Histologically Informed Multiscale Modeling of the Neuronal Elements Activated by TMS

Area of Science:

• Neuroscience
• Computational Biology
• Biophysics

Background:

• The precise neural elements activated by transcranial magnetic stimulation (TMS) are not well understood.
• Computational models are limited by incomplete histological data on neural tissue micro-organization.
• High-resolution electron microscopy, like the H01 dataset, offers detailed axon morphology and myelination patterns.

Purpose of the Study:

• To systematically compare potential TMS-activated neural sites using computer simulations.
• To incorporate extensive histological measurements, including neuron models from the H01 dataset.

Main Methods:

• Developed a pipeline to create realistic multi-compartment neuron models from electron microscopy data.
• Simulated extracted neuron models and parameterized structures (e.g., "ball-and-two-sticks", bends) under uniform electric fields.
• Evaluated activation thresholds of myelinated axons in a realistic human head model.

Main Results:

• Axon terminations require unrealistic full myelination for TMS excitation.
• Partial myelination significantly increases activation thresholds.
• Myelinated axon bends transitioning from cortex to white matter show low activation thresholds.
• These thresholds align with physiological ranges and experimental motor thresholds.

Conclusions:

• Myelinated axons bending from cortex to superficial white matter are identified as potential TMS neural targets.
• Detailed histological and biophysical data are crucial for accurate TMS modeling.