Hemispheric asymmetries of premotor and primary motor cortex in motor control as revealed by "virtual lesion" TMS

It is generally known that the cortical motor system of each hemisphere controls the movements executed with the contralateral body side, such that left motor areas control the right body side, while the right motor areas control the left body side. Interestingly, the primary motor cortex (M1) seems to be also activated when movements are executed with the ipsilateral hand. In this doctoral project, we have used several transcranial magnetic stimulation (TMS) paradigms to investigate which potential mechanisms underlie this ipsilateral facilitation of motor areas. Our first study showed that the cortical excitability in M1 increased when the ipsilateral hand performed rhythmical flexion-extension movements. This facilitation increased further when movements were performed in the context of a complex coordination task requiring that wrist and ankle were moved rhythmically into opposite directions. Furthermore, the facilitation revealed a hemispheric asymmetry, such that more facilitation was seen in the left M1 when the left body side was activated than in the right M1 when a movement was executed with the right body side. We corroborated these findings with our second study using a virtual lesion approach . This TMS technique allows to test a causal relationship of a specific cortical area and a specific behavior. Subjects had to produce an unimanual tapping task while disruptive TMS was applied to the ipsilateral M1. In right handed subjects, more disruptions of the tapping task were observed when left than when right M1 was stimulated, showing that particularly the left ipsilateral M1 is involved in unimanual digit control. However, in left handed subjects we observed two subgroups, such that half of the left handed subjects exhibited more disruptions when the ipsilateral left hemisphere was stimulated while the other half showed more disruptions when the ipsilateral right hemisphere was stimulated. Overall, we showed that the important role of the ipsilateral M1 in unimanual movements is influenced by handedness as well as (left) hemispheric specialization.The potential mechanisms underlying the functional lateralization of the ipsilateral M1 can emerge at different levels of the nervous system. Hemispheric asymmetries of the ipsilateral M1 could either reflect asymmetries in direct uncrossed corticospinal fibers or in transcallosal pathways suggesting that the left M1 has a stronger influence on the right M1 than vice versa. We tried to directly test the second hypothesis, but found no support for the notion that hemispheric asymmetries arise predominantly via transcallosal pathways. Based on our results, we speculate that hemispheric asymmetries might arise from areas upstream from M1, such as the premotor cortex. To test this hypothesis, we explored asymmetries of the premotor involvement in coordination movements using a virtual lesion approach. In our third study we tested lateralization of the dorsal premotor cortex (PMd) during bimanual movements, and found more disruptions of a complex bimanual coordination patternwhen the right PMd than when the left PMd was stimulated. Moreover, this asymmetry was influenced by handedness, as left handed subjects were more frequently disrupted when the non-dominant left PMd was stimulated. In the last study, we applied TMS in a virtual lesion approach over the ventral (PMv) and dorsal (PMd) premotor cortex while right-handed subjects performed either a bimanual coordination task or unimanual movement with the hand ipsilateral to the stimulated hemisphere. We found that particularly the PMv exhibited hemispheric asymmetries in ipsilateral unimanual movements, such that the left PMv was stronger involved in the control of movements executed with the left hand than the right PMv in right handed movements. Moreover, this asymmetry was not seen in the PMd, although we demonstrated the same lateralization as in the 3rd study (i.e. more disruptions when right than when left PMd was stimulated). Overall, we suggest that the left PMv primarily influences the ipsilateral M1 to control movements of the ipsilateral left hand, while the right PMd primarily regulates the transcallosal effects on the non-dominant right M1 to prevent unwanted mirror movements.In summary, the present PhD thesis provides novel insights into the role of the hemisphere ipsilateral to the moving hand. We have demonstrated that the involvement of the ipsilateral motor areas exhibits hemispheric asymmetries which depend on the task that is executed, the investigated motor area and the subject s handedness.status: publishe