Fast ripples reflect increased excitability that primes epileptiform spikes.

The neuronal circuit disturbances that drive interictal and ictal epileptiform discharges remains elusive. Using a combination of extraoperative macro- and micro-electrode interictal recordings in presurgical patients we found that fast ripples (FR; 200-600Hz) frequently occur <300 msec before an interictal intracranial EEG (iEEG) spike. Such FR events are associated with higher spectral power, correlated with more vigorous neuronal firing than solitary FR. By contrast, during the iEEG spike that follows a FR, action potential firing is lower than during a iEEG spike alone. Sites containing a high proportion of FR preceding iEEG spikes correlate with brain areas where seizures begin. Despite this correlation, removal of these sites does not guarantee seizure freedom. These results are consistent with the hypothesis that FR preceding EEG spikes reflect an increase in local excitability that primes EEG spike discharges preferentially in the seizure onset zone and that epileptogenic brain regions are necessary, but not sufficient, for initiating interictal epileptiform discharges.