Interictal Epileptiform Discharges Might Be More Likely During Particular Phases of Brain Activity

Many epilepsy patients exhibit intermittent abnormal brain activity, evident as abnormal electrical events on electroencephalography (EEG), at times when they are not having a seizure. Despite the ease with which these so-called interictal epileptiform discharges (IEDs) can be detected, and a reasonable understanding of the physiological processes occurring during the IED (1), the effect of IEDs on brain function and the nature of their association with seizures remains unclear. Several recent studies of the potential effects of IEDs on brain function have examined activity within the default mode network [DMN; (2)], a major distributed functional network of the healthy brain typically associated with introspective tasks such as autobiographical memories, internal rumination, or random episodic silent thinking [REST; (3)]. Major nodes of the DMN include posterior cingulate/retrosplenial cortex, medial prefrontal cortex, and the inferior parietal lobule (4). It has been postulated that abnormal activity in the DMN may be a causative factor in loss of awareness during seizures (5). Studies of IEDs have demonstrated a temporal association between the discharges and activity changes in nodes of the DMN. For example, deactivation of DMN is observed in several generalized and focal epilepsies (6–10), and activation in DMN is associated with some IED types (11). However, a causal link has not been definitively established: IEDs might cause DMN changes, or there may be certain, perhaps normal, functional states of the brain that are more permissive than others to the occurrence of epileptiform activity (12–15). Lopes et al. have now addressed this issue by measuring the intrinsic functional connectivity of the DMN in patients immediately before, during and after epileptiform activity, and comparing the connectivity in these periods with a baseline well away from the epileptiform activity (16). They utilized sliding-window dynamic functional connectivity, amultivariate approach that assesses correlations in activity between brain regions over relatively short timespans (typically of the order of tens of seconds) (17). Lopes et al. studied both idiopathic generalized epilepsy (IGE) [i.e., genetic generalized epilepsy (GGE) (18)] and temporal lobe epilepsy (TLE). An interesting observation of this study is an overall increase in intrinsic connectivity in portions of the DMN several seconds prior to the onset of IEDs in both GGE and TLE. That this increase is observed prior to the IED suggests it is not the IED causing the change. The authors suggest that the “DMN connectivity may facilitate IED generation.” The fact that the increase in DMN activity in GGE patients occurred bilaterally, while in TLE patients, it occurred mainly in nodes ipsilateral to the affected temporal lobe, is consistent with the authors’ hypothesis. However, while the hypothesis is plausible, there exist other possible explanations. For example, EEG spikes become