the electrode during transcranial direct current stimulation (tDCS). METHODS Numerical methods were used to calculate the current density distribution in a standard spherical head model as well as in a homogeneous cylindrical conductor. RESULTS The calculations using the cylindrical model showed that, for the same I/A ratio, the current density at a fixed depth under the electrode was lower for the smaller of the two electrodes. Using the spherical model, the current density at a fixed target point in the brain under the electrode was found to be a non-linear function of the I/A ratio. For smaller electrodes, more current than predicted by the I/A ratio was required to achieve a predetermined current density in the brain. CONCLUSIONS A non-linear relationship exists between the injected current, the electrode area and the current density at a fixed target point in the brain, which can be described in terms of a montage-specific I-A curve. SIGNIFICANCE I-A curves calculated using realistic head models or obtained experimentally should be used when adjusting the current for different electrode sizes or when comparing the effect of different current-electrode area combinations.

Transcranial direct-current stimulation modulates synaptic mechanisms involved in associative learning in behaving rabbits

Transcranial direct-current stimulation (tDCS) is a noninvasive brain stimulation technique that has been successfully applied for modulation of cortical excitability. tDCS is capable of inducing changes in neuronal membrane potentials in a polarity-dependent manner. When tDCS is of sufficient length, synaptically driven after-effects are induced. The mechanisms underlying these after-effects are largely unknown, and there is a compelling need for animal models to test the immediate effects and after-effects induced by tDCS in different cortical areas and evaluate the implications in complex cerebral processes. Here we show in behaving rabbits that tDCS applied over the somatosensory cortex modulates cortical processes consequent to localized stimulation of the whisker pad or of the corresponding area of the ventroposterior medial (VPM) thalamic nucleus. With longer stimulation periods, poststimulation effects were observed in the somatosensory cortex only after cathodal tDCS. Consistent with the polarity-specific effects, the acquisition of classical eyeblink conditioning was potentiated or depressed by the simultaneous application of anodal or cathodal tDCS, respectively, when stimulation of the whisker pad was used as conditioned stimulus, suggesting that tDCS modulates the sensory perception process necessary for associative learning. We also studied the putative mechanisms underlying immediate effects and after-effects of tDCS observed in the somatosensory cortex. Results when pairs of pulses applied to the thalamic VPM nucleus (mediating sensory input) during anodal and cathodal tDCS suggest that tDCS modifies thalamocortical synapses at presynaptic sites. Finally, we show that blocking the activation of adenosine A1 receptors prevents the long-term depression (LTD) evoked in the somatosensory cortex after cathodal tDCS.

Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields

Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint on the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS).

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.

Elucidating the mechanisms and loci of neuronal excitation by transcranial magnetic stimulation using a finite element model of a cortical sulcus

OBJECTIVE This work aims to elucidate by what physical mechanisms and where stimulation occurs in the brain during transcranial magnetic stimulation (TMS), taking into account cortical geometry and tissue heterogeneity. METHODS An idealized computer model of TMS was developed, comprising a stimulation coil, a cortical sulcus, and surrounding tissues. The distribution of the induced electric field was computed, and estimates of the relevant parameters were generated to predict the locus and type of neurons stimulated during TMS, assuming three different stimulation mechanisms. RESULTS Tissue heterogeneity strongly affects the spatial distribution of the induced electric field and hence which stimulation mechanism is dominant and where it acts. Stimulation of neurons may occur in the gyrus, in the lip of the gyrus, and in the walls of the sulcus. The stimulated cells can be either pyramidal cells having medium to large caliber axons, or intracortical fibers of medium caliber. CONCLUSIONS The results highlight the influence of cortical folding on the action of magnetic and electric fields on cortical tissue. SIGNIFICANCE Tissue geometry and heterogeneity in electrical conductivity both must be taken into account to predict accurately stimulation loci and mechanism in TMS.