Dosimetry for repetitive transcranial magnetic stimulation: a translational study from Alzheimer's disease patients to controlled in vitro investigations.

Objective. Recent studies have indicated that repetitive transcranial magnetic stimulation (rTMS) could enhance cognition in Alzheimer's Disease (AD) patients, but to now the molecular-level interaction mechanisms driving this effect remain poorly understood. While cognitive scores have been the primary measure of rTMS effectiveness, employing molecular-based approaches could offer more precise treatment predictions and prognoses. To reach this goal, it is fundamental to assess the electric field (E-field) and the induced current densities ( J ) within the stimulated brain areas and to translate these values to in vitro systems specifically devoted in investigating molecular-based interactions of this stimulation. Approach. This paper offers a methodological procedure to guide dosimetric assessment to translate the E-field induced in humans (in a specific pilot study) into in vitro settings. Electromagnetic simulations on patients' head models and cellular holders were conducted to characterize exposure conditions and determine necessary adjustments for in vitro replication of the same dose delivered in humans using the same stimulating coil. Main results. Our study highlighted the levels of E-field and J induced in the target brain region and showed that the computed E-field and J were different among patients that underwent the treatment, so to replicate the exposure to the in vitro system, we have to consider a range of electric quantities as reference. To match the E-field to the levels calculated in patients' brains, an increase of at least the 25% in the coil feeding current is necessary when in vitro stimulations are performed. Conversely, to equalize current densities, modifications in the cells culture medium conductivity have to be implemented reducing it to one fifth of its value. Significance. This dosimetric assessment and subsequent experimental adjustments are essential to achieve controlled in vitro experiments to better understand rTMS effects on AD cognition. Dosimetry is a fundamental step for comparing the cognitive effects with those obtained by stimulating a cellular model at an equal dose rigorously evaluated.