A boundary element method of bidomain modeling for predicting cellular responses to electromagnetic fields.

Commonly used cable equation approaches for simulating the effects of electromagnetic fields on excitable cells make several simplifying assumptions that could limit their predictive power. Bidomain or 'whole' finite element methods have been developed to fully couple cells and electric fields for more realistic neuron modeling. Here, we introduce a novel bidomain integral equation designed for determining the full electromagnetic coupling between stimulation devices and the intracellular, membrane, and extracellular regions of neurons.

Activity-driven synaptic translocation of LGI1 controls excitatory neurotransmission.

The fine control of synaptic function requires robust trans-synaptic molecular interactions. However, it remains poorly understood how trans-synaptic bridges change to reflect the functional states of the synapse. Here, we develop optical tools to visualize in firing synapses the molecular behavior of two trans-synaptic proteins, LGI1 and ADAM23, and find that neuronal activity acutely rearranges their abundance at the synaptic cleft.

A Kv2 inhibitor combination reveals native neuronal conductances consistent with Kv2/KvS heteromers.

KvS proteins are voltage-gated potassium channel subunits that form functional channels when assembled into heterotetramers with Kv2.1 ( ) or Kv2.2 ( ).

A Boundary Element Method of Bidomain Modeling for Predicting Cellular Responses to Electromagnetic Fields.

Objective: Commonly used cable equation-based approaches for determining the effects of electromagnetic fields on excitable cells make several simplifying assumptions that could limit their predictive power. Bidomain or "whole" finite element methods have been developed to fully couple cells and electric fields for more realistic neuron modeling. Here, we introduce a novel bidomain integral equation designed for determining the full electromagnetic coupling between stimulation devices and the intracellular, membrane, and extracellular regions of neurons.

Multi-scale model of axonal and dendritic polarization by transcranial direct current stimulation in realistic head geometry.

Background: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation modality that can alter cortical excitability. However, it remains unclear how the subcellular elements of different neuron types are polarized by specific electric field (E-field) distributions.

Objective: To quantify neuronal polarization generated by tDCS in a multi-scale computational model.

Multi-scale model of axonal and dendritic polarization by transcranial direct current stimulation in realistic head geometry.

Background: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation modality that can alter cortical excitability. However, it remains unclear how the subcellular elements of different neuron types are polarized by specific electric field (E-field) distributions.

Objective: To quantify neuronal polarization generated by tDCS in a multi-scale computational model.

Rapid estimation of cortical neuron activation thresholds by transcranial magnetic stimulation using convolutional neural networks.

Background: Transcranial magnetic stimulation (TMS) can modulate neural activity by evoking action potentials in cortical neurons. TMS neural activation can be predicted by coupling subject-specific head models of the TMS-induced electric field (E-field) to populations of biophysically realistic neuron models; however, the significant computational cost associated with these models limits their utility and eventual translation to clinically relevant applications.

Objective: To develop computationally efficient estimators of the activation thresholds of multi-compartmental cortical neuron models in response to TMS-induced E-field distributions.

Dependence of cortical neuronal strength-duration properties on TMS pulse shape.

Objective: The aim of present study was to explore the effects of different combinations of transcranial magnetic stimulation (TMS) pulse width and pulse shape on cortical strength-duration time constant (SDTC) and rheobase measurements.

Methods: Resting motor thresholds (RMT) at pulse widths (PW) of 30, 45, 60, 90 and 120 µs and M-ratios of 0.2, 0.

Responses of model cortical neurons to temporal interference stimulation and related transcranial alternating current stimulation modalities.

Temporal interference stimulation (TIS) was proposed as a non-invasive, focal, and steerable deep brain stimulation method. However, the mechanisms underlying experimentally-observed suprathreshold TIS effects are unknown, and prior simulation studies had limitations in the representations of the TIS electric field (E-field) and cerebral neurons. We examined the E-field and neural response characteristics for TIS and related transcranial alternating current stimulation modalities.

Ideal current dipoles are appropriate source representations for simulating neurons for intracranial recordings.

Objective: To determine whether dipoles are an appropriate simplified representation of neural sources for stereo-EEG (sEEG).

Methods: We compared the distributions of voltages generated by a dipole, biophysically realistic cortical neuron models, and extended regions of cortex to determine how well a dipole represented neural sources at different spatial scales and at electrode to neuron distances relevant for sEEG. We also quantified errors introduced by the dipole approximation of neural sources in sEEG source localization using standardized low-resolution electrotomography (sLORETA).

Transcranial magnetic stimulation of the brain: What is stimulated? - A consensus and critical position paper.

Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field and the stimulated neurons determines axonal depolarization.

Effect of Pulse Duration and Direction on Plasticity Induced by 5 Hz Repetitive Transcranial Magnetic Stimulation in Correlation With Neuronal Depolarization.

High frequency repetitive transcranial magnetic stimulation applied to the motor cortex causes an increase in the amplitude of motor evoked potentials (MEPs) that persists after stimulation. Here, we focus on the aftereffects generated by high frequency controllable pulse TMS (cTMS) with different directions, intensities, and pulse durations. To investigate the influence of pulse duration, direction, and amplitude in correlation to induced depolarization on the excitatory plastic aftereffects of 5 Hz repetitive transcranial magnetic stimulation (rTMS) using bidirectional cTMS pulses.

Simulation of transcranial magnetic stimulation in head model with morphologically-realistic cortical neurons.

Background: Transcranial magnetic stimulation (TMS) enables non-invasive modulation of brain activity with both clinical and research applications, but fundamental questions remain about the neural types and elements TMS activates and how stimulation parameters affect the neural response.

Objective: To develop a multi-scale computational model to quantify the effect of TMS parameters on the direct response of individual neurons.

Methods: We integrated morphologically-realistic neuronal models with TMS-induced electric fields computed in a finite element model of a human head to quantify the cortical response to TMS with several combinations of pulse waveforms and current directions.

Biophysically realistic neuron models for simulation of cortical stimulation.

Objective: We implemented computational models of human and rat cortical neurons for simulating the neural response to cortical stimulation with electromagnetic fields.

Approach: We adapted model neurons from the library of Blue Brain models to reflect biophysical and geometric properties of both adult rat and human cortical neurons and coupled the model neurons to exogenous electric fields (E-fields). The models included 3D reconstructed axonal and dendritic arbors, experimentally-validated electrophysiological behaviors, and multiple, morphological variants within cell types.

Modified cable equation incorporating transverse polarization of neuronal membranes for accurate coupling of electric fields.

Objective: We present a theory and computational methods to incorporate transverse polarization of neuronal membranes into the cable equation to account for the secondary electric field generated by the membrane in response to transverse electric fields. The effect of transverse polarization on nonlinear neuronal activation thresholds is quantified and discussed in the context of previous studies using linear membrane models.

Approach: The response of neuronal membranes to applied electric fields is derived under two time scales and a unified solution of transverse polarization is given for spherical and cylindrical cell geometries.

Design and characterization of a nanopore-coupled polymerase for single-molecule DNA sequencing by synthesis on an electrode array.

Scalable, high-throughput DNA sequencing is a prerequisite for precision medicine and biomedical research. Recently, we presented a nanopore-based sequencing-by-synthesis (Nanopore-SBS) approach, which used a set of nucleotides with polymer tags that allow discrimination of the nucleotides in a biological nanopore. Here, we designed and covalently coupled a DNA polymerase to an α-hemolysin (αHL) heptamer using the SpyCatcher/SpyTag conjugation approach.