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 by ongoing task-related processes or preconditioning. 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 involved in task-related processes are inhibited by the ongoing task. The resulting reduction in excitability can turn high intensity "inhibitory" TMS to low intensity "facilitatory" TMS for these neurons, and as task-related neuronal representations are in the inhibitory range, the outcome is a reduction in signal-to-noise ratio and behavioral impairment.
