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Updated: Jul 5, 2026

TMS: Using the Theta-Burst Protocol to Explore Mechanism of Plasticity in Individuals with Fragile X Syndrome and Autism
Published on: December 28, 2010
Optimized Theta Burst Stimulation with Extended Intervals Enhances Excitatory-Inhibitory Balance
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Electrical theta burst stimulation (TBS) with different inter-train intervals (ITIs) was first used to characterize bidirectional synaptic plasticity in brain slices. Despite a lack of understanding of mechanism, TBS has been adopted by rTMS research and clinical protocols to drive plasticity in the human brain, with variable results. To uncover how TBS modulates excitability in vivo, we systematically screen the impact of electrical TBS with different ITIs on rodent cortical neurons. Short inter-train intervals (4-10s) increased calcium activity in both glutamatergic and GABAergic neurons during stimulation, whereas extended ITIs (20s) yielded modest but significant activation of glutamatergic cells and minimal activation of GABAergic cells. TBS with an ITI of 20s emerged as a plasticity sweet spot that maximized long-term activation of glutamatergic neurons, potentially through suppression of GABAergic neurons. Translating our novel iTBS electrical stimulation protocol to rTMS interventions has the potential to deliver heightened plasticity and improved therapeutic outcomes.
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