Comparison of the two cerebral hemispheres in inhibitory processes operative during movement preparation

Abstract

Neuroimaging and neuropsychological studies suggest that in right-handed individuals, the left hemisphere plays a dominant role in praxis, relative to the right hemisphere. However hemispheric asymmetries assessed with transcranial magnetic stimulation (TMS) has not shown consistent differences in corticospinal (CS) excitability of the two hemispheres during movements. In the current study, we systematically explored hemispheric asymmetries in inhibitory processes that are manifest during movement preparation and initiation. Single-pulse TMS was applied over the left or right primary motor cortex (M1LEFT and M1RIGHT, respectively) to elicit motor-evoked potentials (MEPs) in the contralateral hand while participants performed a two-choice reaction time task requiring a cued movement of the left or right index finger. In Experiments 1 and 2, TMS probes were obtained during a delay period following the presentation of the preparatory cue that provided partial or full information about the required response. MEPs were suppressed relative to baseline regardless of whether they were elicited in a cued or uncued hand. Importantly, the magnitude of these inhibitory changes in CS excitability was similar when TMS was applied over M1LEFT or M1RIGHT, irrespective of the amount of information carried by the preparatory cue. In Experiment 3, there was no preparatory cue and TMS was applied at various time points after the imperative signal. When CS excitability was probed in the cued effector, MEPs were initially inhibited and then rose across the reaction time interval. This function was similar for M1LEFT and M1RIGHT TMS. When CS excitability was probed in the uncued effector, MEPs remained inhibited throughout the RT interval. However, MEPs in right FDI became more inhibited during selection and initiation of a left hand movement, whereas MEPs in left FDI remained relatively invariant across RT interval for the right hand. In addition to these task-specific effects, there was a global difference in CS excitability across experiments between the two hemispheres. When the intensity of stimulation was set to 115% of the resting threshold, MEPs were larger when the TMS probe was applied over the M1LEFT than over M1RIGHT. In summary, while the latter result suggests that M1LEFT is more excitable than M1RIGHT, the recruitment of preparatory inhibitory mechanisms is similar within the two cerebral hemispheres.

Keywords: Competition; Corticospinal excitability; Decision making; Hemisphere; Inhibition; Intermanual; Response selection; Transcranial magnetic stimulation.

Fig. 1

A: Trial types and sequence of events in Experiment 1. A partially informative preparatory cue (“x” or “o”) indicated the hand required for the forthcoming response (left or right respectively), with the actual response (index or pinky) specified by the imperative signal (“<” or “>”). B: Sequence and TMS stimulation timings. Each trial started with the brief presentation (100 ms) of a fixation cross. After a blank screen of 500 ms, the preparatory cue was presented for 100 ms. After a second blank screen of 500 ms, the imperative signal appeared (100 ms). A single TMS pulse was applied over primary motor cortex (M1), during one of two epochs (TMS_BASELINE, TMS_DELAY), with the side of stimulation varied between blocks. C: Intensity of stimulation (% of maximum stimulator output) to elicit motor evoked potentials (MEPs) following right (M1_RIGHT; orange histograms) and left (M1_LEFT; blue histograms) hemisphere in the TMS_115% group (TMS intensity set at 115% of rMT; upper traces) and the TMS_{1 mV} group (TMS intensity set to elicit 1 mV MEPs; lower traces, see “Method” section). rMT = rest Motor Threshold. FDI = First Dorsal Interosseous.

Fig. 2

Intensity of stimulation in Experiment 2 (% of maximum stimulator output) to elicit motor evoked potentials (MEPs) following right (M1_RIGHT; orange histograms) and left (M1_LEFT; blue histograms) hemisphere in the Partially informative session and the Fully informative session (see “Methods” section). rMT = rest Motor Threshold. FDI = First Dorsal Interosseous.

Fig. 3

A: Trial types and sequence of events in Experiment 3. Participants were asked to press a button with the right or left index finger according to the color (blue or red) of an imperative signal. This latter was displayed until a response was performed or for a maximum of 500 ms, followed by visual feedback (1000 ms), indicating a correct (positive score) or incorrect (negative score) response. Positive scores were displayed in green and were proportional to the participants RT (k/RT⁵); negative scores were displayed in red and were always equal to −10. B: Sequence and TMS stimulation timings. Bilateral TMS pulses were applied concurrently over the left and right M1 at one of six possible timings (TMS_BASELINE, TMS_IMP+ timings). C: Amplitude of MEPs elicited by the bilateral TMS pulses at rest. Right and left M1 were stimulated with a 1 ms delay between the pulses to avoid interference between the currents generated in the two coils. The order of the pulses was counterbalanced between participants. Histograms illustrate M1_LEFT (elicited following left M1 stimulation) and M1_RIGHT (elicited following right M1 stimulation) amplitudes (mV) when they were elicited by the first pulse (lighter color) or by the second pulse (darker color). D: Intensity of stimulation (% of maximum stimulator output) to elicit motor evoked potentials (MEPs) following right (M1_RIGHT; orange histograms) and left (M1_LEFT; blue histograms) hemisphere. rMT = rest Motor Threshold. FDI = First Dorsal Interosseous. TMS = Transcranial Magnetic Stimulation. MEP = Motor Evoked Potential.

Fig. 4

Two small coils were used in Experiment 3 (70 mm refers to the outer circle of the butterfly-coil: internal wing diameter = 35 mm). Such coils can be positioned simultaneously on the subjects head without having to choose suboptimal coil positions or to make major adaptations to their orientation. The hotspot was defined for each hemisphere and corresponded to the location at which the coil was at the best position and orientation to elicit the largest MEP amplitude in the contralateral first dorsal interosseous (FDI) muscle.

Fig. 5

RTs for left (light bars) and right hands (dark bars) in the three experiments. A, B: Index finger responses were faster than pinky responses in Experiments 1 & 2. In Experiment 2, RTs were faster when the cue was fully informative compared to when it was partially informative. C: In Experiment 3, button-press occurred approximately 150 ms after EMG RTs. * = significantly different (p-value < 0.05). EMG = electromyographic. RT = reaction time.

Fig. 6

MEP amplitudes following right (M1_RIGHT) and left hemisphere stimulation (M1_LEFT) recorded at TMS_DELAY in the TMS_115% (Panel A, n = 12) or the TMS_{1 mV} (Panel B, n = 12) groups of Experiment 1. MEPs are shown in mV (left panel) and expressed as a percent change with respect to MEPs elicited at TMS_BASELINE (right panel). * = significantly different (p-value < 0.05). MEP suppression at TMS_DELAY was more pronounced in a selected muscle (TMS_DELAY-SEL) than in a non-selected muscle (TMS_DELAY-NSEL). No differences were found between M1_RIGHT and M1_LEFT conditions. ¥ = significantly different (p-value < 0.05) from MEPs elicited at TMS_BASELINE.

Fig. 7

MEP amplitudes following right (M1_RIGHT) and left hemisphere (M1_LEFT) stimulation at TMS_DELAY. MEPs are shown in mV (left side) and expressed as a percent change with respect to MEPs elicited at TMS_BASELINE (right side). * = significantly different (p-value < 0.05). MEP suppression at TMS_DELAY was more pronounced in a selected muscle (TMS_DELAY-SEL) than in a non-selected muscle (TMS_DELAY-NSEL). No differences were found between M1_RIGHT and M1_LEFT conditions. ¥ = significantly different (p-value < 0.05) from MEPs elicited at TMS_BASELINE.

Fig. 8

MEP amplitudes in Experiment 3. A: Evolution of MEPs elicited from a selected (MEP_PREP-SEL) or non-selected (MEP_PREP-NSEL) hand at TMS_BASELINE and in pre-movement windows (TMS_PREP-EARLY, TMS_PREP-LATE). MEPs are suppressed at TMS_PREP-175. At TMS_PREP-LATE, excitability increased in the selected hand but remains suppressed in the non-selected hand. B: MEP amplitudes following M1_RIGHT (filled dots) and M1_LEFT stimulation (empty dots) for the different TMS epochs (see Methods section) in the selected (left) and non-selected hands (right). Note the absence of a HEMISPHERE effect for the selected hand_SEL. For the non-selected hand, inhibition in the left hand was relatively constant (M1_RIGHT stimulation), but showed a non-monotonic profile in the right hand (M1_LEFT stimulation). * and + = significantly different (p-value < 0.05). ¥ = significantly different (p-value < 0.05) from MEPs elicited at TMS_BASELINE.