Multiscale Modeling of Transcranial Alternating Current Stimulation:Induced Electric Field and Cellular Responses
DOI:
https://doi.org/10.71321/wyq6hf65Keywords:
Transcranial alternating current stimulation, computational modeling, induced electric field, multi-compartmental neuronal models, membrane polarization, spike entrainmentAbstract
Transcranial alternating current stimulation (tACS) is a non-invasive neuromodulation technique that generates weak oscillatory electric fields (EFs) in the brain and has shown promise for probing neural oscillations and treating neuropsychiatric disorders. However, its effects on neural activity remain highly variable across studies, and controversies persist regarding whether conventional tACS intensities can genuinely entrain neuronal firing. Experimental approaches alone have limited capacity to resolve these inconsistencies. Computational modeling provides a powerful complementary framework to quantify induced EFs, predict cellular responses, and generate mechanistic hypotheses. In this review, we focus on multiscale models spanning from macroscopic realistic head models to microscopic multi-compartmental neuronal models. Head models elucidate how anatomy, tissue conductivity, stimulation parameters, and electrode montage shape the spatial distribution of tACS-induced fields, while multi-compartmental models reveal how EFs, neuronal morphology, biophysics, and synaptic inputs govern cell-type-specific polarization and spike entrainment. We highlight key insights, unresolved controversies, and emerging trends, including the integration of head and neuronal models, network-level simulations, and the use of artificial intelligence to bridge scales. By critically synthesizing advances in multiscale modeling, we argue that coupling computational frameworks with experimental recordings is essential for explaining the diversity of tACS effects and for translating mechanistic insights into individualized, clinically effective interventions.
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