The Alterations Of Resting-state Brain Functional Connectivity After Physiological Food Intake

ObjectiveThe central nervous system is closely related to the gastrointestinal tract.For example,the pathological changes of the gastrointestinal tract,eating associated central nervous system lesions,homeostasis factors and food reward factors can cause changes in the brain functional connectivity.Previous studies have revealed the neural mechanism of human eating behavior,but there is no specific functional connection analysis for healthy people in resting-state.This study excludes the impact of gastrointestinal pathology and external stimulation,resting-state functional magnetic resonance(rs-fMRI)technology was used as a noninvasive method,the blood and oxygen level dependence(BOLD)images of healthy subjects in resting-state were collected in different time periods(fasting,after breakfast,2 hours after dinner,before lunch).To explore the alterations of resting-state brain functional connectivity between the posterior cingulate cortex(PCC)and the whole brain after physiological food intake.Materials and MethodsForty-five healthy subjects were divided into three groups in a balanced order according to the demographic characteristics(eight male and seven female in each group).To maximize the differences of gastrointestinal activity of the three groups,three medicines were given to the three groups,including Domperidone(promote group),Otilonium Bromide(inhibition group),and dummy(control group).All the participants were given standard experiment diet for breakfast(250ml lactose free milk,4 slices of whole wheat bread and an egg).And the resting state f MRI scanning was performed at 4 different gastrointestinal physiological states,specifically fasting(7:30 a.m,T1),postprandial immediately(8:00 a.m,T2),2h postprandial(10:00 a.m,T3)and before lunch(12:00 a.m,T4).All the subjects monitored the blood glucose level of the fingertips and filling out the starvation scale before each scan.During data analysis,the posterior cingulate cortex(PCC)were selected as the seed to calculate the functional connectivity(FC)throughout the whole brain.Then the repeated measure analysis of variance(ANOVA)was used to investigate the brain areas with significant differences across the time and medicine.The brain regions with significant differences were further extracted the z functional connectivity value which were subsequently involved into the post hoc analysis.The intensity of functional connection in ROI was analyzed by Pearson correlation with blood glucose level and hunger score respectively.Results1.The main effect of time: significant FC changes across time were found in the right orbitofrontal cortex/putamen/thalamus(rOFC/rTL/rPA),right supramar-ginal gyrus(rSMG),and right Rolandic lobe(rRO)(p<0.05).The post-hoc analys-es showed that the activity in these brain areas exhibited different variation trend of FC under four different gastrointestinal states.The changes of the functional connection between the PCC and the rOFC/rTL/rPA were consistent.Compared with the T1 state,FC between the PCC and the rOFC/rTL/rPA was significantly weakened in the T2,T3 and T4 states(p<0.05).Compared with the T1,T2 and T3 states,FC between the PCC and the rOFC/rTL/rPA was significantly weakened in the T4 state(p<0.05).No significant difference was found between the T2 state and T3 state(p>0.05).The rSMG and rRO have the similar level of change under four gastrointestinal physiological states.Compared with the T1 state,FC in the rSMG and rRO was significantly weakened in the T2,T3,and T4 states.2.The results of correlation analyses: Blood glucose level was found to be correlated with connectivity strength in the rOFC/rTL/rPA with statistic signifycance under states.However,In the rSMG and rRO brain regions,no significant correlation between the FC and blood glucose level were found under any of the four different gastrointestinal states.3.The main effect of medicine: significant FC changes across medicine were found in the right precuneus,left middle temporal gyrus,left lingual gyrus,right middle temporal gyrus,right superior frontal gyrus,bilateral orbitofrontal cortex and left middle frontal gyrus(p<0.05).In the promotion group,the FC between the PCC and the right precuneus decreased(p<0.05),the functional connection between PCC and left temporal gyrus and left lingual gyrus was enhanced(p<0.05)compared with the control group.In the inhibition group,the FC between PCC and left lingual gyrus,right middle temporal gyrus,right superior frontal gyrus and bilateral orbital frontal gyrus were weakened(p < 0.05),and functional connectivity between PCC and left middle temporal gyrus and left middle frontal gyrus increased(p < 0.05).Conclusions1.The FC of the food reward systems(rOFC/rTL/rPA),the right thalamus and somatosensory regions(the rSMG and rRO)demonstrated changes after physiol ogical food intake in healthy subjects at 4 different gastrointestinal physiological states,showing a downward trend and right lateralization.2.Gastric motility drugs could also affect brain functional connectivity,while had no effect on the functional connectivity across time.3.This is the first study to show that the changes of functional connectivity between PCC and the whole brain over time in the resting state fMRI;in our experimental time period(7:30-12:00),the functional connectivity between PCC and right orbitofrontal gyrus/putamen /thalamus,right supramarginal gyrus and right opercular showed decreased trend,and,the lateralization advantage of the right hemisphere.