There is a several decade history demonstrating that electrical polarization of neurons can modulate neuronal firing, and that such polarization can suppress (or excite) spiking activity and seizures. In recent years, we uncovered a unification in the computational biophysics of spikes, seizures, and spreading depression (Wei et al J Neurosci 34:11733-11743, 2014). These findings demonstrated that the repertoire of the dynamics of the neuronal membrane encompasses a broad range of dynamics ranging from normal to pathological, and that seizures and spreading depression are manifestations of the inherent properties of those membranes. More recently, we have demonstrated that neuronal polarization can suppress (or enhance), block, or prevent spreading depression, the physiological underpinning of migraine auras and a pathological sequelae following traumatic brain injury or hemorrhage (Whalen et al Scientific Reports, 8: 8769, 2018). Remarkably, this suppression requires qualitatively different stimulation from that required to suppress spikes and seizures, and is fully consistent with the computational biophysical models of spreading depression. Further unexpected findings from these experiments were that suppression of spreading depression does not generate seizures, and vice versa, that when the brain is in seizure activity suppression does not generate spreading depression. Most recently, we have experimentally verified that trajectories of seizures and spreading depression as predicted from unification can be verified in several animal models of epilepsy (Bahari et al BioRxiv 455519, 2018). As the case for unification becomes progressively stronger, a key implication is that we need to consider state-dependent control for pathological brain states.