Objective: This work was undertaken to study the functional connectivity differences between non-seizure-free and seizure-free patients with temporal lobe epilepsy (TLE) and to identify imaging predictors for drug responsiveness in TLE. Methods:In this prospective study, 52 patients with TLE who presented undetermined antiseizure medication responsiveness and 55 demographically matched healthy controls were sequentially recruited from Xiangya Hospital. Functional magnetic resonance imaging data were acquired during a Chinese version of the verbal fluency task. The patients were followed up until the outcome could be classified. The subject groups were compared in terms of activation profile, taskresidual functional connectivity (trFC), and generalized psychophysiological interaction (gPPI) analyses. Moreover, we extracted imaging characteristics for logistic regression and receiver operating characteristic evaluation.Results: With a mean follow-up of 1.1 years, we identified 27 non-seizure-free patients and 19 seizure-free patients in the final analyses. The Chinese character verbal fluency task successfully activated the language network and cognitive control network (CCN) and deactivated the default mode network (DMN). In the non-seizure-freedom group, the trFC between the hippocampus and bilateral brain networks was attenuated (p < .05, familywise error corrected). For the gPPI analysis, group differences were mainly located in the precuneus, middle frontal gyrus, and inferior parietal lobule (p < .001, uncorrected; k ≥ 10). The regression model presented high accuracy when predicting non-seizure-free patients (area under the curve = .879, 95% confidence interval = .761-.998). Significance:In patients with TLE who would not achieve seizure freedom with current antiseizure medications, the functional connectivity between the hippocampus and central nodes of the DMN, CCN, and language network was disrupted, leading to language decline. Independent of hippocampal sclerosis, abnormalities, especially the effective connectivity from the hippocampus to the DMN, were predictive biomarkers of drug responsiveness in patients with TLE.

Purpose Patients with temporal lobe epilepsy (TLE) are at high risk of cognitive impairment. In addition to persistent seizures and antiepileptic drugs (AEDs), genetic factors also play an important role in the progression of cognitive deficits in TLE patients. Defining a cognitive endophenotype for TLE can provide information on the risk of cognitive impairment in patients. This study investigated the cognitive endophenotype of TLE by comparing neuropsychological function between patients with TLE, their unaffected siblings, and healthy control subjects. Patients and Methods A total of 46 patients with TLE, 26 siblings, and 33 control subjects were recruited. Cognitive function (ie, general cognition, short- and long-term memory, attention, visuospatial and executive functions, and working memory) was assessed with a battery of neuropsychological tests. Differences between groups were evaluated by analysis of covariance, with age and years of education as covariates. The Kruskal–Wallis test was used to evaluate data that did not satisfy the homogeneity of variance assumption. Pairwise comparisons were adjusted by Bonferroni correction, with a significance threshold of P<0.05. Results Patients with TLE showed deficits in the information test (P<0.001), arithmetic test (P=0.003), digit symbol substitution test (P=0.001), block design test (BDT; P=0.005), and backward digit span test (P=0.001) and took a longer time to complete the Hayling test Part A (P=0.011) compared to controls. Left TLE patients tended to have worse executive function test scores than right TLE patients. The siblings of TLE patients showed deficits in the BDT (P=0.006, Bonferroni-corrected) relative to controls. Conclusion Patients with TLE exhibit cognitive impairment. Executive function is worse in patients with left TLE than in those with right TLE. Siblings show impaired visuospatial function relative to controls. Thus, cognitive deficits in TLE patients have a genetic component and are independent of seizures or AED use.

Alzheimer's disease (AD), an incurable chronic neurodegenerative disease first described by Alois Alzheimer in 1906, has become a significant public health priority. After 10-15 years of preclinical stage, the symptoms develop from mild cognitive impairment to impaired memory, language difficulties and, at last, death in an average time of seven to ten years after diagnosis.After more than one hundred years of research, researchers had made tremendous progress. Nevertheless, Alzheimer's disease is still marked histologically by the accumulation of amyloid beta (Aβ), the emergence of neurofibrillary tangles, and loss of synapse. However, recently, with endless failure in clinical trials, some researchers are now turning to other symptoms such as aberrant lipid metabolism (Hamilton et al., 2015), abnormal calcium transfer (Dolev et al., 2013), and autophagic malfunction (Li et al., 2017). Mitochondria-associated endoplasmic reticulum membrane (MAM) is pivotal for the pathways mentioned above, which are disturbed in AD. Thus, Area-Gomez et al. proposed that disturbed MAM function is a "coherent and unified explanation" for both familial and sporadic AD: MAM hypothesis (Area-Gomez et al., 2012).In this review, we update the knowledge about MAM's role in pathologies shared by familial and sporadic forms of AD. We also highlight the importance of AD models used in studies.

Objective: Cortical tremor/myoclonus is the hallmark feature of benign adult familial myoclonic epilepsy (BAFME), the mechanism of which remains elusive.A hypothesis is that a defective control in the preexisting cerebellar-motor loop drives cortical tremor. Meanwhile, the basal ganglia system might also participate in BAFME. This study aimed to discover the structural basis of cortical tremor/ myoclonus in BAFME.Methods: Nineteen patients with BAFME type 1 (BAFME1) and 30 matched healthy controls underwent T1-weighted and diffusion tensor imaging scans.FreeSurfer and spatially unbiased infratentorial template (SUIT) toolboxes were utilized to assess the motor cortex and the cerebellum. Probabilistic tractography was generated for two fibers to test the hypothesis: the dentato-thalamo-(M1) (primary motor cortex) and globus pallidus internus (GPi)-thalamic projections.Average fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) of each tract were extracted.

Aim Temporal lobe epilepsy is a neurological network disease in which genetics played a greater role than previously appreciated. This study aimed to explore shared functional network abnormalities in patients with sporadic temporal lobe epilepsy and their unaffected siblings. Methods Fifty‐eight patients with sporadic temporal lobe epilepsy, 13 unaffected siblings, and 30 healthy controls participated in this cross‐sectional study. We examined the task‐based whole‐brain functional network topology and the effective functional connectivity between networks identified by group‐independent component analysis. Results We observed increased global efficiency, decreased clustering coefficiency, and decreased small‐worldness in patients and siblings (p < 0.05, false discovery rate‐corrected). The effective network connectivity from the ventral attention network to the limbic system was impaired (p < 0.001, false discovery rate‐corrected). These features had higher prevalence in unaffected siblings than in normal population and was not correlated with disease burden. In addition, topological abnormalities had a high intraclass correlation between patients and their siblings. Conclusion Patients with temporal lobe epilepsy and their unaffected siblings showed shared topological functional disturbance and the effective functional network connectivity impairment. These abnormalities may contribute to the pathogenesis that promotes the susceptibility of seizures and language decline in temporal lobe epilepsy.