The effect of stimulation interval on plasticity following repeated blocks of intermittent theta burst stimulation

ABSTRACT Introduction Theta burst stimulation (TBS) is a non-invasive brain stimulation paradigm capable of influencing cortical circuits in humans by inducing neural plasticity. Applying spaced blocks of TBS can affect both the direction and magnitude of plasticity, but the impact of interval duration on these interactions following intermittent TBS (iTBS) is unclear. Objectives To assess the effect of interval duration on plasticity magnitude/direction following spaced iTBS. Methods 15 healthy participants received three different iTBS conditions on separate days: single iTBS; spaced iTBS with a 5 minute interval (iTBS-5); and spaced iTBS with a 15 minute interval (iTBS-15). Changes in cortical excitability and short-interval cortical inhibition (SICI) resulting from iTBS were assessed via motor-evoked potentials (MEPs) measured from the first dorsal interosseus muscle before and up to 60 mins following stimulation. Results iTBS-15 increased MEP amplitude up to 60 mins post stimulation, whereas iTBS-5 decreased MEP amplitude. In contrast, MEP amplitude was not altered by single iTBS. Despite the significant effect of iTBS-15 on MEP amplitude at the group level, there was still considerable inter-individual variability, with only 53% of individuals meeting response criteria. Modulation of SICI did not differ between conditions. Conclusions The interval duration between spaced iTBS plays an important role in determining the direction of plasticity on excitatory, but not inhibitory circuits in human motor cortex. While iTBS-15 can increase the magnitude of facilitation in some individuals compared to single iTBS, this approach still suffers from high inter-individual variability.