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. 2021 Sep;132(9):2199-2207.
doi: 10.1016/j.clinph.2021.06.015. Epub 2021 Jul 10.

A reexamination of motor and prefrontal TMS in tobacco use disorder: Time for personalized dosing based on electric field modeling?

Kevin A Caulfield  1 , Xingbao Li  2 , Mark S George  3
Affiliations

A reexamination of motor and prefrontal TMS in tobacco use disorder: Time for personalized dosing based on electric field modeling?

Kevin A Caulfield et al. Clin Neurophysiol. 2021 Sep.

Abstract

Objective: In this study, we reexamined the use of 120% resting motor threshold (rMT) dosing for transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) using electric field modeling.

Methods: We computed electric field models in 38 tobacco use disorder (TUD) participants to compare figure-8 coil induced electric fields at 100% rMT over the primary motor cortex (M1), and 100% and 120% rMT over the DLPFC. We then calculated the percentage of rMT needed for motor-equivalent induced electric fields at the DLPFC and modeled this intensity for each person.

Results: Electric fields from 100% rMT stimulation over M1 were significantly larger than what was modeled in the DLPFC using 100% rMT (p < 0.001) and 120% rMT stimulation (p = 0.013). On average, TMS would need to be delivered at 133.5% rMT (range = 79.9 to 247.5%) to produce motor-equivalent induced electric fields at the DLPFC of 158.2 V/m.

Conclusions: TMS would have to be applied at an average of 133.5% rMT over the left DLPFC to produce equivalent electric fields to 100% rMT stimulation over M1 in these 38 TUD patients. The high interindividual variability between motor and prefrontal electric fields for each participant supports using personalized electric field modeling for TMS dosing to ensure that each participant is not under- or over-stimulated.

Significance: These electric field modeling in TUD data suggest that 120% rMT stimulation over the DLPFC delivers sub-motor equivalent electric fields in many individuals (73.7%). With further validation, electric field modeling may be an impactful method of individually dosing TMS.

Keywords: Electric field modeling; Finite element method; Motor threshold; Personalized dosing; Tobacco use disorder; Transcranial magnetic stimulation (TMS).

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1:
Figure 1:. Experimental and Electric Field Modeling Overview.
1A: Experimental Timeline. Each participant underwent a high-resolution T1w anatomical magnetic resonance imaging (MRI) scan prior to the first TMS visit. Following this, each participant’s resting motor threshold (rMT) was acquired, and 10 active (N = 21) or sham (N = 17) transcranial magnetic stimulation (TMS) treatments were administered. 1B: Coil Positioning. The TMS coil was individually placed based on anatomical landmarks from the MRI scan and uploaded to the neuronavigation software. Here we show the coil position on the scalp surface of the MNI-152 template brain, angled down from the sagittal plane at 45°. 1C: Electric Field Modeling Overview. The electric field modeling pipeline takes five steps, as visualized on a representative participant. First, each participant underwent a high resolution T1w anatomical MRI scan. We then segmented each participant’s brain scan into skin, bone, cerebrospinal fluid, gray matter, and white matter (top to bottom). Next, volumetric meshing combined the tissue layers into a 3D model with different, experimentally determined tissue values. Following this, we computed four electric field models: 1. Primary motor cortex (M1) TMS at 100% resting motor threshold (rMT). 2. Dorsolateral prefrontal cortex (DLPFC) TMS at 100% rMT. 3. DLPFC TMS at 120% rMT. 4. DLPFC TMS at the calculated group percentage required for M1-equivalent stimulation (See Equation 1). Finally, we computed a region of interest (ROI) analysis for each simulation, at the cortical projection underneath the center of the TMS coil (indicated with gray spheres), with 10mm spherical radius ROIs and gray matter masks. This process was repeated for each participant.
Figure 2:
Figure 2:. Correlation Between Electric Fields from 100% Resting Motor Threshold (rMT) Over the Primary Motor Cortex (M1) and Transcranial Magnetic Stimulation (TMS) Machine Output.
M1 electric fields significantly correlated with TMS machine output (p < 0.001). This significant correlation validates E-fields as a method of measuring stimulation intensity.
Figure 3:
Figure 3:. Correlation Between Electric Fields at the Dorsolateral Prefrontal Cortex (DLPFC) and Primary Motor Cortex (M1) with 100% resting motor threshold (rMT) Stimulation.
We found that the transcranial magnetic stimulation (TMS)-induced electric fields at M1 and the DLPFC from 100% rMT stimulation significantly correlate (p < 0.001).
Figure 4:
Figure 4:. Quantitative Comparison of Electric Fields Between the Motor and Prefrontal Cortices.
Using paired t-tests, we found that the induced electric fields produced from 100% resting motor threshold (rMT) stimulation over the primary motor cortex (M1) was significantly greater than 100% rMT stimulation over the dorsolateral prefrontal cortex (DLPFC; ***p < 0.001). In addition, the induced electric fields produced from 100% rMT stimulation over M1 were still significantly greater than 120% rMT stimulation over the DLPFC (*p = 0.013). This suggests that the common use of 120% rMT TMS for DLPFC stimulation may not be sufficient to compensate for increased scalp-to-cortex distance and differing tissue conductivities between M1 and the DLPFC in many participants. When we forced the group average electric field to be the same, it took an average of 133.5% rMT stimulation (range = 79.9–247.5% rMT). over the DLPFC for equivalent electric fields to 100% rMT over M1.
Figure 5:
Figure 5:. Visual Comparison of Electric Fields Between the Motor and Prefrontal Cortices.
Here we averaged the electric fields from all 38 participants and visualized the results in fsaverage Space. Qualitatively, the induced electric fields from 100% resting motor threshold (rMT) stimulation over the primary motor cortex (M1) were similar to the induced electric fields from 133.5% rMT stimulation over the dorsolateral prefrontal cortex (DLPFC). In contrast, 120% rMT and 100% rMT stimulation over the DLPFC produced visually weaker electric fields.
Figure 6:
Figure 6:. Distribution of Percentage of Resting Motor Threshold (rMT) Needed to Produce Equivalent Dorsolateral Prefrontal Cortex (DLPFC) Electric Fields Compared to Motor Electric Fields.
It would take an average of 133.5% rMT stimulation over the DLPFC to produce equivalent electric fields to 100% rMT stimulation over the motor cortex (range = 79.9–247.5%).
Figure 7:
Figure 7:. Correlation Between Electric Field from 100% Resting Motor Threshold (rMT) Stimulation Over the Dorsolateral Prefrontal Cortex (DLPFC) and Percentage Change in Number of Cigarettes Smoked Per Day.
We found that the induced electric field over the DLPFC at the stimulation intensity used in the Tobacco Use Disorder clinical trial (100% rMT) did not significantly impact the change in number of cigarettes smoked per day (p = 0.70).
See this image and copyright information in PMC

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