Plasticity of interhemispheric motor cortex connectivity induced by brain state-dependent cortico-cortical paired-associative stimulation

Transcallosal connectivity between the hand areas of the two primary motor cortices (M1) is important for coordination of unimanual and bimanual hand motor function. Effective connectivity of this M1-M1 pathway can be tested in the form of short-interval interhemispheric inhibition (SIHI) using dual-coil transcranial magnetic stimulation (TMS). Recently, we and others have demonstrated that the phase of the ongoing sensorimotor {micro}-rhythm has significant impact on corticospinal excitability as measured by motor evoked potential (MEP) amplitude, and repetitive TMS of the high-excitability state (trough of the {micro}-rhythm) but not other states resulted in long-term potentiation-like MEP increase. Here, we tested to what extent the phase of the ongoing {micro}-rhythm in the two M1 cortices affects long-term change in SIHI. In healthy subjects we applied cortico-cortical paired associative stimulation (ccPAS) in four different {micro}-phase conditions in the left conditioning M1 and right test M1 (trough-trough, trough-positive peak, positive peak-trough, random phase). We found long-term strengthening of SIHI but no differential effect of phase conditions. Findings point to a distinct regulation of plasticity of corticospinal vs. M1-M1 connectivity. The observed ccPAS-induced strengthening of effective M1-M1 connectivity (SIHI) may be utilized for therapeutic applications that potentially benefit from modification of interhemispheric excitation/inhibition balance.