FMRI Study On The Dynamic Functional Connectivity Network Of Amygdala In Patients With Chronic Non-Specific Low Back Pain

ObjectiveIn order to explore the possible mechanism of the amygdala participating in the central pathological process of chronic non-specific low back pain(CNLBP),the changes of dynamic functional connectivity of amygdala and its relationship with pain characteristics and negative emotions in CNLBP patients were observed based on resting-state functional magnetic resonance imaging(f MRI).MethodsA total of 62 qualified subjects were recruited in this study,including 31 patients with CNLBP and 31 healthy controls with age and gender matched.The general demographic data were collected for all subjects,including age,gender,body mass index,disease course,and other information.The Short Form of Mc Gill Pain Questionnaire(SF-MPQ),Oswestry Disability Index(ODI),Beck Depression Inventory-II(BDI-Ⅱ),Beck Anxiety Inventory(BAI),and Fear Avoidance Beliefs Questionnaires(FABQ)were used to evaluate pain characteristics and negative emotions.The resting-state f MRI data of the included subjects were acquired with a German Siemens 3.0T magnetic resonance scanner.Magnetic resonance imaging data was preprocessed by using CONN 20.b toolbox.Then,the bilateral amygdala was chosen as the region of interest.Sliding window correlation and K-means clustering analysis were conducted by Dynamic BC 2.2 toolbox,so as to measure the dynamic functional connectivity(dFC)between the amygdala seed point and other voxels in the whole brain,including dFC variability,functional connectivity in each state,and temporal attributes of dFC states.Independent samples t-test was used to compare differences between the two groups for normally distributed data,and Mann-Whitney U test was used for non-normally distributed data;the threshold was voxel-level P<0.005,cluster-level FDR correction P<0.05.Finally,correlation analysis was performed between dFC characteristics of brain regions with significant differences between the two groups and clinical behavioral indicators such as clinical scale scores and disease course of CNLBP patients.Results1.General data: There were not statistically significant differences in age,gender,body mass index,and so on between the two groups(P>0.05).For negative emotion,the scores of BDI-Ⅱ,and BAI in the CNLBP group were significantly higher than those in the healthy controls(P<0.001).2.dFC variability: The variability of dFC between the right amygdala and right inferior parietal gyrus,right dorsolateral superior frontal gyrus were significantly increased in the CNLBP group compared with the healthy control group(P<0.05);in contrast,dFC variability was significantly decreased in the right amygdala and left precuneus,right cuneus/precuneus,right middle cingulate & paracingulate gyri,and left paracentral lobule(P<0.05).However,comparison of dFC variability in the left amygdala between the two groups was not statistically significant(P>0.05).3.Temporal attributes of dFC states: 4 repeated transient functional connection states were identified in amygdala both of the left and right hemispheres.The fraction time and mean dwell time of the left amygdala at State 2 in CNLBP group were significantly higher than those in the healthy control group(P<0.05).There was no significant difference between groups in the dFC status temporal attributes of the right amygdala(P>0.05).4.Functional connectivity in each state: Compared with the healthy control group,the functional connectivity between the left amygdala at State 2 and the right inferior temporal gyrus was significantly increased in CNLBP group(P<0.05),but functional connectivity with the left middle cingulate & paracingulate gyri were weaker(P<0.05);the functional connectivity between the right amygdala at State 2 and the right precuneus,left paracentral lobule,and left lingual gyrus were significantly increased in CNLBP group(P<0.05),but its functional connectivity with left anterior cingulate cortex,left ventral posterolateral nucleus of thalamus,right lobule VIIB of cerebellar hemisphere,left lobule VIII of cerebellar hemisphere,left precentral gyrus,right supplementary motor area,bilateral middle frontal gyrus,right inferior occipital gyrus,left lingual gyrus,left medial superior frontal gyrus,and left supramarginal gyrus were weaker(P<0.05).5.Correlation analysis:(1)The dFC variability of the right amygdala and the right dorsolateral superior frontal gyrus was positively correlated with the total score of SF-MPQ,the scores of SF-MPQ pain rating index and its affective pain,SF-MPQ present pain intensity score,ODI score in CNLBP patients(r=0.492,P=0.006;r=0.442,P=0.015;r=0.425,P=0.019;r=0.394,P=0.031;r=0.365,P=0.047),and was positively correlated with FABQ scale score(r=0.406,P=0.026).(2)No significant correlation was found between abnormal temporal attributes of dFC states and clinical behavioral indicators(P>0.05).(3)Functional connectivity of the left amygdala at State 2 and the right inferior temporal gyrus in CNLBP patients was negatively correlated with the total score of SF-MPQ,the scores of SF-MPQ pain rating index and its sensory pain(r=-0.382,P=0.041;r=-0.405,P=0.029;r=-0.432,P=0.019),but the functional connectivity between the left amygdala and left middle cingulate& paracingulate gyri was positively correlated with SF-MPQ pain rating index score(r=0.373,P=0.046);Besides,functional connectivity between the right amygdala at State 2 and the right inferior occipital gyrus were positively correlated with the scores of SF-MPQ pain rating index and its affective pain,ODI score in CNLBP patients(r=0.367,P=0.046;r=0.371,P=0.043;r=0.381,P=0.038).And ODI score of CNLBP patients was negatively correlated with functional connectivity between the right amygdala at State 2 and right precuneus,left paracentral lobule,left lingual gyrus(r=-0.403,P=0.027;r=-0.382,P=0.037;r=-0.562,P=0.001),but was positively correlated with functional connectivity between the right amygdala and right lobule VIIB of cerebellar hemisphere,left lobule VIII of cerebellar hemisphere,left lingual gyrus(r=0.397,P=0.030;r=0.418,P=0.022;r=0.397,P=0.030).Conclusions1.Stability and flexibility of information exchange between the brain regions of right amygdala dFC network in CNLBP patients was insufficient.In particular,poor functional connectivity stability between the right amygdala and right dorsolateral superior frontal gyrus was closely correlated with severe pain symptoms,disability and fear avoidance.2.For CNLBP patients,there were 4 inherent and spontaneously repeated dFC states in amygdala both of the left and right hemispheres,which were mainly characterized by higher occurrence frequency and longer dwell time of State 2 of left amygdala with abnormal connectivity patterns related to the sensory pain intensity appeared repeatedly;besides,right amygdala at State 2 was characterized by some abnormal connectivity patterns related to severity of affective pain and disability,the main feature was weaker functional connectivity.3.The amygdala dFC state with frequent occurrence and weak functional connectivity may be the key state to participate in the central pathological mechanisms of CNLBP,the time-varying characteristics of abnormal neural activity were mainly located between the left amygdala and right inferior temporal gyrus,between the right amygdala and right precuneus,left paracentral lobule,left lingual gyrus,right inferior occipital gyrus,which may be used as underlying objective biological indicators of the CNLBP severity.