Interhemispheric Facilitatory Effect of High-Frequency rTMS: Perspective from Intracortical Facilitation and Inhibition

Abstract

The activity of excitatory and inhibitory neural circuits in the motor cortex can be probed and modified by transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS), noninvasively. At present, not only has a consensus regarding the interhemispheric effect of high frequency rTMS not been reached, but the attributes of these TMS-related circuits are also poorly understood. To address this question comprehensively, we integrated a single- and paired-pulse TMS evaluation with excitatory 20-Hz rTMS intervention in order to probe the interhemispheric effect on the intracortical circuits by high-frequency rTMS. In the rest state, after 20-Hz rTMS, a significant increase of single-pulse MEP and paired-pulse intracortical facilitation (ICF) in the non-stimulated hemisphere was observed with good test–retest reliability. Intracortical inhibition (measured by the cortical silent period) in the unstimulated hemisphere also increased after rTMS. No significant time–course change was observed in the sham-rTMS group. The results provide the evidence that 20-Hz rTMS induced a reliable interhemispheric facilitatory effect. Findings from the present study suggest that the glutamatergic facilitatory system and the GABAergic inhibitory system may vary synchronously.

Classical conditioning of faciliatory paired-pulse TMS

“…In this scenario, transsynaptic activation of most pyramidal cells in the motor cortex by the 1st conditioning TMS stimulus alone might have prevented a relevant facilitatory effect. Such a ceiling effect is well known for intracortical facilitation and has been described by several authors [12][13][14][15][16][17][18][19][20][21][22] . In the context of the present study, single TMS pulses with different stimulation intensities would have allowed us to capture the TMS-response behavior, for example in form of an input-output curve, from weakest to strongest TMS output, with the latter leading to saturated responses indicating the ceiling effect.…”

“…In the present proof-of-concept study, we raised the question whether the faciliatory influence of paired-pulse TMS on motor cortex excitability can be applied to classical conditioning. To this end, we utilized faciliatory paired-pulse TMS with default parameters [12][13][14][15][16][17][18][19][20][21][22] . The first TMS pulse was applied at subthreshold intensity of 95% resting motor threshold, which conditioned the second pulse, 12 ms later, applied at suprathreshold intensity of 130%.…”

“…We used paired-pulse instead of singlepulse TMS and investigated whether its faciliatory influence on the stimulated motor cortex can be applied to classical conditioning. Long intervals between paired TMS pulses (6-20 ms), the first applied at subthreshold intensity and the second at suprathreshold intensity, provoke facilitation of the motor evoked potentials (MEPs) of the target muscle [12][13][14][15][16][17][18][19][20][21][22] . We combined faciliatory paired-pulse TMS, using an interstimulus interval of 12 ms, with a simultaneously presented acoustic stimulus (i.e., simultaneous conditioning).…”