P 158. Neural correlates of Hebbian and anti-hebbian spike-timing-dependent plasticity in human: A TMS–EEG combined study

Abstract

Introduction In a recent work by our group we used transcranial magnetic stimulation (TMS) to repeatedly activate the connection between the posterior parietal cortex (PPC) and the primary motor cortex (M1) of the left dominant hemisphere with a paired associative stimulation (PAS) protocol. By varying inter-pulse interval and the activation of different M1 neuronal populations we were able to induce LTP or LTD-like effects as indexed by Motor Evoked Potentials (MEPs) amplitude modulation that followed either Hebbian or anti-Hebbian temporal rules. Objectives Our aim was to further investigate the effects induced by this cortico-cortical PAS protocol over EEG activity, by means of a TMS–EEG coregistration approach. Materials and methods 13 volunteers underwent our novel PAS protocol. Paired stimuli were applied with PPC-TMS preceding (+5 ms) or following (−5 ms) M1 stimulation. In a third condition, the induced current direction over M1 was changed from postero–anterior (PA) to antero–posterior (AP) and the ISI was set at +5 ms. Eighty single pulse TMS were applied to M1 before and after PAS while continuously acquiring EEG from 21 electrodes and recording MEPs from the first dorsal interosseous muscle. We then analysed (i) functional coupling though event-related coherence (ERcoh) for alpha (8–12 Hz) and beta (13–30 Hz) band, (ii) changes in M1 reactivity through TMS-Evoked Potentials (TEPs) and (iii) MEPs amplitude. Results When PPC preceded M1PA stimulation (+5 ms) MEPs amplitude significantly decreased ( p = 0.001), while there was a concurrent increase in ERcoh for the beta band, topographically restricted to P3–C3 pair ( p = 0.02), representing the closest electrodes to the stimulated regions. TEPs analysis indicated a decrease of those components forming a dipole over left centro-parietal sites peaking at about 13 and 20 ms. When PPC followed M1PA stimulation (−5 ms) an increase in MEPs amplitude was induced (p = 0.01) with a concurrent ERcoh increase in the alpha band for P3–C3 pair ( p = 0.01). TEPs component were again modulated at 13 and 20 ms, with an increased amplitude after PAS administration. The AP condition led to opposite results: an increased MEP amplitude when PPC preceded M1AP stimulation (p). Conclusions These findings shed new light on the cortical mechanisms underlying antithetic learning rules in humans. We found that both post-synaptic long term potentiation or depression are always associated to an increased functional connectivity that exclusively upsurge between the stimulated areas. However, the sign of cortical plasticity in M1 is indexed by different brain oscillation activities in the alpha and beta bands. Finally distinct plastic changes differently modulate M1 reactivity as indexed by opposite changes of TEPs amplitude.