Automated 3-D Computer-Aided Measurement of the Bony Orbit: Evaluation of Correlations among Volume, Depth, and Surface Area.

(1)The study aimed to measure the depth, volume, and surface area of the intact human orbit by applying an automated method of CT segmentation and to evaluate correlations among depth, volume, and surface area. Additionally, the relative increases in volume and surface area in proportion to the diagonal of the orbit were assessed. (2) CT data from 174 patients were analyzed. A ball-shaped mesh consisting of tetrahedral elements was inserted inside orbits until it encountered the bony boundaries. Orbital volume, area depth, and their correlations were measured. For the validation, an ICC was used. (3) The differences between genders were significant (p < 10-7) but there were no differences between sides. When comparing orbit from larger to smaller, a paired sample t-test indicated a significant difference in groups (p < 10-10). A simple linear model (Volume~1 + Gender + Depth + Gender:Depth) revealed that only depth had a significant effect on volume (p < 10-19). The ICCs were 1.0. (4) Orbital volume, depth, and surface area measurements based on an automated CT segmentation algorithm demonstrated high repeatability and reliability. Male orbits were always larger on average by 14%. There were no differences between the sides. The volume and surface area ratio did not differ between genders and was approximately 0.75.

Cost of focality in TDCS: Interindividual variability in electric fields.

BACKGROUND: In transcranial direct current stimulation (TDCS), electric current is applied via two large electrodes to modulate brain activity. Computational models have shown that large electrodes produce diffuse electric fields (EFs) in the brain, which depends on individual head and brain anatomy. Recently, smaller electrodes as well as novel electrode arrangements, including high-definition TDCS (HD-TDCS) montages, have been introduced to improve the focality of EFs. Here, we investigated whether the EFs of focal montages are more susceptible to interindividual anatomical differences. METHODS: Thirteen TDCS montages, including conventional M1-contralateral forehead montages with different stimulating electrode sizes as well as 4 × 1 HD and bipolar HD montages, producing varying EF focalities were modeled using the finite element method in 77 subjects, with individual anatomically realistic models based on magnetic resonance images. RESULTS: Interindividual variability of predicted EFs increased with EF focality for conventional M1-contralateral forehead and 4 × 1 HD montages. 4 × 1 HD-TDCS was found to have the highest EF focality and greatest variability. Bipolar HD montages targeting the region between two small electrodes did not follow this pattern, but produced EF magnitudes comparable to those of 4× 1 HD-TDCS, with a minor decrease in focality and lower interindividual variability. CONCLUSIONS: EF focality in TDCS was achieved at the cost of increased interindividual variability. Hence, individual modeling is required to plan EF doses when focal montages are used. Among the studied montages, bipolar HD montages provided a compromise between inter-individual variability, focality and magnitude of the predicted EFs.

Group-level and functional-region analysis of electric-field shape during cerebellar transcranial direct current stimulation with different electrode montages.

OBJECTIVE: Cerebellar transcranial direct current stimulation (ctDCS) is a neuromodulation scheme that delivers a small current to the cerebellum. In this work, we computationally investigate the distributions and strength of the stimulation dosage during ctDCS with the aim of determining the targeted cerebellar regions of a group of subjects with different electrode montages. APPROACH: We used a new inter-individual registration method that permitted the projection of computed electric fields (EFs) from individual realistic head models (n = 18) to standard cerebellar template for the first time. MAIN RESULTS: Variations of the EF on the cerebellar surface were found to have standard deviations of up to 55% of the mean. The dominant factor that accounted for 62% of the variability of the maximum EFs was the skin-cerebellum distance, whereas the cerebrospinal fluid volume explained 53% of the average EF distribution. Despite the inter-individual variations, a systematic tendency of the EF hotspot emerges beneath the active electrode in group-level analysis. The hotspot can be adjusted by the electrode position so that the most effective stimulation is delivered to a group of subjects. SIGNIFICANCE: Targeting specific cerebellar structures with ctDCS is not straightforward, as neuromodulation depends not only on the placement/design of the electrodes configuration but also on inter-individual variability due to anatomical differences. The proposed method permitted generalizing the EFs to a cerebellum atlas. The atlas is useful for studying the mechanisms of ctDCS, planning ctDCS and explaining findings of experimental studies.

Effects of posture on electric fields of non-invasive brain stimulation.

The brain moves when the orientation of the head changes. This inter-postural motion has been shown to affect the distribution of cerebrospinal fluid (CSF). As CSF layer thickness affects the distribution of electric fields (EF) in non-invasive brain stimulation methods such as transcranial direct current (TDCS) and magnetic (TMS) stimulation, possible differences in body position between sessions could affect the stimulation efficacy. Additionally, inter-postural differences might distort the modeling results of TDCS and TMS, as the models are usually built based on magnetic resonance images (MRI) obtained while the subject is in the supine position, whereas the actual stimulation is given while the subject is in an upright position. Here, we studied the effects of changing the position of the subject between supine, prone, and left lateral on the conformation of the brain. This study aimed to determine whether small inter-postural changes in the shape of the brain can affect TDCS and TMS EFs as hypothesized. We obtained MRI from five subjects in each position and used them to build anatomically realistic models for use in finite element simulations of the EFs. Position was found to affect EFs, with them being approximately 10% stronger and more diffuse while subjects were in the prone and left lateral than in the supine positions for TDCS. In TMS, a similar trend was observed, but the effect was smaller, approximately 2%, than that observed for TDCS. Thus, the effect of posture should be considered in the design of TDCS and TMS experiments.

Can electric fields explain inter-individual variability in transcranial direct current stimulation of the motor cortex?

The effects of transcranial direct current stimulation (tDCS) on motor cortical excitability are highly variable between individuals. Inter-individual differences in the electric fields generated in the brain by tDCS might play a role in the variability. Here, we explored whether these fields are related to excitability changes following anodal tDCS of the primary motor cortex (M1). Motor evoked potentials (MEPs) were measured in 28 healthy subjects before and after 20 min sham or 1 mA anodal tDCS of right M1 in a double-blind crossover design. The electric fields were individually modelled based on magnetic resonance images. Statistical analysis indicated that the variability in the MEPs could be partly explained by the electric fields, subjects with the weakest and strongest fields tending to produce opposite changes in excitability. To explain the findings, we hypothesized that the likely locus of action was in the hand area of M1, and the effective electric field component was that in the direction normal to the cortical surface. Our results demonstrate that a large part of inter-individual variability in tDCS may be due to differences in the electric fields. If this is the case, electric field dosimetry could be useful for controlling the neuroplastic effects of tDCS.

A multi-scale computational approach based on TMS experiments for the assessment of electro-stimulation thresholds of the brain at intermediate frequencies.

In recent years, human exposure to electromagnetic fields (EMF) at intermediate frequencies (300 Hz-10 MHz) has risen, mainly due to the growth of technologies using these fields. The current safety guidelines/standards defined by international bodies (e.g. ICNIRP and IEEE) established basic restrictions for limiting EMF exposure. These limits at intermediate frequencies are derived from threshold values of the internal electric field that may produce transient effects, such as the stimulation of the nervous system. However, there are some discrepancies between the basic restrictions of those guidelines/standards. The aim of this study is to investigate the excitation thresholds of the nervous system exposed to intermediate-frequency electromagnetic fields, with the purpose of extrapolating the threshold-frequency curves which are compared with existing basic restrictions prescribed by the international guidelines/standards. Our investigation was based on transcranial magnetic stimulation (TMS) experiments, physiological measurements, and individualized MRI-based computer simulations for the determination of brain stimulation thresholds. The combined approach with established biological axon models enabled the extrapolation of the measured thresholds for sinusoidally varying electric fields. The findings reveal that the exposure limits are significantly conservative for the brain, especially at frequencies in the range of 300 Hz-5 kHz.

TMS Motor Thresholds Correlate With TDCS Electric Field Strengths in Hand Motor Area.

Transcranial direct current stimulation (TDCS) modulates cortical activity and influences motor and cognitive functions in both healthy and clinical populations. However, there is large inter-individual variability in the responses to TDCS. Computational studies have suggested that inter-individual differences in cranial and brain anatomy may contribute to this variability via creating varying electric fields in the brain. This implies that the electric fields or their strength and orientation should be considered and incorporated when selecting the TDCS dose. Unfortunately, electric field modeling is difficult to perform; thus, a more-robust and practical method of estimating the strength of TDCS electric fields for experimental use is required. As recent studies have revealed a relationship between the sensitivity to TMS and motor cortical TDCS after-effects, the aim of the present study was to investigate whether the resting motor threshold (RMT), a simple measure of transcranial magnetic stimulation (TMS) sensitivity, would be useful for estimating TDCS electric field strengths in the hand area of primary motor cortex (M1). To achieve this, we measured the RMT in 28 subjects. We also obtained magnetic resonance images from each subject to build individual three-dimensional anatomic models, which were used in solving the TDCS and TMS electric fields using the finite element method (FEM). Then, we calculated the correlation between the measured RMT and the modeled TDCS electric fields. We found that the RMT correlated with the TDCS electric fields in hand M1 (R2 = 0.58), but no obvious correlations were identified in regions outside M1. The found correlation was mainly due to a correlation between the TDCS and TMS electric fields, both of which were affected by individual's anatomic features. In conclusion, the RMT could provide a useful tool for estimating cortical electric fields for motor cortical TDCS.

Choice of osteoblast model critical for studying the effects of electromagnetic stimulation on osteogenesis in vitro.

The clinical benefits of electromagnetic field (EMF) therapy in enhancing osteogenesis have been acknowledged for decades, but agreement regarding the underlying mechanisms continues to be sought. Studies have shown EMFs to promote osteoblast-like cell proliferation, or contrarily, to induce differentiation and enhance mineralization. Typically these disparities have been attributed to methodological differences. The present paper argues the possibility that the chosen osteoblast model impacts stimulation outcome. Phenotypically immature cells, particularly at low seeding densities, appear to be prone to EMF-amplified proliferation. Conversely, mature cells at higher densities seem to be predisposed to earlier onset differentiation and mineralization. This suggests that EMFs augment ongoing processes in cell populations. To test this hypothesis, mature SaOS-2 cells and immature MC3T3-E1 cells at various densities, with or without osteo-induction, were exposed to sinusoidal 50 Hz EMF. The exposure stimulated the proliferation of MC3T3-E1 and inhibited the proliferation of SaOS-2 cells. Baseline alkaline phosphatase (ALP) expression of SaOS-2 cells was high and rapidly further increased with EMF exposure, whereas ALP effects in MC3T3-E1 cells were not seen until the second week. Thus both cell types responded differently to EMF stimulation, corroborating the hypothesis that the phenotypic maturity and culture stage of cells influence stimulation outcome.

Electric fields of motor and frontal tDCS in a standard brain space: A computer simulation study.

The electric field produced in the brain is the main physical agent of transcranial direct current stimulation (tDCS). Inter-subject variations in the electric fields may help to explain the variability in the effects of tDCS. Here, we use multiple-subject analysis to study the strength and variability of the group-level electric fields in the standard brain space. Personalized anatomically-accurate models of 62 subjects were constructed from T1- and T2-weighted MRI. The finite-element method was used to computationally estimate the individual electric fields, which were registered to the standard space using surface based registration. Motor cortical and frontal tDCS were modelled for 16 electrode montages. For each electrode montage, the group-level electric fields had a consistent strength and direction in several brain regions, which could also be located at some distance from the electrodes. In other regions, the electric fields were more variable, and thus more likely to produce variable effects in each individual. Both the anode and cathode locations affected the group-level electric fields, both directly under the electrodes and elsewhere. For motor cortical tDCS, the electric fields could be controlled at the group level by moving the electrodes. However, for frontal tDCS, the group-level electric fields were more variable, and the electrode locations had only minor effects on the group average fields. Our results reveal the electric fields and their variability at the group level in the standard brain space, providing insights into the mechanisms of tDCS for plasticity induction. The data are useful for planning, analysing and interpreting tDCS studies.