Paired associative stimulation enforces the communication between interconnected areas

Abstract

Paired associative stimulation (PAS) protocols induce forms of spike-timing-dependent-plasticity (STDP) when paired pulses are repeatedly applied with different timing over interconnected cortical areas such as the posterior parietal cortex (PPC) and the primary motor cortex (M1). However, the assessment of PAS effects is usually limited to M1 through recording of motor-evoked potential (MEP) amplitude. Here, by combining transcranial magnetic stimulation (TMS) with EEG we aimed at investigating PAS effects over both areas (PPC, M1) and the modulation induced on their connectivity in humans. In different PAS conditions, PPC preceded or followed M1 TMS by 5 ms. We found that TMS-evoked potentials (TEPs) changed differently according to the long-term depression (LTD) or potentiation (LTP) after-effect assessed by MEPs, but did not vary at PPC level. Moreover, there was no change in local oscillatory power. However, there was a remarkable increase of coherence between the PPC and the M1 areas. When the PAS protocol induced LTD as revealed by MEPs, there was a specific increase of the coherence between PPC and M1 within the beta band. On the contrary, when PAS induced LTP, the coherence crucially increased in the alpha band. The same LTP results were confirmed when rotating the stimulating coil in M1 during the PAS protocol. In conclusion, we report new evidence that opposite STDP-like effects induced by corticocortical PAS are associated with increased communication between involved brain areas and that antithetic forms of STDP-like after-effects result in distinct cortical rhythms connectivity changes.

Figures

Figure 1.

Schematic representation of the experimental procedure. A, Eighty single pulse TMS were delivered before and after the administration of three different PAS protocols in a randomized order over M1 or PPC of the left dominant hemisphere. For all experiments the interstimulus interval was at 5 ms. The order of pulse delivery was changed across condition, so that positive paring indicate that the PPC input precedes the M1 pulse while negative paring indicate that the PPC input is applied after the M1 pulse. The orientation of the stimulating coil over M1 was also changed from posterior–anterior (M1PA) to anterior–posterior (M1AP). The blue rectangle and coil indicate the first delivered pulse. B, Data processing. An epoch of 1 s of unprocessed data is shown before (left) and after artifacts removal (right) from one representative subject for nine electrodes. Data refers to the stimulation of M1.

Figure 2.

Spatiotemporal dynamics of TEPs. Grand-average of TEPs recorded at all electrodes, superimposed in a butterfly plot as a result of M1 (A) and PPC (B) stimulation. The time of pulse delivery is indicated by a vertical black bar. Data are obtained by collapsing two pre-PAS conditions (PPC-M1PA+5 ms, PPC-M1PA−5 ms). In the lower part of each panel, topographic maps are displayed at specific time points corresponding to the TEP latencies as reported in the Results. Map voltage is color coded according to the minimum (blue) and maximum (red) voltage (μV) of each response.

Figure 3.

Global cortical reactivity changes induced by PAS protocols. For each PAS condition, the GMFP is shown for M1 (left) and PPC (right) stimulation. The central panels indicate the effects of each protocol over the MEP amplitude. The bottom horizontal black lines indicate significant differences between pre-PAS and post-PAS testing. For each significantly modulated peak, the topographic map is also shown. A, PPC-M1PA+5ms. When PPC repeatedly preceded M1 stimulation by 5 ms, single pulse TMS over M1 revealed a significant increase of P1 accompanied with a significant reduction of MEPs amplitude, whereas no changes was detected for PPC testing. B, PPC-M1PA−5ms. When PPC repeatedly followed M1 stimulation by 5 ms, single pulse TMS over M1 revealed a significant decrease of P1 and P4 accompanied with a significant MEP amplitude increment, whereas no changes was detected for PPC testing. C, PPC-M1AP +5ms. When PPC repeatedly preceded M1AP stimulation by 5 ms, a significant decrease of amplitude for P1 and P4 after TMS pulse over M1 was accompanied with a significant MEP amplitude increment, whereas no changes was detected for PPC testing.

Figure 4.

TMS-induced activity. Grand-averaged time-frequency plots are depicted for a representative condition (PPC-M1PA+5 ms) depicted for C3 (A), representing the closest electrode to M1 hot-spot and P3 (B), the closest recording site to PPC, before and after PAS administration. The black graph plotted at the right of each time-frequency plot illustrates the power spectrum profile induced by the TMS pulse at the intersection of the two dotted green lines, indicating the maximum induced power.

Figure 5.

M1 event-related coherence changes induced by distinct PAS protocols. The scalp distribution maps on the right part of each panel show grand average of event-related coherence transformation of all electrodes referenced to C3 electrode (the closest electrode to M1 hot-spot), as a function of the experimental condition and Time (pre-PAS vs post-PAS) for the significantly modulated frequency band. Event-related coherence values are color coded according to the color bar. The middle part of each panel depicts ERcoh changes for a subsample of 9 electrodes surrounding the parietal end motor areas of both hemisphere for the significantly modulated frequency band. On the right for each panel, average data of the ERcoh for the C3–P3 pair before and after PAS stimulation are shown for all investigated frequencies (theta, alpha, and beta). Bars correspond to the SEM, asterisks mark significant differences (p < 0.05). A, PPC-M1PA+5ms resulted in a decrease ERcoh between C3 and central electrodes and a concurrent increase in coherence between C3 and P3. The change in ERcoh was significant for the beta band. B, PPC-M1PA −5ms resulted in a decrease ERcoh between C3 and Cz and a concurrent increase in coherence between C3 and P3. The change in ERcoh was significant for the alpha band. C, PPC-M1AP+5ms resulted in a decrease ERcoh between C3 and Cz and a concurrent increase in coherence between C3 and P3. The change in ERcoh was significant for the alpha band.

Figure 6.

PPC event-related coherence changes induced by distinct PAS protocols. The scalp distribution maps on the right part of each panel show grand average of event-related coherence transformation of all electrodes referenced to the P3 electrode (the closest electrode to PPC hot-spot), as a function of the experimental condition and Time (pre-PAS vs post-PAS) for the significantly modulated frequency band. Event-related coherence values are color coded according to the color bar. The middle part of each panel depicts ERcoh changes for a subsample of 9 electrodes surrounding the parietal end motor areas of both hemisphere for the significantly modulated frequency band. On the right for each panel, average data of the ERcoh for the C3–P3 pair before and after PAS stimulation are shown for all investigated frequencies (theta, alpha, and beta). Bars correspond to the SEM, asterisks mark significant differences (p < 0.05). A, PPC-M1PA+5ms resulted in a decrease ERcoh between C3 and central electrodes and a concurrent increase in coherence between C3 and P3. The change in ERcoh was significant for the beta band. B, PPC-M1PA−5ms resulted in a decreased ERcoh between C3 and Cz and a concurrent increase in coherence between C3 and P3. The change in ERcoh was significant for the alpha band. C, PPC-M1AP+5ms resulted in a decreased ERcoh between C3 and Cz and a concurrent increase in coherence between C3 and P3. The change in ERcoh was significant for the alpha band.