Synaptic and Axonal Plasticity Induction in the Human Cerebral Cortex

Abstract

This chapter summarizes a newly developed method (quadripulse stimulation (QPS)) to induce neural plasticity in the human brain. What Is QPS? One stimulation burst consisting of four monophasic pulses is given every 5 s for 30 min. In total, 360 bursts (1440 pulses) are given in one session. Short-interval QPS potentiates excitability and longer-interval QPS depresses the target area. QPS at intervals of 5 ms (QPS5) induces long-term potentiation (LTP) most efficiently and QPS50 induces long-term depression (LTD) most effectively in the human primary motor cortex (M1). After QPS, no changes were found in the threshold, GABAergic function of M1, or acetylcholine function. In contrast, EPSP summation and sharpness of the IO curve are bidirectionally modulated by QPS. These findings indicate that excitatory synaptic efficacy is bidirectionally modulated by QPS. The effect is specific to the activated neurons. These all are consistent with synaptic LTP/LTD. Dopamine enhanced both LTP of QPS5 and LTD of QPS50. It is again compatible with plasticity induction in animals. These are consistent with the concept that LTD was enhanced by the D1 agonist and LTD by the D1 and D2 agonists together, but the D1 agonist alone or the D2 agonist alone induced no changes in LTD. In PD patients, even at an early stage, QPS induced neither LTP- nor LTD-like effects in the motor cortex. This lack of plasticity was normalized by L-Dopa intake in parallel with motor symptom improvements.