Abstracts

Rationale: Pre-ictal neuronal assembly and inter-ictal spike (IIS) activity are reactivated during post-seizure sleep in ICU patients undergoing intracranial monitoring for Mesial Temporal Lobe Epilepsy (MTLE). This process is called Seizure-Related Consolidation (SRC), because it is similar to Cellular Consolidation observed during post-behavioral sleep following learned behaviors (Bower et al., 2015). While it is known that memories, once consolidated, can persist for a lifetime, less is known about the durability of SRC. Recently, however, longer duration EEG recordings have been obtained from ambulatory patients (Karoly et al., 2017), which provides the opportunity to determine the persistence of changes in neural activity relating to SRC. Methods: We analyzed ambulatory EEG recorded at 400 Hz from human patients with MTLE. Interictal spikes were detected and data windows were extracted ±100 msec around the maximum, absolute IIS voltage. For each IIS on a given channel, correlation coefficients were computed for simultaneous activity on all other channels, regardless of activity on a channel (i.e., presence or absence of a spike). Behavioral epochs were identified at least six hours “Before” seizures, the “Pre-Ictal” 10 min epoch preceding seizures, and multiple epochs occurring at least six hours “After” seizures, but without an intervening seizure. Changes in correlation coefficients were used to compute partial correlation values for activity during the Pre-Ictal vs. After epochs given activity during the Before epoch. Significance across all channels was established by beta regression. Results: In 3 seizures from each of 3 patients (9 seizures total), changes in IIS shape and synchrony observed in the minutes preceding seizures (“Pre-Ictal”) were reactivated After seizures, similar to the SRC observed in MTLE patient data obtained in an ICU setting (p=0.018). When changes in IIS following sequential seizures were examined, clear examples could be found where increased Pre-Ictal IIS correlation resulted in increased IIS correlation during reactivation, while decreased Pre-Ictal IIS correlation resulted in decreased IIS correlation during reactivation, and vice-versa. Finally, SRC was significant for each patient, individually. When SRC was computed for longer-latency “After” epochs, regression showed a half-life of 14.3 days. Conclusions: Seizure-related consolidation (SRC) shares many characteristics with physiological learning: reactivation occurs during slow-wave sleep, it occurs only a subset of electrodes, and it occurs across multiple brain structures. Here, we have shown that the effects of SRC are persistent, ostensibly lasting for weeks, similar to physiological changes associated with learning. Because a rich literature has described these mechanisms in detail and shown how to interfere with those mechanisms to block learning, the possibility exists that epilepsy-related changes in neural tissue may be altered, blocked or even reversed following seizures, suggesting a novel approach for anti-epileptogenic therapies. Funding: none