Neural Basis Of Abnormal Heartbeat Perception Of Patients With Panic Disorder: Case-control And System Review Study

Objective 1. To investigate the behavior mode about heartbeat sensitivity in panic disorder(PD) patients. 2. To explore the neuropathology of panic disorder in heartbeat perception by means of multimodal brain imaging research and system review technology, integrating structural and functional MRI scans.Methods 1. We investigated heartbeat sensitivity in patients with either PD or GAD and in healthy controls using a well-validated mental tracking task. 2. 19 PD patients, 19 GAD patients and 20 healthy volunteers received 3T magnetic resonance imaging acquisition for the structural, heartbeat perception task and a resting-state imaging of brain. Three techniques were used with all subjects: voxel based morphometry(VBM), resting-state functional connectivity analysis and AFNI(Analysis of Functional NeuroImage). We set the left ACC as a region of interest(ROI) to examine the functional connetions. Correlations between clinical symptoms, interoception ability and abnormal structural and functional brain regions were performed, and a significance level was set at α=0.05(2-tails). 3. An electronic search was performed up to Aug 2012. Randomised controlled trials(RCTs) or quasi-randomised trials evaluating rTMS for panic disorder were selected. Two review authors independently selected studies and extracted data and verified it by cross-checking. For binary data, we calculated fixed-effect risk ratio(RR) and its 95% confidence interval(CI). For continuous data, we calculated fixed-effect standardized mean difference(SMD) and its 95% CI.Results 1. 45 PD, 141 GAD patients and 56 healthy controls finished the clinical scales and heartbeat ability assessment. PD patients show Increased cardiac awareness than GAD patients and healthy controls 2.1. PD patients showed significantly increased activity in left cingulate gyrus during heartbeat attention. Increased activity during tone detection could be observed in bilateral precuneus, left medial frontal gyrus, the right supramarginal gyrus, the left inferior parietal lobule, the left post-central gyrus, the middle temporal gyrus among PD patients. The left medial frontal gyrus BOLD signal positively correlated with the BPQ score in PD group(R=0.540;P=0.031). The interoception < extra-perception contrast yielded a network of regions, including the left postcentral gyrus, middle frontal gyrus(including SMA), left cingulate gyrus, bilateral medial frontal, bilateral middle occipital gyrus, left inferior frontal gyrus and left insular. 2.2. The bilateral putamen, subcallosal gyrus, caudate nucleus, anterior cingulated cortex(ACC) and amygdale were significantly increased in PD patients. 2.3. PD patients demonstrated increased connectivity between left ACC and bilateral post-central gyrus, insula and superior temporal gyrus. 3. Only two RCTs of rTMS(n=40) were available and their sample sizes were small. For the primary outcome, one trial with 25 participants reported a superior effect of rTMS on reducing panic symptoms to that of sham rTMS(t = 3.04, df=16.57, P = 0.007). The other trial found no significant difference between real rTMS and sham rTMS(Mann Whitney U test, P>0.05).Conclusion 1. Using heartbeat perception tasks in PD supported the notion of higher interoceptive sensitivity towards heartbeat. 2. For the processing of interoception in PD patients, there are abnormal activation of brain regions including medial frontal gyrus, cingulate gyrus, insula and amygdala. 3. Low frequency rTMS on right DLPFC is effective for PD patients, but the available data are still insufficient for us to draw any conclusions about its efficacy for PD.