Modulation of electrocorticographic seizure features predicts response to closed-loop brain stimulation

Why does closed-loop invasive brain stimulation improve seizure control in some patients with epilepsy, but not others? The RNS System, the only FDA-approved bi-directional brain-computer interface, has been shown to improve seizure control in patients with refractory epilepsy, although the mechanisms behind this success are undefined. We analyzed recordings from the RNS System and discovered two main categories of electrophysiological signatures of stimulation-induced modulation of the seizure network. Direct effects included ictal inhibition and early frequency modulation but did not correlate with improved clinical outcomes. Only indirect effects, those occurring remote from triggered stimulation, predicted improved clinical outcomes. These indirect effects, which included spontaneous ictal inhibition, frequency modulation, fragmentation, and ictal duration modulation, may reflect progressive local epileptogenic network compartmentalization that hinders the spread of pathological synchrony from recruiting neuronal populations. Our findings suggest that responsiveness to RNS may be explained by chronic stimulation-induced modulation of seizure network activity, rather than direct effects on each detected seizure.