Resting-state Functional MRI Study Of Brain Network In Typhoon-related Post-traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a common psychiatry disorder which occurs after a traumatic event, such as military combat, nature disaster, and traffic accident. Clinically, PTSD is characterized by four symptom clusters:re-experiencing, avoidance, negative emotion and cognition, and hyperarousal. Despite of the substantial effects of PTSD symptoms on quality of life, the neural basis of this disorder has not been completely elucidated. A large amount of task-based neuroimaging studies on PTSD have revealed abnormal regional brain function in multiple regions, including the amygdala, medial prefrontal cortex, and hippocampus. However, results of these studies are often inconsistent, perhaps due to different imaging modalities, altered experiment paradigms, and heterogeneous samples. Furthermore, recent research suggests that identifying dysregulated patterns of brain connectivity could shed light on the neural mechanism of PTSD. Resting-state functional MRI is a promising approach for examining brain activity independent of stimulation or goal-directed tasks, and has been applied in brain connectivity analyses of many psychiatric and neurological diseases, In the current study, we use this method to investigate brain function of PTSD patients at three levels, including functional and effective connectivity of the amygdala, resting-state network, and large-scale functional connectivity network.Part I:Altered functional connectivity of the amygdala and its subregions in typhoon-related post-traumatic stress disorderPurpose:Neuroimaging research has implicated abnormal functional connectivity of the amygdala as a whole. The amygdala comprises functionally and structurally heterogeneous subregions, such as the basolateral amygdala (BLA) and centromedial amygdala (CMA). However, few studies have investigated functional connectivity of the amygdala subregions. Moreover, it remains unknown whether altered functional connectivity pattern of the amygdala is specific to PTSD. The present study aims to investigate the effects of trauma and PTSD on functional connectivity of the amygdala and its subregions.Materials and methods:Twenty-seven patients with typhoon-related PTSD,33 trauma-exposed controls (TEC), and 30 healthy controls (HC) were scanned with a 3T MRI scanner. Functional connectivity of the bilateral BLA, CMA, and amygdala as a whole was examined by using a seed-based approach, and then compared between groups by conducting analysis of variance.Results:In PTSD patients, BLA showed altered functional connectivity with multiple regions, while abnormal CMA functional connectivity was limited to few regions. The altered functional connectivity pattern of BLA was similar to that of the whole amygdala. Compared with the PTSD group and the HC group, the TEC group exhibited decreased and increased BLA functional connectivity with the ventral medial prefrontal cortex (vmPFC) and postcentral gyrus (PoCG), respectively. The PTSD group showed increased BLA functional connectivity with the middle frontal gyrus, inferior parietal lobe, and orbitofrontal cortex relative to both control groups. The TEC group showed increased and decreased BLA functional connectivity with the superior temporal gyrus compared with the PTSD group and the HC group, respectively.Conclusion:Decreased BLA-vmPFC functional connectivity and increased BLA-PoCG functional connectivity could reflect resilience factors for PTSD. PTSD patients show abnormal functional connectivity between the salience network and default mode network, as well as between the salience network and executive control network. Trauma leads to decreased connectivity between the BLA and superior temporal gyrus, which could be further aggravated by PTSD. It may be appropriate to use the whole amygdala as a seed for preliminary examination of brain function of the amygdala.Part II:Abnormal effective connectivity of the amygdala in typhoon-related post-traumatic stress disorder revealed by Granger causality analysisPurpose:To determine whether effective connectivity of the amygdala is altered in traumatized subjects with and without PTSD.Materials and methods:Resting-state functional MRI data were obtained for 27 patients with typhoon-related PTSD,33 trauma-exposed controls (TEC), and 30 healthy controls (HC). Effective connectivity of the bilateral amygdala was examined with Granger causality analysis and then compared between groups by conducting analysis of variance.Results:Compared with the HC group, both the PTSD group and the TEC group showed increased amygdala excitatory influence on the medial prefrontal cortex (mPFC). The TEC group showed increased mPFC inhibitory influence on the amygdala relative to the HC group. Compared with the TEC group, the PTSD group showed increased excitatory influence from the amygdala to the supplementary motor area (SMA) but increased inhibitory influence from the SMA to the amygdala. Both the PTSD group and the TEC group showed decreased excitatory influence from the superior temporal gyrus (STG) to the amygdala relative to the HC group. Compared with the HC group, the TEC group showed increased inhibitory influence from the amygdala to the dorsolateral prefrontal cortex (dlPFC), while both the PTSD group and the TEC group showed decreased inhibitory influence from the dlPFC to the amygdala. The PTSD group showed decreased inhibitory influence from the precuneus to the amygdala relative to both control groups but increased inhibitory influence from the amygdala to the precuneus relative to the HC group.Conclusion:Trauma leads to increased down-top excitation from the amygdala to the mPFC and reduced regulation of the dlPFC over the amygdala. Increased regulation of the mPFC over the amygdala may reflect a resilience factor. Altered amygdala-SMA and amygdala-STG effective connectivity may reflect compensatory mechanisms of brain function. The changes of effective connectivity between the precuneus and amygdala suggest disrupted equilibrium between the salience network and default mode network.Part â…¢:Abnormal brain connectivity within and between resting-state networks in typhoon-related post-traumatic stress disorder revealed by independent component analysisPurpose:Functional connectivity studies based on region of interest approach suggest altered functional connectivity of the default mode network (DMN), executive control network (ECN), and salience network (SN). The aim of this study is to determine whether intranetwork and internetwork brain connectivity are altered in both PTSD patients and traumatized subjects without PTSD using a data-driven approach.Materials and methods:Resting-state functional MRI data were acquired for 27 patients with typhoon-related PTSD,33 trauma-exposed controls (TEC), and 30 healthy controls (HC). Functional connectivity within the DMN, ECN, and SN as well as functional and effective connectivity between these resting-state networks were examined with independent component analysis, and then compared between groups by conducting analysis of variance.Results:Within the DMN, the TEC group showed decreased and increased functional connectivity in the superior frontal gyrus compared with the PTSD group and the HC group, respectively. The TEC group showed increased angular functional connectivity within the DMN and decreased functional connectivity in the superior temporal gyrus/posterior insula within the SN relative to the HC group. Compared with the TEC group, the PTSD group showed increased functional connectivity in the middle frontal gyrus and supplementary motor area within the ECN as well as in the inferior frontal gyrus/anterior insula within the SN. The PTSD group showed decreased functional connectivity in the supplementary motor area within the SN relative to both control groups. Moreover, the PTSD showed increased excitatory influence from the ECN to DMN compared with both control groups, while the TEC group showed increased inhibitory influence from the DMN to ECN compared with the HC group.Conclusion:Intranetwork functional connectivity within the DMN and SN is altered in traumatized subjects irrespective of PTSD diagnosis. PTSD patients also showed altered intranetwork functional connectivity within the ECN. Distinct changes of effective connectivity between the DMN and ECN in the PTSD group and TEC group may reflect different compensatory mechanisms for rebalance of resting-state networks in the two groups.Part IV:Altered whole brain functional connectivity and brain network topology in typhoon-related post-traumatic stress disorderPurpose:To investigate changes of whole brain functional connectivity and brain network topology in traumatized subjects with and without PTSD.Materials and methods:Twenty-seven patients with typhoon-related PTSD,33 trauma-exposed controls (TEC), and 30 healthy controls (HC) underwent resting-state functional MRI scanning. Whole brain functional connectivity network was constructed based on the automated anatomical labeling atlas. Graph theory method was used to analyze topological property of the large-scale functional connectivity network. Whole brain functional connectivity and the network topological property were compared between groups by conducting analysis of variance.Results:Compared with the PTSD group and the HC group, the TEC group showed increased functional connectivity between the hippocampus and postcentral gyrus (PoCG). The PTSD group showed increased dorsal cingulate cortex (dACC) functional connectivity with the PoCG and paracentral lobe relative to both control groups. Furthermore, functional connectivity network of each group showed typical small world property. Compared with the HC group, both the PTSD group and the TEC group showed increased connectivity strength and nodal efficiency in the insula. The TEC group showed increased connectivity strength in the putamen relative to both the PTSD group and the HC group. Compared with both control groups, the PTSD group showed increased nodal betweenness centrality in the precuneus.Conclusion:Heighted hippocampus-PoCG functional connectivity and increased connectivity strength in the putamen may be resilience factors for PTSD. Trauma can induce increased connectivity strength and nodal efficiency in the insula, which may be related to hyperarousal symptoms in traumatized subjects. Increased dACC functional connectivity with the somatosensory area, and higher betweenness centrality in the precuneus are relatively specific to PTSD. More longitudinal studies are needed to determine whether brain function changes are predisposing risk factors or acquired deficits of PTSD.