A Resting-state Fmri Study Of Alterations Of Interhemispheric Function In Patients With Alcohol Dependence

Background and Objective: Alcohol dependence(AD)is a relapsing mental disorder characterized by compulsive alcohol seeking and consumption despite adverse consequences.The phenomenon of alcohol abuse and dependence is very common,and the harmful use of alcohol is one of the primary risk factors that endanger human health in the world.However,it is not clear how alcohol affects human biological behavior through complex neurobiological mechanisms.We hope to explore the mechanism of AD in order to guide prevention and treatment.Although more and more studies have suggested structural and functional impairments in the brains of AD patients,few studies have investigated whether there is an abnormal interhemispheric interactions in AD patients and whether there is a frequency dependence of such abnormalities.Voxel-mirrored homotopic connectivity(VMHC),as an analysis method of resting-state functional magnetic resonance imaging(rs-f MRI),provide a means to examine the functional interactions between mirrored interhemispheric voxels.The phenomenon of alcohol and nicotine co-dependence(AND)is very common,however,most previous AD studies did not consider the impact of smoking factors,so an AND group was set up in this study for comparative study.Therefore,in this study,we will use the VMHC method to explore the homotopic connectivity between AD and AND patients and its specificity of frequency bands.Methods: Experiment 1: Collected rs-f MRI data of 24 AD patients,30 AND patients,and 35 healthy controls(HC)matched with gender,age,and education level.Then,calculated the VMHC and seed-based functional connectivity of the three groups.The main effect of group,group differences of VMHC and seed-based functional connectivity were analyzed.The VMHC value and functional connectivity value of the regions with group differences of AD group were extracted and analyzed with clinical data for correlation relationship.Experiment 2: Collected rs-f MRI data of 24 AD patients,30 AND patients,and 35 HC matched with gender,age,and education level.Then,calculated the VMHC and seed-based functional connectivity of the three groups in slow-5(0.01-0.027 Hz)and slow-4(0.027-0.073 Hz)frequency bands.The main effect of group,the main effect of frequency,interaction between frequency band and group,group differences of VMHC and seed-based functional connectivity in slow-5 and slow-4 band were analyzed.The VMHC value and functional connectivity value of the regions with group differences of AD group in slow-5 and slow-4 band were extracted and analyzed with clinical data for correlation relationship.Results: Experiment 1: In typical frequency band,the AD group demonstrated significantly reduced VMHC in bilateral cerebellum posterior lobe(CPL)and increased VMHC in bilateral middle frontal gyrus(MFG),relative to HC.Moreover,extracting the VMHC difference area as a seed to perform whole brain functional connectivity,the abnormal functional connectivity areas were also distributed in the mirrored area of the contralateral hemisphere.The abnormal VMHC and functional connectivity of AD group were respectively correlated to AUDIT and alcohol intake.No significant differences were found between the AND and HC or AD groups.Experiment 2: In slow-4 frequency band,the AD group demonstrated significantly reduced VMHC in bilateral CPL and increased VMHC in bilateral MFG,relative to HC.Moreover,extracting the VMHC difference area as a seed to perform whole brain functional connectivity,the abnormal functional connectivity areas were also distributed in the mirrored area of the contralateral hemisphere.The abnormal VMHC and functional connectivity in the slow-4 frequency band of the AD group were respectively correlated to AUDIT and alcohol intake.Finally,the group differences in intrinsic connectivity can be more easily detected in the slow-4 band than in the slow-5 band.Conclusions: Our findings of abnormalities in CPL and MFG provide further evidence of the role of disruptions within brain circuitry supporting cognitive control in development of AD.Alterations of neural activities in those regions might be a biomarker of dependence severity in AD patients.Meanwhile,because of the frequency-specific feature in VMHC,we have to consider frequency effects in future f MRI study of AD.Finally,no finding observed in AND group need further study.