Thalamic feedback shapes brain responses evoked by cortical stimulation in mice and humans.

Cortical stimulation with single electrical or magnetic pulses is a popular technique in clinical practice and research. However, we still do not understand the extent to which non-cortical circuits contribute to the associated evoked potentials (EPs). Here we optogenetically dissect the underlying circuit in mice, demonstrating that the late component of this EP depends critically on thalamic hyperpolarization and rebound. The magnitude of this late component correlates with the bursting frequency and synchronicity of thalamic neurons, modulated by the subject's behavioral state and by the cortico-thalamic synaptic connectivity profile. A simulation of the thalamo-cortical circuit highlights that both thalamic intrinsic currents as well as cortical GABAergic neurons contribute to this response profile. We find a remarkably similar EP in humans, with a late component similarly modulated by subject's behavioral state. It is therefore likely that the mechanisms underlying these evoked potentials are preserved across different species and stimulation modalities.