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 (R 2 = 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.

Background: Transcranial focused ultrasound (tFUS) is a noninvasive brain stimulation method that may modulate deep brain structures. This study investigates whether sonication of the right anterior thalamus would modulate thermal pain thresholds in healthy individuals. Methods: We enrolled 19 healthy individuals in this three-visit, double-blind, sham-controlled, crossover trial. Participants first underwent a structural MRI scan used solely for tFUS targeting. They then attended two identical experimental tFUS visits (counterbalanced by condition) at least one week apart. Within the MRI scanner, participants received two, 10-min sessions of either active or sham tFUS spread 10 min apart targeting the right anterior thalamus [fundamental frequency: 650 kHz, Pulse repetition frequency: 10 Hz, Pulse Width: 5 ms, Duty Cycle: 5%, Sonication Duration: 30s, Inter-Sonication Interval: 30 s, Number of Sonications: 10, ISPTA. 0 995 mW/cm2, ISPTA. 3 719 mW/cm2, Peak rarefactional pressure 0.72 MPa]. The primary outcome measure was quantitative sensory thresholding (QST), measuring sensory, pain, and tolerance thresholds to a thermal stimulus applied to the left forearm before and after right anterior thalamic tFUS. Results: The right anterior thalamus was accurately sonicated in 17 of the 19 subjects. Thermal pain sensitivity was significantly attenuated after active tFUS. The pre-post x active-sham interaction was significant (F(1,245.95) = 4.03, p = .046). This interaction indicates that in the sham stimulation condition, thermal pain thresholds decreased 1.08 °C (SE = 0.28) pre-post session, but only decreased .51 °C (SE = 0.30) pre-post session in the active stimulation group. Conclusions: Two 10-min sessions of anterior thalamic tFUS induces antinociceptive effects in healthy individuals. Future studies should optimize the parameter space, dose and duration of this effect which may lead to multi-session tFUS interventions for pain disorders.

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Transcranial direct current stimulation (tDCS) is a widely used noninvasive brain stimulation technique with mixed results to date. A potential solution is to apply more efficient stimulation to ensure that each participant receives sufficient cortical activation. In this four-part study, we used electric field (E-field) modeling to systematically investigate the cortical effects of conventional and novel tDCS electrode montages, with the goal of creating a new easily adoptable form of tDCS that induces higher and more focal E-fields. We computed 3000 anatomically accurate, MRI-based E-field models using 2 mA tDCS to target the left primary motor cortex in 200 Human Connectome Project (HCP) participants and tested the effects of: 1. Novel Electrode Position, 2. Electrode Size, and 3. Inter-Electrode Distance on E-field magnitude and focality. In particular, we examined the effects of placing electrodes surrounding the corticomotor target in the anterior and posterior direction (anterior posterior pad surround tDCS; APPS-tDCS). We found that electrode position, electrode size, and inter-electrode distance all significantly impact the cortical E-field magnitude and focality of stimulation (all p < 0.0001). At the same 2 mA scalp stimulation intensity, APPS-tDCS with smaller than conventional 1 × 1 cm electrodes surrounding the neural target deliver more than double the on-target cortical E-field (APPS-tDCS: average of 0.55 V/m from 2 mA; M1-SO and bilateral M1: both 0.27 V/m from 2 mA) while stimulating only a fraction of the off-target brain regions; 2 mA optimized APPS-tDCS produces 4.08 mA-like cortical E-fields. In sum, this new optimized APPS-tDCS method produces much stronger cortical stimulation intensities at the same 2 mA scalp intensity. APPS-tDCS also more focally stimulates the cortex at the intended target, using simple EEG coordinate locations and without MRI scans. This APPS-tDCS method is adoptable to any existing, commercially available tDCS device and can be used to ensure sufficient cortical activation in each person. Future directions include testing whether APPS-tDCS produces larger and more consistent therapeutic tDCS effects.