Abstracts

Rationale: Focal epilepsies, such as temporal lobe epilepsy (TLE), are known to disrupt network activity in areas outside the epileptogenic zone (Tracy et al., in press). While EEG data has demonstrated dynamic regional connectivity changes on a small time scale within the regions of ictal activity (Honey et al., 2007), little is known about the temporal dynamics of the larger brain networks. We devise a measure of temporal stability of functional resting-state connectivity, capturing temporal variations of BOLD correlations between brain regions. Using this new measure, we investigate healthy controls and TLE patients, focusing on the ventral default mode network (vDMN), a network associated with episodic memory, the key cognitive deficit in TLE. Methods: We obtained a 5-minute resting-state fMRI from 80 adults with refractory TLE (44 left/36 right) and 35 normal controls (NCs). After standard preprocessing of the data, a model-independent measure of FC stability was computed between pairs of brain regions within the vDMN. The vDMN was defined by performing a whole group probabilistic ICA, and using dual regression to obtain subject-specific component maps, masked by the group map. The stability index (SI) measured the differences over time in correlation between vDMN regions (Fig. 1). SI was computed for each region pair as the sum of squared differences in correlation between adjacent non-overlapping time windows (24 volumes/window). SIs were compared across region pairs and between groups using non-parametric ANOVA and t-tests. A repeated measures ANOVA on SI was used to assess the stability of FC constrained to region-pairs that were either ipsilateral or contralateral to the seizure focus. Results: The TLE groups did not differ in any clinical or demographic characteristics (Table 1). In general, NCs had significantly lower levels of temporal variability than TLE patients within vDMN regions (Fig. 1). No difference was found between left and right TLE. Individual region-pairs showed significant TLE/NC differences in stability in (i) left and right middle temporal lobe, (ii) right middle temporal/right inferior parietal cortex, and (iii) right middle temporal/left inferior parietal. No significant group differences in SI were found for other regional connection pairs. Lastly, no significant group differences in SI were found between vDMN region pairs as a function of ipsilateral, contralateral, or inter-hemispheric status. Conclusions: These findings indicate that temporal stability may characterize healthy brain to some degree, and that, compared to controls, functional connectivity in TLE patients show an abnormal instability over time. It is unclear whether such instability arises as a pathologic mechanism from the impact of seizures or as a protective mechanism to prevent functional integrity and seizure spread (Tracy et al., 2014). Given the link of the vDMN network with episodic memory, our findings raise questions on the possibility that the memory disorder observed in TLE might be related to the observed instability of vDMN networks.