Dosage considerations for transcranial direct current stimulation in children: a computational modeling study

Abstract

Transcranial direct current stimulation (tDCS) is being widely investigated in adults as a therapeutic modality for brain disorders involving abnormal cortical excitability or disordered network activity. Interest is also growing in studying tDCS in children. Limited empirical studies in children suggest that tDCS is well tolerated and may have a similar safety profile as in adults. However, in electrotherapy as in pharmacotherapy, dose selection in children requires special attention, and simple extrapolation from adult studies may be inadequate. Critical aspects of dose adjustment include 1) differences in neurophysiology and disease, and 2) variation in brain electric fields for a specified dose due to gross anatomical differences between children and adults. In this study, we used high-resolution MRI derived finite element modeling simulations of two healthy children, ages 8 years and 12 years, and three healthy adults with varying head size to compare differences in electric field intensity and distribution. Multiple conventional and high-definition tDCS montages were tested. Our results suggest that on average, children will be exposed to higher peak electrical fields for a given applied current intensity than adults, but there is likely to be overlap between adults with smaller head size and children. In addition, exposure is montage specific. Variations in peak electrical fields were seen between the two pediatric models, despite comparable head size, suggesting that the relationship between neuroanatomic factors and bioavailable current dose is not trivial. In conclusion, caution is advised in using higher tDCS doses in children until 1) further modeling studies in a larger group shed light on the range of exposure possible by applied dose and age and 2) further studies correlate bioavailable dose estimates from modeling studies with empirically tested physiologic effects, such as modulation of motor evoked potentials after stimulation.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Segmented structures.

Segmented tissue masks (skin, skull, CSF, gray matter, and white matter respectively) for the two children (P1, P2) and three adults (S1,S2,S3).

Figure 2. Intervening tissue thickness.

Skin and skull thickness are among important factors that determine the flow of current through the brain. The region from which the measurements were taken are shown for the 8 year old case (A1,B1). The skin and skull thickness for the 8 year old was 6.0 ± 0.30 mm and 2.8 ± 0.28 mm, respectively.

Figure 3. Electric field plots on the cortical surface of the pediatric and adult brains for the M1-SO montage.

The center of anode (red) was positioned on the motor strip and the cathode (black) was positioned over the contraletral supraorbital area (A-E). At 2 mA, the peak electric field was 0.66 V/m, 0.88 V/m, 0.72 V/m, 0.58 V/m, 0.56 V/min for P1, P2, S1, S2, and S3 respectively (A.1a,b,d- E.1a,b,d). A.2a,b,d, B.2a,b,d - show EF plots at 1 mA, for the pediatric heads. Cross-sectional coronal electric field plots were taken from the center of the anode (A.1c, A.2c, B.1c, B.2c, C.1c, D.1c, E.1c).

Figure 4. Electric field plots on the cortical surface of the pediatric and adult brains for HD-tDCS montage.

For 4x1 high definition tDCS the center of the anode (red) was positioned on the motor strip and the four returns (black) were placed around the center in a circular fashion with a 5cm distance from the center of the anode to the center of the return (F-L). The peak electric field, at 2 mA, for 4x1 HD-tDCS was 0.68 V/m, 0.90 V/m, 0.88 V/m, 0.48 V/m, and 0.22 V/m in P1, P2, S1, S2, and S3, respectively, at a 5 cm separation (center of anode to center of cathode distance). An additional smaller ring (2.5 cm separation) was modeled for the adolescents (see methods) (G, I). At a 2.5 cm separation, the peak electric field was 0.42 V/m and 0.68 V/m, for P1 and P2 respectively. False color maps of 0.5 mA, 1 mA, and 1.5 mA of current are shown, respectively, in the adolescents and adults (F.1-3a, G.1-3a, H.1-3a, I.1-3a, J.1-3a, K.1-3a, L.1-3a). Cross-sectional coronal electric field plots were taken from the center of the anode (F.1-3b, G.1-3b, H.1-3b, I.1-3b, J.1-3b, K.1-3b, L.1-3b).

Figure 5. Electric Field plots on the cortical surface of the Pediatric and Adult Brains for Lateralized Motor montage.

The center of anode (red) was positioned on the motor strip and the cathode (black) was positioned contralateral to the anode (M-O). At 2 mA, the peak electric field was 0.88 V/m, 0.80 V/m, 0.42 V/m for P1, P2 and S3 respectively (M.1a,b,d- O.1a,b,d). M.2a-d, N. 2a-d – show EF plots at 1 mA, for the pediatric heads. Cross-sectional coronal electric field plots were taken from the center of the anode (M.1c, M.2c, N. 1c, N. 2c, O.1c).

Figure 6. Electric field plots on the cortical surface of the pediatric and adult brains for Lateralized Temporal montage.

The center of anode (red) was positioned over the left temporal lobe and the cathode (black) was positioned contralateral to the anode (M-O). At 2 mA, the peak electric field was 1.00 V/m, 0.92 V/m, 0.66 V/m for P1, P2 and S3 respectively (P.1a,b,d- R.1a,b,d). P.2a-d, Q.2a-d - show EF plots at 1 mA, for the pediatric heads. Cross section coronal electric field plots were taken from the center of the anode. Cross-sectional coronal electric field plots were taken from the center of the anode (P.1c, P.2c, Q.1c, Q.2c, R.1c).

Figure 7. Electric field plots on the cortical surface of the pediatric and adult brains for Lateralized Prefrontal montage.

The center of anode (red) was positioned over the left frontal lobe (F3 electrode location in the 10-20 International System) and the cathode (black) was positioned contralateral to the anode (F4). At 2 mA, the peak electric field was 0.29 V/m, 0.34 V/m, 0.29 V/m, 0.27 V/m, 0.25 V/m for P1, P2, S1, S2, and S3 respectively (S.1a,b,d- W.1a,b,d). S.2a-d, T.2a-d - show EF plots at 1 mA, for the pediatric heads. Cross-sectional coronal electric field plots were taken from the center of the anode (S.1-2c, T.1-2c, U.1c-W.1c).

Figure 8. Directionality plots for the lateralized motor montage.

The center of anode (red) is positioned on the motor strip and cathode (black) is positioned contralateral to the anode (M-O) (A1-A5). False color map are plotted for 2 mA. The red corresponds to current flowing inwards, the green corresponds to a net flow of zero, and the blue corresponds to current flowing outwards (B1-B5).

Figure 9. Approaches to normalize dose across populations.

Top- Even in cases when individual modeling is practical for every subject in a study, criterion (based on population response) may be rewired to selected desired brain electric field parameters. Bottom: For each given montage and age range, there is a distribution of sensitivity (defines as the electric field in the brain per mA of current applied). In cases where the peak electric field is outside the nominal target (as is typical the case for sponge montages) further consideration should include both brain wide peak electric field and local electrical field maxima inside the nominal target. In the case of 4x1 HD-tDCS, the peak electric field is inside the ring so at the nominal target. When determining a normalized dose for a pediatric population is thus important to recognize scaling will be both montage and age dependent.