Hyeon Seo

Computational Study on Subdural Cortical Stimulation - The Influence of the Head Geometry, Anisotropic Conductivity, and Electrode Configuration

Subdural cortical stimulation (SuCS) is a method used to inject electrical current through electrodes beneath the dura mater, and is known to be useful in treating brain disorders. However, precisely how SuCS must be applied to yield the most effective results has rarely been investigated. For this purpose, we developed a three-dimensional computational model that represents an anatomically realistic brain model including an upper chest. With this computational model, we investigated the influence of stimulation amplitudes, electrode configurations (single or paddle-array), and white matter conductivities (isotropy or anisotropy). Further, the effects of stimulation were compared with two other computational models, including an anatomically realistic brain-only model and the simplified extruded slab model representing the precentral gyrus area. The results of voltage stimulation suggested that there was a synergistic effect with the paddle-array due to the use of multiple electrodes; however, a single electrode was more efficient with current stimulation. The conventional model (simplified extruded slab) far overestimated the effects of stimulation with both voltage and current by comparison to our proposed realistic upper body model. However, the realistic upper body and full brain-only models demonstrated similar stimulation effects. In our investigation of the influence of anisotropic conductivity, model with a fixed ratio (1∶10) anisotropic conductivity yielded deeper penetration depths and larger extents of stimulation than others. However, isotropic and anisotropic models with fixed ratios (1∶2, 1∶5) yielded similar stimulation effects. Lastly, whether the reference electrode was located on the right or left chest had no substantial effects on stimulation.

The computational study of subdural cortical stimulation: A quantitative analysis of voltage and current stimulation

We investigated the effect of electrode type and stimulation condition (voltage stimulation and current stimulation) in bi-polar subdural cortical stimulation (SCS). For this study, we developed a 3D realistic head model using MRI data with 1 mm3 spatial resolution and simulated the model using the finite element method (FEM). For each study, we used three types of electrodes - disc, ring, and covered-disc - and three efficiency measures - effective depth of penetration, effective volume, and amount of CSF leakage current - to compare the effectiveness of the stimulation between two stimulation conditions. With voltage stimulation, there was no difference in effectiveness between the disc and ring electrodes. However, the amount of CSF leakage current for the covered-disc type was lower than that for the others. The effective depth of penetration and volume for the ring and disc type electrodes were higher than those for the covered-disc type. The current stimulation using the covered-disc electrode penetrated deeper than the other types of electrodes, and the CSF leakage current was still low. The result for voltage and current stimulation was quite different, as the substrate design manipulated the impedance and output current. In the current simulation, if the electrode was covered with the substrate, more current flowed to the cortex. On the other hand, with voltage stimulation, this substrate design makes the impedance between electrodes high, and the total current is reduced.

Effect of Anatomically Realistic Full-Head Model on Activation of Cortical Neurons in Subdural Cortical Stimulation—A Computational Study

Electrical brain stimulation (EBS) is an emerging therapy for the treatment of neurological disorders, and computational modeling studies of EBS have been used to determine the optimal parameters for highly cost-effective electrotherapy. Recent notable growth in computing capability has enabled researchers to consider an anatomically realistic head model that represents the full head and complex geometry of the brain rather than the previous simplified partial head model (extruded slab) that represents only the precentral gyrus. In this work, subdural cortical stimulation (SuCS) was found to offer a better understanding of the differential activation of cortical neurons in the anatomically realistic full-head model than in the simplified partial-head models. We observed that layer 3 pyramidal neurons had comparable stimulation thresholds in both head models, while layer 5 pyramidal neurons showed a notable discrepancy between the models; in particular, layer 5 pyramidal neurons demonstrated asymmetry in the thresholds and action potential initiation sites in the anatomically realistic full-head model. Overall, the anatomically realistic full-head model may offer a better understanding of layer 5 pyramidal neuronal responses. Accordingly, the effects of using the realistic full-head model in SuCS are compelling in computational modeling studies, even though this modeling requires substantially more effort.

Computational Study of Subdural Cortical Stimulation: Effects of Simulating Anisotropic Conductivity on Activation of Cortical Neurons

Subdural cortical stimulation (SuCS) is an appealing method in the treatment of neurological disorders, and computational modeling studies of SuCS have been applied to determine the optimal design for electrotherapy. To achieve a better understanding of computational modeling on the stimulation effects of SuCS, the influence of anisotropic white matter conductivity on the activation of cortical neurons was investigated in a realistic head model. In this paper, we constructed pyramidal neuronal models (layers 3 and 5) that showed primary excitation of the corticospinal tract, and an anatomically realistic head model reflecting complex brain geometry. The anisotropic information was acquired from diffusion tensor magnetic resonance imaging (DT-MRI) and then applied to the white matter at various ratios of anisotropic conductivity. First, we compared the isotropic and anisotropic models; compared to the isotropic model, the anisotropic model showed that neurons were activated in the deeper bank during cathodal stimulation and in the wider crown during anodal stimulation. Second, several popular anisotropic principles were adapted to investigate the effects of variations in anisotropic information. We observed that excitation thresholds varied with anisotropic principles, especially with anodal stimulation. Overall, incorporating anisotropic conductivity into the anatomically realistic head model is critical for accurate estimation of neuronal responses; however, caution should be used in the selection of anisotropic information.

Comparison of neuronal excitation between extruded slab partial head model and full head model in subdural cortical stimulation

Cortical stimulation (CS) is an appealing and emerging treatment for neurological disorders. CS is known to promote functional recovery effectively; however, its underlying mechanism and the optimal parameters for the effective treatment are not clearly understood. In this work, we developed a realistic three-dimensional full head and chest model for subdural CS. Our proposed model was compared at the neuron level with an existing simplified extruded slab partial head model depicting around precentral gyral cortex only. Each model was coupled with the pyramidal neuronal model in order to investigate an extent of neuronal excitation. We found that the crown of the cortex was the most excitable area in the unipolar stimulation, while in the bipolar stimulation, the lip and bank were excited more easily than other areas. Finally, it was evident that our proposed model was substantially different in excitation threshold from the existing simplified model, which is compelling to do computational CS study on more realistic head models.

A comparative study of the 3D precentral gyrus model for unipolar and bipolar current stimulations

Cortical stimulation (CS) is an appealing method for treating stroke and other disorders by promoting functional recovery. It is necessary to study the effect of different cortical stimulation types through numerical simulations in order to understand the underlying mechanism. In this paper, we simulated four types of invasive CS - unipolar ECS (epidural CS), bipolar ECS, unipolar SCS (subdural CS), and bipolar SCS - to investigate and compare the effects of stimulation types. Current stimulation was considered to increase the observability of the comparison between ECS and SCS. The simulation results obtained from the 3D precentral gyrus model showed ECS and SCS had similar current density distributions with higher stimulated current. However, the differences between bipolar and unipolar stimulation are significant with higher stimulated current. As stimulated current increased, unipolar CS penetrated deeper and wider regions than bipolar CS, so it can be more effective for functional recovery.

The Effect of a Transcranial Channel as a Skull/Brain Interface in High-Definition Transcranial Direct Current Stimulation—A Computational Study

A transcranial channel is an interface between the skull and brain; it consists of a biocompatible and highly conductive material that helps convey the current induced by transcranial direct current stimulation (tDCS) to the target area. However, it has been proposed only conceptually, and there has been no concrete study of its efficacy. In this work, we conducted a computational investigation of this conceptual transcranial model with high-definition tDCS, inducing focalized neuromodulation to determine whether inclusion of a transcranial channel performs effectively. To do so, we constructed an anatomically realistic head model and compartmental pyramidal neuronal models. We analyzed membrane polarization by extracellular stimulation and found that the inclusion of a transcranial channel induced polarization at the target area 11 times greater than conventional HD-tDCS without the transcranial channel. Furthermore, the stimulation effect of the transcranial channel persisted up to approximately 80%, even when the stimulus electrodes were displaced approximately 5 mm from the target area. We investigated the efficacy of the transcranial channel and found that greatly improved stimulation intensity and focality may be achieved. Thus, the use of these channels may be promising for clinical treatment.

Multi-Scale Computational Models for Electrical Brain Stimulation

Electrical brain stimulation (EBS) is an appealing method to treat neurological disorders. To achieve optimal stimulation effects and a better understanding of the underlying brain mechanisms, neuroscientists have proposed computational modeling studies for a decade. Recently, multi-scale models that combine a volume conductor head model and multi-compartmental models of cortical neurons have been developed to predict stimulation effects on the macroscopic and microscopic levels more precisely. As the need for better computational models continues to increase, we overview here recent multi-scale modeling studies; we focused on approaches that coupled a simplified or high-resolution volume conductor head model and multi-compartmental models of cortical neurons, and constructed realistic fiber models using diffusion tensor imaging (DTI). Further implications for achieving better precision in estimating cellular responses are discussed.

Effects of electrode displacement in high-definition transcranial direct current stimulation: A computational study

In order to understand better the ways in which cortical excitability is linked to target brain areas, this study describes the effects of focalized high-definition transcranial direct current stimulation (HD-tDCS), and investigates the way in which these effects persisted after the stimulus electrodes were displaced from the target area. We constructed a 3D volume conduction model of an anatomically realistic head that is ideal for HD-tDCS, as well as compartmental models of layer 3 and layer 5 pyramidal neurons. Using extracellular approaches, we observed stimulus-induced electric fields and simulated neuronal responses by combining stimulus-induced potential fields with pyramidal neuronal models coupled with the head model. We found that the stimulus-induced electric fields were focused on the hand-knob when the electrodes were placed directly above the target region; further, the neuronal responses varied, such that the upper parts of the dendrites were hyperpolarized, while the soma and axons were depolarized. The magnitude of the electric fields, as well as the maximum polarizations at each compartment decreased according to the displacement of the electrodes from the target area. Considerable excitability at the target area within the range of 5 mm displacement between electrodes and the target area was shown by means of stimulus-induced electric fields and membrane polarization. In conclusion, using detailed computational approaches, we discovered the ways in which excitability in the target area persisted even with increased distance from the active electrode.In order to understand better the ways in which cortical excitability is linked to target brain areas, this study describes the effects of focalized high-definition transcranial direct current stimulation (HD-tDCS), and investigates the way in which these effects persisted after the stimulus electrodes were displaced from the target area. We constructed a 3D volume conduction model of an anatomically realistic head that is ideal for HD-tDCS, as well as compartmental models of layer 3 and layer 5 pyramidal neurons. Using extracellular approaches, we observed stimulus-induced electric fields and simulated neuronal responses by combining stimulus-induced potential fields with pyramidal neuronal models coupled with the head model. We found that the stimulus-induced electric fields were focused on the hand-knob when the electrodes were placed directly above the target region; further, the neuronal responses varied, such that the upper parts of the dendrites were hyperpolarized, while the soma and axons were depolarized. The magnitude of the electric fields, as well as the maximum polarizations at each compartment decreased according to the displacement of the electrodes from the target area. Considerable excitability at the target area within the range of 5 mm displacement between electrodes and the target area was shown by means of stimulus-induced electric fields and membrane polarization. In conclusion, using detailed computational approaches, we discovered the ways in which excitability in the target area persisted even with increased distance from the active electrode.