A Study Of Attention And Relationship With Cerebello-cerebral Functional Connection Networks In Temporal Lobe Epilepsy With And Without FBTCS

Objectives Focal to bilateral tonic-clonic seizure(FBTCS)is highly associated with lower quality of life,sudden death,cognitive impairment,and seizures related injuries in epilepsy patients.Attention involves the whole process of cognitive activities,and attention deficit is a common complication of epilepsy.The cerebellum is involved in cognitive activities and could modulate attention,and there is complex functional connectivity between the cerebellum and the cerebrum.The complex functional connectivity is the basis for the complex and fine regulation of the cerebellum and the cerebrum for attentional activities.The objective of this study was to explore the characteristics of changes in attention function in TLE with and without FBTCS and the relationship with t cerebello–cerebral functional connectivity networks.Methods We consecutively recruited 44 Temporal lobe epilepsy(TLE)patients(22 with FBTCS and 22 without FBTCS)and 22 demographically matched healthy controls.(1)Attention Network Test(ANT)was used to evaluate the attention of the three groups of subjects,and compared the attention among the three groups.(2)Analysis of functional connectivity in cerebellocerebral circuits:The deep cerebellar nuclei(dentate nuclei,fastigial nuclei and interposed nuclei)were used as regions of interest(ROI)to construct functional connectivity networks(dynamic and static connectivity)with every voxel in the whole cerebrum.Used cerebral cortex(frontal lobe,parietal lobe,occipital lobe and temporal lobe)as ROI to constructed the functional connectivity maps(dynamic and static connection)with every voxel in the whole cerebellum.The dynamic and static functional connection in cerebello-cerebral circuits were compared among three groups and the correlations between attention and significantly disruptedFC in two patient groups were analyzed.(3)Static functional brain network topological properties analysis:Using graph theory analysis method,the large-scale static cerebello-cerebral functional network of every subject was constructed respectively,and the topological properties were compared among the three groups and the correlations between the attention and altered topological properties were analyzed in two patient groups.(4)Dynamic functional brain network topological properties analysis:Flexible Least Squares FLS technology combined with graph theory analysis method was used to construct the large-scale dynamic cerebello-cerebral functional network for every subject,and compared topological properties among three groups in every state,and the correlations between the attention and altered topological properties were analyzed in two patient groups.Results 1.There were significant differences in intrinsic alertness,phase alertness,alertness efficiency and orienting efficiency among the three groups.In the post hoc analysis,it was further found that the intrinsic alertness(P=0.005),phase alertness(P=0.003)and orienting efficiency(P=0.015)in the TL-FBTCS group were significantly lower than those in the healthy controls.2.Compared with the group without FBTCS,sFC between the right dentate nucleus and the left hemisphere,included the middle frontal gyrus,superior temporal gyrus,superior medial frontal gyrus and cingulate gyrus were significantly reduced in the FBTCS group,while dFC from the right middle nucleus to the contralateral precuneus was significantly increased.sFC between the right dentate nucleus and the left middle frontal gyrus was significantlyreduced in the FBTCS group compared to the healthy controls.3.Compared with TLE patients without FBTCS,TLE patients with FBTCS had significantly improved small-worldness,normalized clustering coefficient(γ)and global efficiency(gE).TLE without FBTCS had significantly lower small-worldness,normalized clustering coefficient(γ)and global efficiency(gE),while the normalized characteristic path length(λ)was significantly longer than the healthy controls.gE may be negatively correlated with intrinsic and phase alertness in TLE patients without FBTCS.4.We analyzed topological properties among the patient groups with and without FBTCS and healthy controls in 5states.Main findings included:(1)In state 2 and state 5,TLE without FBTCS demonstrated significantly lessσthan the healthy controls.In state 3,TLE without FBTCS was significantly lower gE than the healthy controls.(2)In state4,TLE without FBTCS exhibited significantly higher than healthy controls.(3)In state 5,TLE without FBTCS had significantly lowerγthan healthy controls.TLE with and without FBTCS has different network properties among different states.Conclusions 1.The TLE patient with FBTCS have comprehensive attention dysfunction,which may prioritize selective impairment of alertness and orientation;It is suggested that attention disorder may be the main symptom of early cognitive impairment of FBTCS.2.There were different the pattern of disrupted sFC or dFC within specific cerebello-cerebral cicuits in TLE patients with and without FBTCS,which might characterize the attentional dysfunction pathophysiology.3.Although the functional brain network of TLE with and without FBTCS were small-worldness network,these were low efficient network in pathological state.TLE with and without FBTCS exhibited decreased of information separation and integration,and the balance betweenthem,especially TLE without FBTCS.4.The whole brain functional network of TLE patients with and without FBTCS may have dynamic and transient pathological states,especially TLE-none-FBTCS.