REVISITING MOTOR HAND AREA TARGETING WITH ELECTRIC FIELD MODELING
DOI: Pending DOI
Synopsis
C3 in the 10-20 system is commonly used to target the motor hand area for transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), but whether C3 optimally reflects the cortical motor hand representation remains unclear. Using electric field (e-field) modeling in 144 individuals, we compared electroencephalography (EEG)-based targets, with spatial optimization along the Cz–C3 trajectory for TMS. For tDCS, CP1 and CP3 yielded higher mean e-fields than C3. For TMS, C3h showed the highest mean e-field, and optimization estimated the peak e-field location at 83–84% of the distance from Cz toward C3 (approximately 17% of the preauricular-to-preauricular distance). These findings suggest that C3 stimulation may not be the best approach for motor hand targeting.
Background
Non-invasive brain stimulation (NIBS), including tDCS and TMS, is widely used to modulate the contralateral hand area in research and clinical practice. When individualized motor hotspot localization using TMS with electromyography (EMG) is not feasible, standardized EEG landmarks, such as C3 or C4 in the international 10-20 system, are commonly used as surrogate targets for the motor hand area. However, prior studies [1–3] have raised concerns that these conventional landmarks may not be the optimal targets for the cortical hand representation. The purpose of this study was to evaluate, through e-field modeling, the concern previously raised in the literature that the C3 region may not be the optimal target for the motor hand area. Based on prior studies [1–5], we hypothesized that stimulation at C3 would not produce the highest mean e-field in M1 compared with other electrode locations.
Methods
A total of 144 T1-weighted MRI scans obtained from OpenNeuro, McLean Hospital, Brigham and Women’s Hospital, and Butler Hospital were analyzed using SimNIBS 4.1.0. Mean e-field strength was calculated within spherical regions of interest (ROI) centered at two Montreal Neurological Institute (MNI) coordinates associated with the motor hand area: [-37, -21, 58] [6] and [-36, -24, 56] [7]. For tDCS simulations, the anode was placed at one of seven EEG-based locations (FC1, FC3, C1, C3h, C3, CP1, or CP3), while the cathode was fixed at Fp2, reflecting a commonly used motor cortex montage [8]. Stimulation intensity was set to 1 mA. For TMS simulations, the coil center was positioned at the same seven candidate locations, oriented 45° toward the cranial midline, using a Magstim D70 coil model at 50% maximum stimulator output. To further refine the optimal TMS target, an additional continuous spatial analysis was performed along the Cz–C3 trajectory. Thirty-six equally spaced points between Cz and C3 were sampled, and Gaussian curve fitting was applied to estimate the location yielding the maximal mean e-field within the motor hand area.
Results
In tDCS simulations, stimulation at CP1 and CP3 produced higher mean e-field strengths within the motor hand area compared with the conventional C3 target at both MNI coordinates. In TMS simulations, coil placement at C3h generated higher mean e-field strength than C3 at both target coordinates, suggesting that the conventional C3 landmark may be suboptimal when individualized hotspot localization is unavailable. Continuous spatial optimization along the Cz–C3 trajectory further demonstrated that the peak mean e-field occurred at approximately 83–84% of the distance from Cz toward C3, corresponding to approximately 17% of the preauricular-to-preauricular distance from Cz (MNI [-37, -21, 58]: 16.78%; MNI [-36, -24, 56]: 16.64%). This location closely approximates C3h rather than C3. Across both stimulation modalities, the conventional assumption that C3 provides the most effective EEG-based approximation of the motor hand area was not supported.
Discussion
These findings suggest that default reliance on C3 as a surrogate target for the right-hand motor representation may not provide optimal stimulation for either tDCS or TMS. In the 10-20 system, C3 is located at 20% of the preauricular-to-preauricular distance from Cz, whereas our estimated peak location corresponded to approximately 17%. This estimate is conceptually similar to the alternative landmark proposed by Silva and colleagues [5], who used MRI-based localization of the anatomical hand knob and corresponding scalp projection to suggest a location at approximately 13% for improved motor hand targeting. Although our simulations showed that tDCS with the anode positioned at CP1/CP3 and the cathode at Fp2 produced higher mean e-fields in M1 than the conventional C3-based montage, and that TMS targeting near C3h yielded higher mean e-fields than conventional C3 stimulation, these findings should not be interpreted as evidence that these configurations represent the optimal stimulation targets. More systematic modeling, particularly across a broader range of tDCS electrode montages and electrode sizes [cf. [4]], as well as varying TMS coil orientations, will be needed, along with physiological validation and future studies examining whether such differences translate into meaningful differences in clinical efficacy.
Disclosures
SHS effort is supported by the NIH (K23MH121657 and R21MH126271), the Brain and Behavior Research Foundation Young Investigator Grant, the Baszucki Brain Research Fund, and the Department of Veterans Affairs (I01CX002293). SHS serves as a consultant for Kaizen Brain Center, Acacia Mental Health, and Magnus Medical. SHS owns stock in BrainsWay Inc (publicly traded) and Magnus Medical (not publicly traded). SHS owns independent intellectual property on the use of brain network mapping to target neuromodulation.
LLC discloses consulting income from Neurolief, Ltd., Netanya Israel; Neuronetics, Malvern, PA; Universal Brain, Los Altos, CA; Suven Pharma, India; Cyclerion, Cambridge MA; Kintsugi, Berkely, CA; and PharPoint Research, Durham NC. Her research is supported by clinical trial contracts between Butler Hospital, Providence, RI, and Neurolief, Ltd., Neuronetics, Neumarker Inc, and Gray Matters Health.
JCB receives financial support as an editorial stipend from Elsevier. JCB discloses consulting income and/or equity from NRx Pharmaceuticals and Zeta Surgical. JCB is supported by the National Institute of General Medical Sciences (P20GM130452), the National Institutes of Health (R01MH1389697), the Department of Defense Advanced Research Projects Agency (HR00112320037: the views, opinions and/or findings expressed are those of the author and should not be interpreted as representing the official views or policies of the National Institutes of Health, the Department of Defense, or the U.S. Government), the Brain and Behavior Research Foundation Young Investigator Grant (#31748), the Cindy & Paul Gamble Fund, and the McLean Hospital Center of Excellence in Depression and Anxiety Disorders.
References
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