Regional electric field induced by electroconvulsive therapy in a realistic finite element head model: influence of white matter anisotropic conductivity

Abstract

We present the first computational study investigating the electric field (E-field) strength generated by various electroconvulsive therapy (ECT) electrode configurations in specific brain regions of interest (ROIs) that have putative roles in the therapeutic action and/or adverse side effects of ECT. This study also characterizes the impact of the white matter (WM) conductivity anisotropy on the E-field distribution. A finite element head model incorporating tissue heterogeneity and WM anisotropic conductivity was constructed based on structural magnetic resonance imaging (MRI) and diffusion tensor MRI data. We computed the spatial E-field distributions generated by three standard ECT electrode placements including bilateral (BL), bifrontal (BF), and right unilateral (RUL) and an investigational electrode configuration for focal electrically administered seizure therapy (FEAST). The key results are that (1) the median E-field strength over the whole brain is 3.9, 1.5, 2.3, and 2.6 V/cm for the BL, BF, RUL, and FEAST electrode configurations, respectively, which coupled with the broad spread of the BL E-field suggests a biophysical basis for observations of superior efficacy of BL ECT compared to BF and RUL ECT; (2) in the hippocampi, BL ECT produces a median E-field of 4.8 V/cm that is 1.5-2.8 times stronger than that for the other electrode configurations, consistent with the more pronounced amnestic effects of BL ECT; and (3) neglecting the WM conductivity anisotropy results in E-field strength error up to 18% overall and up to 39% in specific ROIs, motivating the inclusion of the WM conductivity anisotropy in accurate head models. This computational study demonstrates how the realistic finite element head model incorporating tissue conductivity anisotropy provides quantitative insight into the biophysics of ECT, which may shed light on the differential clinical outcomes seen with various forms of ECT, and may guide the development of novel stimulation paradigms with improved risk/benefit ratio.

Fig. 1

Schematic illustration of the methods for generating a realistic finite element (FE) head model incorporating white matter (WM) anisotropic conductivity for E-field simulation and region of interest (ROI) analysis of ECT. T1-weighted MRI and diffusion-weighted MRI data sets of the subject are acquired. The T1-weighted MRI images are segmented into five tissues: scalp (yellow), skull (blue), cerebrospinal fluid (CSF, green), gray matter (red), and WM (gray). A diffusion tensor (DT) matrix and a fractional anisotropy (FA) map are computed from the diffusion-weighted MRI data. The color-coded FA map represents the principal orientations (largest eigenvectors) of the tensors (red: left-right, green: anterior-posterior, and blue: superior-inferior). ECT electrode representations—bilateral frontotemporal (BL), bifrontal (BF), right unilateral (RUL), or focal electrically administered seizure therapy (FEAST)—are added to the head model. The complete 3D ECT models are discretized into FE meshes, and the E-field distribution is calculated using the FE method. The E-field is then analyzed both globally and in specific brain ROIs. ROI outlines in white from top to bottom show frontal pole, subcallosal cingulate cortex (SCC), hypothalamus, and hippocampus.

Fig. 2

(a) Partial volume rendering of the human head model. The cropped section shows the five segmented tissue compartments. (b) A transaxial conductivity map with the principal orientations (the largest eigenvectors) of the WM conductivity tensors projected as black bars onto the WM regions. (c) Enlarged view of the region framed in white in (b).

Fig. 3

Cut-away 3D rendering of the head model (top row) and the E-field magnitude spatial distribution in the anisotropic head model for BL, BF, RUL, and FEAST electrode configurations (second to bottom rows, respectively) with 800 mA current. Columns from left to right show axial, coronal, and sagittal views, respectively. The color map is clamped at an upper limit of 8 V/cm for good visibility of the electric field distribution. L: left.

Fig. 4

Descriptive statistics of the regional E-field magnitude generated by the four ECT electrode configurations in the left and right hemispheres of the anisotropic head model. The E-field strength (y-axis) is shown on a logarithmic scale. The boxes indicate the interquartile range (25th to 75th percentile) with the median marked by a thick horizontal black line. The whiskers delimit the minimum and maximum of the regional E-field distribution.

Fig. 5

Comparison of the isotropic and anisotropic model simulations. (a) A coronal slice conductivity map using the same display conventions as in Fig. 2. (b) Enlarged view of the region framed in white in (a). (c–f) View corresponding to (b) of the E-field magnitude distribution (in color scale) and current density vector field of the isotropic (left) and anisotropic (right) head models for BL (middle row) and RUL (bottom row) electrode configurations. L: left.

Fig. 6

Relative error of the E-field magnitude in the isotropic versus the anisotropic head model for the various brain ROIs and ECT electrode configurations. Relative error is defined in equation (6).

Fig. 7

E-field magnitude relative error in the whole brain between the anisotropic head model (WM σ_long = 0.65 S/m and σ_trans = 0.065 S/m) and the isotropic model with WM conductivity ranging from σ_iso = 0.065 S/m to 0.65 S/m. The four curves correspond to the four ECT electrode configurations.