The sleeping brain exhibits characteristic slow-wave activity which decays over the course of the night. This decay is thought to result from homeostatic synaptic downscaling. Transcranial electrical stimulation can entrain slow-wave oscillations (SWO) in the human electro-encephalogram (EEG). A computational model of the underlying mechanism predicts that firing rates are predominantly increased during stimulation. Assuming that synaptic homeostasis is driven by average firing rates, we expected an acceleration of synaptic downscaling during stimulation, which is compensated by a reduced drive after stimulation. We show that 25 minutes of transcranial electrical stimulation, as predicted, reduced the decay of SWO in the remainder of the night. Anatomically accurate simulations of the field intensities on human cortex precisely matched the effect size in different EEG electrodes. Together these results suggest a mechanistic link between electrical stimulation and accelerated synaptic homeostasis in human sleep.

Epilepsy is a devastating disease affecting /spl sim/1% of the world's population. Although drug therapy is effective in many patients, 25% are not responsive to anticonvulsants. In addition, up to 50% of those receiving regular mediation suffer major side effects. Surgical resection is another treatment also associated with serious complications. An alternative method to control seizure activity is electrical stimulation. Several electrical stimulation protocols have been developed in animal models of epilepsy that can reduce or completely suppress seizures. Moreover, in over 5000 patients worldwide, electrical stimulation has been used to control seizures. The mechanisms underlying some of the techniques of seizure control are not understood. Some stimulation protocols, such as DC stimulation, rely on the effects of fields and currents on the membrane polarization. Other methods using single pulses, such as phase-resetting, desynchronization, and chaos control rely on the modulation of the dynamic properties of the neuronal networks. Both low- and high-frequency periodic stimulation can suppress seizures not only during stimulation, but also by inducing long-term changes in brain function. The purpose of this review is to present these approaches and to discuss their underlying mechanisms and potential for clinical implementation.