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Updated: Apr 20, 2026
Standardized Induction and Assessment of Long-term Potentiation-like Cortical Plasticity Using Transcranial Magnetic Stimulation
Published on: November 7, 2025
Cellular and molecular changes to cortical neurons following low intensity repetitive magnetic stimulation at
Stephanie Grehl1, Helena M Viola2, Paula I Fuller-Carter3
1School of Animal Biology, University of Western Australia, Perth, Australia; Sorbonne Universités, UPMC Univ Paris 06 & CNRS, IBPS-B2A UMR 8256 Biological Adaptation and Ageing, Paris, France.
Background:
Repetitive transcranial magnetic stimulation is increasingly used as a treatment for neurological dysfunction. Therapeutic effects have been reported for low intensity rTMS (LI-rTMS) although these remain poorly understood.
Objective:
Our study describes for the first time a systematic comparison of the cellular and molecular changes in neurons in vitro induced by low intensity magnetic stimulation at different frequencies.
Methods:
We applied 5 different low intensity repetitive magnetic stimulation (LI-rMS) protocols to neuron-enriched primary cortical cultures for 4 days and assessed survival, and morphological and biochemical change.
Results:
We show pattern-specific effects of LI-rMS: simple frequency pulse trains (10 Hz and 100 Hz) impaired cell survival, while more complex stimulation patterns (theta-burst and a biomimetic frequency) did not. Moreover, only 1 Hz stimulation modified neuronal morphology, inhibiting neurite outgrowth. To understand mechanisms underlying these differential effects, we measured intracellular calcium concentration during LI-rMS and subsequent changes in gene expression. All LI-rMS frequencies increased intracellular calcium, but rather than influx from the extracellular milieu typical of depolarization, all frequencies induced calcium release from neuronal intracellular stores. Furthermore, we observed pattern-specific changes in expression of genes related to apoptosis and neurite outgrowth, consistent with our morphological data on cell survival and neurite branching.
Conclusions:
Thus, in addition to the known effects on cortical excitability and synaptic plasticity, our data demonstrate that LI-rMS can change the survival and structural complexity of neurons. These findings provide a cellular and molecular framework for understanding what low intensity magnetic stimulation may contribute to human rTMS outcomes.
