Transcranial electrical stimulation motor threshold can estimate individualized tDCS dosage from reverse-calculation electric-field modeling

Abstract

Background: Unique amongst brain stimulation tools, transcranial direct current stimulation (tDCS) currently lacks an easy or widely implemented method for individualizing dosage.

Objective: We developed a method of reverse-calculating electric-field (E-field) models based on Magnetic Resonance Imaging (MRI) scans that can estimate individualized tDCS dose. We also evaluated an MRI-free method of individualizing tDCS dose by measuring transcranial magnetic stimulation (TMS) motor threshold (MT) and single pulse, suprathreshold transcranial electrical stimulation (TES) MT and regressing it against E-field modeling. Key assumptions of reverse-calculation E-field modeling, including the size of region of interest (ROI) analysis and the linearity of multiple E-field models were also tested.

Methods: In 29 healthy adults, we acquired TMS MT, TES MT, and anatomical T1-weighted MPRAGE MRI scans with a fiducial marking the motor hotspot. We then computed a "reverse-calculated tDCS dose" of tDCS applied at the scalp needed to cause a 1.00 V/m E-field at the cortex. Finally, we examined whether the predicted E-field values correlated with each participant's measured TMS MT or TES MT.

Results: We were able to determine a reverse-calculated tDCS dose for each participant using a 5 × 5 x 5 voxel grid region of interest (ROI) approach (average = 6.03 mA, SD = 1.44 mA, range = 3.75-9.74 mA). The Transcranial Electrical Stimulation MT, but not the Transcranial Magnetic Stimulation MT, significantly correlated with the ROI-based reverse-calculated tDCS dose determined by E-field modeling (R² = 0.45, p < 0.001).

Conclusions: Reverse-calculation E-field modeling, alone or regressed against TES MT, shows promise as a method to individualize tDCS dose. The large range of the reverse-calculated tDCS doses between subjects underscores the likely need to individualize tDCS dose. Future research should further examine the use of TES MT to individually dose tDCS as an MRI-free method of dosing tDCS.

Keywords: Electric field modeling; Individualized dosing; Transcranial direct current stimulation; Transcranial electrical stimulation; Transcranial magnetic stimulation; tDCS; tDCS dosing.

Fig. 1.. TES MT Materials and Methods.

1A: Experimental set-up with labeled devices and electrodes. 1B: Image of the constant current stimulator (Digitimer DS7A) and settings that were used to acquire TES MTs. 1C: Modified PEST program window showing an example in which 5 pulses of TES determined a TES MT of 50 mA.

Fig. 2.. ROAST E-Field Modeling Pipeline Overview.

2A: MRI segmentation in SPM12 run by ROAST. 2B: Anatomical MRI Scan with an arrow pointing at the fiducial on the scalp indicating the motor hotspot coordinates (visualized in MRICroGL). 2C: Using ROAST, an anodal electrode was placed at the left motor hotspot and the cathode was placed on the left neck to approximate the TES electrode montage. 2D: ROAST E-field model output after the FEM was solved. 2E: Our 5 × 5 x 5 voxel grid ROI analysis measured the E-field average in a cuboidal volume that was immediately underneath the center of the anodal electrode in each participant. See Fig. 3 for detailed description.

Fig. 3.. Detailed Visual Representation of the 5 × 5 × 5 Voxel Grid ROI Analysis.

In order to standardize the exact location for the 5 × 5 x 5 voxel grid ROI analysis across participants, we centered the ROI at the cortex on the same XY plane as the center of the anodal electrode on the scalp. We then lowered the Z plane value until we reached the first coordinate with a grey matter voxel. This location served as the center of the 5 × 5 voxel grid in the XY plane. We created the 5 × 5 voxel grid by moving 2 voxels left, 2 voxels right, 2 voxels anterior, and 2 voxels posterior of this center voxel. We recorded the E-field values of each grey matter voxel in this grid and did not count any voxel without grey matter tissue. We repeated this method a total of 5 times, moving down one axial plane at a time by keeping the same X and Y coordinates and subtracting 1 from the Z plane for each level. In this example, the X and Y coordinates stay at 58 and 96 respectively, while the Z value changes with each grey matter tissue level from 206 through 202. After measuring all the grey matter voxels with E-field values, we computed the average and used this to calculate the reverse-calculation dose for a 1.00 V/m E-field at the cortex (Fig. 4).

Fig. 4.. Reverse-Calculation Modeling Formula.

4A: Since E-field modeling relies only upon the proper segmentation of tissue and different tissue conductivities, a single E-field model can be used to estimate the tDCS dose at the scalp that would be required to produce any threshold of E-field at the cortex(33). 4B: Example of how one E-field model produced by a 3 mA input can be used to reverse-calculate the required dose to produce a 1.00 V/m E-field. In this example, a 3 mA dose produced an ROI average E-field of 0.5542 V/m and the reverse-calculation dose was 5.43 mA.

Fig. 5.

A–C: Descriptive data for TMS MT, TES MT, and reverse-calculation doses for 1.00 V/m.

Fig. 6.

TMS MT Does Not Correlate with Reverse-Calculated tDCS Dose, F(1,27) = F(1,27) = 0.045, R² = 0.002, p = 0.834.

Fig. 7.

TES MT Significantly Correlates with Reverse-Calculated tDCS Dose, F(1,27) = 21.88, R² = 0.45, p < 0.001.