Modulation of preparatory volitional motor cortical activity by paired associative transcranial magnetic stimulation

Abstract

Paired associative transcranial magnetic stimulation (PAS) has been shown to induce long-term potentiation (LTP)-like or long-term depression (LTD)-like change in excitability of human primary motor cortex (M1), as probed by motor evoked potential (MEP) amplitude. In contrast, little is known about PAS effects on volitional motor cortical activity. In 10 healthy subjects, movement related cortical potentials (MRCP) were recorded to index volitional motor cortical activity during preparation of simple thumb abduction (prime mover: abductor pollicis brevis, APB) or wrist extension movements (prime mover: extensor carpi radialis, ECR). PAS(LTP) increased, PAS(LTD) decreased, and PAS(control) did not change MEP(APB), while MEP(ECR), not targeted by PAS, remained unchanged in all PAS conditions. PAS(LTP) decreased MRCP negativity during the late Bereitschaftspotential (-500 to 0 ms before movement onset), only in the APB task, and predominantly over central scalp electrodes contralateral to the thumb movements. This effect correlated negatively with the PAS(LTP) induced increase in MEP(APB). PAS(LTD) and PAS(control) did not affect MRCP amplitude. Findings indicate a specific interference of PAS with preparatory volitional motor cortical activity, suggestive of a net result caused by increased M1 excitability and disrupted effective connectivity between premotor areas and M1.

Figure 1

Experimental design and time line of MRCP and MEP measurements before and after one of three different paired associative stimulation protocols (PAS_LTP, PAS_LTD, PAS_control). For details, see Methods section.

Figure 2

MEP amplitudes (in mV) pre‐PAS (light gray columns) vs. post‐PAS (dark gray columns, mean ± S.E.M) in the APB (left diagram) and ECR (right diagram). MEP amplitudes in the APB increased after PAS_LTP and decreased after PAS_LTD (*P < 0.05; **P < 0.01) while there were no changes in MEP amplitude in the ECR.

Figure 3

Superimposition of the grand average (n = 10 subjects) MRCP waveforms (in μV) recorded from the C1 electrode for the APB task (upper row) and the ECR task (lower row) before (black curves) and after (red curves) PAS_LTP (left column), or PAS_LTD (middle column), or PAS_control (right column). Vertical dotted lines mark the onset of the voluntary EMG burst in the task muscle. Note the reduction of the MRCP negativity specifically after PAS_LTP in the APB task, but no MRCP change after PAS_LTD or PAS_control or in the ECR task. In addition, the averaged rectified EMG from right and left APB (RAPB, LAPB) and ECR (RECR, LECR) are shown. Calibrations, 1000 ms and 200 μV.

Figure 4

Current source density map of the PAS induced MRCP voltage change (difference of post‐PAS minus pre‐PAS). Left part of the diagram: early BP; right part of the diagram: late BP; upper row: APB task; lower row: ECR task. A PAS effect was noted only after PAS_LTP, only for the late BP (reduction of BP negativity) and only in the APB task. This effect was localized over the central scalp area, predominantly in the left hemisphere. Those electrodes with a statistically significant PAS_LTP effect are indicated by blue dots (CZA, C1, and C1P).

Figure 5

Linear regression analyses between PAS_LTP induced late BP change in the APB task (dependent variable, y‐axis, in μV) and PAS_LTP induced MEP change in the APB (independent variable, x‐axis, in mV) at those electrodes that showed a significant PAS_LTP effect on the late BP amplitude (cf. Fig. 4). A significant negative correlation was found at the C1 electrode (r = −0.73, P = 0.016).