Enhancing the effects of theta-burst magnetic stimulation over the motor cortex: the role of muscular activity and stimulation intensity

Introduction: Metaplasticity refers to the activity-dependent modification of the ability of synapses to undergo subsequent potentiation or depression, and is thought to maintain homeostasis of cortical excitability. Theta-burst stimulation is a novel repetitive magnetic stimulation protocol used to model changes of synaptic efficacy in human motor cortex. It consists of 50Hz-bursts of 3 magnetic stimuli at 80% of the active motor threshold (AMT) repeated at 5Hz. Two modalities of TBS have been established: intermittent TBS (iTBS) and continuous TBS (cTBS). ITBS generates a facilitatory effect reflected by an increase in the amplitude of compound muscle action potentials (cMAPs) evoked by single pulse TMS, whereas cTBS (600 pulses) induces inhibitory effects. Previous studies found that a voluntary contraction after TBS enhanced the facilitatory effect of iTBS and reversed the inhibitory effect of cTBS into facilitation and thus, providing evidence for rapid meta-plasticity.

Objective: Here we aimed at evaluating the influence of prior or subsequent muscular activity on the effects induced by cTBS or iTBS given at a higher but still subthreshold intensity 90% of the AMT.

Methods: The cMAPs amplitude in the abductor pollicis brevis was measured within one hour after TBS applying 8 pulses per minute. The amplitudes were averaged in blocks of 10 minutes. A repeated-measures analysis of variance (ANOVA) with the factors time (seven levels: baseline vs. six post-stimulation blocks), contraction (two levels: prior vs. subsequent) and group (iTBS vs. cTBS) was applied.

Results: A significant time effect was found (F (6,108)=7.959, p=0.0001). Post-hoc tests revealed that in comparison to baseline a significant increase of cMAPs amplitude occured from the second to the sixth time block (20 to 60min) after TBS). Neither contraction (F(5, 90)=1,3229, p=0.26159) nor group (F(5, 90)=1,1245, p=0.35316) effects were observed. No interactions were found.

Conclusion: Both TBS protocols delivered at 90% of the AMT induced a significant increase of motor cortical excitability which lasted longer than the original protocols using 80% of the AMT. No inhibitory effect was observed with cTBS. Thus, the intensity of stimulation in combination with intrinsic cortical activity may play a crucial role in the after-effects of TBS. The data challenge the current concept of meta-plasticity induced by activity either prior a single application of TBS or after stimulation.