Theta priming of 1Hz repetitive transcranial magnetic stimulation in healthy volunteers

Abstract

Objectives: Originally derived from animal experiments, the concept of priming in rTMS experiments refers to a pre-treatment or pre-protocol stimulation that enhances the effect of the protocol. The purpose of this study was to investigate the use of theta priming with 1 Hz rTMS to the motor cortex to induce corticospinal inhibition. The main question was whether there was any benefit in using theta priming instead of simply a longer period of 1Hz rTMS. To address this, we compared 1 Hz rTMS with and without theta priming, using a protocol in which the total period of stimulation was the same.

Methods: 11 healthy volunteer participants aged between 18 and 45 (mean 27.6± 7.4) were given rTMS to the right primary motor cortex in 3 separate sessions, in which the participant received one of three protocols: 1) 1 Hz rTMS for 10 minutes, 2) 5 minutes of 5 Hz theta priming followed by 5 minutes of 1 Hz rTM or 3) 10 minutes of 1 Hz sham rTMS using a placebo coil. In each session reaction times and pinchgrip and handgrip dynamometry were measured, followed by recording of active and resting motor evoked potentials from the left first dorsal interosseus muscle. One of three protocols was then administered, the order counterbalanced across participants, and this was followed by re-testing of motor evoked potentials, dynamometry and reaction times, in that order. Results: There was a significant effect of 1 Hz rTMS alone on both RMEP and AMEP amplitude, p<0.05: both were significantly lower after 1Hz rTMS compared to sham. RMEP amplitude was unchanged compared to sham rTMS after the priming protocol, p=0.001. 1Hz rTMS with and without theta priming significantly reduced right unimanual reaction time compared to sham. There was no significant effect of either protocol on cortical silent period or muscle strength, compared to sham rTMS. Conclusions: While theta priming abolished or interfered with the inhibitory effect of 1Hz rTMS on corticospinal excitability, the effect on ipsilateral reaction times was the same. The negative effect of priming can be interpreted as a functional interference of the priming pre-protocol with the 1Hz protocol. The dissociation between the effects on MEP amplitude and ipsilateral reaction times suggests that MEP amplitude may not always predict behavioural changes mediated by transcallosal inhibitory mechanisms. Furthermore, the findings suggest that primed rTMS may have no benefit over the use of longer durations of 1Hz stimulation.