Low-frequency electrical stimulation reduces cortical excitability in the human brain

Abstract Effective seizure control remains challenging for about 30% of epilepsy patients who are resistant to present-day pharmacotherapy. Novel approaches that not only reduce the severity and frequency of seizures, but also have limited side effects are therefore desirable. Accordingly, various neuromodulation approaches such as cortical electrical stimulation have been implemented to reduce seizure burden; however, the underlying mechanisms are not completely understood. Given that the initiation and spread of epileptic seizures critically depend on cortical excitability, understanding the neuromodulatory effects of cortical electrical stimulation on cortical excitability levels is paramount. Based on observations that synchronization in the electrocorticogram closely tracks brain excitability level, the effects of low-frequency (1 Hz) intracranial brain stimulation on the levels of cortical phase synchronization before, during, and after 1 Hz electrical stimulation were assessed in twelve patients. Analysis of phase synchronization levels across three broad frequency bands (1–45 Hz, 55–95 Hz, and 105–195 Hz) revealed that in patients with stimulation sites in the neocortex, phase synchronization levels were significantly reduced within the 55–95 Hz and 105–195 Hz bands during post-stimulation intervals compared to baseline; this effect persisted for at least 30 min post-stimulation. Similar effects were observed when phase synchronization levels were examined in the classic frequency bands, whereby a significant reduction was found during the post-stimulation intervals in the alpha, beta, and gamma bands. The anatomical extent of these effects was then assessed. Analysis of the results from six patients with intracranial electrodes in both hemispheres indicated that reductions in phase synchronization in the 1–45 Hz and 55–95 Hz frequency ranges were more prominent in the stimulated hemisphere. Overall, these findings demonstrate that low-frequency electrical stimulation reduces phase synchronization and hence cortical excitability in the human brain. Low-frequency stimulation of the epileptic focus may therefore contribute to the prevention of impending epileptic seizures.