Neuroplasticity induction in humans : Basic mechanisms and clinical application

Abstract

The neuroplasticity, especially synaptic plasticity, plays critical roles for maintaining great flexibility of the nervous system in humans. Several non–invasive stimulation methods have been reported to induce such plasticity in human brain, such as transcranial magnetic stimulation, direct or alternative current stimulation, high voltage electric stimulation and so on. In this communication, I will summarize a new stimulation method (quadripulse stimulation, QPS) and show several clinical applications of repetitive transcranial magnetic stimulation (rTMS).

QPS : In this intervention, a burst of four monophasic magnetic pulses separated by a certain inter–stimulus interval (ISI) was given once five seconds (inter–burst interval IBI of 5 seconds) for 30 minutes over the target area (the primary motor cortex in this communication) with a magnetic coil. The motor evoked potentials (MEPs) were recorded before and after the intervention, and the time course of those amplitudes was used to evaluate the motor cortical excitability changes for estimating the motor cortical plasticity. QPS with an ISI of (QPS5) was most effective to induce the long term potentiation (LTP), and QPS with an ISI of 50ms (QPS50) for the long term depression (LTD). Several physiological characters of QPS were consistent with the synaptic plasticity. Its resistance to BDNF polymorphism and less interindividual variability have been reported recently.

Dopamine and QPS : Dopamine is one of the substances to modify the degree of plasticity. We studied effects of dopamine (D1, D2) and dopamine agonist (D2) on the plasticity induced by QPS. The dopamine enhanced both LTP and LTD whereas the agonist had no effects on either LTP or LTD. Based on these results, we concluded that the plasticity studied by QPS over M1 should reflect the synaptic plasticity within M1 modified by ventral tegmentum (VTA)–M1 dopamine projection and should have no correlation with the basal ganglia–motor–cortical loop directly influenced by substantia nigra.

Clinical applications of rTMS for the treatment : We summarized previous clinical or preclinical rTMS trails for Parkinson disease, cortical myoclonus and paraparesis.