A novel technique for accurate electrode placement over cortical targets for transcranial electrical stimulation (tES) clinical trials

Abstract

Objective. We present an easy-to-implement technique for accurate electrode placement over repeated transcranial electrical stimulation (tES) sessions across participants and time. tES is an emerging, non-invasive neuromodulation technique that delivers electrical stimulation using scalp electrodes.Approach.The tES electrode placement technique was developed during an exploratory clinical trial aimed at targeting a specific MNI-atlas cortical coordinate inN= 59 depressed participants (32 F, mean age: 31.1 ± 8.3 SD). Each participant completed 12 sessions of active or sham stimulation, administered using high-definition (HD) or conventional sized electrode montages placed according to the proposed technique. Neuronavigation data measuring the distances between the identified and the intended stimulation site, simulations, and cerebral blood flow (CBF) data at baseline and post-treatment were acquired to evaluate the targeting characteristics of the proposed technique.Main results.Neuronavigation measurements indicate accurate electrode placement to within 1 cm of the stimulation target on average across repeated sessions. Simulations predict that these placement characteristics result in minimal electric field differences at the stimulation target (>0.90 correlation, and <10% change in the modal electric field and targeted volume). Additionally, significant changes in %CBF (relative to baseline) under the stimulation target in the active stimulation group relative to sham confirmed that the proposed placement technique introduces minimal bias in the spatial location of the cortical coordinate ultimately targeted. Finally, we show proof of concept that the proposed technique provides similar accuracy of electrode placement at other cortical targets.Significance.For voxel-level cortical targets, existing techniques based on cranial landmarks are suboptimal. Our results show that the proposed electrode placement approach provides high consistency for the accurate targeting of such specific cortical regions. Overall, the proposed technique now enables the accurate targeting of locations not accessible with the existing 10-20 system such as scalp-projections of clinically-relevant cortical coordinates identified by brain mapping studies. Clinical trial ID: NCT03556124.

Keywords: cortical targeting; electrode placement; neuromodulation; neuronavigation; transcranial direct current stimulation (tDCS); transcranial electrical stimulation (tES).

Conflict of interest statement

Declaration of conflicts of interest:

The authors confirm that there are no known conflicts of interest associated with this publication.

© 2021 IOP Publishing Ltd.

Figures

Figure 1:. Montages and study design.

1A shows the montages employed. The stimulation target was chosen to be the scalp projection (individualized to each participant) of x=−46, y=44, z=38 mm (MNI coordinates). For the high-definition (HD) montage, 2×2 cm sized electrodes were used in a 4×1 ring montage, with the anode positioned on the stimulation target, and the cathodes placed 5cm away from the anode, and equidistant from the two neighboring cathode electrodes. For the Conventional montage, 5×7 cm sponge electrodes were used with the anode positioned on the stimulation target and the cathode placed over x=56, y=30, z=−1 (MNI coordinates), approximating the F8 location. 1B shows the acquisition of study-relevant data over the course of the study for each participant, with (i) T1 structural data acquired at visit 0, (ii) neuronavigation data acquired at mid-trial (visit 6), and (iii) cerebral blood flow (CBF) data acquired using arterial spin labeling (ASL) MRI at baseline and post-treatment (visits 1 and 12). Note that neuronavigation was used at baseline to locate and mark the individualized stimulation-target on the participant’s cap (as described in Methods, Electrode Placement section). Any observed displacements at this initial visit were corrected to ensure accurate localization of the stimulation-target for subsequent treatments.

Figure 2:. Cap Placement technique.

EEG caps are individually fit to each participant as follows: The cap is first secured using a chin strap, and the position of the strap is marked so that it can be secured with the same tension at follow-up sessions (2.A, green arrow). Next, the nasion to inion distance is measured, and the cap is adjusted such that the midpoint of the line joining Fp1 and Fp2 is 10% of the nasion-to-inion distance (2.B). Following this, the cap is adjusted to ensure that the T7 and T8 reference points are at identical distances from the left and right tragus (2.C). Finally, the cap is secured by taping it down over the participant’s upper cheeks and between the eyebrows. The nasion to Fp1/Fp2 distance, along with the tragus to T7/T8 distances are recorded. For all subsequent sessions with the same participant, the cap is placed to match these distances to within 0.2cm. When investigating the accuracy of the proposed technique for other brain targets, piloting indicated that using the left tragus to C3, right tragus to C4, and left/right tragus to Cz provided slightly better accuracy than the T7/T8 reference points. Consequently, these reference points were utilized instead of T7 and T8 (shown in 2.C, light-green arrows). Note that the exact correspondence of the reference points on the cap to the actual T7, T8 etc. is not important, what is crucial for correct cap-placement is to ensure that the distances of the reference points to anatomical landmarks are within the 0.2 cm tolerance.

Figure 3:. Distribution of the electric field at zero displacement.

Figure shows the distribution of the (a) the electric field (E-field) strength, and (b) electric field normal to the cortical surface, in the 1cm spherical ROI centered at the stimulation target in the ideal zero-displacement case for both the conventional and high-definition tES montages. In all cases, the distribution was observed to be heavy-tailed, providing motivation for the use of the modal electric field as a summary statistic rather than the mean. The modal electric field was calculated after data-binning using the Freedman-Diaconis (41) criterion for heavy-tailed distributions

Figure 4:. CBF increases near the stimulation target.

A significant increase in the percentage-change cerebral blood flow (%ch-CBF, post-treatment relative to baseline) was observed in the active stimulation group relative to sham in the left DLPFC (p = 0.046). The left DLPFC region was defined using an anatomical ROI from the Sallet atlas (51), and is shown in green. Within this region, the peak significant voxel was observed to be at x=−27, y=42, z=19.5 mm (MNI co-ordinates), and was located using posthoc t-tests that were performed voxel-wise (p < 0.05, and shown with the red-yellow colormap). For comparison, the cortical stimulation target is shown with a white arrow. Note that the stimulation target was located at x=−46, y=44, z=38 mm, which is approximately in the same coronal slice (within the 7.5 mm smoothing threshold) at an angle of 44.2 degrees in the coronal plane.