Biology subjects

Haueisen, J.

Publications and source records attributed to Haueisen, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Individual versus fixed parametrization of an electrocutaneous warning signal during manual work tasks

Electrocutaneous stimulation provides a means to warn workers of potential hazards. Our previous parameter studies were conducted at rest or under controlled external influences such as vibration, temperature, and humidity, whereas actual work tasks have not yet been addressed. As a step towards greater practical applicability, we conducted two studies in which a circumferential electrocutaneous warning signal was applied to the upper right arm while participants performed a reading task, screw-driving, and polishing. In study 1 (n = 32), the pulse interval was adjusted individually to evoke a vibrating sensation, and the intolerance threshold was determined. In study 2 (n = 29), a fixed pulse interval of 36 ms was applied to all participants, the warning threshold was determined in addition to the intolerance threshold, and muscle twitches were documented both by participant report and by an independent observer. Study 1 demonstrated that electrocutaneous warning during work tasks is feasible, with a median intolerance threshold higher during polishing (16.5 mA) than during reading or screw-driving (14 mA each). In study 2, the fixed parameter setting elicited the intended pulsating or vibrating sensation at rest in 89 % of the participants in both presentations. The median warning threshold was 8 mA and did not differ between the three work tasks, whereas the intolerance threshold was lower during reading (18 mA) than during screw-driving and polishing (20 mA each). Muscle twitches were largely absent at the warning threshold and became frequent towards the intolerance threshold, with a ventral dominance of their location in both studies. An individual parametrization is therefore not required for the majority of users when a binary warning is to be conveyed, and operating the system slightly above the warning threshold provides a usable amplitude range while minimizing muscle twitches. Future work will focus on electrode optimization and on the objective measurement of motor responses.

neuroscience↗

bioRxiv2026

Low Intensity Multi-Channel Steering TMS Array for Network Level Neuromodulation

Objective: Low-intensity transcranial magnetic stimulation (LI-TMS) is being investigated as a gel-free alternative to transcranial electrical stimulation (tES), but existing systems remain almost exclusively single-channel and cannot electronically steer the induced electric field. We present the design, modeling, and experimental measurement of a wearable whole-head, multichannel, steerable LI-TMS array. Methods: The system comprises a 102-channel conformal coil array with independently controlled drivers capable of arbitrary waveform synthesis, together with a boundary element fast multipole method (BEM-FMM) framework that computes the coil currents required to produce prescribed cortical field patterns. A 12-channel prototype was characterized by coil-current, electric-field, and thermal measurements. Results: The prototype produced a peak primary electric field of approximately 1 V/m measured in air 4 cm from the inner helmet surface. Whole-array modeling attained cortical fields of up to 1.5 V/m, reproduced the field distribution of a clinically validated low-intensity stimulator to within 3%-5%, and demonstrated focal targeting of the dorsolateral prefrontal cortex, simultaneous delivery of electric field to the default mode network nodes, and synthesis of electric fields following the traveling alpha wave. Conclusion: Electronically steerable, whole-head LI-TMS is feasible using accessible microprocessor-controlled power electronics. Significance: The array reaches the cortical field regime of tES without scalp contact or the associated shunting of current through the scalp, offering a route to testing network-level, phaselocked weak-field neuromodulation.

bioengineering↗

bioRxiv2026

Charge Based Boundary Element Method with Residual Driven Adaptive Mesh Refinement for High Resolution Electrical Simulation Modeling

Accurate transcranial electrical stimulation (TES), electroconvulsive therapy (ECT), and electroencephalography (EEG) forward modeling requires resolving numerical singularities in the charge density near electrodes and tissue interfaces. We present an adaptive mesh refinement (AMR) strategy for the charge based boundary element method (BEM) accelerated by the fast multiple method (BEM-FMM) including electrode and interface singularities. We derive a new error estimator which considers both local and nonlocal contributions of the single-layer potential operator and construct a refinement criterion based on the difference in charge solution across AMR iterations. We evaluate this approach on a 5-layer sphere model and on multiple subject-specific head models derived from the 7-tissue SimNIBS (headreco) and 40-tissue Sim4Life (head40) segmentations, using both voltage-controlled and current-controlled electrode formulations. Through convergence analysis on the white matter and deep hippocampal targets, we find electric fields with relative residual errors below 0.1% and 1% for SimNIBS and Sim4Life models, respectively. Our results indicate that the residual based AMR applied to BEM-FMM leads to numerically stable TES and EEG forward solutions in realistic head models.

neuroscience↗

bioRxiv2025

High-Resolution EEG Source Reconstruction from PCA-Corrected BEM-FMM Reciprocal Basis Funcions: A Study with Visual Evoked Potentials from Intermittent Photic Stimulation

Modern automated human head segmentations can generate high-resolution computational meshes involving many non-nested tissues. However, most source reconstruction software is limited to 3 -4 nested layers of low resolution and a small number of dipolar sources[~] 10, 000. Recently, we introduced modeling techniques for source reconstruction of magnetoencephalographic (MEG) signals using the reciprocal approach and the boundary element fast multipole method (BEM-FMM). The technique of BEM-FMM can process both nested and non-nested models with as many as 4 million surface elements. In this paper, we present an analogue technique for source reconstruction of electroencephalographic (EEG) signals based on cortical global basis functions. The present work uses Helmholtz reciprocity to relate the reciprocally-generated lead-field matrices to their direct counterpart, while resolving the issue of possible biases toward the reference electrode. Our methodology is tested with experimental EEG data collected from a cohort of 12, young and healthy, volunteers subjected to intermittent photic stimulation (IPS). Our novel high-resolution source reconstruction models can have impact on mental health screening as well as brain-computer inter-faces.

neuroscience↗

bioRxiv2025

Converting Spectral Evoked-to-Background Ratio intoTime-Domain Signal-to-Noise Ratio - Validation for HighFrequency Oscillations

N -Interval Fourier Transform Analysis (N -FTA) allows for spectral separation of an evoked target signal from uncorrelated background activity. It computes the frequency-dependent evoked-to-background ratio (EBR). The developed method allows for conversion of the spectral EBR into expected values for improvement of signal-to-noise ratio with progressing sweep count. Our study presents the mathematical basis for this conversion along with a validation for simulated and recorded data. The major findings are: O_LIThree factors enter the calculus of the expected SNR: the ratio of durations of the single sweep cycle and the evoked response window, the mean EBR in the spectral target band, and the sweep count. By conversion of all factors to dB, the expected SNR is defined by their sum. C_LIO_LIThe two fundamental theories governing the improvement of SNR with increasing sweep count, the law of large numbers and the uncertainty principle of signal processing, deliver identical results. C_LIO_LIConversion of EBR to expected SNR was successfully validated by simulated and recorded data and can be applied to all types of evoked data. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/662283v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@6f34d6org.highwire.dtl.DTLVardef@f5d607org.highwire.dtl.DTLVardef@1b6a18eorg.highwire.dtl.DTLVardef@1288e35_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Influence of neck tissue conductivities on the phrenic nerve activation threshold during non-invasive electrical stimulation

Phrenic nerve stimulation can be used as an artificial ventilation method to reduce the adverse effects of mechanical ventilation. Detailed computational models and electromagnetic simulations are used to determine appropriate stimulation parameters. Therefore, tissue parameters have to be selected, but they vary widely in the literature. Here, we evaluated the phrenic nerve activation threshold using minimum and maximum electrical conductivity values found in the literature of each modeled neck tissue type. To calculate the phrenic nerve activation threshold, an anatomical detailed finite element model of the neck and a biophysiological nerve model were used. Considerable changes in nerve activation thresholds were found for the following tissue conductivities (with decreasing effects): muscle, skin, soft tissue, subcutaneous fat, and nerve tissue. Changes in the nerve activation threshold due to changes in skin conductivity occurred due to the bridging effect, which is an unwanted and avoidable effect during stimulation. In conclusion, fat, muscle, nerve, and soft tissue require the most accurate tissue properties and geometric representation within the model.

neuroscience↗

bioRxiv2025

Improved Source Localization of Auditory Evoked Fields using Reciprocal BEM-FMM

The precise localization of auditory evoked fields (AEFs) from magnetoencephalography (MEG) data is very important for the functional understanding of the auditory cortex in medicine and cognitive neuroscience. The numerical solution of the field equations in the human head using the boundary element method (BEM) is a powerful tool for achieving this. We hypothesized that the spatial resolution of the BEM is crucial for the achievable accuracy. However, in classical BEM (as implemented, e.g., in MNE-Python), very high resolutions are impractical due to the associated prohibitive computational effort. In contrast, our recently introduced reciprocal boundary element fast multipole method (reciprocal BEM-FMM) allows for hitherto unprecedented spatial resolution. In this work, we apply our reciprocal BEM-FMM technique for source estimation to localize AEFs, and we compare our results with the source estimates produced using a 3-layer BEM model (standard BEM) via MNE-Python. We first validate our methodology through comparison of source estimates of simulated N1m components of AEFs using a receiver operating characteristic (ROC) measure. While we obtain ROC measures of about 80% for the standard BEM, reciprocal BEM-FMM reaches about 90%, a significant statistical improvement. We then apply this methodology to analyze the source estimates of experimental data obtained from a cohort of 7 participants subjected to binaural auditory stimulation. Using a dispersion measurement to quantify the focality of localized sources, we find improvements upwards of 30% using reciprocal BEM-FMM over the standard BEM. Analyses from both simulated and experimental data show localization of AEFs using high-resolution reciprocal BEM-FMM is significantly better in terms of accuracy and focality than those estimates of the low-resolution standard BEM. We therefore recommend using the high-resolution reciprocal BEM-FMM to utilize high spatial anatomical precision for the modeling of neural activity.

neuroscience↗

bioRxiv2025

High-Definition MEG Source Estimation using the Reciprocal Boundary Element Fast Multipole Method

Magnetoencephalographic (MEG) source estimation relies on the computation of the gain (lead-field) matrix, which embodies the linear relationship between the amplitudes of the sources and the recorded signals. However, with a realistic forward model, the calculation of the gain matrix in a "direct" fashion is a computationally expensive task because the number of dipolar sources in standard MEG pipelines is often limited to [~]10,000. We propose a fast approach based on the reciprocal relationship between MEG and transcranial magnetic stimulation (TMS). This approach couples naturally with the charge-based boundary element fast multipole method (BEM-FMM), which allows us to efficiently generate gain matrices for high-resolution multi-layer non-nested meshes involving source spaces of up to a [~]1 million dipoles. We evaluate our approach by performing MEG source reconstruction against simulated data (at varying noise levels) obtained from the direct computation of MEG readings from 2000 different dipole positions over the cortical surface of 5 healthy subjects. Additionally, we test our methods with real MEG data from evoked somatosensory fields by right-hand median nerve stimulation in these same 5 subjects. We compare our experimental source reconstruction results against the standard MNE-Python source reconstruction pipeline.

neuroscience↗

bioRxiv2025

Comparison of TENS electrodes and textile electrodes for electrocutaneous warning

Electrocutaneous stimulation can be employed to alert workers in potentially hazardous situations. To determine the feasibility of a novel textile electrode cuff in comparison to previously used TENS electrodes, two studies were conducted. In a study on n = 30 participants, perception, attention, muscle twitch, and intolerance thresholds as well as qualitative and spatial perceptions, were determined for eight pairs of electrodes circumferentially placed around the upper right arm for TENS and for textile electrodes. In a second study on n = 36 participants, these thresholds were also determined during vibration, and a warning signal pattern was presented during vibration. We found smaller perception thresholds for the textile electrodes in comparison to the TENS electrodes for all 8 electrode pairs and occasional differences for the attention and intolerance thresholds, which might be mainly explained by the varying electrode sizes due to the manual production process of the textile electrodes. Stimulation using textile electrodes within the cuff showed less frequent muscle twitches compared to TENS electrodes. Other qualitative and spatial perceptions appeared comparable. The perception, attention, and intolerance thresholds increased during vibration comparable to previous results with TENS electrodes. The feasibility of using the textile electrodes during vibration and for the application of a warning signal was successfully demonstrated. Occasional cases occurred where the transition impedance was too high while using the textile electrodes. Future studies will focus on electrode optimization to achieve a wearable solution with both low electrode-skin transition impedance and minimal muscle twitching.

neuroscience↗

bioRxiv2024

Interspecies hybridization as a route of accessory chromosome origin in fungal species infecting wild grasses

Many fungal plant pathogens have dynamic genomic architectures that can contribute to rapid evolution and adaptation to new niches. Zymoseptoria tritici, an important fungal pathogen of wheat, has a compartmentalized and rapidly evolving genome. In the genome of the reference isolate Z. tritici IPO323, 8 of the 21 chromosomes are accessory. In spite of the profound impact on genome organization, the origin of accessory chromosomes in Z. tritici is still poorly understood. Combining genomics, transcriptomics and epigenomics, we discovered a new chromosome in Z. tritici isolates infecting wild grasses from the genus Aegilops, and we use this discovery to study the origin of accessory chromosomes. The newly identified chromosome presents similar characteristics to known accessory chromosomes in Zymoseptoria species, including presence-absence variation, low gene expression in vitro and in planta, and enrichment with heterochromatin-associated histone methylation marks (H3K27me3). Interestingly, we found an orthologous chromosome in Zymoseptoria ardabiliae, a closely related fungal species also infecting wild grasses. This ortholog chromosome also presents accessory chromosomes characteristics, but lacks the enrichment of heterochromatin-associated methylation marks. Transcriptomic analyses revealed that the orthologous chromosome in Z. ardabiliae harbors active transposable elements (TEs) congruent with lower signatures of host-genome defense mechanisms against TE expansion and spread (quantified as repeat-induced-point (RIP) mutation signatures). Our findings suggest that the chromosome has been exchanged between Z. tritici and Z. ardabiliae by introgressive hybridization events underlining the relevance of hybridization in the evolution of new accessory chromosomes. We speculate that the regulation of TEs has not yet occurred on this new accessory chromosome in Z. ardabiliae, contributing to its rapid evolution.

evolutionary biology↗

bioRxiv2024

Host specialization defines the emergence of new fungal plant pathogen populations

Host-driven selection can be considered a strong driver of pathogen evolution. To successfully infect, colonize and complete their life cycle, plant pathogens are under constant selective pressures imposed by hosts, leading to genetic adaptation and possibly lineage radiation or speciation. Population and comparative genomics approaches are powerful tools to identify signatures of selection associated with host specialization in pathogen genomes and further allow recapturing population histories. Implementing such approaches, we identified evolutionary signatures of divergent host specialisation in distinct lineages of the fungal pathogen Zymoseptoria tritici, a major disease causing-agent of wheat. Unique collections of Z. tritici were isolated from wild (Aegilops spp.) and domesticated (Triticum aestivum) host grasses in the Middle East and whole-genome sequencing was performed in a selected subset of isolates from each collection. We observed distinct population structure between the two host-diverging pathogens and identified particular genomic features in the Aegilops-infecting isolates that may have shaped their evolutionary history. Phylogenomic analyses revealed that A. cylindrica and A. tauchii -infecting populations of Z. tritici form separate clusters, possibly reflecting incipient speciation driven by divergent host specialization. Using infection experiments, we confirm that Z. tritici isolates collected from Aegilops spp. only infect their respective host species and not T. aestivum. Population genomics analyses and demographic inference furthermore allowed us to detect signatures of recent selection and show that divergence of the wheat-infecting lineage likely coincided with wheat domestication. At last, we confirm a virulence-related role for one candidate effector located in a selective sweep region of the A. cylindrica-infecting pathogen. Taken together, our findings highlight the interplay between agricultural and wild hosts on the evolution of fungal plant pathogens and illustrate host specialization as a possible route of rapid pathogen emergence.

evolutionary biology↗

bioRxiv2024

Emergence of sympatric host-specific lineages of the fungal plant pathogen Zymoseptoria passerinii in natural ecosystems

O_LIThe barley disease Septoria Speckled Leaf Blotch, caused by the fungal pathogen Zymoseptoria passerinii, had its last outbreak in North America in the early 2000s. Although rare in agricultural settings, field sampling of wild grasses in the Middle East revealed the disease persistence in wild barley. C_LIO_LIIdentification of Z. passerinii in distinct wild barley species led us to investigate signatures of host specialization using genomics to address the mode of emergence by host tracking or host range expansion. Furthermore, we applied virulence assays and confocal laser microscopy to evaluate if the disease development differs between wild and domesticated barley. C_LIO_LIWild- and domesticated-host infecting populations have diverged, and phylogenetic relationships support the emergence of sympatric host-specific lineages. Cross-virulence assays showed that Zymoseptoria passerinii from domesticated hosts infect domesticated barley and its wild ancestor, Hordeum spontaneum. However, wild isolates from Iran did not infect domesticated barley. Wild and domesticated pathosystems have similar disease timing and progression, suggesting its persistence in natural ecosystems might be tied to environmental conditions. C_LIO_LIThe study supports that a wide range of hosts can foster the emergence of host-specific lineages in sympatry and provide novel insights into the evolution of understudied fungal pathogens on wild crop relatives. C_LI

evolutionary biology↗

bioRxiv2024

Fast and Accurate EEG/MEG BEM-Based Forward Problem Solution for High-Resolution Head Models

A BEM (boundary element method) based approach is developed to accurately solve an EEG/MEG forward problem for a modern high-resolution head model in approximately 60 seconds using a common workstation. The method utilizes a charge-based BEM with fast multipole acceleration (BEM-FMM) and a "smart" mesh pre-refinement (called b-refinement) close to the singular source(s). No costly matrix-filling or direct solution steps typical for the standard BEM are required; the method generates on-skin voltages as well as MEG magnetic fields for high-resolution head models in approximately 60 seconds after initial model assembly. The method is verified both theoretically and experimentally.

neuroscience↗

bioRxiv2024

Accuracy of dipole source reconstruction in the 3-layerBEM model against the 5-layer BEM-FMM model

ObjectiveTo compare cortical dipole fitting spatial accuracy between the widely used yet highly simplified 3-layer and modern more realistic 5-layer BEM-FMM models with and without adaptive mesh refinement (AMR) methods. MethodsWe generate simulated noiseless 256-channel EEG data from 5-layer (7-compartment) meshes of 15 subjects from the Connectome Young Adult dataset. For each subject, we test four dipole positions, three sets of conductivity values, and two types of head segmentation. We use the boundary element method (BEM) with fast multipole method (FMM) acceleration, with or without (AMR), for forward modeling. Dipole fitting is carried out with the FieldTrip MATLAB toolbox. ResultsThe average position error (across all tested dipoles, subjects, and models) is [~]4 mm, with a standard deviation of [~]2 mm. The orientation error is [~]20{degrees} on average, with a standard deviation of [~]15{degrees}. Without AMR, the numerical inaccuracies produce a larger disagreement between the 3- and 5-layer models, with an average position error of [~]8 mm (6 mm standard deviation), and an orientation error of 28{degrees} (28{degrees} standard deviation). ConclusionsThe low-resolution 3-layer models provide excellent accuracy in dipole localization. On the other hand, dipole orientation is retrieved less accurately. Therefore, certain applications may require more realistic models for practical source reconstruction. AMR is a critical component for improving the accuracy of forward EEG computations using a high-resolution 5-layer volume conduction model. SignificanceImproving EEG source reconstruction accuracy is important for several clinical applications, including epilepsy and other seizure-inducing conditions.

bioinformatics↗

bioRxiv2023

Stimulation of Neurons and Astrocytes via Temporally Interfering Electric Fields

A novel non-invasive electrical stimulation method, temporal interference stimulation (TIS), has been proposed to enable spatially steerable stimulation and to selectively activate different brain regions. However, TIS has not been studied with cell cultures that can provide an indepth assessment of its effects on neuronal cells. We successfully established an in vitro TIS setup using rat cortical neurons on microelectrode arrays. Stimulations involved 1) TIS with 653 Hz and 643 Hz, resulting in a 10 Hz frequency envelope, 2) low-frequency stimulation (LFS) at 10 Hz, 3) high-frequency stimulation (HFS) at 653 Hz, and 4) no electrical stimulation (control/sham). HFS and LFS had the least effect on neuronal activity, but TIS elicited neuronal electrophysiological responses, especially 24 hours after stimulation. We also assessed TIS in neuron-astrocyte co-cultures. Interestingly, co-cultures seemed to counteract the TIS effects. Hence, our findings deepen the current understanding of the electrical modulation of neurons during TIS. HighlightsO_LITemporal interference stimulation (TIS) is a new technique for brain stimulation. C_LIO_LITIS setup was established and combined with microelectrode array (MEA) system. C_LIO_LIRat cortical neurons and astrocytes were stimulated with TIS in vitro. C_LIO_LINeurons responded to TIS more prominently without astrocyte support. C_LI

neuroscience↗

bioRxiv2023

Unleashing the secrets of plant-fungal interactions using a transformation-free confocal staining technique that supports AI-assisted quantitative analysis

Laser scanning confocal microscopys ability to generate high-contrast 3D images has become essential to studying plant-fungal interactions. Techniques such as visualization of native fluorescence, fluorescent protein tagging of microbes, GFP/RFP-fusion proteins, and fluorescent labelling of plant and fungal proteins have been widely used to aid in these investigations. Use of fluorescent proteins have several pitfalls including variability of expression in planta and the requirement of gene transformation. Here we used the unlabeled pathogens Parastagonospora nodorum, Pyrenophora teres f. teres, and Cercospora beticola infecting wheat, barley, and sugar beet respectively, to show the utility of a staining and imaging technique that uses propidium iodide (PI), which stains RNA and DNA, and wheat germ agglutinin labeled with fluorescein isothiocyanate (WGA-FITC), which stains chitin, to visualize fungal colonization of plants. This method relies on the use of KOH to remove the cutin layer of the leaf, increasing its permeability. This permeability allows the staining solution to penetrate and efficiently bind to its targets, resulting in a consistent visualization of cellular structures. We have also used this staining technique in conjunction with machine learning to analyze fungal volume, which indicates the fitness of the pathogen in planta, as well as quantifying nuclear breakdown, an early indicator of programmed cell death (PCD). This technique is simple to use, robust, consistent across host species, and can be applied to any plant-fungal interaction. Therefore, this technique can be used to characterize model systems as well as non-model interactions where transformation is not routine.

plant biology↗

bioRxiv2023

Modeling the Effects of Transcranial Magnetic Stimulation on Spatial Attention

ObjectivesTranscranial magnetic stimulation (TMS) has been widely used to modulate brain activity in healthy and diseased brains, but the underlying mechanisms are not fully understood. Previous research leveraged biophysical modeling of the induced electric field (E-field) to map causal structure-function relationships in the primary motor cortex. This study aims at transferring this localization approach to spatial attention, which helps to understand the TMS effects on cognitive functions, and may ultimately optimize stimulation schemes. ApproachThirty right-handed healthy participants underwent a functional magnetic imaging (fMRI) experiment, and seventeen of them participated in a TMS experiment. The individual fMRI activation peak within the right inferior parietal lobule (rIPL) during a Posner-like attention task defined the center target for TMS. Thereafter, participants underwent 500 Posner task trials. During each trial, a 5-pulse burst of 10 Hz repetitive TMS (rTMS) was given over the rIPL to modulate attentional processing. The TMS-induced E-fields for every cortical target were correlated with the behavioral modulation to identify relevant cortical regions for attentional orientation and reorientation. Main resultsWe did not observe a robust correlation between E-field strength and behavioral outcomes, highlighting the challenges of transferring the localization method to cognitive functions with high neural response variability and complex network interactions. Nevertheless, TMS selectively inhibited attentional reorienting in five out of seventeen subjects, resulting in task-specific behavioral impairments. The BOLD-measured neuronal activity and TMS-evoked neuronal effects showed different patterns, which emphasizes the principal distinction between the neural activity being correlated with (or maybe even caused by) particular paradigms, and the activity of neural populations exerting a causal influence on the behavioral outcome. SignificanceThis study is the first to explore the mechanisms of TMS-induced attentional modulation through electrical field modeling. Our findings highlight the complexity of cognitive functions and provide a basis for optimizing attentional stimulation protocols.

neuroscience↗

bioRxiv2022

Transferability of cathodal tDCS effects from the primary motor to the dorsolateral prefrontal cortex: a multimodal TMS-EEG study

Neurophysiological effects of transcranial direct current stimulation (tDCS) have been extensively studied over the primary motor cortex (M1). Much less is however known about its effects over non-motor areas, such as the prefrontal cortex (PFC), which is the neuronal foundation for many high-level cognitive functions and involved in neuropsychiatric disorders. In this study, we, therefore, explored the transferability of cathodal tDCS effects over M1 to the PFC. Eighteen healthy human participants (11 males and 8 females) were involved in eight randomized sessions, in which four cathodal tDCS dosages, low, medium, and high, as well as sham stimulation, were applied over the M1 and PFC. After-effects of tDCS were evaluated via transcranial magnetic stimulation (TMS)-electroencephalography (EEG), and TMS-elicited motor evoked potentials (MEP), for the outcome parameters TMS-evoked potentials (TEP), TMS-evoked oscillations, and MEP amplitude alterations. TEPs were studied both at the regional and global scalp levels. The results indicate a regional dosage-dependent nonlinear neurophysiological effect of M1 tDCS, which is not one-to-one transferable to PFC tDCS. Low and high dosages of M1 tDCS reduced early positive TEP peaks (P30, P60), and MEP amplitudes, while an enhancement was observed for medium dosage M1 tDCS (P30 and MEP amplitudes). In contrast, prefrontal low, medium and high dosage tDCS uniformly reduced the early positive TEP peak amplitudes. Furthermore, for both cortical areas, regional tDCS-induced modulatory effects were not observed for late TEP peaks, nor TMS-evoked oscillations. However, at the global scalp level, widespread effects of tDCS were observed for both, TMS-evoked potentials and oscillations. This study provides the first direct physiological comparison of tDCS effects applied over different brain areas and therefore delivers crucial information for future tDCS applications. SIGNIFICANCE STATEMENTModulatory effects of tDCS over the M1 were largely taken as a template so far for the use of this intervention over non-motor regions. However, the neurophysiological effects of tDCS over non-motor regions, such as the prefrontal cortex (PFC), have been much less explored. In the current study, we, using concurrent transcranial magnetic stimulation- electroencephalography, systematically explored the transferability of cathodal tDCS effects on cortical excitability from M1 to the PFC. The results indicate a dosage-dependent nonlinear neurophysiological effect of motor cortex tDCS, which is not one-to-one transferable to prefrontal tDCS. This study provides the first direct physiological comparison of tDCS effects applied over different brain areas, which will further consolidate the rationale for the extension of tDCS applications at both, basic and clinical levels.

neuroscience↗