Study On The Brain Imaging Features Of Frontal Limbic Circuit In General Anxiety Disorder And Panic Disorder

Background: Previous studies have revealed extensive brain structural and functional deficits in patients with anxiety disorders,particularly in the prefrontal and associated limbic system.However,the relationship of these deficits with clinical features and how they changed with treatment remain unknown.This study aimed to investigate the brain imaging characteristics of the prefrontal-limbic system in drug-naive patients with general anxiety disorder(GAD)and panic disorder(PD),and the changes after treatment;and provide valuable clues for the pathological mechanism and prediction of treatment effects in anxiety disorders.Methods: A total of 122 drug-naive patients with anxiety disorders(65in GAD group,57 in PD group)and 63 healthy controls(HCs)were recruited.A total of 64 GAD patients,54 PD patients and 61 HCs completed the resting-state magnetic resonance imaging scans at baseline.Among them,96 patients with anxiety disorders(52 in GAD group,44 in PD group)completed a 4-week paroxetine treatment.Based on the human brainnetome atlas,the differences of local brain functional activity(fractional amplitude of low-frequency fluctuation,f ALFF)and gray matter volume of the three groups were compared by using the brain regions of interest(ROI)(including the amygdala,cingulate gyrus,insula,hippocampi,orbitofrontal lobe)and whole-brain analysis.Finally,Granger Causality analysis(GCA)was applied to explore causal connections between brain regions with structural and/or functional defects and other brain regions.Results: 1.Compared with HCs,GAD and PD patients showed decreased f ALFF in the right c Hipp subregion of hippocampus;and increased f ALFF in the left A23 d,A24cd and bilateral A32 sg subregions of cingulate gyrus,left A14 m and bilateral A12/47 L subregions of orbitofrontal lobe.The f ALFF values in the left A24 cd subregion were significantly higher in PD than those of GAD,while no significant difference was found in other ROI regions between the two patient groups.Whole-brain analysis revealed that abnormal functional activity regions were mainly in the anterior and posterior cingulate gyrus/paracingulate gyrus,inferior and middle orbitalfrontal gyrus and medial orbitalfrontal gyrus in GAD and PD patients.After 4 weeks of treatment,f ALFF values in the bilateral A14 m,right A11 l and A13 subregions of orbitofrontal lobe were significantly decreased in the GAD group.f ALFF values in the right A24 cd subregion of cingulate gyrus were significantly decreased in the PD group.Support vector machine(SVM)results suggested that f ALFF in the left A24 cd subregion of cingulate gyrus,left A14 m and right A12/47 L subregions of orbitofrontal lobe may be a potential imaging marker to distinguish patients with anxiety disorders from HCs.Further support vector regression(SVR)results suggested that f ALFF in the right A13 subregion of orbitofrontal lobe and right A24 cd subregion of cingulate gyrus could predict treatment response in patients with anxiety disorders.2.Compared with HCs,GAD and PD patients showed decreased gray matter volume in the bilateral A24 cd subregions of cingulate gyrus,while there was no significant difference between GAD and PD groups.Voxelbased morphometry(VBM)analysis also revealed decreased gray matter volume in the cingulate gyrus in PD patients.Further SVM analysis showed that gray matter volume in the left A24 cd subregion of cingulate gyrus may be a potential imaging marker to distinguish GAD patients from HCs.No gray matter volume alterations were observed after treatment by the ROI and whole brain analysis.3.The left A24 cd subregion of cingulate gyrus with overlapped functional and structural defects was selected as the seed.Compared with HCs,unidirectional causal connections between limbic-superior temporal gyrus temporal pole and limbic-precentral/middle frontal gyrus were enhanced in both GAD and PD patients(from the left A24 cd subregion of cingulate gyrus to the right superior temporal gyrus temporal pole,and from the left A24 cd subregion of cingulate gyrus to the right precentral/middle frontal gyrus).Compared with PD,the limbic-precuneus unidirectional causal connection was enhanced in GAD patients;Cerebellum crus1-limbic has a positive feedback effect.Conclusions: 1.There were common and unique changes in local brain functional activity in GAD and PD patients.Abnormal functional activity in the right c Hipp subregion of hippocampus,left A23 d and bilateral A32 sg subregions of cingulate gyrus,left A14 m and bilateral A12/47 L subregions of orbitofrontal lobe may be the shared imaging changes of anxiety disorders.The increased f ALFF in the left A24 cd subregion may be a unique neurobiological feature of PD patients.The f ALFF in the left A24 cd of cingulate gyrus and left A14 m and right A12/47 L of orbitalfrontal lobe may be potential imaging markers to distinguish patients with anxiety disorders from HCs,and have diagnostic significance.Treatment with antidepressants may modulate brain functional activity of some subregions.Increased f ALFF level in the right A13 subregion of the orbitalfrontal lobe and right A24 cd subregion of the cingulate gyrus could predict treatment response in patients with anxiety disorders.2.GAD and PD patients only showed decreased gray matter volume in the bilateral A24 cd subregions of cingulate gyrus.Combined with results of the first part,the left A24 cd subregion of cingulate gyrus is the only subregion that has both structural and functional changes.3.The anatomical and functional defects in the left A24 cd subregion of cingulate gyrus may partially affect the cortical-limbic-temporal circuitry,and the unidirectional causal effect from the left A24 cd subregion of cingulate gyrus to the right superior temporal gyrus temporal pole may be the shared imaging alterations by anxiety disorders.The causal effect of left A24 cd subregion of cingulate gyrus to precuneus might be related to the neurobiology of GAD.