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bioRxiv · 10.1101/2025.09.15.676379

High-density theta burst stimulation (hdTBS) at 100 Hz triples the aftereffects of the conventional intermittent TBS

Carney, A. F.·Scott, T.·Varlas, O.·Haque, M. M.·Nguyen, H.·Yang, Y. F.·Lu, H.
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Abstract

Slice electrophysiological studies have experimentally demonstrated that theta burst stimulation, consisting of electrical pulses delivered at 10 ms (100 Hz) inter-pulse intervals, optimally induces long-term potentiation in the hippocampus. Inspired by this observation, a novel transcranial magnetic stimulation (TMS) paradigm, 100 Hz high-density theta burst stimulation (100 Hz hdTBS), is presented. This paradigm delivers 6 pulses per burst with an inter-pulse interval of 10 ms - doubling the pulse frequency and total pulse count of the conventional intermittent TBS (iTBS). The effect of this new paradigm was studied in the motor cortex of awake rats using a rat-specific focal TMS coil and a hdTBS stimulator developed in house. Results reveal that 100 Hz hdTBS triples the after-effects of conventional iTBS. In a separate group of animals that received two consecutive iTBS session back-to-back (prolonged iTBS), we observed an inhibitory effect. Since that prolonged iTBS matches the total pulse count of 100 Hz hdTBS but produced opposite after-effects, our results underscore the critical roles of the temporal structure of TMS pulses--not merely the total number of pulses--in driving neuroplasticity. This new paradigm has the potential to significantly enhance therapeutic efficacy if confirmed to be safe and effective in humans.

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Carney, A. F., Scott, T., Varlas, O., Haque, M. M., Nguyen, H., Yang, Y. F., Lu, H.. 2025-09-17. High-density theta burst stimulation (hdTBS) at 100 Hz triples the aftereffects of the conventional intermittent TBS. https://doi.org/10.1101/2025.09.15.676379

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