Abstracts

Rationale: Ripples (80-150 Hz) recorded from clinical macroelectrodes have been shown to be an accurate biomarker of epileptogenic brain tissue. We investigated coupling between epileptiform spike phase and ripple amplitude to better understand the mechanisms that generate this type of pathological ripple (pRipple) event. Methods: We quantified phase amplitude coupling (PAC) between epileptiform EEG spike phase and ripple amplitude recorded from intracranial depth macroelectrodes during episodes of sleep in 12 patients with mesial temporal lobe epilepsy. PAC was determined by 1) a phasor transform that corresponds to the strength and rate of ripples coupled with spikes, and a 2) ripple-triggered average to measure the strength, morphology, and spectral frequency of the modulating and modulated signals. Coupling strength was evaluated in relation recording sites within and outside the seizure onset zone (SOZ). Results: Both the phasor transform and ripple-triggered averaging methods showed ripple amplitude was often robustly coupled with epileptiform EEG spike phase. Coupling was more regularly found inside than outside the SOZ and coupling strength correlated with the likelihood a macroelectrode's location was within the SOZ (p < 0.01). The ratio of the rate of ripples coupled with EEG spikes inside the SOZ to rates of coupled ripples in non-SOZ was greater than the ratio of rates of ripples on spikes detected irrespective of coupling (p < 0.05). Coupling strength correlated with an increase in mean normalized ripple amplitude (p < 0.01) and a decrease in mean ripple spectral frequency (p < 0.05). Conclusions: Generation of low-frequency (80-150 Hz) pRipples in the SOZ involves coupling between epileptiform spike phase and ripple amplitude. Changes in excitability during epileptiform spikes may cause clusters of pathologically interconnected neurons to grow and synchronize in to aberrantly large neuronal assemblies. Funding: Dr. Weiss is supported by an Epilepsy Foundation Award Research and Training Fellowship for Clinicians, Dr. Orosz by the Otfrid-Foerster grant of the German Epilepsy Society, Miss. Van 't Klooster was supported by the Ter Meulen Grant of the Royal Netherlands Academy of Arts and Science (KNAW) and the University Utrecht Short Stay PhD fellowship, Dr. Fried by NINDS grant NS033221, Dr. Engel by NS033310, Dr. Staba by NS071048, and Dr. Bragin by NS065877.