Bidirectional long‐term motor cortical plasticity and metaplasticity induced by quadripulse transcranial magnetic stimulation

Abstract

Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising tool to induce plastic changes that are thought in some cases to reflect N -methyl-d-aspartate-sensitive changes in synaptic efficacy. As in animal experiments, there is some evidence that the sign of rTMS-induced plasticity depends on the prior history of cortical activity, conforming to the Bienenstock-Cooper-Munro (BCM) theory. However, experiments exploring these plastic changes have only examined priming-induced effects on a limited number of rTMS protocols, often using designs in which the priming alone had a larger effect than the principle conditioning protocol. The aim of this study was to introduce a new rTMS protocol that gives a broad range of after-effects from suppression to facilitation and then test how each of these is affected by a priming protocol that on its own has no effect on motor cortical excitability, as indexed by motor-evoked potential (MEP). Repeated trains of four monophasic TMS pulses (quadripulse stimulation: QPS) separated by interstimulus intervals of 1.5-1250 ms produced a range of after-effects that were compatible with changes in synaptic plasticity. Thus, QPS at short intervals facilitated MEPs for more than 75 min, whereas QPS at long intervals suppressed MEPs for more than 75 min. Paired-pulse TMS experiments exploring intracortical inhibition and facilitation after QPS revealed effects on excitatory but not inhibitory circuits of the primary motor cortex. Finally, the effect of priming protocols on QPS-induced plasticity was consistent with a BCM-like model of priming that shifts the crossover point at which synaptic plasticity reverses from depression to potentiation. The broad range of after-effects produced by the new rTMS protocol opens up new possibilities for detailed examination of theories of metaplasticity in humans.

Homeostatic and Nonhomeostatic Modulation of Learning in Human Motor Cortex

“…2c), whereas PAS still exerted significant effects on subsequent motor learning. This observation is in agreement with studies in rat hippocampus (Huang et al, 1992) and human motor cortex (Hamada et al, 2008) which demonstrated homeostatic metaplasticity even in the absence of altered synaptic excitability by the conditioning stimulation. Furthermore, this dissociation is consistent with the BCM model of bidirectional synaptic plasticity which proposes changes in the history of postsynaptic activity but not necessarily induction of synaptic plasticity as the determinant of homeostatic metaplasticity (Bienenstock et al, 1982).…”

A metaplasticity view of the interaction between homeostatic and Hebbian plasticity

“…It was first examined in the visual system, where sensory experience could be altered and the subsequent effect on synaptic modification rules could be examined. Evidence for the sliding modification threshold was eventually obtained in multiple brain regions beyond the visual system [7][8][9][10][11][12][13].…”

Effects of the motor cortical quadripulse transcranial magnetic stimulation (QPS) on the contralateral motor cortex and interhemispheric interactions

“…We only performed the poststimulus evaluation at 30 min after the end of QPS. We chose this time point because the strong effect on the stimulated M1 was reported at this time window (Hamada et al 2008). We could not completely exclude the possibility that some changes may be induced in other parameters at different time points.…”

“…This delivers a total of 360 trains, or 1,440 pulses. We chose these two parameters because QPS-5 is the most effective parameter for a long-term potentiation (LTP)-like effect over the stimulated M1, and QPS-50 is most effective for a long-term depression (LTD)-like effect over the stimulated M1 (Hamada et al 2008). …”

“…We recently reported one form of the patterned rTMS, quadripulse transcranial magnetic stimulation (QPS) (Hamada et al 2007(Hamada et al , 2008. QPS was able to induce bidirectional plasticity in the stimulated M1.…”