Biology subjects

Weise, K.

Publications and source records attributed to Weise, K..

29 records · Page 2Linked to original sources

bioRxiv2024

Electromagnetic Modeling within a Microscopically Realistic Brain - Implications for Brain Stimulation

Modeling brain stimulation at the microscopic scale may reveal new paradigms for various stimulation modalities. We present the largest map to date of extracellular electric field distributions within a layer L2/L3 mouse primary visual cortex brain sample. This was enabled by the automated analysis of serial section electron microscopy images with improved handling of image defects, covering a volume of 250 x 140 x 90 m3. The map was obtained by applying a uniform brain stimulation electric field at three different polarizations and accurately computing microscopic field perturbations using the boundary element fast multipole method. We used the map to identify the effect of microscopic field perturbations on the activation thresholds of individual neurons. Previous relevant studies modeled a macroscopically homogeneous cortical volume. Our result shows that the microscopic field perturbations - an electric field spatial noise with a mean value of zero - only modestly influence the macroscopically predicted stimulation field strengths necessary for neuronal activation. The thresholds do not change by more than 10% on average. Under the stated limitations and assumptions of our method, this result justifies the conventional theory of "invisible" neurons embedded in a macroscopic brain model for transcranial magnetic and transcranial electrical stimulation. However, our result is solely sample-specific and largely neglects the effect of the microcapillary network. Furthermore, we only considered the uniform impressed field and a single- pulse stimulation time course. Significance statementThis study is arguably the first attempt to model brain stimulation at the microscopic scale, enabled by automated analysis of modern scanning electron microscopy images of the brain. It concentrates on modeling microscopic perturbations of the extracellular electric field caused by the physical cell structure and is applicable to any type of brain stimulation. Data availability statementPost-processed cell CAD models (383, stl format), microcapillary CAD models (34, stl format), post-processed neuron morphologies (267, swc format), extracellular electric field and potential distributions at different polarizations (267x3, MATLAB format), *.ses projects files for biophysical modeling with Neuron software (267x2, Neuron format), and computed neuron activating thresholds at different conditions (267x8, Excel tables, without the sample polarization correction from Section 2.8) are made available online through BossDB, a volumetric open-source database for 3D and 4D neuroscience data.

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bioRxiv2023

An Adaptive H-Refinement Method for the Boundary Element Fast Multipole Method for Quasi-static Electromagnetic Modeling

ObjectiveIn our recent work pertinent to modeling of brain stimulation and neurophysiological recordings, substantial modeling errors in the computed electric field and potential have sometimes been observed for standard multi-compartment head models. The goal of this study is to quantify those errors and, further, eliminate them through an adaptive mesh refinement (AMR) algorithm. The study concentrates on transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES), and electroencephalography (EEG) forward problems. ApproachWe propose, describe, and systematically investigate an AMR method using the Boundary Element Method with Fast Multipole Acceleration (BEM-FMM) as the base numerical solver. The goal is to efficiently allocate additional unknowns to critical areas of the model, where they will best improve solution accuracy. The implemented AMR methods accuracy improvement is measured on head models constructed from 16 Human Connectome Project subjects under problem classes of TES, TMS, and EEG. Errors are computed between three solutions: an initial non-adaptive solution, a solution found after applying AMR with a conservative refinement rate, and a "silver-standard" solution found by subsequent 4:1 global refinement of the adaptively-refined model. Main ResultsExcellent agreement is shown between the adaptively-refined and silver-standard solutions for standard head models. AMR is found to be vital for accurate modeling of TES and EEG forward problems for standard models: an increase of less than 25% (on average) in number of mesh elements for these problems, efficiently allocated by AMR, exposes electric field/potential errors exceeding 60% (on average) in the solution for the unrefined models. SignificanceThis error has especially important implications for TES dosing prediction - where the stimula t ion strength plays a central role - and for EEG lead fields. Though the specific form of the AMR method described here is implemented for the BEM-FMM, we expect that AMR is applicable and even required for accurate electromagnetic simulations by other numerical modeling packages as well.

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bioRxiv2023

Electrical field based dosing improves non-invasive brain stimulation

AbstractTranscranial magnetic stimulation (TMS) is an invaluable non-invasive brain stimulation (NIBS) technique to modulate cortical activity and behavior, but high within- and between-participant variability limits its efficacy and reliability. Here, we explore the potential of electric field (e-field) based TMS dosing to reduce its variability and discuss current challenges as well as future pathways. In contrast to previous dosing approaches, e-field dosing better matches the stimulation strength across cortical areas, both within and across individuals. Challenges include methodological uncertainties of the e-field simulation, target definitions, and comparability of different stimulation thresholds across cortical areas and NIBS protocols. Despite these challenges, e-field dosing promises to substantially improve NIBS applications in neuroscientific research and personalized medicine. Outstanding Questions Box O_TEXTBOXOutstanding Questions O_LIDoes the cortical threshold for effective stimulation differ between primary regions and higher-level association areas? How large is the impact of cytoarchitectonic differences between regions on a stimulation threshold? C_LIO_LIDo cortical stimulation thresholds differ across individuals? Are thresholds stable within an individual across the lifespan? What are the physiological factors influencing these thresholds? C_LIO_LICan a cortical stimulation threshold measured with single-pulse TMS be transferred to repetitive TMS protocols for the study of cognition? C_LIO_LIHow does the cortical stimulation threshold interact with the current brain state? C_LI C_TEXTBOX Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/551253v2_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@16d6e44org.highwire.dtl.DTLVardef@1626d90org.highwire.dtl.DTLVardef@10713e7org.highwire.dtl.DTLVardef@1abdcaa_HPS_FORMAT_FIGEXP M_FIG C_FIG

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bioRxiv2023

Directional Sensitivity of Cortical Neurons Towards TMS Induced Electric Fields

We derived computationally efficient average response models of different types of cortical neurons, which are subject to external electric fields from Transcranial Magnetic Stimulation. We used 24 reconstructions of pyramidal cells (PC) from layer 2/3, 245 small, nested, and large basket cells from layer 4, and 30 PC from layer 5 with different morphologies for deriving average models. With these models, it is possible to efficiently estimate the stimulation thresholds depending on the underlying electric field distribution in the brain, without having to implement and compute complex neuron compartment models. The stimulation thresholds were determined by exposing the neurons to TMS-induced electric fields with different angles, intensities, pulse waveforms, and field decays along the somato-dendritic axis. The derived average response models were verified by reference simulations using a high-resolution realistic head model containing several million neurons. Differences of only 1-2% between the average model and the average response of the reference cells were observed, while the computation time was only a fraction of a second compared to several weeks using the cells. Finally, we compared the model behavior to TMS experiments and observed high correspondence to the orientation sensitivity of motor evoked potentials. The derived models were compared to the classical cortical column cosine model and to simplified ball-and-stick neurons. It was shown that both models oversimplify the complex interplay between the electric field and the neurons and do not adequately represent the directional sensitivity of the different cell types. The derived models are simple to apply and only require the TMS induced electric field in the brain as input variable. The models and code are available to the general public in open-source repositories for integration into TMS studies to estimate the expected stimulation thresholds for an improved dosing and treatment planning in the future.

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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.

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bioRxiv2022

High-Resolution EEG Source Reconstruction with Boundary Element Fast Multipole Method Using Reciprocity Principle and TES Forward Model Matrix

BackgroundAccurate high-resolution EEG source reconstruction (localization) is important for several tasks, including rigorous and rapid mental health screening. ObjectiveThe present study has developed, validated, and applied a new source localization algorithm utilizing a charge-based boundary element fast multipole method (BEM-FMM) coupled with the Helmholtz reciprocity principle and the transcranial electrical stimulation (TES) forward solution. MethodsThe unknown cortical dipole density is reconstructed over the entire cortical surface by expanding into global basis functions in the form of cortical fields of active TES electrode pairs. These pairs are constructed from the reading electrodes. An analog of the minimum norm estimation (MNE) equation is obtained after substituting this expansion into the reciprocity principle written in terms of measured electrode voltages. Delaunay (geometrically balanced) triangulation of the electrode cap is introduced first. Basis functions for all electrode pairs connected by the edges of a triangular mesh are precomputed and stored in memory. A smaller set of independent basis functions is then selected and employed at every time instant. This set is based on the highest voltage differences measured. ResultsThe method is validated against the classic, yet challenging problem of median nerve stimulation and the tangential cortical sources located at the posterior wall of the central sulcus for an N20/P20 peak (2 scanned subjects). The method is further applied to perform source reconstruction of synthesized tangential cortical sources located at the posterior wall of the central sulcus (12 different subjects). In the second case, an average source reconstruction error of 7 mm is reported for the best possible noiseless scenario. ConclusionsOnce static preprocessing with TES electrodes has been done (the basis functions have been computed), our method requires fractions of a second to complete the accurate high-resolution source localization.

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bioRxiv2022

Effect of contact pressure on porcine postmortem brain tissue impedance

In this experimental study we demonstrate the influence of contact pressure on porcine postmortem brain tissue impedance using a movable electrode array and a load cell. We show that the variation of the contact pressure between the tissue and the measurement probe leads to a coefficient of variation in the measured impedance of under 3%. Its influence can therefore be neglected. Further, we fit the measured impedances to an equivalent circuit model and compare the resistance as well as the cell density of grey and white matter brain tissue based on the model parameters.

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bioRxiv2021

A four-point measurement probe for brain tissue conductivity and permittivity characterization

We present a measurement probe consisting of four platinum electrodes fused into soda-lime glass. The probe is based on a four-terminal sensing technique that uses separate pairs of current-carrying and voltage-sensing electrodes and performs more accurate measurements than the simpler and more usual two-terminal sensing technique. The electrodes are aranged within an area of 1 mm2 allowing for local characterization of different brain tissues. The operation of the probe is demonstrated in situ on post mortem porcine brain tissue by measuring the impedance spectra of grey and white matter in a frequency range of 1 kHz < f < 1 MHz. The conductivity and relative permittivity are derived from the impedance spectra using the geometry factor of the probe. The geometry factor is obtained experimentally by measuring the impedances of an electrolytical dilution series with known conductivities. The obtained conductivity of grey matter is in the order of 0.11 S/m and of white matter is in the order of 0.07 S/m over the acquired frequency range.

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bioRxiv2021

Efficient high-resolution TMS mapping of the human motor cortex by nonlinear regression

Transcranial magnetic stimulation (TMS) is a powerful tool to investigate causal structure-function relationships in the human brain. However, a precise delineation of the effectively stimulated neuronal populations is notoriously impeded by the widespread and complex distribution of the induced electric field. Here, we propose a method that allows rapid and feasible cortical localization at the individual subject level. The functional relationship between electric field and behavioral effect is quantified by combining experimental data with numerically modelled fields to identify the cortical origin of the modulated effect. Motor evoked potentials (MEPs) from three finger muscles were recorded for a set of random stimulations around the primary motor area. All induced electric fields were nonlinearly regressed against the elicited MEPs to identify their cortical origin. We could distinguish cortical muscle representation with high spatial resolution and localized them primarily on the crowns and rims of the precentral gyrus. A post-hoc analysis revealed exponential convergence of the method with the number of stimulations, yielding a minimum of about 180 random stimulations to obtain stable results. Establishing a functional link between the modulated effect and the underlying mode of action, the induced electric field, is a fundamental step to fully exploit the potential of TMS. In contrast to previous approaches, the presented protocol is particularly easy to implement, fast to apply, and very robust due to the random coil positioning and therefore is suitable for practical and clinical applications.

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bioRxiv2020

In situ impedance measurements on postmortem porcine brain

The paper presents an experimental study where the distinctness of grey and white matter of an in situ postmortem porcine brain by impedance measurements is investigated. Experimental conditions that would allow to conduct the same experiment on in vivo human brain tissue are replicated. https://doi.org/10.1515/cdbme-2019-XXXX

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bioRxiv2019

A novel approach to localize cortical TMS effects

Despite the widespread use of transcranial magnetic stimulation (TMS), the precise cortical location underlying the physiological and behavioral stimulation effects are still only coarsely known. So far, mapping strategies rely on center of gravity approaches and therefore localize the stimulated cortical site only approximately and indirectly. Focusing on the motor cortex, we present a novel method to reliably determine the effectively stimulated cortical site at the individual subject level. The approach combines measurements of motor evoked potentials (MEPs) at different coil positions and orientations with numerical modeling of induced electric fields. We identify sharply bounded cortical areas around the gyral crowns and rims of the motor hand area as the origin of MEPs and show that the tangential component and the magnitude of the electric field is most relevant for the observed effect. To validate our approach, we determined motor thresholds for coil positions and orientations for the predicted cortical target. Our methods allows for the identification of optimal coil positions and orientations. Moreover, we used extensive uncertainty and sensitivity analyses to verify the robustness of the method and identify the most critical model parameters. Our generic approach improves the localization of the cortex area stimulated by TMS and may be transferred to other modalities such as language mapping.

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