Abstracts

Rationale: MRI methods measuring inter-regional brain signaling at rest are powerful tools to probe organizational properties of functional networks. In temporal lobe epilepsy (TLE), abnormal mesiotemporal functional connectivity has been attributed to epileptogenic or functionally compensatory processes (1). Our aim was to determine the extent to which resting connectivity in TLE is associated with co-localized structural pathology. In line with the distributed nature of structural damage in this condition, we used independent component analysis that optimizes sensitivity to wide-scale resting signaling, correcting for voxel-wise grey-matter density. In addition, we assessed the relationship between resting signaling and white matter microstructure using tract-based spatial statistics. Methods: We acquired resting state fMRI, diffusion tensor imaging and high-resolution anatomical MRI data in 35 patients with drug-resistant TLE (mean age: 34 ± 9 years) and 20 healthy subjects (mean age: 29 ± 7 years) on a 3Tesla scanner. Using Melodic Independent Component Analysis (2) applied to our healthy controls, we identified 10 resting state networks based on visual neuroanatomical correspondence and cross-correlation with consistently identified resting state networks described in the literature. A dual regression approach (3) was used to derive the matching spatial networks, and their time-courses, in every patient and control. Subsequently, functional connectivity within each network was compared between groups using ‘randomize' permutation testing. A voxel-wise grey matter covariate was generated using automated tissue class segmentation to determine the association between resting fMRI connectivity and grey matter volume. Finally, resting functional connectivity values from clusters showing between-group differences were used as covariates in Tract-Based Spatial Statistics analyses (4) to assess relationships between functional connectivity and voxel-wise fractional anisotropy. Results: Compared to controls, patients showed altered functional connectivity between the hippocampus, anterior temporal, precentral cortices and the default mode and sensorimotor networks (p<0.05) (Fig 1). Reduced network integration of the hippocampus was explained by variations in grey matter density (Fig1), while functional connectivity of the parahippocampus, and frontal and temporal neocortices showed atypical associations with white matter coherence within pathways carrying connections of these regions (p<0.05) (Fig 2). Conclusions: Our multimodal MRI study provides strong indication that in TLE hippocampal atrophy and microstructural white matter damage impact functional resting connectivity. Structural damage may explain previously reported discrepancy between increased interictal EEG synchronicity and decreased mesiotemporal fMRI signaling (5). References: (1) Bettus G., J Neurol Neurosurg Psychiatry, 2010 (2) Beckmann CF., Phil. Trans. Roy. Soc. Lond., 2005 (3) Khalili-Mahani N., HBM, 2011 (4) Smith S., Neuroimage, 2006 (5) Bettus G., HBM, 2009