Abstracts

Rationale: Functional MRI (fMRI) images show decreased connectivity in resting state (RS) networks in patients with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis and this could reflect cognitive and psychiatric co-morbidities (Liao et al, PloS one 2010, 5:e8525; Pittau et al, Epilepsia 2012, 53:1013-1023). However, there is no definitive information about abnormal functional connectivity patterns in patients with TLE and normal MRI (TLE-NL). We aimed to evaluate brain regions with relative abnormal function in patients with TLE-NL through a functional interactivity (FI) analysis. Methods: We included RS fMRIs (180 dynamics, voxel size=3x3x3mm³, 40 slices, no gap, TR=2sec, TE=30msec, matrix of 80x80mm) of 12 TLE-NL patients and 20 healthy controls. RS fMRIs were analyzed with FI analysis, which proposes the definition of cumulative R scores for each brain voxel singly correlated to several regions throughout the cortex. For the RS processing and analysis we used the UF²C toolbox with SPM8. The overall FI analysis used a cubic seed (64 voxels) placed in all possible positions that retained at least 40 voxels overlapping with the cortex. For each seed an average time series was extracted and the linear correlation was estimated for all brain voxels, generating a statistical map for each seed position. Finally, they were summed creating an overall FI map. The resultant maps of each individual were used to perform a second level analysis: five right-TLE patients (and the same proportion of controls) had their images flipped (left-right) aiming to lateralize the epileptogenic zone to the left side. Two sample t-test (p<0.05 FWE corrected, cluster with at least 10 voxels) were applied to compare controls and TLE-NL. Results: Compared to controls, TLE-NL patients presented lower FI manly in the ipsilateral superior temporal gyrus (t-value=9.98) and in the contralateral parahippocampal gyrus (t-value=6.83). In addition, we found significant alterations on the ipsilateral thalamus (t-value=7.32) and in the contralateral medial frontal gyrus (t-value=6.80) (Figure). Conclusions: Patients with TLE-NL have a network of areas with decreased interactivity including temporal and thalamic regions, more evident ipsilateral to the epileptogenic zone. These abnormalities may be associated with cognitive impairments or co-morbidities. In addition, the similarity of these findings with functional network changes associated with inter-ictal epileptiform discharges (Coan et al, Epilepsia 2014 Epub ahead) raises the hypothesis of the influence of inter-ictal activity in the brain dysfunction of patients with TLE-NL.