Background It has been assumed that effects caused by tDCS or tACS neuromodulation are due to electric current flow within brain structures. However, to date, direct current density distributions in the brains of human subjects have not been measured. Instead computational models of tDCS or tACS have been used to predict electric current and field distributions for dosimetry and mechanism analysis purposes. Objective/Hypothesis We present the first in vivo images of electric current density distributions within the brain in four subjects undergoing transcranial electrical stimulation. Methods Magnetic resonance electrical impedance tomography (MREIT) techniques encode current flow in phase images. In four human subjects, we used MREIT to measure magnetic flux density distributions caused by tACS currents, and then calculated current density distributions from these data. Computational models of magnetic flux and current distribution, constructed using contemporaneously collected T1-weighted structural MRI images, were co-registered to compare predicted and experimental results. Results We found consistency between experimental and simulated magnetic flux and current density distributions using transtemporal (T7–T8) and anterior-posterior (Fpz-Oz) electrode montages, and also differences that may indicate a need to improve models to better interpret experimental results. While human subject data agreed with computational model predictions in overall scale, differences may result from factors such as effective electrode surface area and conductivities assumed in models. Conclusions We believe this method may be useful in improving reproducibility, assessing safety, and ultimately aiding understanding of mechanisms of action in electrical and magnetic neuromodulation modalities.

We present the first in vivo images of anisotropic conductivity distribution in the human head, measured at a frequency of approximately 10 Hz. We used magnetic resonance electrical impedance tomography techniques to encode phase changes caused by current flow within the head via two independent electrode pairs. These results were then combined with diffusion tensor imaging data to reconstruct full anisotropic conductivity distributions in 5-mm-thick slices of the brains of two participants. Conductivity values recovered in this paper were broadly consistent with literature values. We anticipate that this technique will be of use in many areas of neuroscience, most importantly in functional imaging via inverse electroencephalogram. Future studies will involve pulse sequence acceleration to maximize brain coverage and resolution.

Convection enhanced delivery (CED) is a promising novel technology to treat neural diseases, as it can transport macromolecular therapeutic agents greater distances through tissue by direct infusion. To minimize off-target delivery, our group has developed 3D computational transport models to predict infusion flow fields and tracer distributions based on magnetic resonance (MR) diffusion tensor imaging data sets. To improve the accuracy of our voxelized models, generalized anisotropy (GA), a scalar measure of a higher order diffusion tensor obtained from high angular resolution diffusion imaging (HARDI) was used to improve tissue segmentation within complex tissue regions of the hippocampus by capturing small feature fissures. Simulations were conducted to reveal the effect of these fissures and cerebrospinal fluid (CSF) boundaries on CED tracer diversion and mistargeting. Sensitivity analysis was also conducted to determine the effect of dorsal and ventral hippocampal infusion sites and tissue transport properties on drug delivery. Predicted CED tissue concentrations from this model are then compared with experimentally measured MR concentration profiles. This allowed for more quantitative comparison between model predictions and MR measurement. Simulations were able to capture infusate diversion into fissures and other CSF spaces which is a major source of CED mistargeting. Such knowledge is important for proper surgical planning.

Background Phosphene generation is an objective physical measure of potential transcranial alternating current stimulation (tACS) biological side effects. Interpretations from phosphene analysis can serve as a first step in understanding underlying mechanisms of tACS in healthy human subjects and assist validation of computational models. Objective/Hypothesis This preliminary study introduces and tests methods to analyze predicted phosphene occurrence using computational head models constructed from tACS recipients against verbal testimonies of phosphene sensations. Predicted current densities in the eyes and the occipital lobe were also verified against previously published threshold values for phosphenes. Methods Six healthy subjects underwent 10 Hz tACS while being imaged in an MRI scanner. Two different electrode montages, T7-T8 and Fpz-Oz, were used. Subject ratings of phosphene experience were collected during tACS and compared against current density distributions predicted in eye and occipital lobe regions of interest (ROIs) determined for each subject. Calculated median current densities in each ROI were compared to minimum thresholds for phosphene generation. Main Results All subjects reported phosphenes, and predicted median current densities in ROIs exceeded minimum thresholds for phosphenes found in the literature. Higher current densities in the eyes were consistently associated with decreased phosphene generation for the Fpz-Oz montage. There was an overall positive association between phosphene perceptions and current densities in the occipital lobe. Conclusions These methods may have promise for predicting phosphene generation using data collected during in-scanner tACS sessions and may enable better understanding of phosphene origin. Additional empirical data in a larger cohort is required to fully test the robustness of the proposed methods. Future studies should include additional montages that could dissociate retinal and occipital stimulation.

Prenatal cerebrovascular stroke can cause permanent damage to the brain followed by deficits in neuro-muscular functioning. We hypothesize that recovery can be enhanced by transcranial direct current stimulation (tDCS) through changes in cortical plasticity. Unilateral hypoxia-ischemia (HI) was produced in rats on postnatal day 7 (P7). At P21, anodal tDCS was given to HI pups for 7 days. tDCS treated HI pups showed improved weight, grip strength, gait, motor function, and concentrations of brain-derived neurotropic factor cortex ratios compared to non-treated HI animal controls. These findings support tDCS following HI as an effective therapeutic for neonatal stroke.

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