Evidence of transcranial direct current stimulation-generated electric fields at subthalamic level in human brain in vivo

Abstract

Background: Transcranial direct current stimulation (tDCS) is a promising brain modulation technique for several disease conditions. With this technique, some portion of the current penetrates through the scalp to the cortex and modulates cortical excitability, but a recent human cadaver study questions the amount. This insufficient intracerebral penetration of currents may partially explain the inconsistent and mixed results in tDCS studies to date. Experimental validation of a transcranial alternating current stimulation-generated electric field (EF) in vivo has been performed on the cortical (using electrocorticography, ECoG, electrodes), subcortical (using stereo electroencephalography, SEEG, electrodes) and deeper thalamic/subthalamic levels (using DBS electrodes). However, tDCS-generated EF measurements have never been attempted.

Objective: We aimed to demonstrate that tDCS generates biologically relevant EF as deep as the subthalamic level in vivo.

Methods: Patients with movement disorders who have implanted deep brain stimulation (DBS) electrodes serve as a natural experimental model for thalamic/subthalamic recordings of tDCS-generated EF. We measured voltage changes from DBS electrodes and body resistance from tDCS electrodes in three subjects while applying direct current to the scalp at 2 mA and 4 mA over two tDCS montages.

Results: Voltage changes at the level of deep nuclei changed proportionally with the level of applied current and varied with different tDCS montages.

Conclusions: Our findings suggest that scalp-applied tDCS generates biologically relevant EF. Incorporation of these experimental results may improve finite element analysis (FEA)-based models.

Keywords: Body resistance; Deep brain stimulation; Dose-dependence; Transcranial direct current stimulation; Voltage-current relationship.

Figure 1

An overview of the clinical procedure interspersed with the experimental procedure.

Figure 2. Voltage change across DBS electrodes change linearly to tDCS dose and is montage specific

(A) Schematic diagram of bitemporal tDCS montage: Anode is positioned on the left temporal region and cathode is positioned on the right temporal region. tDCS current flows in a general direction from left to right (red arrow); (B) Schematic diagram of occipitofrontal tDCS montage: Anode is positioned on the inion and cathode is positioned on the middle of the forehead. tDCS current flows in a general direction from posterior to anterior (red arrow); (C–E) Subject 1 implanted with single 4-channel DBS lead in the left ventrointermediate nucleus (VIM) with lead marked with white arrow on axial section of the MRI (C). The subject underwent 2 mA of bitemporal tDCS. When chest reference was used (D), all four channels/electrodes/contact points detected about 4 mV of voltage (green traces, color coded to the electrode contact points as shown) that coincide to the ramp-up, plateau and ramp-down of tDCS current (blue trace), but not when channel 2 was used as a reference (E). Measured body resistance through tDCS pads was ~4 kΩ that slowly decreased over time in the plateau phase of tDCS and then increased again as tDCS current ramped down (orange trace); (F–I) Subject 2 (F, G) and 3 (H, I) with bilateral implantation of 4-channel DBS leads in subthalamic nucleus (STN, F) and internal globus pallidus (GPi, H), respectively, show dose-dependent changes in voltage change with tDCS application in bitemporal montage, but not in the occipitofrontal montage. Interindividual variability in tDCS-generated voltage changes (compare G to I) can be explained by inter-electrode distance (2.36 cm for Subject 2 versus 4.35 cm for Subject 3 – see Table 2). Also, body resistance is lower with 4 mA tDCS application when compared with 2 mA tDCS application irrespective of montage (orange traces, with gray dashed line for comparison). All traces were segment-wise detrended to minimize any DC bias and DC slew artifact. Slow cortical potentials are still apparent in traces even after detrending. Channel numbers on DBS leads follow Medtronic convention. Start and end of tDCS application is marked with magenta and yellow lines, respectively, that span through injected tDCS current (blue) and DBS lead voltage measurements.