Transcranial direct current stimulation (tDCS) is gaining momentum both in the research community and in the general public as an attractive tool for neuromodulation. However, the mechanism of tDCS in the brain is not fully understood. In this study, we conducted a concurrent tDCS–magnetic resonance current density imaging (MRCDI) experiment to measure the primary direction and magnitude of current in a human brain undergoing direct current stimulation. Our results show that current flow deviates significantly from its desired distribution based on human head models and that the current mostly flows through the white matter and cerebrospinal fluid.
Participants: Eleven healthy subjects (4 male and 7 female; average age = 29.4) were recruited for the study. Written informed consent was obtained from participants.
Experimental Design: Each subject underwent 4 different tDCS scans with different electrode positions. The direction and distribution of current in each session were measured by simultaneous MRCDI.
tDCS: One common electrode (5x7cm²) was attached to the back of neck and four test electrodes (4x5 cm²) were attached (1) between T4 and F8, (2) between F8 and Fp2, (3) Fpz, and (4) between Fp1 and F7 in 10-20 EEG System (Fig. 1). The electrodes were positioned to maximize the current presumed to flow in a direction perpendicular to B0 since the MRCDI only measured the induced Bz component of field. Low frequency sinusoidally varying current (±1 mA; 30 second period) was delivered in the magnet using a homemade constant current source for 6 minutes between the common electrode and each of the four test electrodes. The total stimulation was 24 minutes for each subject.
MRCDI Data Acquisition: Phase contrast images were acquired during 6 minute scans to obtain the ΔBz component of magnetic field induced by the injected current. We employed a spiral sequence with TR/TE = 2000/30 ms, 30 4 mm slices, 3.43x3.43 mm in-plane resolution, and 150 time frames. ΔBz maps were calculated from the phase Φm using
Φm = (γ x ΔBz x TE)mod(2π)
MRCDI Data Analysis: A standard fMRI GLM processing pipeline was employed to obtain field maps, where the timeseries phase data were correlated with a 0.033 Hz sine & cosine wave to generate T-score maps of the signed field. Ampere’s Law was used to solve for Jx and Jy; we only have partial information, namely ∂Bz/∂y and ∂Bz/∂x.
Jx = ∂Bz/∂y - ∂By/∂z, Jy = ∂Bx/∂z - ∂Bz/∂x
In order to characterize the distribution of current with respect to brain tissue type, we segmented the anatomical images into three tissue types: gray matter, white matter, and CSF. We then calculated the flux of J for each coronal slice through each tissue type within that slice using the co-registered current maps. If the current had no preference for any tissue, the three curves in the flux/pixel plot (Fig. 4) would be equal at every slice. Therefore, these plots give a basic quantification of the current’s tissue preference as it flows between electrodes. We also calculated the average angle of current flow in the XY plane from atan(Jy, Jx) (Fig. 2C).
Primary Direction of Current: Contrary to what would be expected from a direct current flow between electrodes, the average angle of current did not differ significantly between the four electrode positions. (Fig.3).
Distribution of Current in Different Tissue Types: In Figures 4A,B, the current essentially distributes itself according to the volume of each tissue within the head, where white matter dominates, followed by gray matter, followed by CSF. However, when normalized by tissue volume (Figs. 4C,D), the current has a strong preference for CSF, especially in regions close to the middle of the brain.
1. Stagg, C.J., A. Antal, and M.A. Nitsche, Physiology of Transcranial Direct Current Stimulation. Journal of Electroconvulsive Therapy, 2018. 34(3): p.144-152.
2. Yavari, F., et al., Basic and Functional Effects of Transcranial Electrical Stimulation (tES) - An Introduction. Neuroscience & Biobehavioral Reviews, 2018. 85: p.81-92.
3. Berryhill, M.E., et al., Hits and Misses: Leveraging tDCS to Advance Cognitive Research. Frontiers in Psychology, 2014. 5. doi:10.3389/fpsyg.2014.00800.
4. Tremblay, S., et al., The Uncertain Outcome of Prefrontal tDCS. Brain Stimulation, 2014. 7(6): p.773-783.
5. Loo, C.K., et al., International Randomized-Controlled Trial of Transcranial Direct Current Stimulation in Depression. Brain Stimulation, 2018 11(1): p.125-133.
6. Sadleir, R.J., et al., Transcranial Direct Current Stimulation (tDCS) in a Realistic Head Model. NeuroImage, 2010. 51(4): p.1310-1318.
Fig.4: Typical distribution of current in cerebrospinal Fluid (CSF), gray matter (GM), and white matter (WM): (A),(B) without density compensation; (C),(D) normalized by tissue volume.