Entropy of the resting state cortex in epilepsy

Epilepsy has long been conceptualised as a disorder in which aberrant brain dynamics extend beyond the epileptogenic zone. Evidence demonstrates that loss of entropy is a generic feature of pathological dynamics in the brain, including the ictal state. However, the impact of recurrent seizures on entropy in the interictal state remains unknown. Resting state magnetoencephalography (MEG) scans and resection masks of 32 individuals with epilepsy who had Engel I outcome post-surgery were retrospectively retrieved. Using co-registered FreeSurfer parcellations, we reconstructed the source localised MEG time series and computed sample entropy for 114 regions of interest. We then tested the association of entropy with the resected volume of the brain, and additional clinical variables including the age of seizure onset, seizure frequency and duration of epilepsy. To further understand the temporal relationship between seizure onset and entropy in the interictal state, we collected and computed sample entropy for week-long EEG traces from leucine-rich glioma inactivated 1 monoclonal antibody (LGI1-mAb) rodent models of autoimmune encephalitis (n=5) and control rats (n=5). We found that in individuals with epilepsy, a lower age of seizure onset was associated with lower mean sample entropy of the whole cortex (Spearman's rho =0.60, p<0.001; partial correlation =0.41, p=0.021). Entropy did not differ between the resected and non-resected regions of the brain. Furthermore, in an exploratory analysis, LGI1-mAb treated rodents showed lower sample entropy as compared to control rats, after the onset of seizures. Together, these results suggest that cortical entropy may serve as a marker of long-term alterations in cortical dynamics associated with recurrent seizures.