Neuroanatomical Predictors of Transcranial Direct Current Stimulation (tDCS)-Induced Modifications in Neurocognitive Task Performance in Typically Developing Individuals.

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique gaining more attention in neurodevelopmental disorders (NDDs). Due to the phenotypic heterogeneity of NDDs, tDCS is unlikely to be equally effective in all individuals. The present study aimed to establish neuroanatomical markers in typically developing (TD) individuals that may be used for the prediction of individual responses to tDCS. Fifty-seven male and female children received 2 mA anodal and sham tDCS, targeting the left dorsolateral prefrontal cortex (DLPFCleft), right inferior frontal gyrus, and bilateral temporoparietal junction. Response to tDCS was assessed based on task performance differences between anodal and sham tDCS in different neurocognitive tasks (N-back, flanker, Mooney faces detection, attentional emotional recognition task). Measures of cortical thickness (CT) and surface area (SA) were derived from 3 Tesla structural MRI scans. Associations between neuroanatomy and task performance were assessed using general linear models (GLM). Machine learning (ML) algorithms were employed to predict responses to tDCS. Vertex-wise estimates of SA were more closely linked to differences in task performance than measures of CT. Across ML algorithms, highest accuracies were observed for the prediction of N-back task performance differences following stimulation of the DLPFCleft, where 65% of behavioral variance was explained by variability in SA. Lower accuracies were observed for all other tasks and stimulated regions. This suggests that it may be possible to predict individual responses to tDCS for some behavioral measures and target regions. In the future, these models might be extended to predict treatment outcome in individuals with NDDs.

Targeted tDCS Mitigates Dual-Task Costs to Gait and Balance in Older Adults.

OBJECTIVE: Among older adults, the ability to stand or walk while performing cognitive tasks (ie, dual-tasking) requires coordinated activation of several brain networks. In this multicenter, double-blinded, randomized, and sham-controlled study, we examined the effects of modulating the excitability of the left dorsolateral prefrontal cortex (L-DLPFC) and the primary sensorimotor cortex (SM1) on dual-task performance "costs" to standing and walking. METHODS: Fifty-seven older adults without overt illness or disease completed 4 separate study visits during which they received 20 minutes of transcranial direct current stimulation (tDCS) optimized to facilitate the excitability of the L-DLPFC and SM1 simultaneously, or each region separately, or neither region (sham). Before and immediately after stimulation, participants completed a dual-task paradigm in which they were asked to stand and walk with and without concurrent performance of a serial-subtraction task. RESULTS: tDCS simultaneously targeting the L-DLPFC and SM1, as well as tDCS targeting the L-DLPFC alone, mitigated dual-task costs to standing and walking to a greater extent than tDCS targeting SM1 alone or sham (p < 0.02). Blinding efficacy was excellent and participant subjective belief in the type of stimulation received (real or sham) did not contribute to the observed functional benefits of tDCS. INTERPRETATION: These results demonstrate that in older adults, dual-task decrements may be amenable to change and implicate L-DPFC excitability as a modifiable component of the control system that enables dual-task standing and walking. tDCS may be used to improve resilience and the ability of older results to walk and stand under challenging conditions, potentially enhancing everyday functioning and reducing fall risks. ANN NEUROL 2021;90:428-439.

Local and Distributed fMRI Changes Induced by 40 Hz Gamma tACS of the Bilateral Dorsolateral Prefrontal Cortex: A Pilot Study.

Over the past few years, the possibility of modulating fast brain oscillatory activity in the gamma (γ) band through transcranial alternating current stimulation (tACS) has been discussed in the context of both cognitive enhancement and therapeutic scenarios. However, the effects of tACS targeting regions outside the motor cortex, as well as its spatial specificity, are still unclear. Here, we present a concurrent tACS-fMRI block design study to characterize the impact of 40 Hz tACS applied over the left and right dorsolateral prefrontal cortex (DLPFC) in healthy subjects. Results suggest an increase in blood oxygenation level-dependent (BOLD) activity in the targeted bilateral DLPFCs, as well as in surrounding brain areas affected by stimulation according to biophysical modeling, i.e., the premotor cortex and anterior cingulate cortex (ACC). However, off-target effects were also observed, primarily involving the visual cortices, with further effects on the supplementary motor areas (SMA), left subgenual cingulate, and right superior temporal gyrus. The specificity of 40 Hz tACS over bilateral DLPFC and the possibility for network-level effects should be considered in future studies, especially in the context of recently promoted gamma-induction therapeutic protocols for neurodegenerative disorders.

Drug-Responsive Inhomogeneous Cortical Modulation by Direct Current Stimulation.

OBJECTIVE: Cathodal direct current stimulation (cDCS) induces long-term depression (LTD)-like reduction of cortical excitability (DCS-LTD), which has been tested in the treatment of epilepsy with modest effects. In part, this may be due to variable cortical neuron orientation relative to the electric field. We tested, in vivo and in vitro, whether DCS-LTD occurs throughout the cortical thickness, and if not, then whether drug-DCS pairing can enhance the uniformity of the cortical response and the cDCS antiepileptic effect. METHODS: cDCS-mediated changes in cortical excitability were measured in vitro in mouse motor cortex (M1) and in human postoperative neocortex, in vivo in mouse somatosensory cortex (S1), and in a mouse kainic acid (KA)-seizure model. Contributions of N-methyl-D-aspartate-type glutamate receptors (NMDARs) to cDCS-mediated plasticity were tested with application of NMDAR blockers (memantine/D-AP5). RESULTS: cDCS reliably induced DCS-LTD in superficial cortical layers, and a long-term potentiation (LTP)-like enhancement (DCS-LTP) was recorded in deep cortical layers. Immunostaining confirmed layer-specific increase of phospho-S6 ribosomal protein in mouse M1. Similar nonuniform cDCS aftereffects on cortical excitability were also found in human neocortex in vitro and in S1 of alert mice in vivo. Application of memantine/D-AP5 either produced a more uniform DCS-LTD throughout the cortical thickness or at least abolished DCS-LTP. Moreover, a combination of memantine and cDCS suppressed KA-induced seizures. INTERPRETATION: cDCS aftereffects are not uniform throughout cortical layers, which may explain the incomplete cDCS clinical efficacy. NMDAR antagonists may augment cDCS efficacy in epilepsy and other disorders where regional depression of cortical excitability is desirable. ANN NEUROL 2020;88:489-502.

Realistic modeling of mesoscopic ephaptic coupling in the human brain.

Several decades of research suggest that weak electric fields may influence neural processing, including those induced by neuronal activity and proposed as a substrate for a potential new cellular communication system, i.e., ephaptic transmission. Here we aim to model mesoscopic ephaptic activity in the human brain and explore its trajectory during aging by characterizing the electric field generated by cortical dipoles using realistic finite element modeling. Extrapolating from electrophysiological measurements, we first observe that modeled endogenous field magnitudes are comparable to those in measurements of weak but functionally relevant self-generated fields and to those produced by noninvasive transcranial brain stimulation, and therefore possibly able to modulate neuronal activity. Then, to evaluate the role of these fields in the human cortex in large MRI databases, we adapt an interaction approximation that considers the relative orientation of neuron and field to estimate the membrane potential perturbation in pyramidal cells. We use this approximation to define a simplified metric (EMOD1) that weights dipole coupling as a function of distance and relative orientation between emitter and receiver and evaluate it in a sample of 401 realistic human brain models from healthy subjects aged 16-83. Results reveal that ephaptic coupling, in the simplified mesoscopic modeling approach used here, significantly decreases with age, with higher involvement of sensorimotor regions and medial brain structures. This study suggests that by providing the means for fast and direct interaction between neurons, ephaptic modulation may contribute to the complexity of human function for cognition and behavior, and its modification across the lifespan and in response to pathology.

Impact of network-targeted multichannel transcranial direct current stimulation on intrinsic and network-to-network functional connectivity.

Dynamics within and between functional resting-state networks have a crucial role in determining both healthy and pathological brain functioning in humans. The possibility to noninvasively interact and selectively modulate the activity of networks would open to relevant applications in neuroscience. Here we tested a novel approach for multichannel, network-targeted transcranial direct current stimulation (net-tDCS), optimized to increase excitability of the sensorimotor network (SMN) while inducing cathodal inhibitory modulation over prefrontal and parietal brain regions negatively correlated with the SMN. Using an MRI-compatible multichannel transcranial electrical stimulation (tES) device, 20 healthy participants underwent real and sham tDCS while at rest in the MRI scanner. Changes in functional connectivity (FC) during and after stimulation were evaluated, looking at the intrinsic FC of the SMN and the strength of the negative connectivity between SMN and the rest of the brain. Standard, bifocal tDCS targeting left motor cortex (electrode ~C3) and right frontopolar (~Fp2) regions was tested as a control condition in a separate sample of healthy subjects to investigate network specificity of multichannel stimulation effects. Net-tDCS induced greater FC increase over the SMN compared to bifocal tDCS, during and after stimulation. Moreover, exploratory analysis of the impact of net-tDCS on negatively correlated networks showed an increase in the negative connectivity between SMN and prefrontal/parietal areas targeted by cathodal stimulation both during and after real net-tDCS. Results suggest preliminary evidence of the possibility of manipulating distributed network connectivity patterns through net-tDCS, with potential relevance for the development of cognitive enhancement and therapeutic tES solutions.

Genetic variants in Argentinean isolates of Spodoptera frugiperda Multiple Nucleopolyhedrovirus.

The fall armyworm, Spodoptera frugiperda (JE Smith) is a key pest in the Americas. Control strategies are mainly carried out by use of chemical insecticides and transgenic crops expressing Bacillus thuringiensis toxins. In the last years, resistance of S. frugiperda populations to transgenic corn was reported in different Latin American countries. The baculovirus Spodoptera frugiperda Multiple Nucleopolyhedrovirus (SfMNPV) is a pathogenic agent for the fall armyworm and a potential alternative for its control in integrated pest management strategies. In this work, we analyze some characteristics of two baculovirus isolates collected from maize (SfMNPV-M) and cotton (SfMNPV-C) fields from Argentina. The isolates were compared by restriction enzymes patterns and the analysis reveals the presence of genotypic variants in the SfMNPV-M isolate. We confirmed a deletion by sequencing fragments encompassing egt gene and most part of its contiguous gene (orf A) in a SfMNVP-M genotypic variant. Additionally, we estimated the 50% lethal dose and median survival time of each isolate in bioassays with S. frugiperda larvae.

Evaluation of hydrolytic enzyme activities from digestive fluids of Anthonomus grandis (Coleoptera: Curculionidae).

The cotton boll weevil, Anthonomus grandis, is a major pest of cotton crops in South America. In this work, partial biochemical characterizations of (hemi) cellulases and pectinases activities in the digestive system (head- and gut- extracts) of A. grandis were evaluated. Gut extract section from third instar larvae exhibited endoglucanase, xylanase, ß-glucosidase, and pectinase activities. The endoglucanase and xylanase activities were localized in the foregut, whereas ß-glucosidase activity was mainly detected in the hindgut. In addition, no difference in pectinase activity was observed across the gut sections. Thus, A. grandis digestive system is a potentially interesting reservoir for further lignocellulolytic enzymes research.

Cervical trans-spinal direct current stimulation: a modelling-experimental approach.

BACKGROUND: Trans-spinal direct current stimulation (tsDCS) is a non-invasive technique with promising neuromodulatory effects on spinal cord (SC) circuitry. Computational studies are essential to guide effective tsDCS protocols for specific clinical applications. This study aims to combine modelling and experimental studies to determine the electrode montage that maximizes electric field (E-field) delivery during cervical tsDCS. METHODS: Current and E-field distributions in the cervical SC were predicted for four electrode montages in a human realistic model using computational methods. A double-blind crossover and randomized exploratory study was conducted using the montage that maximized E-field delivery. tsDCS was applied for 15 min in 10 healthy subjects (anodal, cathodal, sham, with polarity assigned to the cervical electrode), with a current intensity of 2.5 mA, resulting in a total current charge density delivery of 90 mC/cm2. Upper limb motor (transcranial magnetic stimulation) and sensory evoked potentials (MEP, SEP), M-waves, H-reflex and F-wave responses were analysed. Central and peripheral conduction times were determined using MEP. Repeated measures ANOVA and Friedman test were used for statistical analysis (significance level α = 0.05). RESULTS: All montages presented higher current density and E-field magnitudes in the cervical SC region between the electrodes. However, electrodes at C3 and T3 spinous processes (C3-T3) originated the highest E-field magnitude (0.50 V/m). Using C3-T3 montage we observed significant changes in N9 SEP latency (p = 0.006), but significance did not persist in pairwise comparisons (sham-anodal: p = 0.022; sham-cathodal: p = 0.619; anodal-cathodal: p = 0.018; α = 0.017, Bonferroni corrected). MEP latency and central motor conduction time (CMCT) modified significantly on stimulation (p = 0.007 and p = 0.015, respectively). In addition, pairwise comparisons confirmed significant differences between sham and cathodal conditions after Bonferroni correction for MEP latency (sham-anodal: p = 0.868; sham-cathodal: p = 0.011; anodal-cathodal: p = 0.023) and CMCT (sham-anodal: p = 0.929; sham-cathodal: p = 0.010; anodal-cathodal: p = 0.034). CONCLUSIONS: Computational models predicted higher E-field delivery in the cervical SC for the C3-T3 montage. Polarity-dependent effects in motor responses were reported using this montage consistent with spinal motor modulation. tsDCS experimental protocol designs should be guided by modelling studies to improve effectiveness.

Analysis of a chitinase from EpapGV, a fast killing betabaculovirus.

The main function of baculoviral chitinase protein (V-CHIA) is to promote the final liquefaction of infected host larvae, facilitating the dispersion of occlusion bodies (OBs) in the environment. In this study, a v-chiA from Epinotia aporema Granulovirus (EpapGV) was identified and characterized. The 1,713 base pairs long open reading frame encodes a protein of 570 amino acids with a predicted molecular weight of 63 kDa. EpapGV V-CHIA sequence alignment resulted 62 % identical to Pieris rapae GV and Blastp search revealed a high conservation among all baculovirus chitinases. Amino acid sequence analysis indicated that the C-terminal KDEL present in most alphabaculovirus chitinases is absent in EpapGV V-CHIA, as well as in the rest of the betabaculoviruses. Phylogenetic analysis was performed with bacterial, lepidopteran, and baculoviral chitinase sequences available in databases. Using an AcMNPV bacmid (bApGOZA) a recombinant Ac-chiAEpapGV was obtained in order to overexpress EpapGV V-CHIA in cell culture. The presence of chitinase was detected in purified AcMNPV-chiAEpapGV OBs. Peritrophic membranes of Anticarsia gemmatalis larvae fed with recombinant OBs showed an altered structure. The results presented in this study show that EpapGV chitinase overexpression in recombinant baculovirus can cause association of this protein with OBs, and suggest that this could be used to evaluate the protein role in early stages of baculoviral infections.

Transcriptomic survey of the midgut of Anthonomus grandis (Coleoptera: Curculionidae).

Anthonomus grandis Boheman is a key pest in cotton crops in the New World. Its larval stage develops within the flower bud using it as food and as protection against its predators. This behavior limits the effectiveness of its control using conventional insecticide applications and biocontrol techniques. In spite of its importance, little is known about its genome sequence and, more important, its specific expression in key organs like the midgut. Total mRNA isolated from larval midguts was used for pyrosequencing. Sequence reads were assembled and annotated to generate a unigene data set. In total, 400,000 reads from A. grandis midgut with an average length of 237 bp were assembled and combined into 20,915 contigs. The assembled reads fell into 6,621 genes models. BlastX search using the NCBI-NR database showed that 3,006 unigenes had significant matches to known sequences. Gene Ontology (GO) mapping analysis evidenced that A. grandis is able to transcripts coding for proteins involved in catalytic processing of macromolecules that allows its adaptation to very different feeding source scenarios. Furthermore, transcripts encoding for proteins involved in detoxification mechanisms such as p450 genes, glutathione-S-transferase, and carboxylesterases are also expressed. This is the first report of a transcriptomic study in A. grandis and the largest set of sequence data reported for this species. These data are valuable resources to expand the knowledge of this insect group and could be used in the design of new control strategies based in molecular information.

Network-targeted transcranial direct current stimulation of the hypothalamus appetite-control network: a feasibility study.

The hypothalamus is the key regulator for energy homeostasis and is functionally connected to striatal and cortical regions vital for the inhibitory control of appetite. Hence, the ability to non-invasively modulate the hypothalamus network could open new ways for the treatment of metabolic diseases. Here, we tested a novel method for network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in the control of appetite. Based on the resting-state functional connectivity map of the hypothalamus, a 12-channel net-tDCS protocol was generated (Neuroelectrics Starstim system), which included anodal, cathodal and sham stimulation. Ten participants with overweight or obesity were enrolled in a sham-controlled, crossover study. During stimulation or sham control, participants completed a stop-signal task to measure inhibitory control. Overall, stimulation was well tolerated. Anodal net-tDCS resulted in faster stop signal reaction time (SSRT) compared to sham (p = 0.039) and cathodal net-tDCS (p = 0.042). Baseline functional connectivity of the target network correlated with SSRT after anodal compared to sham stimulation (p = 0.016). These preliminary data indicate that modulating hypothalamus functional network connectivity via net-tDCS may result in improved inhibitory control. Further studies need to evaluate the effects on eating behavior and metabolism.

Multichannel tDCS with Advanced Targeting for Major Depressive Disorder: A Tele-Supervised At-Home Pilot Study.

Introduction: Proof-of-principle human studies suggest that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve depression severity. This open-label multicenter study tested remotely supervised multichannel tDCS delivered at home in patients (N=35) with major depressive disorder (MDD). The primary aim was to assess the feasibility and safety of our protocol. As an exploratory aim, we evaluated therapeutic efficacy: the primary efficacy measure was the median percent change from baseline to the end of the 4-week post-treatment follow-up period in the observer-rated Montgomery-Asberg Depression Mood Rating Scale (MADRS). Methods: Participants received 37 at-home stimulation sessions (30 minutes each) of specifically designed multichannel tDCS targeting the left DLPFC administered over eight weeks (4 weeks of daily treatments plus 4 weeks of taper), with a follow-up period of 4 weeks following the final stimulation session. The stimulation montage (electrode positions and currents) was optimized by employing computational models of the electric field generated by multichannel tDCS using available structural data from a similar population (group optimization). Conducted entirely remotely, the study employed the MADRS for assessment at baseline, at weeks 4 and 8 during treatment, and at 4-week follow-up visits. Results: 34 patients (85.3% women) with a mean age of 59 years, a diagnosis of MDD according to DSM-5 criteria, and a MADRS score ≥20 at the time of study enrolment completed all study visits. At baseline, the mean time since MDD diagnosis was 24.0 (SD 19.1) months. Concerning compliance, 85% of the participants (n=29) completed the complete course of 37 stimulation sessions at home, while 97% completed at least 36 sessions. No detrimental effects were observed, including suicidal ideation and/or behavior. The study observed a median MADRS score reduction of 64.5% (48.6, 72.4) 4 weeks post-treatment (Hedge's g = -3.1). We observed a response rate (≥ 50% improvement in MADRS scores) of 72.7% (n=24) from baseline to the last visit 4 weeks post-treatment. Secondary measures reflected similar improvements. Conclusions: These results suggest that remotely supervised and supported multichannel home-based tDCS is safe and feasible, and antidepressant efficacy motivates further appropriately controlled clinical studies.

The electric field in the cortex during transcranial current stimulation.

The electric field in the cortex during transcranial current stimulation was calculated based on a realistic head model derived from structural MR images. The aim of this study was to investigate the effect of tissue heterogeneity and of the complex cortical geometry on the electric field distribution. To this end, the surfaces separating the different tissues were represented as accurately as possible, particularly the cortical surfaces. Our main finding was that the complex cortical geometry combined with the high conductivity of the CSF which covers the cortex and fills its sulci gives rise to a very distinctive electric field distribution in the cortex, with a strong normal component confined to the bottom of sulci under or near the electrodes and a weaker tangential component that covers large areas of the gyri that lie near each electrode in the direction of the other electrode. These general features are shaped by the details of the sulcal and gyral geometry under and between the electrodes. Smaller electrodes resulted in a significant improvement in the focality of the tangential component but not of the normal component, when focality is defined in terms of percentages of the maximum values in the cortex. Experimental validation of these predictions could provide a better understanding of the mechanisms underlying the acute effects of tCS.

[Venous thromboembolic prophylaxis. Guidelines for adults in Argentina]. / Guía de recomendaciones para la profilaxis de la enfermedad tromboembólica venosa en adultos en la Argentina.

The venous thromboembolic disease (VTD) in adults has a high morbidity and mortality. It can be also associated to disabling chronic conditions. In spite of this, prophylaxis in healthcare assistance is still underused. In this article, the available evidence in thromboprophylaxis was analyzed to offer recommendations (1) or suggestions (2) classified according to different levels of evidence (A, B or C). Different medical scenarios and types of thromboprophylaxis were analyzed. In major orthopedic surgeries low molecular weight heparins, LMWH, inhibitors of the Xa and IIa factors are recommended (1B) to be started during hospitalization and continued for 35 days in hip replacement surgery and for 10 days in total knee replacement surgery. Knee arthroscopy and spine surgery do not require pharmacologic treatment (2B) unless the patient has other risks factors for thrombosis. In such cases, LMWH are recommended. Non-surgical patients who have at least one risk factor should receive LMWH, NFH or fondaparinux (1B) if they are to be bedridden or unable to walk for three or more days. Patients undergoing neurosurgery or with intracranial hemorrhage should receive mechanic prophylaxis (2C), and accordingly they should start LMWH or NFH 24 to 72 hours afterwards (2C). The latter two drugs are recommended for critically ill patients. Patients with low risk for VTD undergoing other type of surgeries should be prescribed with mechanical prophylaxis (2C) and encouraged to walk promptly (2C), while those with high risk should be prescribed with LMWH or NFH (1B or 2C according to bleeding risk factors).

Effects of Mixed Baculovirus Infections in Biological Control: A Comprehensive Historical and Technical Analysis.

Baculoviruses are insect-specific DNA viruses that have been exploited as bioinsecticides for the control of agricultural and forest pests around the world. Mixed infections with two different baculoviruses have been found in nature, infecting the same host. They have been studied to understand the biology of virus interactions, their effects on susceptible insects, and their insecticidal implications. In this work, we summarize and analyze the in vivo baculovirus co-infections reported in the literature, mainly focusing on pest biocontrol applications. We discuss the most common terms used to describe the effects of mixed infections, such as synergism, neutralism, and antagonism, and how to determine them based on host mortality. Frequently, baculovirus co-infections found in nature are caused by a combination of a nucleopolyhedrovirus and a granulovirus. Studies performed with mixed infections indicated that viral dose, larval stage, or the presence of synergistic factors in baculovirus occlusion bodies are important for the type of virus interaction. We also enumerate and discuss technical aspects to take into account in studies on mixed infections, such as statistical procedures, quantification of viral inocula, the selection of instars, and molecular methodologies for an appropriate analysis of baculovirus interaction. Several experimental infections using two different baculoviruses demonstrated increased viral mortality or a synergistic effect on the target larvae compared to single infections. This can be exploited to improve the baculovirus-killing properties of commercial formulations. In this work, we offer a current overview of baculovirus interactions in vivo and discuss their potential applications in pest control strategies.

Spherical harmonics representation of the steady-state membrane potential shift induced by tDCS in realistic neuron models.

Objective.We provide a systematic framework for quantifying the effect of externally applied weak electric fields on realistic neuron compartment models as captured by physiologically relevant quantities such as the membrane potential or transmembrane current as a function of the orientation of the field.Approach.We define a response function as the steady-state change of the membrane potential induced by a canonical external field of 1 V m-1as a function of its orientation. We estimate the function values through simulations employing reconstructions of the rat somatosensory cortex from the Blue Brain Project. The response of different cell types is simulated using the NEURON simulation environment. We represent and analyze the angular response as an expansion in spherical harmonics.Main results.We report membrane perturbation values comparable to those in the literature, extend them to different cell types, and provide their profiles as spherical harmonic coefficients. We show that at rest, responses are dominated by their dipole terms (ℓ=1), in agreement with experimental findings and compartment theory. Indeed, we show analytically that for a passive cell, only the dipole term is nonzero. However, while minor, other terms are relevant for states different from resting. In particular, we show howℓ=0andℓ=2terms can modify the function to induce asymmetries in the response.Significance.This work provides a practical framework for the representation of the effects of weak electric fields on different neuron types and their main regions-an important milestone for developing micro- and mesoscale models and optimizing brain stimulation solutions.

Biophysical modeling of the electric field magnitude and distribution induced by electrical stimulation with intracerebral electrodes.

Intracranial electrodes are used clinically for diagnostic or therapeutic purposes, notably in drug-refractory epilepsy (DRE) among others. Visualization and quantification of the energy delivered through such electrodes is key to understanding how the resulting electric fields modulate neuronal excitability, i.e. the ratio between excitation and inhibition. Quantifying the electric field induced by electrical stimulation in a patient-specific manner is challenging, because these electric fields depend on a number of factors: electrode trajectory with respect to folded brain anatomy, biophysical (electrical conductivity / permittivity) properties of brain tissue and stimulation parameters such as electrode contacts position and intensity. Here, we aimed to evaluate various biophysical models for characterizing the electric fields induced by electrical stimulation in DRE patients undergoing stereoelectroencephalography (SEEG) recordings in the context of pre-surgical evaluation. This stimulation was performed with multiple-contact intracranial electrodes used in routine clinical practice. We introduced realistic 3D models of electrode geometry and trajectory in the neocortex. For the electrodes, we compared point (0D) and line (1D) sources approximations. For brain tissue, we considered three configurations of increasing complexity: a 6-layer spherical model, a toy model with a sulcus representation, replicating results from previous approaches; and went beyond the state-of-the-art by using a realistic head model geometry. Electrode geometry influenced the electric field distribution at close distances (∼3 mm) from the electrode axis. For larger distances, the volume conductor geometry and electrical conductivity dominated electric field distribution. These results are the first step towards accurate and computationally tractable patient-specific models of electric fields induced by neuromodulation and neurostimulation procedures.

Towards a mesoscale physical modeling framework for stereotactic-EEG recordings.

Objective.Stereotactic-electroencephalography (SEEG) and scalp EEG recordings can be modeled using mesoscale neural mass population models (NMMs). However, the relationship between those mathematical models and the physics of the measurements is unclear. In addition, it is challenging to represent SEEG data by combining NMMs and volume conductor models due to the intermediate spatial scale represented by these measurements.Approach.We provide a framework combining the multi-compartmental modeling formalism and a detailed geometrical model to simulate the transmembrane currents that appear in layer 3, 5 and 6 pyramidal cells due to a synaptic input. With this approach, it is possible to realistically simulate the current source density (CSD) depth profile inside a cortical patch due to inputs localized into a single cortical layer and the induced voltage measured by two SEEG contacts using a volume conductor model. Based on this approach, we built a framework to connect the activity of a NMM with a volume conductor model and we simulated an example of SEEG signal as a proof of concept.Main results.CSD depends strongly on the distribution of the synaptic inputs onto the different cortical layers and the equivalent current dipole strengths display substantial differences (of up to a factor of four in magnitude in our example). Thus, the inputs coming from different neural populations do not contribute equally to the electrophysiological recordings. A direct consequence of this is that the raw output of NMMs is not a good proxy for electrical recordings. We also show that the simplest CSD model that can accurately reproduce SEEG measurements can be constructed from discrete monopolar sources (one per cortical layer).Significance.Our results highlight the importance of including a physical model in NMMs to represent measurements. We provide a framework connecting microscale neuron models with the neural mass formalism and with physical models of the measurement process that can improve the accuracy of predicted electrophysiological recordings.