Aberrant Structural And Functional Connectivity Of Insular Sub-regions In Game Players

The insula has an important role in addiction,and it evinces both functional and structural anterior-posterior heterogeneity,which is rather evident in the studies of addiction.Therefore,to better understand how insula is involved in addiction,we need to study it based on the idea of the functional and structural differentiation inherent in the insula.However,although a great many studies have explored the whole-brain functional connectivity of different sub-regions of the insula in various types of addiction(including addiction-like disorder),little is known about the structural connectivity of different subregions of the insula in addiction and addiction-like disorder.Moreover,there are some methodological defects in the previous(also limited)studies of tractography-based insular parcellation(such as low diffusion-weighted imaging quality,small sample size,etc.).Hence,in study one,we collected optimized diffusion-weighted imaging data and used the latest tractography-based brain parcellation technology to perform more accurate sub-regions segmentation of insula in a larger sample(N=98),and then compared the structural and functional connectivity patterns among these sub-regions to clarify the structural connectivity heterogeneity and latent functional organization of insula.In study two,we conducted a preliminary study to probe into potential abnormalities in the wholebrain structural connectivity and functional connectivity in the different sub-regions of the insula(acquired from study one)by comparing the internet game players with addiction-like symptoms and healthy non-players.In the first study,following the Automatic Tractography-based Parcellation Pipeline developed by previous studies,the diffusion tensor imaging data of 98 healthy undergraduates were analyzed to parcellate the insula based on its voxel-wise whole brain structural connectivity.Then,using the parcellated sub-regions of insula as seeds,we conducted seed-based whole-brain tractography and resting-state functional connectivity(rsFC)analysis in another independent sample of 25 undergraduates.The results showed that consistent with previous studies,the sub-regions of insula manifested intrinsic structural anterior-posterior heterogeneity.Left insula was divided into two subregions(anterior and posterior portions),and right insula was divided into two subregions(posterior,ventral anterior,and dorsal anterior portions),which resembled the previous tractography-based and rsFC-based insular parcellations.Moreover,the anterior-posterior heterogeneity of insula was again revealed in structural connectivity patterns as well as functional connectivity patterns among insular sub-regions in the independent sample.The anterior portion of bilateral insula showed relatively stronger structural and functional connectivity with prefrontal cortex(orbitofrontal cortex[OFC],dorsolateral prefrontal cortex[DLPFC]),limbic regions(anterior cingulate cortex[ACC]),precuneus,temporal lobe(superior temporal gyrus[STG]/ middle temporal gyrus[MTG])and subcortical nuclei(putamen).The posterior portion,on the other hand,showed relatively more structural and functional connectivity with rolandic operculum,parietal lobe(superior parietal lobule,parietal operculum),somatosensory and motor regions(postcentral gyrus,supplementary motor area[SMA]).Specifically,the connectivity between the right ventral anterior insula and OFC,between the right dorsal anterior insula and DLPFC were also relatively strong.In study two,we recruited 20 undergraduates who are playing the online game called League of Legends.21 undergraduates with roughly matched age,gender and education who never plays League of Legends and other similar online games were chosen as healthy controls.Then the structural and functional connectivity patterns in different insular sub-regions between the game players and non-players were compared between two groups.Compared with the non-players,three portions of right insula exhibited similar reduced structural connectivity probability with precuneus in game players.In addition,we found the reduced structural connectivity between right posterior insula and right postcentral gyrus and calcarine fissure cortex,as well as the reduced structural connectivity of right ventral anterior insula with left cuneus.The functional connectivity of insula among the game players,on the other hand,mainly lied in the STG,DLPFC and partial regions of parietal and occipital cortex.Specifically,compared to health nonplayers,all sub-regions of insula in game players showed poor rsFC with STG,and moreover,right ventral anterior insula showed poor rsFC with SMA,left thalamus;by contrast,right posterior insula showed stronger rsFC with DLPFC.Moreover,the rsFC of left posterior insula with bilateral postcentral gyrus,as well as the rsFC of all right insular sub-regions with MFG were positively correlated with the severity of addiction.On the other hand,the rsFC of left posterior insula with left FP and big partial ACC,the rsFC of right posterior insula with left angular gyrus and right calcarine fissure cortex,the rsFC of right ventral anterior insula with left parahippocampal gyrus and left angular gyrus,and the rsFC of right dorsal anterior insula with left calcarine fissure cortex as well as left angular gyrus and left STG,were all negatively correlated with the severity of addiction.In summary,the current study divided insula into 5 sub-regions(anterior and posterior portions in left side;posterior,ventral anterior and dorsal anterior portions in right side)based on the heterogeneity of structural connectivity in a larger sample,which is relatively stable given it resembled most previous studies.Moreover,this study revealed the abnormalities of the white matter structural connectivity of the insular sub-regions in addiction(or more cautiously,addiction-like disorder)for the first time in the current field.With the emerged aberrant functional connectivity of insular sub-regions in game players,the results showed that the abnormalities beneath the structural and functional connectivity of insula mainly lied in salience network(ACC),default-mode network(precuneus and angular gyrus),central-executive network(DLPFC),sensory and motor regions(postcentral gyrus,SMA,occipital cortex),indicating the latent dysfunction and even pathological changes in insular abilities of switching between different networks and of processing and integrating the sensory and motor signals in game players with addiction-like symptoms.On the other hand,the abnormal connection between the bilateral insula and STG may also indicate that the decision-making dysfunction in game players,which may increase the severity of addiction.Furthermore,the joint and differential structural and functional connectivity patterns in distinct sub-regions of insula confirmed the connectivity variability as well as the structural and functional heterogeneity and conformability inherent in insula,adding great value to the concept of investigating the role of insula in various disorders and diseases(e.g.addiction)based on distinct sub-regions of insula.Since the present study is only a preliminary study,more studies will be needed to explore the possible abnormalities in the structural connectivity of insula in various types of addiction,and to achieve better understanding of the role and abnormalities of insula in addiction.