Temporal Lobe Epilepsy: Altered Default Mode Network Functional Connectivity And Their Relationships With Executive Function

Epilepsy is the most common neurological disorder.Although most patients with epilepsy can be relieved by antiepileptic drugs,approximately 30%of epileptic patients still have recurrent seizures and are resistant,leading to the development of epilepsy as intractable epilepsy.Temporal lobe epilepsy(TLE)is the most common drug-resistant epilepsy.Long-term transmission of epileptic activity can cause structural,functional impairment in the extensive brain regions outside the temporal lobe.The default mode network(DMN)is a brain area with highly functional connectivity,which is active in a resting state and suppressed when performing related tasks.A number of studies have shown that the patients with TLE had abnormal structure and function of DMN,these abnormal changes may be associated with cognitive impairment in the patients with TLE.This study applied a seed-based connectivity analysis to study the functional connectivity characteristics of DMN in patients with TLE.The dynamic changes of DMN,the possible compensatory mechanism and the potential impact of oxcarbazepinefor(OXC)on the functional connection and executive function in patients with unilateral TLE were analyzed before andafter the application of OXC for 3 years.Based on degree centrality method to analyze the relationship between brain function network and executive function in patients with refractory temporal lobe epilepsy,and further explore the brain function network and cognition of patients with TLE.Part 1: Functional magnetic resonance study on functional connectivity of default mode network in patients with temporal lobe epilepsy[Objective] To study functional connectivity and differencesin patients with unilateral temporal lobe epilepsy by resting-state functional magnetic resonance.[Methods] 73 patients with TLE were recruited from the Epilepsy Clinic at the First Affiliated Hospital of Guangxi Medical University,and the diagnosis of TLE was based on the diagnostic manual from the International League Against Epilepsy,including 36 patients with left temporal lobe epilepsy and 37 patients with right temporal lobe epilepsy.At the same time,36 normal control groups(NC)were enrolled.All participants were scanned with 3D high-resolution resting state MRI on a 3T Achieva MRI scanner(Philips).Using the SeeCAT toolbox,the posterior cingulated cortex(PCC)was used as the seed point,and Pearson correlation analysis was performed between the whole brain voxels,the whole brain-related brain area which based on the seed point functional connection method was obtained.The functional connectivity brain regions of L-TLE group,R-TLE group and control group were separately masked,and two independent sample t-tests were performed within the mask,to obtain brain regions with significant differences.The distribution of brain regions with significant differences were compared between three groups.[Results] Compared with control group,the functional connectivity(FC)with the right superior medial frontal gyrus,bilateral medial frontal gyrus,the left calcarine gyrus and left middle Occipital in patients with L-TLE decreased.The FC with the right anterior cingulate gyrus and left middle cingulate gyrus inpatients with right TLE decreased,simultaneously the FC with the left precuneus and the bilateral inferior parietal lobe in patients with R-TLE increased.[Conclusions] The patients with unilateral TLE showed abnormal functional connectivity of the default mode network in resting state.The brain regions with abnormal functional connectivity of DMN in L-TLE patients were more widely distributed than that in right TLE patients.Patients with R-TLE exhibited functional compensation in the brain networks.Part 2: Altered Functional Connectivity of DMN and executive function before and after treatment of OXC in Patients with TLE[Objective] Using multimodal functional MRI(f MRI)and seed-based analysis methods,retrospectively analyzed the changes of the functional connectivity within DMN and executive function in patients with TLE between newly diagnosed(baseline group,P0)and after 3 years of treatment of OXC(treatment group,P3).[Methods] 19 patients with TLE and 20 health persons(control group)were recruited from the Epilepsy Clinic at the First Affiliated Hospital of Guangxi Medical University,and the diagnosis of TLE was based on the diagnostic manual from the International League Against Epilepsy.All participants were scanned with 3D high-resolution resting state MRI on a 3T Achieva MRI scanner(Philips).Imaging data of R-Sf MRI were preprocessed using the DPARSF software(http://resting-fmri.sourceforge.net)in MATLAB.The process includes: time correction,head motion correction,space standardization,and spatial smoothing.Then,using the See CAT toolbox,the posterior cingulated cortex(PCC)was used as the seed point,and Pearson correlation analysis was performed between the whole brain voxels,the whole brain-related brain area which based on the seed point functional connection method was obtained.The functional connectivity brain regions of TLE group and control group were separately masked,and two independent sample t-tests were performed within the mask,to obtain brain regions with significant differences.All participants were observed by attention network test(ANT).The brain regions with different FC were obtained by two independent sample t-tests,then Pearson correlation analysis was performed between the executive control reaction time and Z-valued FC in different brain regions of the patients with TLE.[Results] Compared with control group,the functional connectivity(FC)with the right superior medial frontal gyrus in patients with R-TLE decreased at baseline,the FC with the right anterior cingulate gyrus and left calcarine gyrus decreased in patients with L-TLE at baseline.Compared with control group,the FC of the left inferior cerebellum decreased and the FC of the right angular gyrus increased in n patients with R-TLE after treatment,and no difference was found in the patients with L-TLE after treatment.Compared with the patients at baseline,the patients with L-TLE exhibited increased FC in the right medial frontal gyrus and decreased FC in the left fusiform gyrus after treatment.Compared with normal group,the executive control reaction efficiency of the patients with left TLE decreased before and after treatment.There is no correlation between the executive control reaction efficiency and FC value in the right anterior cingulate gyrus and left calcarine gyrus.Compared to the baseline group,no significant difference in the executive control reaction efficiency was found after treatment.There was no significant difference in patients with right TLE between the three groups.[Conclusions] The damage to the DMN by epileptic seizures is inhomogeneous.Free-seizure cannot completely inhibit the occurrence and development of brain function network abnormalities.OXC may control some seizures and reverse some of the brain's functional activity;L-TLE patients have executive dysfunction and OXC can not improve its executive function,while no significant negative effect.L/R-TLE has different cognitive functions due to DMN damage,and executive dysfunction has left laterality;Part3: Investigation of Abnormal Degree Centrality and Executive Function in Patients with intractable TLE Based on Graph Theory[Objective] Using the degree-centrality method based on graph theory,we studied the relationship between brain function network changes and executive function in patients with intractable temporal lobe epilepsy(ITLE).[Methods] 32 patients with ITLE and 35 health persons(control group)were recruited from the Epilepsy Clinic at the First Affiliated Hospital of Guangxi Medical University.All participants were observed by attention network test(ANT)and resting-state functional magnetic resonance imaging(rs-f MRI).The brain regions with different DC values were obtained by two independent sample t-tests,then Pearson correlation analysis was performed between the executive control reaction time(RT)and Z-valued DC in different brain regions of the patients with ITLE.[Results] Compared with the control group,the executive control RT of patient group was significantly longer than that of the control group(P <0.01),and DC values decreased in the right temporal lobe and bilateral frontal lobes in patients group.DC value of right temporal lobe was negatively correlated with executive control RT(P <0.05).[Conclusions] The changes of brain network node center status may be related to the abnormal executive function in patients with ITLE.The change of “Hubs”with the right temporal lobe may be an important feature of patients with ITLE.