Callosal anatomical and effective connectivity between primary motor cortices predicts visually cued bimanual temporal coordination performance

Default in-phase coupling of hand movements needs to be suppressed when temporal coordination is required for out-of-phase bimanual movements. There is lack of knowledge on how the brain overrides these default in-phase movements to enable a required interval of activity between hands. We used a visually cued bimanual temporal coordination (vc-BTC) paradigm with a constant rhythmical time base of 1 s, to test the accuracy of in-phase and out-of-phase (0.1, 0.2,…,0.9) finger tapping. We hypothesized that (1) stronger anatomical and effective interhemispheric connectivity between the hand areas of the primary motor cortex (M1_HAND) predict higher temporal offsets between hands in the out-of-phase conditions of the vc-BTC; (2) patients with relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) have reduced interhemispheric connectivity and altered between-hand coupling. Anatomical connectivity was determined by fractional anisotropy of callosal hand motor fibers (FA-hCMF). Effective connectivity was probed by short interval interhemispheric inhibition (S-IHI) using paired-coil transcranial magnetic stimulation (TMS). In healthy subjects, higher FA-hCMF and S-IHI correlated with higher temporal offsets between hands in the out-of-phase conditions of the tapping test. FA-hCMF was reduced in patients with RRMS but not in CIS, while S-IHI was reduced in both patient groups. These abnormalities were associated with smaller temporal offsets between hands leading to less deviation from the required phasing in the out-of-phase tapping conditions. Findings provide multiple levels of evidence that callosal anatomical and effective connectivity between the hand areas of the motor cortices play important roles in visually cued bimanual temporal coordination performance.