Common framework for virtual lesion and state-dependent TMS: the facilitatory/suppressive range model of online TMS effects on behavior

The behavioral effects of Transcranial Magnetic Stimulation (TMS) are often nonlinear; factors such as stimulation intensity and brain state can modulate the impact of TMS on observable behavior in qualitatively different manner. Here we propose a theoretical framework to account for these effects. In this model, there are distinct intensity ranges for facilitatory and suppressive effects of TMS: low intensities facilitate neural activity and behavior whereas high intensities induce suppression. The key feature of the model is that these ranges are shifted by changes in neural excitability: consequently, a TMS intensity, which normally induces suppression, can have a facilitatory effect if the stimulated neurons are being inhibited. For example, adaptation reduces excitability of adapted neurons; the outcome is that TMS intensities which inhibit non-adapted neurons induce a facilitation on adapted neural representations, leading to reversal of adaptation effects. In conventional virtual lesion paradigms, similar effects occur because neurons not tuned to the target stimulus are inhibited. The resulting reduction in excitability can turn high intensity inhibitory TMS to low intensity facilitatory TMS for these neurons (whereas neurons tuned to the target stimulus are inhibited), leading to a reduction in signal-to-noise ratio. Thus differential excitability levels of neural populations contributing to behavior, combined with nonlinear neural effects, can explain how TMS modulates behavior.