New paper: Models explaining TMS E-field thresholds
Brain Stimulation, Volume 18, Issue 2p280-286 March-April, 2025
Statistical method accounts for microscopic electric field distortions around neurons when simulating activation thresholds
Konstantin Weisea ∙ Sergey N. Makaroff∙ Ole Numssen∙ Marom Bikson ∙ Thomas R. Knöscheb
Highlights
• Microscopic field inhomogeneity alters neuron activation in neuromodulation models.
• Classical models miss the impact of brain microstructure on electric field effects.
• A novel statistical approach improves prediction of TMS neuronal activation thresholds.
• The results match experimental TMS thresholds, improving model predictions.
Abstract
Introduction
Notwithstanding advances in computational models of neuromodulation, there are mismatches between simulated and experimental activation thresholds. Transcranial Magnetic Stimulation (TMS) of the primary motor cortex generates motor evoked potentials (MEPs). At the threshold of MEP generation, whole-head models predict macroscopic (at millimeter scale) electric fields (50–70 V/m) which are considerably below conventionally simulated cortical neuron thresholds (175–350 V/m).
Methods
We hypothesize that this apparent contradiction is in part a consequence of electrical field warping by brain microstructure. Classical neuronal models ignore the physical presence of neighboring neurons and microstructure and assume that the macroscopic field directly acts on the neurons. In previous work, we performed advanced numerical calculations considering realistic microscopic compartments (e.g., cells, blood vessels), resulting in locally inhomogeneous (micrometer scale) electric field and altered neuronal activation thresholds. Here we combine detailed neural threshold simulations under homogeneous field assumptions with microscopic field calculations, leveraging a novel statistical approach.
Results
We show that, provided brain-region specific microstructure metrics, a single statistically derived scaling factor between microscopic and macroscopic electric fields can be applied in predicting neuronal thresholds. For the cortical sample considered, the statistical method matches TMS experimental thresholds.
Conclusions
Our approach can be broadly applied to neuromodulation models, where fully coupled microstructure scale simulations may not be computationally tractable.
