Abstracts

Rationale: The application of network analysis has provided valuable information on alterations in functional and anatomical brain networks in epilepsy. However, it remains unknown how modularity which underlies the functionality of most complex networks is affected in epilepsy and its association with cognitive impairment. Here we investigated the disruption of modular organization of brain structural network constructed from regional volumes in controls and TLE patients with unilateral hippocampal atrophy. Methods: Whole brain T1 images were acquired from 86 left TLE (48±10yrs, 35 males) and 70 right TLE (37±12yrs, 25 males) patients and 116 controls (46±12yrs, 39 males) on a 3T Philips scanner. Native images were processed/parcellated into 80 cortical and subcortical regions, using Freesurfer5.3. We then constructed full-weighted brain structural networks (80x80) for all groups by calculating the absolute Pearson correlation coefficient across individuals between all pairs of the regional volumes after removing the effects of age, gender, age-gender interaction and mean volumes. Next, we identified modular structures for control group and investigated how they were affected in TLE patients. Last, using a ‘sliding window' approach, we examined how network properties such as global efficiency (gE), local efficiency (locE) and intramodular connectivity (IC) were associated with mean duration (both groups) and memory scores (55 combined subjects) of TLE patients. Results: In NC group, we identified six major modules labeled from I to VI (fig. 1A) that can be associated with the visual (V), motor/sensory (M/S, basal ganglia), memory (limbic), sensory integration, default mode network (DMN) and auditory/language (A/L) brain functions, respectively. Both TLE groups demonstrated reduced modularity compared with NC (fig. 1B, inset). LTLE networks also exhibited reduced connectivity (p<0.05) in the memory, DMN and A/L modules while RTLE patients only demonstrated significant decreases in DMN and A/L modules. LTLE patients displayed negative correlations between gE/locE and mean duration while RTLE showed positive correlation between locE and mean duration (fig. 2a/b). gE and locE of TLE patients demonstrated positive and negative correlations with verbal memory scores of TLE patients (fig. 2 c/d), respectively. Modular connectivity of the two limbic systems (M/S and memory) in TLE patients decrease as verbal memory scores decreases (fig. 2e/f). However, only the visual and A/L modules were positively correlated with the visual memory scores. Conclusions: We used network neuroimaging methods to show that epilepsy causes disruption within distinct, healthy, human intrinsic modular structures. Compared with LTLE group, RTLE patients sustained less connectivity loss in the limbic system and had positive correlation between local efficiency with duration which might indicate a better underlying compensation mechanism. Our results also provide first evidence in linking the cognitive impairment observed in TLE patients with the disrupted connectivity of modular structures in the TLE structural brain networks.