Dosing Transcranial Magnetic Stimulation of the Primary Motor and Dorsolateral Prefrontal Cortices With Multi-Scale Modeling

Zsolt Turi; Nicholas Hananeia; Sina Shirinpour; Alexander Opitz; Peter Jedlicka; Andreas Vlachos

doi:10.3389/fnins.2022.929814

Dosing Transcranial Magnetic Stimulation of the Primary Motor and Dorsolateral Prefrontal Cortices With Multi-Scale Modeling

Front Neurosci. 2022 Jul 8:16:929814. doi: 10.3389/fnins.2022.929814. eCollection 2022.

Authors

Zsolt Turi¹, Nicholas Hananeia², Sina Shirinpour³, Alexander Opitz³, Peter Jedlicka², Andreas Vlachos^{1

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Affiliations

¹ Department of Neuroanatomy, Faculty of Medicine, Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany.
² Faculty of Medicine, Interdisciplinary Centre for 3Rs in Animal Research, Justus-Liebig-University, Giessen, Germany.
³ Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, United States.
⁴ Center BrainLinks-BrainTools, University of Freiburg, Freiburg, Germany.
⁵ Center for Basics in Neuromodulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Abstract

Transcranial magnetic stimulation (TMS) can depolarize cortical neurons through the intact skin and skull. The characteristics of the induced electric field (E-field) have a major impact on specific outcomes of TMS. Using multi-scale computational modeling, we explored whether the stimulation parameters derived from the primary motor cortex (M1) induce comparable macroscopic E-field strengths and subcellular/cellular responses in the dorsolateral prefrontal cortex (DLPFC). To this aim, we calculated the TMS-induced E-field in 16 anatomically realistic head models and simulated the changes in membrane voltage and intracellular calcium levels of morphologically and biophysically realistic human pyramidal cells in the M1 and DLPFC. We found that the conventional intensity selection methods (i.e., motor threshold and fixed intensities) produce variable macroscopic E-fields. Consequently, it was challenging to produce comparable subcellular/cellular responses across cortical regions with distinct folding characteristics. Prospectively, personalized stimulation intensity selection could standardize the E-fields and the subcellular/cellular responses to repetitive TMS across cortical regions and individuals. The suggested computational approach points to the shortcomings of the conventional intensity selection methods used in clinical settings. We propose that multi-scale modeling has the potential to overcome some of these limitations and broaden our understanding of the neuronal mechanisms for TMS.

Keywords: dorsolateral prefrontal cortex; electric field; multi-scale modeling; primary motor cortex; repetitive transcranial magnetic stimulation; transcranial magnetic stimulation.