Functional Magnetic Resonance Imaging Study Of Abberant Brain Circuit In Panic Disorder

Objective: Panic Disorder(PD)is characterized by sudden and recurrent panic attacks that are accompanied by intense distress,fear and various physical symptoms.Anticipatory anxiety and harm avoidance are essential features of PD.Studies have suggested that PD patients may have weakened cognitive regulation of the Cognitive Control Network(CCN)and enhanced negative emotion reaction of the Mood Regulating Circuit(MRC),which may be associated with the disease mechanism of PD.And during anticipatory anxiety,phasic threat responding appears to be mediated by the amygdala,while sustained threat responding seems related to the bed nucleus of the stria terminalis(BNST).In this study,we analyzed the difference of brain activity in PD patients and healthy controls(HC)by resting-state and task-state functional magnetic resonance imaging(f MRI)in order to explore the possible abnormalities of neural mechanism in PD,and to provide evidence for future research and clinical treatment.Methods: We use cross-sectional case-control study.20 PD patients from hospital outpatients or wards was contained according to the Diagnostic and Statistical Manual of Mental Disorder,Fifth Edition(DSM-5).And 20 healthy controls were recruited from the community.Then,the demographic data,clinical data and f MRI data were collected.The general demographic data and the score of Hamilton Anxiety Scale(HAMA)were analyzed by using independent sample t-test.Additionally,Granger Causality Analysis(GCA)and two-sample t test utilizing the BNST as a seed region were used to compare the causal relationship between BNST and the whole brain under resting state.At last,the two-sample t test was used to compare the differences in the activation of CCN and MRC between the two groups.Results: 1.In resting state:(1)Compared with healthy controls,PD patients showed enhanced causal connectivity from these brain regions to the left BNST: The right precentral gyrus(Pre CG)(MNI:60,-6,33;t=4.58;p<0.01),left parahippocampal(MNI:-24,-12,-21;t=3.24;p<0.01).(2)PD patients exhibited weakened causal connectivity from these brain regions to the left BNST: The right dorsolateral prefrontal cortex(dl PFC)(MNI:39,54,12;t=-3.96;p<0.01),left temporal(MNI:-63,-36,6;t=-2.98;p<0.01).(3)PD patients demonstrated increased causal connectivity from these brain regions to the right BNST: The right Pre CG(MNI:57,-6,27;t=5.01;p<0.01),right insula(MNI:36,-21,21;t=4.10;p<0.01),right temporal(MNI:42,-60,21;t=3.26;p<0.01).(4)PD patients revealed decreased causal connectivity from these brain regions to the right BNST: The left dl PFC(MNI:-42,42,24;t=-2.95;p<0.01),left cerebellum(MNI:-9,-54,-30;t=-3.40;p<0.01).(5)PD patients relative to controls displayed significantly increased causal connectivity from the left BNST to the whole brain,including: The right dl PFC(MNI:48,45,6;t=4.03;p<0.01),left temporal(MNI:-57,-39,-12;t=3.13;p<0.01),left inferior frontal gyrus(MNI:-45,36,-12;t=3.93;p<0.01).(6)PD patients showed decreased causal connectivity from the left BNST to these brain regions: The left Pre CG(MNI:-54,-9,45;t=-3.61;p<0.01),right Pre CG(MNI:60,-6,30;t=-5.57;p<0.01),left dorsomedial prefrontal cortex(dm PFC)(MNI:-6,60,30;t=-5.00;p<0.01),right insula(MNI:39,-9,15;t=-3.98;p<0.01),right fusiform(MNI:39,-9,-42;t=-4.65;p<0.01),right temporal(MNI:54,-36,6;t=-3.03;p<0.01).(7)PD patients exhibited enhanced causal connectivity from the right BNST to these brain regions: The left dl PFC(MNI:-42,42,24;t=5.42;p<0.01),right dl PFC(MNI:45,54,9;t=3.44;p<0.01),left temporal(MNI:-45,15,-18;t=3.31;p<0.01).(8)PD patients showed decreased causal connectivity from the right BNST to these brain regions: The left Pre CG(MNI:-51,-6,30;t=-3.30;p<0.01),right Pre CG(MNI:51,-3,24;t=-4.30;p<0.01),right lingual(MNI:6,-78,-12;t=-4.13;p<0.01),right insula(MNI:39,-9,15;t=-4.14;p<0.01),right temporal(MNI:51,-24,-3;t=-4.26;p<0.01),right cerebellum(MNI:24,-66,-18;t=-3.72;p<0.01).2.In task state:(1)Taking the neutral emotion picture as the baseline control,PD patients showed decreased activation in these brain regions when observing the negative emotion pictures: The left dl PFC(MNI:-21,3,60;t=-3.15;p<0.05),right dl PFC(MNI:21,0,66;t=-2.70;p<0.05),left d ACC(dorsal anterior cingulate cortex)(MNI:-6,15,24;t=-1.82;p<0.05),right d ACC(MNI:6,-12,30;t=-3.04;p<0.05),right thalamus(MNI:18,-9,0;t=-2.56;p<0.05),left precuneus(MNI:-12,-66,51;t=-2.86;p<0.05),left DH(dorsolateral hippocampus)(MNI:-18,-36,6;t=-1.80;p<0.05).(2)And showed increased activation in these brain regions: The left VH(ventromedial hippocampus)(MNI:-18,-15,-18;t=2.06;p<0.05),left vm PFC(ventromedial prefrontal cortex)(MNI:-6,45,-9;t=2.48;p<0.05).Conclusions: 1.The pathogenesis of panic disorder may be related to the aberrant causal connectivity between the BNST and the whole brain.The increased causal effects from MRC to BNST and the enhanced causal connectivity from the BNST to the CCN may be the neuropathological features of PD patients.The MRC of healthy people receives regulation from the CCN through BNST,whereas the PD patients have the opposite circuit.2.PD patients may have weakened cognitive regulation of the CCN and enhanced negative emotion reaction of the MRC,which may be associated with the pathogenesis of PD.