Assistant Central South University, Hunan, China (People's Republic)
Rationale: Our previous study has demonstrated morphological abnormalities in subregions of hippocampus in patients with temporal lobe epilepsy (TLE) and their unaffected siblings. This work aims to further evaluate whether functional connectivity (FC) is disrupted between the subregions of hippocampus and default mode network (DMN) in patients with TLE and their unaffected siblings, and how this connectivity relates to cognition and white matter integrity. Methods: A total of 54 sporadic non-lesional TLE patients (28 right TLE, 26 left TLE), their 18 unaffected full siblings (12 with right TLE patients, six with left TLE patients), and 20 matched healthy controls (HCs) were assessed, using resting functional MRI, 3-D T1, and diffusion tensor imaging. FCs were calculated by seed-based functional connectivity between the subregions of hippocampus (divided into three equal sections along the A-P axis) and DMN (mainly in posterior cingulate cortex, precuneus, temporal lobe, prefrontal cortex and parietal cortex); white matter (correlated with hippocampus and DMN) values were extracted using tract-based spatial statistics (TBSS). We corrected the analyses for age, sex, and level of education and performed Pearson’s correlations for neuropsychological tests. Results: Compared with HCs, both left and right TLE patients showed poorer performance (p< .05) in cognitive tests. TBSS analysis demonstrated significant (p< .05) reduced fractional anisotropy (FA) and increased mean diffusivity (MD) in TLE patients. We detected significant (primary threshold p< .001, 5000 permutations, component-wise corrected p< .05) diminished hippocampal recruitment with DMN in both patients’ groups compared with HCs. Dysfunction was found between left hippocampus (anterior & middle hippocampus) and DMN in left TLE patients, while abnormal FCs were more present within hippocampal subregions and between DMN and right anterior hippocampus in right TLE patients. In addition, altered FCs in left TLE patients correlated with more white matter disruptions (p< .05). Several altered FCs were significantly (p< .05) correlated with memory and attention cognitive scores. For siblings vs. HCs, although the MD value of corpus callosum splenium was significantly increased in siblings of right TLE patients, no FC abnormality was found. Conclusions: We suggest that cognitive impairment in left TLE patients may be due to broader structural and functional network disruption, whereas the cognitive impairment in right TLE patients may more depend on hippocampal abnormalities. We detected shared white matter injury rather than functional abnormalities in TLE patients and their unaffected siblings, this white matter structural neuroimaging trait could represent an endophenotype of TLE, which might precede the onset of epilepsy, whereas functional impairment might mainly occur after the onset of epilepsy in these individuals. Funding: Please list any funding that was received in support of this abstract.: National Natural Science Foundation of China (NSFC:81671300), Research Project of the Ministry of Science and Technology of China (2016YFC0904400), Natural Science Foundation of Hunan province (2020JJ5914).