Influence Of Acupuncture On Functional Brain Connectivity Network Of Hippocampus In Functional Constipation Patients

ObjectiveThis study aimed to explore the characteristics of the central nervous system response to acupuncture treatment on patients with functional constipation(FC)by functional Magnetic Resonance Imaging(fMRI)combining the functional brain network analysis and functional connectivity,in order to provide more scientific evidence for clinical acupuncture treatment of FC.Methods1.54 FC patients and 30 healthy subjects(HS)were recruited in this study and all of the subjects have received the f MRI scan.Firstly,we chose the variable node between FC patients and HS as the regions of interest(ROI)based on the functional brain network analysis,then investigated the differences in functional connectivity between FC patients and HS.The Patient Assessment of Constipation Symptom(PAC-SYM)and Patient Assessment of Constipation Quality of Life(PAC-QOL)were used to evaluate the patients' clinical variables.Finally,the correlation analysis between the clinical variables and the functional brain network(nodal characteristics and functional connectivity)was conducted to explore the abnormal alterations of cerebral activities,to give reference for the central mechanism study of acupuncture for FC.2.FC patients were randomly assigned to three groups with a ratio of 1:1:1,including Group A(acupuncture at acupoints),Group B(sham acupuncture at non-acupoints),and Group C(waiting treatment).The subjects of the two acupuncture groups received 10 times treatment for two weeks.The subjects of the waiting treatment group did not receive any intervention during the study period.PAC-SYM and PAC-QOL were used to evaluate the clinical efficacy after two weeks' treatment.This study designed two levels to explore the central mechanism of acupuncture for FC.The first level explored the differences in clinical efficacy and functional brain network between Group AB(combine Group A and Group B)with Group C.The second level explored the differences in clinical efficacy and the functional brain network between Group A and Group B.Results1.The abnormal characteristics of functional brain connectivity network53 FC patients and 30 HS completed the first f MRI scanning.Compared to HS,the nodal betweenness,nodal degree and nodal efficiency of left rostral hippocampus decreased.Regarding the left rostral hippocampus as ROI,the functional connectivity of left rostral hippocampus-right rectus gyrus,right orbital part of middle frontal gyrus,left caudate nucleus,bilateral orbital part of superior frontal gyrus,left orbital part of inferior frontal gyrus,left insula,left superior temporal gyrus,left median cingulate and paracingulate gyrus,right anterior cingulate gyrus and paracingulate gyrus,left medial superior frontal gyrus,right opercular part of inferior frontal gyrus,left supplementary motor area,left dorsolateral superior frontal gyrus,left precuneus,right superior occipital gyrus,right middle frontal gyrus,right superior frontal gyrus,right inferior cerebellar lobe were decreased.The functional connectivity of left rostral hippocampus-left precuneus,right rectus gyrus,left inferior orbital gyrus and right opercular part of inferior frontal gyrus were negatively related to physical discomfort;the functional connectivity of left rostral hippocampus-left supplementary motor area and right superior frontal gyrus were negatively related to psychosocial discomfort.2.The influence of different interventions on the central mechanism50 FC patients completed the second f MRI scanning.Group A included 16 patients,Group B included 16 patients,and Group C included 18 patients.(1)Evaluation of clinical efficacy:(1)Comparisons Group AB with Group CWithin the group: after treatment,the scores of the total PAC-SYM,the rectal symptoms subscale and abdominal symptoms subscale;the total PAC-QOL and subscales of PAC-QOL of Group AB showed significantly decreased after treatment(p<0.05).The scores of the total PACSYM,stool symptoms subscale and rectal symptoms subscale;the total PAC-QOL and physical discomfort subscale in Group C showed significantly decreased after waiting period(p<0.05).Between two groups: after treatment,the improvement of the total PAC-QOL,worries/concerns subscale,psychosocial discomfort subscale,and satisfaction subscale of Group AB were significantly greater than that in Group C(p<0.05).(2)Comparisons Group A with Group BWithin the group: after treatment,the scores of the total PAC-SYM and abdominal symptoms subscale;the total PAC-QOL worries/concerns,psychosocial discomfort,and satisfaction subscale of Group A showed significantly decreased after acupuncture treatment(p<0.05).The scores of the total PAC-QOL and the total PAC-SYM of Group B showed significantly decreased after sham acupuncture on non-acupoints(p<0.05).Between two groups: after treatment,the improvement of the abdominal symptoms subscale and satisfaction subscale in Group A was significantly greater than that in Group B(p<0.05).(2)The influence of different interventions on the functional brain network connectivity(1)Comparisons Group AB with Group CFunctional brain network Within the group: after treatment,the nodal efficiency of right rostral temporal thalamus of Group AB was decreased,the nodal degree of left rostral hippocampus of Group AB was increased.The nodal characteristics of left caudoposterior superior temporal sulcus,bilateral inferior parietal lobule,and left V5/MT area of lateral occipital cortex of Group C decreased;the nodal characteristics of left 12/47 area of orbital gyrus,left head and face region of precentral gyrus,left dorsal granular insula and left lateral amygdala of Group C were increased.Functional connectivity Within the group: after treatment,the functional connectivity of left rostral hippocampus-bilateral opercular part of inferior frontal gyrus,bilateral insula,left triangular part of inferior frontal gyrus,left middle frontal gyrus,left superior temporal gyrus,right precentral gyrus,right supramarginal gyrus of Group AB were increased.The functional connectivity of left rostral hippocampus-right rectus gyri,right orbital part of inferior frontal gyrus,right putamen and right amygdala of Group C were increased.Compared to the baseline,the functional connectivity of left rostral hippocampus-right opercular part of inferior frontal gyrus,bilateral insula and right triangular part of inferior frontal gyrus were increased of Group AB;the functional connectivity of left rostral hippocampus-right orbital part of inferior frontal gyrus and superior frontal gyrus were increased of Group C.The altered functional connectivity of left rostral hippocampus-left insula was positively related to the changes of rectal symptoms subscale and the total PAC-QOL of Group AB;The altered functional connectivity of left rostral hippocampus-right orbital part of inferior frontal gyrus was positively related to the changes of stool symptoms subscale of Group C.Between two groups: after treatment,the functional connectivity alterations of left rostral hippocampus-opercular part of inferior frontal gyrus of Group AB were greater than that in Group C.(2)Comparisons Group A with Group BFunctional brain network Within the group: after treatment,the nodal characteristics of left rostral hippocampus of Group A were increased,the nodal characteristics of right dorsal caudate dorsal,right rostral temporal thalamus of Group A were decreased.There was no significant altered nodes of Group B.Functional connectivity Within the group: after treatment,the functional connectivity of left rostral hippocampus-left cingulate gyrus,left supramarginal gyrus,left occipital pole,right inferior frontal gyrus,left rolandic operculum,right inferior cerebellar lobe of Group A was increased.The functional connectivity of left rostral hippocampus-bilateral insula,right opercular part of inferior frontal gyrus,right precentral gyrus,right middle temporal gyrus of Group B was increased.Conclusions1.The nodal characteristics of left rostral hippocampus in FC patients were abnormal,and the functional connectivity of left rostral hippocampus-prefrontal regions,cingulate gyrus,orbitofrontal regions,insula,precuneus were decreased.The abnormal Papez loop with the hippocampus as the core may be an important central pathological feature of FC.2.Regulating the functional connectivity network of the Papez loop with the hippocampus as the core,especially the altered functional connectivity network of hippocampus-cingulate gyrus,may be the central mechanism of acupuncture in FC treatment.