Isometric Agonist And Antagonist Muscle Activation Interacts Differently With 140-Hz Transcranial Alternating Current Stimulation Aftereffects At Different Intensities

During transcranial electric stimulation, increasing intracellular Ca2+ levels beyond those needed for inducing long term potentiation (LTP) may collapse aftereffects. State-dependent plastic aftereffects are reduced when applied during muscle activation as compared with rest. Cortical surround inhibition by antagonistic muscle activation inhibits the center-innervated agonist. The objective of this study is to determine the interaction of state dependency of transcranial alternating current stimulation (tACS) aftereffects at rest and under activation of agonist and antagonist muscles during stimulation with different intensities. In 13 healthy participants, we measured motor-evoked potential (MEP) amplitudes before and after applying tACS at 140 Hz over the motor cortex in nine single-blinded sessions using sham, 1 mA, and 2 mA stimulation intensities during rest and activation of agonist and antagonist muscles. During rest, only 1 mA tACS produced a significant MEP increase, whereas the 2 mA stimulation produced no significant MEP size shift. During agonist activation 1 mA did not induce MEP changes; after 2 mA, first a decrease and later an increase of MEPs were observed. Antagonist activation under sham tACS led to an inhibition, which was restored to baseline by 1 and 2 mA tACS. Increasing stimulation intensity beyond 1mA does not increase excitability, compatible with too strong intracellular Ca2+ increase. Antagonist innervation leads to MEP inhibition, supporting the concept of surround inhibition, which can be overcome by tACS at both intensities. During agonist innervation, a tACS dose-dependent relationship exists. Our results integrate concepts of "leaky membranes" under activation, surround inhibition, intracellular Ca2+ I increase, and their role in the aftereffects of tACS.NEW & NOTEWORTHY Stimulation intensity and activation of center versus surround muscles affect cortical excitability alterations generated by 140-Hz tACS. At rest, excitatory aftereffects were induced by tACS with 1 mA, but not 2 mA stimulation intensity. With agonistic muscle activation, excitability first decreases, and then increases with 2 mA. For antagonist activation, the MEP amplitude reduction observed in the sham condition is counteracted upon by 1 and 2 mA tACS. This reflects the relation of LTP-like aftereffects to Ca2+ concentration alterations.