Simulating tDCS electrode placement to stimulate both M1 and SMA enhances motor performance and modulates cortical excitability depending on current flow direction.

Introduction: The conventional method of placing transcranial direct current stimulation (tDCS) electrodes is just above the target brain area. However, this strategy for electrode placement often fails to improve motor function and modulate cortical excitability. We investigated the effects of optimized electrode placement to induce maximum electrical fields in the leg regions of both M1 and SMA, estimated by electric field simulations in the T1and T2-weighted MRI-based anatomical models, on motor performance and cortical excitability in healthy individuals. Methods: A total of 36 healthy volunteers participated in this randomized, triple-blind, sham-controlled experiment. They were stratified by sex and were randomly assigned to one of three groups according to the stimulation paradigm, including tDCS with (1) anodal and cathodal electrodes positioned over FCz and POz, respectively, (A-P tDCS), (2) anodal and cathodal electrodes positioned over POz and FCz, respectively, (P-A tDCS), and (3) sham tDCS. The sit-to-stand training following tDCS (2 mA, 10 min) was conducted every 3 or 4 days over 3 weeks (5 sessions total). Results: Compared to sham tDCS, A-P tDCS led to significant increases in the number of sit-to-stands after 3 weeks training, whereas P-A tDCS significantly increased knee flexor peak torques after 3 weeks training, and decreased short-interval intracortical inhibition (SICI) immediately after the first session of training and maintained it post-training. Discussion: These results suggest that optimized electrode placement of the maximal EF estimated by electric field simulation enhances motor performance and modulates cortical excitability depending on the direction of current flow.

Electric field envelope focality in superficial brain areas with linear alignment montage in temporal interference stimulation.

Temporal interference stimulation (TIS) uses two pairs of conventional transcranial alternating current stimulation (tACS) electrodes, each with a different frequency, to generate a time-varying electric field (EF) envelope (EFE). The EFE focality in primary somatosensory and motor cortex areas of a standard human brain was computed using newly defined linear alignment montages. Sixty head volume conductor models constructed from magnetic resonance images were considered to evaluate interindividual variability. Six TIS and two tACS electrode montages were considered, including linear and rectangular alignments. EFEs were computed using the scalar-potential finite-difference method. The computed EFE was projected onto the standard brain space for each montage. Computational results showed that TIS and tACS generated different EFE and EF distributions in postcentral and precentral gyri regions. For TIS, the EFE amplitude in the target areas had lower variability than the EF strength of tACS. However, bipolar tACS montages showed higher focality in the superficial postcentral and precentral gyri regions than in TIS. TIS generated greater EFE penetration than bipolar tACS at depths <5-10 mm below the brain surface. From group-level analysis, tACS with a bipolar montage was preferred for targets <5-10 mm in depth (gyral crowns) and TIS for deeper targets. TIS with a linear alignment montage could be an effective method for deep structures and sulcal walls. These findings provide valuable insights into the choice of TIS and tACS for stimulating specific brain regions.

Thresholds and mechanisms of human magnetophosphene perception induced by low frequency sinusoidal magnetic fields.

BACKGROUND: Virtually everyone is exposed to power-frequency MF (50/60 Hz), inducing in our body electric fields and currents, potentially modulating brain function. MF-induced electric fields within the central nervous system can generate flickering visual perceptions (magnetophosphenes), which form the basis of international MF exposure guidelines and recommendations protecting workers and the general public. However, magnetophosphene perception thresholds were estimated 40 years ago in a small, unreplicated study with significant uncertainties and leaving open the question of the involved interaction site. METHODS: We used a stimulation modality termed transcranial alternating magnetic stimulation (tAMS), delivering in situ sinusoidal electric fields comparable to transcranial alternating current stimulation (tACS). Magnetophosphene perception was quantified in 81 volunteers exposed to MF (eye or occipital exposure) between 0 and 50 mT at frequencies of 20, 50, 60 and 100 Hz. RESULTS: Reliable magnetophosphene perception was induced with tAMS without any scalp sensation, a major advantage as compared to tACS. Frequency-dependent thresholds were quantified using binary logistic regressions hence allowing to establish condition dependent probabilities of perception. Results support an interaction between induced current density and retinal rod cells. CONCLUSION: Beyond fundamental and immediate implications for international safety guidelines, and for identifying the interaction site underlying phosphene perception (ubiquitous in tACS experiments), our results support exploring the potential of tAMS for the differential diagnosis of retinal disorders and neuromodulation therapy.

Verification of neuronavigated TMS accuracy using structured-light 3D scans.

Objective.To investigate the reliability and accuracy of the manual three-point co-registration in neuronavigated transcranial magnetic stimulation (TMS). The effect of the error in landmark pointing on the coil placement and on the induced electric and magnetic fields was examined.Approach.The position of the TMS coil on the head was recorded by the neuronavigation system and by 3D scanning for ten healthy participants. The differences in the coil locations and orientations and the theoretical error values for electric and magnetic fields between the neuronavigated and 3D scanned coil positions were calculated. In addition, the sensitivity of the coil location on landmark accuracy was calculated.Main results.The measured distances between the neuronavigated and 3D scanned coil locations were on average 10.2 mm, ranging from 3.1 to 18.7 mm. The error in angles were on average from two to three degrees. The coil misplacement caused on average a 29% relative error in the electric field with a range from 9% to 51%. In the magnetic field, the same error was on average 33%, ranging from 10% to 58%. The misplacement of landmark points could cause a 1.8-fold error for the coil location.Significance.TMS neuronavigation with three landmark points can cause a significant error in the coil position, hampering research using highly accurate electric field calculations. Including 3D scanning to the process provides an efficient method to achieve a more accurate coil position.

Is activation of the vestibular system by electromagnetic induction a possibility in an MRI context?

In recent years, an increasing number of studies have discussed the mechanisms of vestibular activation in strong magnetic field settings such as occur in a magnetic resonance imaging scanner environment. Amid the different hypotheses, the Lorentz force explanation currently stands out as the most plausible mechanism, as evidenced by activation of the vestibulo-ocular reflex. Other hypotheses have largely been discarded. Nonetheless, both human data and computational modeling suggest that electromagnetic induction could be a valid mechanism which may coexist alongside the Lorentz force. To further investigate the induction hypothesis, we provide, herein, a first of its kind dosimetric analysis to estimate the induced electric fields at the vestibular system and compare them with what galvanic vestibular stimulation would generate. We found that electric fields strengths from induction match galvanic vestibular stimulation strengths generating vestibular responses. This review examines the evidence in support of electromagnetic induction of vestibular responses, and whether movement-induced time-varying magnetic fields should be further considered and investigated.

Small effects of electric field on motor cortical excitability following anodal tDCS.

The dose-response characteristics of transcranial direct current stimulation (tDCS) remain uncertain but may be related to variability in brain electric fields due to individual anatomical factors. Here, we investigated whether the electric fields influence the responses to motor cortical tDCS. In a randomized cross-over design, 21 participants underwent 10 min of anodal tDCS with 0.5, 1.0, 1.5, or 2.0 mA or sham. Compared to sham, all active conditions increased the size of motor evoked potentials (MEP) normalized to the pre-tDCS baseline, irrespective of anterior or posterior magnetic test stimuli. The electric field calculated in the motor cortex of each participant had a nonlinear effect on the normalized MEP size, but its effects were small compared to those of other participant-specific factors. The findings support the efficacy of anodal tDCS in enhancing the MEP size but do not demonstrate any benefits of personalized electric field modeling in explaining tDCS response variability.

Predicting the hotspot location and motor threshold prior to transcranial magnetic stimulation using electric field modelling.

Objective.To investigate whether the motor threshold (MT) and the location of the motor hotspot in transcranial magnetic stimulation (TMS) can be predicted with computational models of the induced electric field.Approach.Individualized computational models were constructed from structural magnetic resonance images of ten healthy participants, and the induced electric fields were determined with the finite element method. The models were used to optimize the location and direction of the TMS coil on the scalp to produce the largest electric field at a predetermined cortical target location. The models were also used to predict how the MT changes as the magnetic coil is moved to various locations over the scalp. To validate the model predictions, the motor evoked potentials were measured from the first dorsal interosseous (FDI) muscle with TMS in the ten participants. Both computational and experimental methods were preregistered prior to the experiments.Main results.Computationally optimized hotspot locations were nearly as accurate as those obtained using manual hotspot search procedures. The mean Euclidean distance between the predicted and the measured hotspot locations was approximately 1.3 cm with a 0.8 cm bias towards the anterior direction. Exploratory analyses showed that the bias could be removed by changing the cortical target location that was used for the prediction. The results also indicated a statistically significant relationship (p< 0.001) between the calculated electric field and the MT measured at several locations on the scalp.Significance.The results show that the individual TMS hotspot can be located using computational analysis without stimulating the subject or patient even once. Adapting computational modelling would save time and effort in research and clinical use of TMS.

Functional relevance of the extrastriate body area for visual and haptic object recognition: a preregistered fMRI-guided TMS study.

The extrastriate body area (EBA) is a region in the lateral occipito-temporal cortex (LOTC), which is sensitive to perceived body parts. Neuroimaging studies suggested that EBA is related to body and tool processing, regardless of the sensory modalities. However, how essential this region is for visual tool processing and nonvisual object processing remains a matter of controversy. In this preregistered fMRI-guided repetitive transcranial magnetic stimulation (rTMS) study, we examined the causal involvement of EBA in multisensory body and tool recognition. Participants used either vision or haptics to identify 3 object categories: hands, teapots (tools), and cars (control objects). Continuous theta-burst stimulation (cTBS) was applied over left EBA, right EBA, or vertex (control site). Performance for visually perceived hands and teapots (relative to cars) was more strongly disrupted by cTBS over left EBA than over the vertex, whereas no such object-specific effect was observed in haptics. The simulation of the induced electric fields confirmed that the cTBS affected regions including EBA. These results indicate that the LOTC is functionally relevant for visual hand and tool processing, whereas the rTMS over EBA may differently affect object recognition between the 2 sensory modalities.

Estimation method for the anisotropic electrical conductivity ofin vivohuman muscles and fat between 10 kHz and 1 MHz.

Objective.In low frequency dosimetry the variability in the electrical conductivity values assigned to body model tissues represents a major source of uncertainty. The aim of this study is to propose a method for estimating the conductivity of human anisotropic skeletal muscle and fatin vivoin the frequency range from 10 kHz to 1 MHz.Approach.A method based on bounded electrical impedance tomography was used. Bioimpedance measurements were performed on the legs of ten subjects. Anatomically realistic models of the legs were then created using magnetic resonance images. The inverse problem of the tissue conductivities was solved using the finite element method. The results were validated using resampling techniques. These findings were also used to study the effects of muscle anisotropy on magnetic field exposure.Main results.The estimated conductivities for anisotropic muscle were found to be in good agreement with values found in existing literature and the anisotropy was shown to decrease with increasing frequency, with the ratio of lateral to longitudinal conductivity increasing from 37% to 64%. The conductivity of fat was found to be almost a constant 0.07 S m-1in the frequency range considered.Significance.The proposed method was shown to be a viable option when estimatingin vivoconductivity of human tissue. The results can be used in numerical dosimetry calculations or as limits in future investigations studying conductivity with bioimpedance measurements.

The Effect of Inter-pulse Interval on TMS Motor Evoked Potentials in Active Muscles.

Objective: The time interval between transcranial magnetic stimulation (TMS) pulses affects evoked muscle responses when the targeted muscle is resting. This necessitates using sufficiently long inter-pulse intervals (IPIs). However, there is some evidence that the IPI has no effect on the responses evoked in active muscles. Thus, we tested whether voluntary contraction could remove the effect of the IPI on TMS motor evoked potentials (MEPs). Methods: In our study, we delivered sets of 30 TMS pulses with three different IPIs (2, 5, and 10 s) to the left primary motor cortex. These measurements were performed with the resting and active right hand first dorsal interosseous muscle in healthy participants (N = 9 and N = 10). MEP amplitudes were recorded through electromyography. Results: We found that the IPI had no significant effect on the MEP amplitudes in the active muscle (p = 0.36), whereas in the resting muscle, the IPI significantly affected the MEP amplitudes (p < 0.001), decreasing the MEP amplitude of the 2 s IPI. Conclusions: These results show that active muscle contraction removes the effect of the IPI on the MEP amplitude. Therefore, using active muscles in TMS motor mapping enables faster delivery of TMS pulses, reducing measurement time in novel TMS motor mapping studies.

Magneto- and electrophosphene thresholds in the retina: a dosimetry modeling study.

Objective.Sensations of flickering light produced by time-varying magnetic fields or electric currents are called magneto- or electrophosphenes. Phosphene thresholds have been used in international guidelines and standards as an estimate of the thresholds of exposure that produce effects in the central nervous system (CNS). However, the estimated threshold values have a large range of uncertainty.Approach.Phosphene thresholds were approximated by simulating five phosphene threshold experiments. Retinal electric fields and currents induced by electric and magnetic stimulation were calculated using the finite element method and 14 anatomically realistic computational models of human heads.Main results.The radial component of retinal current density was determined to be in the range of 6.0-20.6 mA m-2. This study produces more accurate estimates for threshold current density in the retina using detailed anatomical models and the estimates had a reduced range of uncertainty compared to earlier studies.Significance.The results are useful for studying the mechanisms of retinal phosphenes and for the development of exposure limits for the CNS.

A probabilistic transcranial magnetic stimulation localization method.

Objective.Transcranial magnetic stimulation (TMS) can be used to safely and noninvasively activate brain tissue. However, the characteristic parameters of the neuronal activation have been largely unclear. In this work, we propose a novel neuronal activation model and develop a method to infer its parameters from measured motor evoked potential signals.Approach.The connection between neuronal activation due to an induced electric field and a measured motor threshold is modeled. The posterior distribution of the model parameters are inferred from measurement data using Bayes' formula. The measurements are the active motor thresholds obtained with multiple stimulating coil locations, and the parameters of the model are the location, preferred direction of activation, and threshold electric field value of the activation site. The posterior distribution is sampled using a Markov chain Monte Carlo method. We quantify the plausibility of the model by calculating the marginal likelihood of the measured thresholds. The method is validated with synthetic data and applied to motor threshold measurements from the first dorsal interosseus muscle in five healthy participants.Main results.The method produces a probability distribution for the activation location, from which a minimal volume where the activation occurs with 95% probability can be derived. For eight or nine stimulating coil locations, the smallest such a volume obtained was approximately 100 mm3. The 95% probability volume intersected the pre-central gyral crown and the anterior wall of the central sulcus, and the preferred direction was perpendicular to the central sulcus, both findings being consistent with the literature. Furthermore, it was not possible to rule out if the activation occurred either in the white or grey matter. In one participant, two distinct activations sites were found while others exhibited a unique site.Significance.The method is both generic and robust, and it lays a foundation for a framework that enables accurate analysis and characterization of TMS activation mechanisms.

A 50 Hz magnetic field affects hemodynamics, ECG and vascular endothelial function in healthy adults: A pilot randomized controlled trial.

Application of exposure to 50/60 Hz magnetic fields (MFs) has been conducted in the treatment of muscle pain and fatigue mainly in Japan. However, whether MFs could increase blood flow leading to muscle fatigue recovery has not been sufficiently tested. We investigated the acute effects of a 50 Hz sinusoidal MF at Bmax 180 mT on hemodynamics, electrocardiogram, and vascular endothelial function in healthy young men. Three types of regional exposures to a 50 Hz MF, i.e., forearm, upper arm, or neck exposure to MF were performed. Participants who received three types of real MF exposures had significantly increased ulnar arterial blood flow velocity compared to the sham exposures. Furthermore, after muscle loading exercise, MF exposure recovered hemoglobin oxygenation index values faster and higher than sham exposure from the loading condition. Moreover, participants who received real MF exposure in the neck region had significantly increased parasympathetic high-frequency activity relative to the sham exposure. The MF exposure in the upper arm region significantly increased the brachial artery flow-mediated dilation compared to the sham exposure. Computer simulations of induced in situ electric fields indicated that the order-of-magnitude estimates of the peak values were 100-500 mV/m, depending on the exposure conditions. This study provides the first evidence that a 50 Hz MF can activate parasympathetic activity and thereby lead to increase vasodilation and blood flow via a nitric oxide-dependent mechanism. Trial registration: UMIN Clinical Trial Registry (CTR) UMIN000038834. The authors confirm that all ongoing and related trials for this drug/intervention are registered.

ECG Localization Method Based on Volume Conductor Model and Kalman Filtering.

The 12-lead electrocardiogram was invented more than 100 years ago and is still used as an essential tool in the early detection of heart disease. By estimating the time-varying source of the electrical activity from the potential changes, several types of heart disease can be noninvasively identified. However, most previous studies are based on signal processing, and thus an approach that includes physics modeling would be helpful for source localization problems. This study proposes a localization method for cardiac sources by combining an electrical analysis with a volume conductor model of the human body as a forward problem and a sparse reconstruction method as an inverse problem. Our formulation estimates not only the current source location but also the current direction. For a 12-lead electrocardiogram system, a sensitivity analysis of the localization to cardiac volume, tilted angle, and model inhomogeneity was evaluated. Finally, the estimated source location is corrected by Kalman filter, considering the estimated electrocardiogram source as time-sequence data. For a high signal-to-noise ratio (greater than 20 dB), the dominant error sources were the model inhomogeneity, which is mainly attributable to the high conductivity of the blood in the heart. The average localization error of the electric dipole sources in the heart was 12.6 mm, which is comparable to that in previous studies, where a less detailed anatomical structure was considered. A time-series source localization with Kalman filtering indicated that source mislocalization could be compensated, suggesting the effectiveness of the source estimation using the current direction and location simultaneously. For the electrocardiogram R-wave, the mean distance error was reduced to less than 7.3 mm using the proposed method. Considering the physical properties of the human body with Kalman filtering enables highly accurate estimation of the cardiac electric signal source location and direction. This proposal is also applicable to electrode configuration, such as ECG sensing systems.

Nonuniform Exposure to the Cornea from Millimeter Waves.

ABSTRACT: This study examines the nonuniform exposure to the cornea from incident millimeter waves at 94-100 GHz. Two previous studies measured temperature increases in the rhesus cornea exposed to brief (1-6 s) pulses of high-fluence millimeter waves (94 GHz), one of which also estimated thresholds for corneal damage (reported as ED50, the dose resulting in a visible lesion 50% of the time). Both studies noted large variations in the temperature increase across the surface of the cornea due to wave interference effects. This study examines this variability using high-resolution simulations of mm-wave absorption and temperature increase in the human cornea from exposures to plane wave energy at 100 GHz. Calculations are based on an earlier study. The simulations show that the peak temperature increases in the cornea from short exposures (up to 10 s) to high-intensity mm-wave pulses are 1.7-2.8 times the median increase depending on the polarization of the incident energy. A simple one-dimensional "baseline" model provides a good estimate of the median temperature increase in the cornea. Two different estimates are presented for the thresholds for producing thermal lesions, expressed in terms of the minimum fluence of incident 100 GHz pulses. The first estimate is based on thresholds for thermal damage from pulsed infrared energy, and the second is based on a thermal damage model. The mm-wave pulses presently considered far exceed current IEEE or ICNIRP exposure limits but may be produced by some nonlethal weapons systems. Interference effects due to wave reflections from structures in and near the eye result in highly localized variations in energy absorbed in the cornea and surrounding facial tissues and are important to consider in a hazard analysis for exposures to intense pulsed millimeter waves.

Human exposure to radiofrequency energy above 6 GHz: review of computational dosimetry studies.

International guidelines/standards for human protection from electromagnetic fields have been revised recently, especially for frequencies above 6 GHz where new wireless communication systems have been deployed. Above this frequency a new physical quantity 'absorbed/epithelial power density' has been adopted as a dose metric. Then, the permissible level of external field strength/power density is derived for practical assessment. In addition, a new physical quantity, fluence or absorbed energy density, is introduced for protection from brief pulses (especially for shorter than 10 s). These limits were explicitly designed to avoid excessive increases in tissue temperature, based on electromagnetic and thermal modeling studies but supported by experimental data where available. This paper reviews the studies on the computational modeling/dosimetry which are related to the revision of the guidelines/standards. The comparisons with experimental data as well as an analytic solution are also been presented. Future research needs and additional comments on the revision will also be mentioned.

Review on biophysical modelling and simulation studies for transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is a technique for noninvasively stimulating a brain area for therapeutic, rehabilitation treatments and neuroscience research. Despite our understanding of the physical principles and experimental developments pertaining to TMS, it is difficult to identify the exact brain target as the generated electric field exhibits a non-uniform distribution owing to the complicated and subject-dependent brain anatomy and the lack of biomarkers that can quantify the effects of TMS in most cortical areas. Computational dosimetry has progressed significantly and enables TMS assessment by computation of the induced electric field (the primary physical agent known to activate the brain neurons) in a digital representation of the human head. In this review, TMS dosimetry studies are summarised, clarifying the importance of the anatomical and human biophysical parameters and computational methods. This review shows that there is a high consensus on the importance of a detailed cortical folding representation and an accurate modelling of the surrounding cerebrospinal fluid. Recent studies have also enabled the prediction of individually optimised stimulation based on magnetic resonance imaging of the patient/subject and have attempted to understand the temporal effects of TMS at the cellular level by incorporating neural modelling. These efforts, together with the fast deployment of personalised TMS computations, will permit the adoption of TMS dosimetry as a standard procedure in medical applications.

Inter-individual variations in electric fields induced in the brain by exposure to uniform magnetic fields at 50 Hz.

The International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines and the Institute of Electrical and Electronics Engineers (IEEE) standard establish safety limits for human exposure to electromagnetic fields. At low frequencies, only a limited number of computational body models or simplified geometrical shapes are used to relate the internal induced electric fields and the external magnetic fields. As a consequence, both standard/guidelines derive the exposure reference levels for the external magnetic field without considering the variability between individuals. Here we provide quantitative data on the variation of the maximum electric field strengths induced in the brain of 118 individuals when exposed to uniform magnetic fields at 50 Hz. We found that individual characteristics, such as age and skull volume, as well as incident magnetic field direction, have a systematic effect on the peak electric field values. Older individuals show higher induced electric field strengths, possibly due to age-related anatomical changes in brain. Peak electric field strengths are found to increase for larger skull volumes, as well as for incident magnetic fields directed along the lateral direction. Moreover, the maximum electric fields provided by the anatomical models used by ICNIRP for deriving exposure limits are considerably higher than those obtained here. On the contrary, the IEEE elliptical exposure model produces a weaker peak electric field strength. Our findings are useful for the revision and harmonization of the current exposure standard and guidelines. The present investigation reduces the dosimetric uncertainty of the induced electric field among different anatomical induction models. The obtained results can be used as a basis for the selection of appropriate reduction factors when deriving exposure reference levels for human protection to low-frequency electromagnetic exposure.

TMS activation site estimation using multiscale realistic head models.

OBJECTIVE: Transcranial magnetic stimulation (TMS) activates brain structures non-invasively. Computational models can be used to elucidate the activation site; however, the exact activation site is controversial. The aim is to present an imaging technique of the TMS activation cortical site estimation using individualized multi-scale realistic head models based on experimentally-derived TMS fields. APPROACH: The induced electric field (EF) was computed using subject-specific head models and experimental-specific TMS coil configuration during suprathreshold stimulation for relaxed muscles. The experimentally-derived EFs were used to calculate the activation of pyramidal tract model embedded in the head models to derive the activation site on the cortical surface at the macroscopic level. MAIN RESULTS: The TMS activation site was located at the anterior wall of the central sulcus, which agreed with a concurrent TMS/fMRI study. In contrast, the EF strength was not entirely consistent with TMS/fMRI studies. Multiscale physical modelling is a feasible imaging technique to investigate the activation site for TMS. SIGNIFICANCE: By combining subject-specific multiscale modelling with experimental TMS measurements, we showed that this method could serve as a TMS imaging technique at suprathreshold condition.

Cost of focality in TDCS: Interindividual variability in electric fields.

BACKGROUND: In transcranial direct current stimulation (TDCS), electric current is applied via two large electrodes to modulate brain activity. Computational models have shown that large electrodes produce diffuse electric fields (EFs) in the brain, which depends on individual head and brain anatomy. Recently, smaller electrodes as well as novel electrode arrangements, including high-definition TDCS (HD-TDCS) montages, have been introduced to improve the focality of EFs. Here, we investigated whether the EFs of focal montages are more susceptible to interindividual anatomical differences. METHODS: Thirteen TDCS montages, including conventional M1-contralateral forehead montages with different stimulating electrode sizes as well as 4 × 1 HD and bipolar HD montages, producing varying EF focalities were modeled using the finite element method in 77 subjects, with individual anatomically realistic models based on magnetic resonance images. RESULTS: Interindividual variability of predicted EFs increased with EF focality for conventional M1-contralateral forehead and 4 × 1 HD montages. 4 × 1 HD-TDCS was found to have the highest EF focality and greatest variability. Bipolar HD montages targeting the region between two small electrodes did not follow this pattern, but produced EF magnitudes comparable to those of 4× 1 HD-TDCS, with a minor decrease in focality and lower interindividual variability. CONCLUSIONS: EF focality in TDCS was achieved at the cost of increased interindividual variability. Hence, individual modeling is required to plan EF doses when focal montages are used. Among the studied montages, bipolar HD montages provided a compromise between inter-individual variability, focality and magnitude of the predicted EFs.