Alteration Of Cingulate Gyrus And Related Brain Network In Patients With Temporal Lobe Epilepsy And Its Relationship With Executive Function:A Resting State FMRI Study

Temporal lobe epilepsy(TLE)is the most common refractory epilepsy.According to previous study,the damage of epileptic recurrent abnormal discharge to the brain area is far beyond the scope of the temporal lobe itself,and more brain areas besides the temporal lobe structure are also involved,including the frontal lobe,parietal lobe and limbic system,which may have abnormal functional or structural changes.As the most important part of the limbic system,the cingulate gyrus is considered to be a key brain region involved in temporal lobe epilepsy and plays a crucial role in regulating cognitive,sensory,motor,and emotional processes.In present study,we focus on the whole brain connectivity patterns of cingulate subregions and related brain network,spontaneous brain activity and default mode network longitudinal trajectory changes,as well as the relationship between these changes and executive function by using resting state functional magnetic resonance imaging(fMRI),and further investigate the underlying neural mechanisms of impairment or possible compensatory mechanisms,and their impact on executive function.The main research content includes the following four aspects:Part 1.Aberrant functional connectivity of the cingulate subregions in right-sided temporal lobe epilepsy[Objective]Patients with temporal lobe epilepsy(TLE)have been indicated to exhibit abnormal resting-state functional connectivity(rsFC)of the cingulate cortex.However,it has remained elusive whether cingulate subregions show different connectivity patterns in TLE.The present study aimed to investigate the differences in rsFC of each cingulate subregion between patients with right-sided TLE(rTLE)and healthy controls(HCs),as well as their association with executive control performance in rTLE.[Methods]A total of 27 patients with rTLE and 20 age-,sex-and education-matched healthy controls were recruited and all participants underwent resting-state functional MRI and an attention network test for the assessment executive control function.In each hemisphere,the cingulate gyrus(CG)was divided into CG-1(dorsal area 23;A23d),CG-2(rostroventral area 24;A24rv),CG-3(pregenual area 32;A32p),CG-4(ventral area 23;A23v),CG-5(caudodorsal area 24;A24cd),CG-6(caudal area 24;A23c)and CG-7(subgenual area 32;A32sg).Pearson’s correlation analysis was performed to assess the correlation between the altered FC’s of the cingulate subregions and clinical variables.[Results]In patients with rTLE,the majority of the cingulate subregions exhibited decreased rsFC;this was primarily restricted to the right CG-2,the bilateral CG-6 and the bilateral CG-7.Increased rsFC was only detected in rTLE restricted to the left CG-1.Impairments in executive control efficiency were identified in patients with rTLE in comparison with the HCs.[Conclusions]Significant alterations in rsFC between the cingulate subregion and the brain regions were mostly decreased(and some slightly increased),suggesting that FC may potentially have a left-side advantage in patients with rTLE.FC variations of the cingulate subregions were indicated to be specific to rTLE.In addition,increased connectivity in the left CG-1 and left superior frontal gyrus negatively correlated with executive control performance,suggesting a compensatory mechanism on executive control deficits in pathological conditions.This information on differentially altered FC patterns of the cingulate subregions may provide a deeper understanding of the complex neurological mechanisms and executive control dysfunctions underlying rTLE.Part 2.Altered Effective Connectivity of the Anterior Cingulate Subregions in Temporal Lobe Epilepsy[Objective]Temporal lobe epilepsy(TLE),a common form of focal epilepsy,is associated with structural and functional changes in the frontal lobe and the anterior cingulate cortex(ACC).The ACC is a part of the limbic system and includes various subregions with different connectivity patterns.However,a systematic evaluation of the effective connectivity of the dorsal and rostral ACC regions in TLE has not been conducted.[Methods]In the current study,we investigated the effective connectivity of ACC subregions in TLE by using resting-state functional magnetic resonance imaging(fMRI)data from 22 patients with TLE and 20 healthy controls.All participants performed the Attention Network Test(ANT)for further assessment of executive control functions.[Results]Decreased effective connectivity from the left and right dACC to the left superior frontal gyrus and increased effective connectivity from the right lingual gyrus to the right rACC were found in patients with TLE compared to healthy controls.Executive control dysfunction was found in patients with TLE relative to healthy controls.In addition,effective connectivity from the left dACC to the left superior frontal gyrus was negatively correlated with the duration of disease.[Conclusions]These findings provided evidence for aberrant effective connectivity patterns of ACC subregions and demonstrated that the subregions might be implicated in executive control deficits in patients with TLE.Our current study might offer additional insights into the pathophysiology of TLE.Part 3.Aberrant Connectivity Patterns of Default Mode Network and Executive Control Network Related to Cingulate Gyrus in Patients with Right-Sided Temporal Lobe Epilepsy[Objective]As a key part of limbic system,cingulate gyrus is closely related to brain function network.This study aimed to explore functional and effective connectivity of the executive control networks(ECNs)and the default mode network(DMN)related to cingulate gyrus in patients with right-sided temporal lobe epilepsy(rTLE)by applying resting-state functional magnetic resonance imaging(rs-fMRI).[Methods]In this study,27 patients with rTLE and 20 healthy controls matched for age,gender and educational level underwent rs-fMRI.Group independent component analysis(ICA)was firstly adopted to extract the spatial patterns of the left executive control network(LECN),the right executive control network(RECN)and the default mode network(DMN).Their associated time courses were determined by ICA,and data were compared between rTLE patients and healthy controls in order to assess alternations of functional connectivity(FC).These above-mentioned significant brain regions were used as the regions of interest(ROIs)for the subsequent ROI-wise and voxel-wise Granger causal analysis(GCA).Pearson correlations between functional,effective connectivity and neuropsychological tests were also performed(p<0.05).[Results]The FC analysis showed that,within the RECN,patients with rTLE demonstrated reduced FC strength in the right inferior parietal gyrus(IPG)relative to healthy controls.In the DMN,the FC values of the right middle temporal gyrus(MTG)were decreased in patients with rTLE.As for the LECN,the left superior temporal gyrus(STG)displayed reduced FC values whereas the left thalamus revealed increased FC values in patients with rTLE.Moreover,based on ROI-wise GCA patterns,patients with rTLE displayed a significantly increased causal influence from the left thalamus to the left STG.Meanwhile,enhanced causal influence from the right IPG to the right MTG was found in patients with rTLE compared to the healthy groups.Furthermore,based on the voxel-wise GCA approach,the left thalamus revealed positive effective connectivity to the left insula while the right middle occipital gyrus(MOG)exhibited increased effective connectivity to the right MTG in patients.The increased functional connectivity in the left thalamus showed a negative association with neuropsychological tests(conflict effect)in patients with rTLE.[Conclusions]The present study exhibited aberrant FC strength and effective connectivity in patients with rTLE.We speculate that recurrent seizures take effect on disruption among the aforementioned cingulate gyrus related brain networks,and self-modulation occurs simultaneously to compensate for cognitive decline.Our findings reveal new insights on the neuropathophysiological mechanisms of rTLE.Part 4.Longitudinal Assessment of Brain Spontaneous Activity and Default Mode Network in Temporal Lobe Epilepsy:a Resting State fMRI Study[Objective]In this study,we aimed to detect longitudinal alterations in local spontaneous brain activity and functional connectivity(FC)of the default mode network(DMN)in patients with temporal lobe epilepsy(TLE)over a two-year follow-up.Amplitude of low-frequency fluctuation(ALFF)analysis and independent component analysis(ICA)were used to explore differences in local spontaneous brain activity and FC strength.[Methods]In total,33 participants(16 TLE patients and 17 age-and gender-matched healthy controls)were recruited in this study.All participants performed the Attention Network Test(ANT)for evaluation in executive control function.[Results]Compared to the patients at baseline,patients with TLE at follow-up exhibited increased ALFF values in the left medial frontal gyrus,as well as reduced FC values in the left inferior parietal gyrus within DMN.Patients with TLE revealed executive dysfunction but no progressive deterioration was observed during follow-up.[Conclusions]This work revealed abnormal distribution of ALFF value and Rs-FC changes over a two-year follow-up period in TLE,both of which demonstrated different reorganization trajectories and loss of efficiency.