The Impact Of Stressful Life Events On Functional Brain Network

Stressful life events refer to the negative life changes that people may experience in their daily life and that bring significant stress to individuals(e.g. breaking up with romantic partners, the death of relatives or good friends). Experiencing stressful life events can cause subsequent cognitive, behavioral, emotional and somatic problems. Stress-related mental disorders including the anxiety disorder, major depression disorder and post-traumatic stress disorder are directly linked to the stress that comes together with the life events. What happens in our brain that transforms our response to stress to emotional disorders? Recently, the development of noninvasive neuroimaging technologies, especially Magnetic Resonance Imaging(MRI), provides us with a novel perspective to think about this question.Our understanding of how the brain process the information of stress has a focus on the amygdala, hippocampus and the prefrontal cortex circuit. This neural circuit is involved in the regulation of acute and chronic stress across specials. Previous studies have investigated the role of this circuit in acute stress response and stress-related disorders. However, few studies have used the resting-state functional MRI to explore how the stressful life events affect the intrinsic functional brain network in human.Resting-state fMRI is an approach to map brain function, especially the spontaneous brain activity and interaction between different brain regions when the subject does not perform certain explicit tasks. One of the key concepts in resting-state fMRI is functional connectivity. Functional connectivity can capture the correlation of Blood-oxygen-level dependent(BOLD) signal in different brain regions. The stronger functional connectivity suggests the better synchronism and information communication. This project combined both the hypothesis-driven and data-driven MRI data analysis approach. We used the amygdala-based functional connectivity to study the effect of stressful life events on amygdala-network and used the voxel-level degree centrality(DC) to investigate the effect of stressful life events on whole-brain functional connectivity.In Study 1, we analyzed the data from a longitudinal dataset with large samplesize(N=97), focusing on how the stressful life events on the longitudinal change of neural measurements between two scans(mean interval between two scans: 515 days). We found that stressful life events score negatively correlated with the decreased DC between two scans in cuneus/precuneus, midbrain/parahippocampal gyrus, insula, medial prefrontal cortex/sgACC and increased DC in the cerebellum. In addition, the stressful life events score positively correlate with the connectivity strength between the amygdala and the DLPFC, medial prefrontal cortex, fusiform gyrus and the cerebellum and are accompanied by the increased functional connectivity between the amygdala and the cerebellum between the two scans.In Study 2, we compared the group difference between the older adults who lost their only child and healthy controls. The older adults who lost their only child exhibited an ineffective coping style and more depression symptoms. They also showed decreased distant and local DC in the precuneus and left inferior parietal lobule and decreased distant DC in the bilateral dorsolateral prefrontal cortex(DLPFC). Furthermore, the decreased local and distant DC of these regions and the decreased DLPFC-precuneus connectivity strength were negatively correlated with negative coping scores in the loss group but not in the controls. Furthermore, using the amygdala and sub-regions based functional connectivity analysis, we found the reduced functional connectivity between the amygdala and medial prefrontal cortex, insula, orbitofrontal cortex, subgenual anterior cingulate(sgACC) cortex, inferior parietal lobule(IPL) and the cerebellum and that the connectivity between the left superficial amygdala and IPL negatively correlated with the years after the death of the only child.The results of study 1 and 2 suggest that stressful life events can affect the individuals’ emotional state and cope style. More importantly, stressful life events affect the efficiency of information communication of brain hubs(e.g. precuneus and IPL) in the whole-brain network and the prefrontal-amygdala circuit which is involved in top-down emotion regulation and the connectivity between the amygdala and cerebellum which are involved in emotion reactivity. Those changes of functional connectivity could be the biomarker of the effect of stress on the human brain and the underlying biological mechanism for future psychopathology. As the progress of the investigation of stress using neuroimaging, it could be possible to measure objectively the risk for mental disorders after the traumatic experience based on MRI.