Alterations Of Regional Spontaneous Neuronal Activity And Metabolites Revealed By Resting State Functional Magnetic Resonance Imaging Combined With Magnetic Resonance Spectroscopy In Migraine Without Aura

Objective To investigate the underlying mechanism of migraine without aura by exploring the alterations of neurochemical metabolites using proton magnetic resonance spectroscopy(MRS)and changes of cerebral cortex activity and functional connectivity(FC)on resting state functional magnetic resonance imaging(rs-fMRI)? Methods Interictal migraine without aura patients(n=16)and genders and age matched healthy subjects(n=16)were recruited.Clinical evaluations,including the Visual Analogue Scale(VAS)of pain,Headache Impact Test-6(HIT-6),Migraine Disability Assessment questionnaire(MIDAS)were evaluated prior to MR scanning.This study selected the occipital cortex as the region of interest(ROI).The metabolites of the occipital cortex were detected by a PRESS(Point Resolved Spectroscopy Sequence)of MRS using a 3T MR scanner.The metabolites were quantitatively analyzed by LCmodel.Gradient-echo EPI sequence was performed in all subjects.Amplitude of low-frequency fluctuation(ALFF),regional homogeneity(Reho)and seed-based functional connectivity(FC)were employed to observe the changes of cerebral cortex activity and full brain functional connectivity.A two independent sample T test was performed for statistical analysis of the changes of metabolites.Spearman correlation analyses were performed to examine the relationship between the metabolite levels,ALFF values,Reho values and clinical scores Results The migraine without aura(MwoA)group and health control(HC)group did not significantly differ by age and gender(p>0.05).The WoA group indicated significantly lower levels of N-acetylaspartate(NAA)/creatine + phosphocreatine(total creatine,tCr)over HC group(p=0.036)in the occipital cortex.Compared with the control group,ALFF values in MwoA group had a significant decrease in the bilateral superior occipital gyrus,bilateral middle occipital gyrus,bilateral calcarine,bilateral lingual gyrus and bilateral cuneus.No brain regions with increased ALFF were found in MwoA group compared with HC group.Compared with the control group,Reho values in MwoA group had a significant decrease in right cuneus,bilateral calcarine and bilateral lingual gyrus,significant increase in right middle frontal gyrus.Left periaqueductal gray(PAG)had an increased functional connectivity with left lingual gyrus,left cerebellum,bilateral calcarine,right inferior occipital gyrus,left middle occipital gyrus and left cuneus in MwoA group compared with HC group.Right PAG had an increased functional connectivity with bilateral calcarine,bilateral lingual gyrus,left cuneus,bilateral cerebellum,right inferior occipital gyrus,left middle occipital gyrus,left precentral gyrus and left postcentral gyrus in MwoA group compared with HC group.Spearman correlation analysis showed that ALFF values was positively correlated with the frequency of MwoA patients(r=0.57,P < 0.05).Reho values was positively correlated with the MIDAS score and frequency of MwoA patients(r= 0.55,0.54 respectively,P < 0.05).Conclusion our findings suggest that the occipital lobe region may be the key area of migraine attack.The decreased activity of occipital region and the increased functional connectivity with the PAG region during the interictal period may be the result of body's selfprotection mechanism,which may help prevent the onset of migraine attack and prepare for the analgesic adjustment of impending headache.