Resting-State Functional MRI Study Of The Neuropathological Mechanism Of Post-Traumatic Stress Disorder Using Functional Connectivity Analysis

Post-traumatic stress disorder(PTSD)is an anxiety disorder that follows exposure to extreme stressful experiences,which causes considerable damage to patient's mental health.When experiencing acute stress events,most people will have acute psychological stress response but soon recover,however,about 8%of these subjects will develop to PTSD.PTSD is characterized by three hallmark symptoms:re-experiencing of the traumatic event and fear component,avoiding any scene that can cause traumatic memories,and hyperarousal or increased startle responses.PTSD causes serious damage to the patient's psychological healthy and social functions,and even result in the lifelong loss of work and life skills.The neuropathology of PTSD is still unclear now.Accumulating evidence from neuroimaging studies has showed evidence of the abnormal cortico-limbic circuitry(especially the amygdale-medial prefrontal cortex-hippocampus)in PTSD.Resting-state functional MRI(rs-fMRI),with the advantages of non-invasive,high-resolution and easy application,has been widely used in cognitive neuroscience and many neuropsychiatric disorders.Among the techonologies in rs-fMRI,functional connectivity,which focuse on the temporal synchrony or correlation between two or more spatially separate regions,is one of the most used analysis algorithms.In the present study,functional connectivity rs-fMRI was used to investigate the neuropathological mechanism of PTSD.There are three parts in this graduation thesis.First,the independent component analysis and correlation analysis were used to observe the changes of brain default mode network in PTSD patients.Second,whole-brain functional connectivity based on the AAL(Automated Anatomical Labeling)template in PTSD patients was performed.Final,we explore the alteration of the effective connectivity between amygdale and other brain regions,especially the prefrontal cortex,in posttraumatic stress disorder(PTSD)patients.Part I.Altered Brain Default Mode Network in Posttraumatic Stress DisorderPurpose:Brain default mode network plays an important role in maintaining the cognitive function of the human brain in the resting state.We plan to explore the changes of brain default mode network in posttraumatic stress disorder(PTSD)in this study.Methods:Seventy-two PTSD patients and eighty-six trauma-exposed non-PTSD age and gender matched controls underwent standard resting state functional MRI scan.The components representing DMN were picked out after separation of independent component analysis.One and two sample t-tests were used to observe the changes of spatial pattern of DMN in the patients in contrast to the controls(p<0.05,multiple comparison correction with Alphasim).In addition,the time series of eight DMN regions were extracted(MPFC[medial prefrontal cortex],posterior cingulate cortex/precuneus[PCC/PCUN],bilateral IPL[inferior parietal lobe],ITG[inferior temporal gyrus]and PHG[parahippocampal gyrus]),then the temporal correlation coefficients of each pair of these eight ROIs was calculated and compared between PTSD and control groups.Results:Typically spatial distributions of the DMN were found in both PTSD patients and controls.Comparison result revealed that there was significant dissociation of DMN in PTSD patients:increased functional connectivity in the MPFC and reduced functional connectivity in the PCC/PCUN,and bilateral IPL.Within the DMN,the functional connectivities between the left ITG-MPFC,left ITG-PCC/PCUN,and left ITG-bilateral IPL reduced in PTSD patients(p<0.05,uncorrected).Conclusion:Resting state functional MRI may be used to observe DMN changes in PTSD patients.There is dissociation of anterior and posterior DMN,and disturbed inter-correlation within DMN in PTSD patients.Abnormalities of DMN in PTSD may realte to the impaired cognitive function in patients.Part ?.Whole Brain Resting State Functional Connectivity Abnormalities in Treatment-Naive Post-traumatic Stress Disorder Patients-without Comorbid ConditionsPurpose:Convergent studies have highlighted the dysfunction of the cortico-limbic circuitry dysfunction in post-traumatic stress disorder(PTSD).However,little is known about the integration between these brain regions in PTSD patients.The aim of this study was to investigate the changes of AAL(Automated Anatomical Labeling)template based whole-brain functional connectivity in PTSD patients.Methods:Seventy-two PTSD patients and eighty-six trauma-exposed non-PTSD controls participated in the resting-state fMRI study.The cerebrum was segmented into 90 anatomical regions of interest(ROI)according to the Automated Anatomical Labeling(AAL)template.These 90 ROIs were used to define the reference time series.Functional connectivities between these 90 paired brain regions were calculated and compared between PTSD patients.and non-PTSD controls.Results:Compared with non-PTSD controls,PTSD patients showed widespread abnormal functional connectivity.In detail,patients showed seven weaker positive connectivities:between left middle prefrontal cortex(mPFC)and right amygdala,bilateral hippocampus,parahippocampal gyri,and right rectus,as well as between left inferior orbitofrontal cortex and right hippocampus.In addition,PTSD patients showed two stronger negative connectivity:between posterior cingulate cortex(PCC)and bilateral insula.The Clinician-Administered PTSD Scale(CAPS)scores in PTSD patients negatively correlated with the connectivity between the amygdala and mPFC.The other abnormal connectivities had no correlation with the CAPS scores.Conclusion:PTSD patients showed abnormalities in the whole brain functional connectivity,primarily affecting the connectivities between mPFC and limbic system,and connectivity between PCC and insula.These findings indicate that the information transfer or integration between brain regions was disrupted in PTSD patients.Part ?.Altered Effective Connectivity Network of the Amygdala in Posttraumatic Stress Disorder:A Study Based on Granger Causality AnalysisPurpose:Previous neuroimaging studies showed that the amygdala,which mediates symptoms of hyperarousal,palys an important role in the posttraumatic stress disorder(PTSD).This study was to explore the alteration of the effective connectivity between amygdala and other brain regions(especially the prefrontal cortex)in PTSD patients.Methods:Seventy-two PTSD patients and eighty-six trauma-exposed non-PTSD controls participated in the resting-state fMRI study.Granger causality was performed to compare the effective connectivity network of amygdala between PTSD patients and controls,and Pearson correlation was performed between abnormal regional Granger causality and the Clinician-Administered PTSD Scale(CAPS)score of patients.Results Compared with controls,PTSD patients showed decreased influence from amygdala to medial frontal gyrus,cingulate cortex,superior and inferior frontal gyri,superior and inferior temporal gyri,putmen,and inceased influence from amygala to hippocampus,parahipocampal gyrus,cuneus,precuneus and thalamus.Furthermore,PTSD patients exhibited decreased influence from medial and middle frontal gyri,superior/middle temporal gyri,nsular,and putmen to amygdala,and increased influence from cuneus,precuneus and parahippocampal gyrus to amygdala.The CAPS score of PTSD patients negatively correlated with effective connectivity from amygdala to superior and inferior temporal gyri,from middle frontal gyrus to amygdala,and positively correlated with effective connectivity from amgdala to precuneus.Conclusion:The effective connectivity network of amygdala is widespreadly disrupted in PTSD patients,and is partly correlated with their disease severity.