Dissociation of the pathways mediating ipsilateral and contralateral motor-evoked potentials in human hand and arm muscles

Abstract

1. Growing evidence points toward involvement of the human motor cortex in the control of the ipsilateral hand. We used focal transcranial magnetic stimulation (TMS) to examine the pathways of these ipsilateral motor effects. 2. Ipsilateral motor-evoked potentials (MEPs) were obtained in hand and arm muscles of all 10 healthy adult subjects tested. They occurred in the finger and wrist extensors and the biceps, but no response or inhibitory responses were observed in the opponens pollicis, finger and wrist flexors and the triceps. 3. The production of ipsilateral MEPs required contraction of the target muscle. The threshold TMS intensity for ipsilateral MEPs was on average 1.8 times higher, and the onset was 5.7 ms later (in the wrist extensor muscles) compared with size-matched contralateral MEPs. 4. The corticofugal pathways of ipsilateral and contralateral MEPs could be dissociated through differences in cortical map location and preferred stimulating current direction. 5. Both ipsi- and contralateral MEPs in the wrist extensors increased with lateral head rotation toward, and decreased with head rotation away from, the side of the TMS, suggesting a privileged input of the asymmetrical tonic neck reflex to the pathway of the ipsilateral MEP. 6. Large ipsilateral MEPs were obtained in a patient with complete agenesis of the corpus callosum. 7. The dissociation of the pathways for ipsilateral and contralateral MEPs indicates that corticofugal motor fibres other than the fast-conducting crossed corticomotoneuronal system can be activated by TMS. Our data suggest an ipsilateral oligosynaptic pathway, such as a corticoreticulospinal or a corticopropriospinal projection as the route for the ipsilateral MEP. Other pathways, such as branching of corticomotoneuronal axons, a transcallosal projection or a slow-conducting monosynaptic ipsilateral pathway are very unlikely or can be excluded.

Figure 7. Magnetic resonance imaging (MRI) scans and ipsilateral and contralateral MEPs of one patient with complete agenesis of the corpus callosum

A, T1-weighted mid-sagittal (left) and proton density-weighted axial MRI (right) of the patient with agenesis of the corpus callosum and septum pellucidum cyst. The anterior commissure is preserved. B, in this patient, large ipsilateral MEPs (top traces) and normal contralateral MEPs (bottom traces) were elicited in the contracting FDI by focal TMS of the left (left panels) and right motor cortex (right panels). The delay in onset latency between the ipsilateral and contralateral MEP of 9.6 ms on both sides was within the normal range.

Figure 5. Preferred current direction for ipsilateral and contralateral MEPs in the FDI

A, polar plot of ipsilateral (grey) and contralateral (black) MEPs in 1 subject. The angles around the perimeter indicate the direction of the current induced in the left hemisphere. Ipsilateral and contralateral MEP sizes are normalized to the maximum ipsilateral or contralateral MEP (= 1), respectively. Pairs of contralateral (top) and ipsilateral MEP recordings (bottom) are displayed around the polar plot at the positions corresponding to current direction. All traces are averages of 20 trials. The EMG recordings for the ipsilateral MEP are full-wave rectified. Note that the preferred direction for activation of the contralateral MEP in this subject was approximately orthogonal to the line of the central sulcus, while it was in parallel for the ipsilateral MEP. B, preferred direction of current induced in the left motor cortex for activation of contralateral MEPs (dotted line) and ipsilateral MEPs (arrows) in all 10 subjects tested. The inset illustrates the different current directions in the left hemisphere. Note that the preferred current direction for contralateral MEPs was 45-90 deg in all subjects, while it was different by 45-135 deg in all but 1 subject for the ipsilateral MEPs.

Figure 2. Ipsilateral MEPs in various muscles of the hand and arm

A, single trial rectified and averaged (n = 20) EMG recordings of various muscles ipsilateral to high-intensity TMS of the left motor cortex in 1 representative subject (FDI, first dorsal interosseus; ADM, abductor digiti minimi; OPP, opponens pollicis; EXT, wrist and finger extensors; FLEX, wrist and finger flexors; BB, biceps brachii; TB, triceps brachii). Each muscle was recorded in a separate block of trials while being activated isometrically at 30 % of maximum voluntary contraction. Note that ipsilateral MEPs are clearly visible in the FDI, ADM, EXT and BB, while OPP and FLEX did not show a significant ipsilateral response. The response in the TB was purely inhibitory. The size of the ipsilateral MEPs is given as the area under the EMG curve exceeding the level of the prestimulus EMG. B, frequency distribution of excitatory responses, no responses and inhibitory responses in the different target muscles after TMS of the ipsilateral motor cortex across all 10 subjects tested and C, mean size (+1 s.e.m.) of these responses given as the area under the EMG curve exceeding the level of the prestimulus EMG (μV ms). * Significant difference from zero (P < 0.01).

Figure 1. EMG recordings of ipsilateral MEPs

Ten consecutive EMG recordings of ipsilateral MEPs in the tonically active left FDI of 1 representative subject. TMS was delivered to the left motor cortex at maximum stimulator output. Note the trial-to-trial variability in MEP amplitude and latency.

Figure 3. Effect of the level of contraction on the size of the ipsilateral MEP in the FDI

A, EMG recordings from 1 representative subject at increasing levels of contraction given as the percentage of maximum voluntary contraction on the left. All traces are averages of 20 rectified trials. TMS was given at an intensity of 100 % of maximum stimulator output to the left motor cortex. B, mean (± 1 s.e.m.) size of the ipsilateral MEP in 5 subjects plotted against the level of voluntary contraction. The filled symbols indicate that the distribution of ipsilateral MEPs was significantly different from zero (P < 0.05).

Figure 4. Mapping of ipsilateral and contralateral MEPs in the FDI

Comparison of the centres of gravity (COG) of the maps for the ipsilateral (filled triangles) and the contralateral MEP (□) in 7 subjects (a-g). The grey symbols show the means of the COG across subjects. In four subjects (a-d), the COG of the ipsilateral map was clearly more lateral compared with the contralateral map, while a medial shift was not observed in any of the subjects. The point 0/0 refers to the coil location, which was considered the optimal position for eliciting contralateral MEPs during the experiment.

Figure 6. Effects of lateral head rotation on ipsilateral and contralateral MEPs in wrist extensor muscles

A, EMG recordings of ipsilateral MEPs (top) and size-matched contralateral MEPs (bottom) from the voluntarily activated wrist extensors of 1 representative subject. All traces are single-trial rectified averages of 20 trials. The thin black lines refer to the head straight condition, thick black lines are the head turn toward the target muscle conditions, and grey lines are the head turn away from the target muscle conditions. The arrows and numbers indicate the MEP onset latencies. Intensity of TMS was 100 % of maximum stimulator output for the ipsilateral MEP and 34 % for the contralateral MEP. It was always the left motor cortex that was stimulated. Note that for the ipsilateral MEP, turning the head toward the ipsilateral muscle was associated with a marked increase in MEP amplitude and a decrease in MEP onset latency. In contrast, for the contralateral MEP, turning the head toward the contralateral muscle was associated with a decrease in MEP amplitude but no concomitant change in MEP onset latency (17.5 ms for all 3 directions of the head). B and C, group data (8 subjects) on the effects of head rotation on ipsilateral (▪, recording from left wrist extensors and TMS of left motor cortex) and contralateral MEPs (^, recording from right wrist extensors and TMS of left motor cortex; ▵, recording from left wrist extensors and TMS of right motor cortex). Increments (MEP size) or differences (MEP onset latency) between the head turn conditions (away from or toward the ipsi- or contralateral target muscle) and the head straight condition are displayed. Error bars are ± 1 s.e.m.