Abstracts

Rationale: Seizures and interictal spikes in mesial temporal lobe epilepsy (MTLE) are likely to reflect an epileptic network of brain regions functionally connected during seizure and spike generation, rather than simply a single epileptic focus (Bartolomei, 2001). Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) studies demonstrate a functional network in which hemodynamic changes are time-locked to spikes. However, whether this reflects the propagation of neuronal activity from a ‘focus', or conversely the activation of a network linked to spike generation remains unknown. We hypothesized that altered functional network connectivity emerges immediately prior to the generation of interictal spikes. Methods: 12 MTLE patients (6 females, mean age: 38 years; 6 males, mean age: 42 years) underwent continuous EEG-fMRI during rest. Spikes were identified on EEG and three 10 seconds(s) epochs defined relative to spike onset: spike (0s to 10s), pre-spike (-10s to 0s) and rest (-20s to -10s, with no previous spikes in the preceding 45s). fMRI datasets were left-right flipped so all patients had a left hemisphere focus. Preprocessing was carried out with SPM8, and canonical event-related analysis in an a priori hippocampal region of interest identified a significant (p<0.05 FWE corrected) spike-related left hippocampal activation cluster. This cluster was then used as a seed region for examining functional connectivity during the spike, pre-spike and rest epochs. We report only results that reached a threshold of p <0.002. Results: Altered functional connectivity was observed in the pre-spike network compared to the spike and rest networks. At rest, activity in the left hippocampus correlated strongly with activity in the right hippocampus, the vermis and the parahippocampal gyri, amygdalae and cerebellar cortex bilaterally. Interestingly, a similar pattern of connectivity with the left hippocampus was seen during the spike epoch. Critically however, during the pre-spike epoch, connectivity with the right hippocampus and both parahippocampal gyri was reduced. Conclusions: A fundamental finding of this study is the significant change in functional connectivity patterns before the appearance of electrographic spikes. Supporting previous findings of abnormal inter-hemispheric hippocampal connectivity (Morgan et al., 2011), our findings specifically link reduced connectivity to the period immediately before interictal spikes. This brief decoupling of the hippocampal network may reflect cellular loss in the sclerotic hippocampus, local hypometabolism often seen in MTLE, or potentially a deficit in mutual (inter-hemispheric) inhibition. These findings have important implications for our understanding of functional network changes involved in the generation of spikes.