Changes in corticospinal excitability and the direction of evoked movements during motor preparation: a TMS study

Abstract

Background: Preparation of the direction of a forthcoming movement has a particularly strong influence on both reaction times and neuronal activity in the primate motor cortex. Here, we aimed to find direct neurophysiologic evidence for the preparation of movement direction in humans. We used single-pulse transcranial magnetic stimulation (TMS) to evoke isolated thumb-movements, of which the direction can be modulated experimentally, for example by training or by motor tasks. Sixteen healthy subjects performed brisk concentric voluntary thumb movements during a reaction time task in which the required movement direction was precued. We assessed whether preparation for the thumb movement lead to changes in the direction of TMS-evoked movements and to changes in amplitudes of motor-evoked potentials (MEPs) from the hand muscles.

Results: When the required movement direction was precued early in the preparatory interval, reaction times were 50 ms faster than when precued at the end of the preparatory interval. Over time, the direction of the TMS-evoked thumb movements became increasingly variable, but it did not turn towards the precued direction. MEPs from the thumb muscle (agonist) were differentially modulated by the direction of the precue, but only in the late phase of the preparatory interval and thereafter. MEPs from the index finger muscle did not depend on the precued direction and progressively decreased during the preparatory interval.

Conclusion: Our data show that the human corticospinal movement representation undergoes progressive changes during motor preparation. These changes are accompanied by inhibitory changes in corticospinal excitability, which are muscle specific and depend on the prepared movement direction. This inhibition might indicate a corticospinal braking mechanism that counteracts any preparatory motor activation.

Figure 1

Schematic representation of the events in a go trial with an early precue. In each trial a warning signal and a response signal were presented. The precue was presented at either 600 ms (early precue) or 100 ms (late precue) before the response signal. A response was required in go trials only (green coloured response signal; 80% probability). In a random 280 (~78%) of the 360 early-precue trials, TMS was applied at either 900, 300, or 100 ms before, or 250 ms after the response signal. A trial can be divided into three epochs. The epoch before the precue is termed the baseline interval; the epoch between precue and response signal is termed the preparatory interval; the epoch after the response signal is termed the response interval. These epochs are marked using shades of grey, also in the following figures.

Figure 2

Example acceleration vectors of voluntary thumb movements. First-peak acceleration vectors from early-precue trials without TMS. Data from one subject. The plot shows that each of the five precues induced a thumb movement in a different direction, with little overlap between movements in response to different precues.

Figure 3

Muscle activity during voluntary thumb movements. Mean (± SE) root-mean-square amplitude across subjects (N= 16) of the EMG activity during the initial 150 ms of the voluntary response, for each of the five precues and each of the three EMG channels.

Figure 4

Reaction time. Mean (± SE) reaction time (RT) across subjects (N = 16), as a function of precue onset and stimulation time. The RT difference between the late- and the early-precue condition strongly suggests that at least parts of the thumb movement were programmed before the response signal occurred. The early-precue trials without TMS were also compared to early-precue trials with TMS. The post-hoc comparisons showed that TMS reduced the reaction times even further, and that this reduction was stronger the earlier the TMS pulse was applied. **p < 0.01.

Figure 5

Example acceleration vectors of TMS-evoked movements. First-peak acceleration vectors of TMS-evoked movements of one of the subjects at the four stimulation times, for all precues combined. Black lines show acceleration vectors (magnitude-direction) of individual movements. The thick red line depicts the average angle of movements evoked during the baseline interval (-900 ms). This angle was used to define the baseline zone (± 30°), which is marked in light red. Baseline, preparatory, and response intervals are marked by light, medium, or dark grey background, respectively (see Figure 1). The plots show a decrease in the proportion of TMS-evoked movements that fell into the baseline zone, at the end of the preparatory interval. This proportion further decreased during the response interval.

Figure 6

TMS-evoked movements. Mean proportion (± SE) of TMS-evoked movements as a function of time that fell (A) outside the ± 30° zone around the baseline direction, or (B) inside the ± 30° zone around the precue. Baseline, preparatory, and response intervals are marked by light, medium, or dark grey background, respectively (see Figure 1). Compared to the baseline interval, increasingly more TMS-evoked movements fell outside the baseline zone. Thus, the angles of the TMS-evoked movements were modulated over time, indicating changes in the thumb movement cortical representation. However, there was no increase in the number of TMS-evoked movements that fell into the ± 30° zone around the precued direction. *p < 0.05, **p < 0.01.

Figure 7

Motor-evoked potentials. Mean (± SE) normalised motor-evoked potential (MEP) amplitudes (N = 16) as a function of time and precued direction, for the abductor pollicis brevis (A), first dorsal interosseus (B), and flexor carpi radialis (C) of the moving hand. Baseline, preparatory, and response intervals are marked by light, medium, or dark grey background, respectively (see Figure 1). In (A) the stars denote the significance level of omnibus F-test (one-way ANOVA), the corresponding post-hoc comparisons are specified in Table 1. In (B) the stars denote the significance levels of post-hoc comparisons. *p < 0.05, **p < 0.01, and ***p < 0.001. The MEP amplitudes in the APB and the FDI were significantly modulated during the preparatory and the response interval. For the APB, there was a significant effect of the precued direction at -100 ms and 250 ms (see Table 1). The MEPs of the FDI were not differentially modulated by the precue, but generally decreased over time. The MEP amplitudes in the FCR did not change significantly.

Figure 8

Experimental setup. The right arm was fixed with Velcro straps. Thumb movements were measured by two miniature uni-axial accelerometers that were mounted on the proximal phalanx of the thumb, in orthogonal planes. Electromyographic activity from the thumb muscle (abductor pollicis brevis), index finger muscle (first dorsal interosseus), and wrist muscle (flexor carpi radialis; not visible on photo) was recorded using adhesive Ag/AgCl surface electrodes.

Figure 9

Example EMG and accelerometer traces. Example traces of responses to TMS, from two of the subjects. Of each of the two subjects, six arbitrary TMS-trials were selected and the EMG and accelerometer signals recorded in those trials are plotted. The upper six sets are EMG traces; the lower four sets are accelerometer traces. The vertical lines mark the time when the TMS pulse was applied.