Time course of functional connectivity between dorsal premotor and contralateral motor cortex during movement selection

Abstract

The left dorsal premotor cortex (PMd) is thought to play a dominant role in the selection of movements made by either hand. We used transcranial magnetic stimulation to study the functional connectivity of the left PMd and right primary motor cortex (M1) during an acoustic choice reaction time (RT) task involving contraction of the thumb and forefinger. The facilitatory and inhibitory pathways that can be demonstrated between left PMd and right M1 at rest were suppressed during most of the reaction period. However, they were activated briefly at the start of the reaction period, depending on whether the cue indicated that the forthcoming movement had to be made with the left or the right hand. The facilitatory pathway was active at 75 ms in those trials in which the subjects were required to move the left hand, whereas the inhibitory pathway was active at 100 ms in trials in which the subjects had to move the right hand. These changes in excitability did not occur in hand muscles not used in the task. There were no significant changes in the excitability of intracortical circuits [short intracortical inhibition (SICI) and intracortical facilitation (ICF)] in the right M1. Interhemispheric interactions between the right PMd and left M1 were mainly inhibitory at rest and showed the same temporal profile of interhemispheric inhibition as for left PMd-right M1, although no evidence was found for facilitatory interactions. The results illustrate the importance of PMd not only in facilitating cued movements but also in suppressing movements that have been prepared but are not used.

Figure 1.

Schematic representation of the experimental procedure. A, Subjects were required to activate the right or left FDI muscle as quickly as possible, performing a rapid isometric contraction of either hand as soon they heard a cue sound. Each trial began with an auditory warning. The reaction signal was given randomly 1–3 s later and consisted of either a high- or low-frequency tone pulse that indicated which hand to contract according to the instructions given to the subjects. The intertrial interval was 6 s. At the start of each block of trials the high and low tones were assigned randomly to indicate that the subjects had to react with the right or left hand (choice RT). TMS was delivered over the left or right M1 at different delays (50, 75, 100, 125, 150, 200 ms) after the cue sound (TS). The intensity of the TS was adjusted to evoke an MEP of ∼1 mV peak to peak in the relaxed left FDI. In one-half of the trials the M1 TMS was preceded by a CS delivered 8 ms earlier over the contralateral PMd (B). At rest the CS over the left PMd at 80% AMT increased the MEPs evoked from the right M1 by 28% (C), whereas if the intensity of the CS was increased to 110% RMT, then the MEPs were reduced in amplitude by 22% (D). Conditioning the right PMd at 80% AMT had no effect on MEPs from the left M1 (E). However, conditioning stimuli at 110% RMT led to a decrease by 18% in MEPs from the left M1 (F). Asterisks indicate significance at p < 0.05 (paired t test). Error bars indicate SEM.

Figure 2.

Time course of the excitability of the right motor cortex at different delays from the acoustic cue during the choice RT task. Unconditioned mean MEP amplitudes from the left FDI were obtained in all sessions. Motor cortex excitability changed, depending on which hand was selected for movement. A significant difference among sides emerged at later delays of 150 and 200 ms, with an opposite trend toward increase for the left hand and toward reduction for the right hand. Asterisks indicate a significant value at paired t test; p < 0.05. Error bars indicate SEM.

Figure 3.

Effects of low-intensity (80% AMT) left PMd conditioning on contralateral M1 excitability at different delays after the cue signal. A, B, MEP amplitudes recorded from the left FDI during either condition (single TMS or ppTMS) at different time points at which the left (A) or the right (B) hand was selected for movement. C, Mean percentage values of the change on MEP amplitudes during left PMd conditioning. Significant transcallosal facilitation was observed only at 75 ms when the left hand was to move. Asterisks indicate a significant value at paired t test; p < 0.05. Error bars indicate SEM.

Figure 4.

Effects of high-intensity (110% AMT) left PMd conditioning on contralateral M1 excitability at different delays after the cue signal. A, B, MEP amplitudes recorded from the left FDI during either condition (single TMS or ppTMS) at different time points at which the left (A) or the right (B) hand was selected for movement. C, Mean percentage values of the change on MEP amplitudes during left PMd conditioning. Significant transcallosal inhibition was observed only at 100 ms when the right hand was to move. Asterisks indicate a significant value at paired t test; p < 0.05. Error bars indicate SEM.

Figure 5.

Mean RTs in different experimental conditions. No significant effect was induced by PMd conditioning. A, B, Values for high-intensity stimulation (110% RMT) when the left (A) or the right (B) hand was selected for movement. C, D, Mean RT for low-intensity (80% AMT) PMd conditioning in which the left (C) or the right (D) hand had to move. Open circles indicate values obtained during the right M1 stimulation and filled circles during the paired PMd–M1 TMS. Error bars indicate SEM.

Figure 6.

Mean percentage values of the change on MEP amplitudes for SICI at 3 ms ISI (A) and ICF at 10 ms ISI (B) obtained in experiment 2 with ppTMS of the right M1. Strong inhibition and facilitation were found, although no difference across time and sides emerged. Black bars indicate an instruction to move right; gray bars indicate an instruction to move left. Error bars indicate SEM.

Figure 7.

Effects of interhemispheric projections on the excitability of left FDI and ADM hand muscles recorded at critical points of 75 ms after the cue sound with a low CS intensity (80% AMT) in which the left hand is selected (A) and at 100 ms delay with a high CS intensity (110% RMT) in which the right hand is chosen for movement (B). In both conditions the effects are observable only for FDI, but not for ADM. Asterisks indicate a significant value at post hoc analysis; p < 0.05. Error bars indicate SEM.

Figure 8.

Effects of low-intensity (80% AMT) right PMd conditioning on contralateral M1 excitability at different delays after the cue signal. A, B, MEP amplitudes recorded from the right FDI during either condition (single TMS or ppTMS) at different time points at which the left (A) or the right (B) hand was selected for movement. C, Mean percentage values of the change on MEP amplitudes during right PMd conditioning. No significant effect was observed during the task. Error bars indicate SEM.

Figure 9.

Effects of high-intensity (110% AMT) right PMd conditioning on contralateral M1 excitability at different delays after the cue signal. A, B, MEP amplitudes recorded from the right FDI during either condition (single TMS or ppTMS) at different time points at which the left (A) or the right (B) hand was selected for movement. C, Mean percentage values of the change on MEP amplitudes during right PMd conditioning. Significant transcallosal inhibition was observed only at 100 ms when the left hand was to move. Asterisks indicate a significant value at paired t test; p < 0.05. Error bars indicate SEM.