Altered blood oxygen level-dependent signal variability in chronic post-traumatic stress disorder during symptom provocation

Abstract

Jun Ke,1,* Li Zhang,2,* Rongfeng Qi,1,* Qiang Xu,1 Weihui Li,2 Cailan Hou,3 Yuan Zhong,1 Zhiqiang Zhang,1 Zhong He,4 Lingjiang Li,2,5 Guangming Lu11Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, 2Mental Health Institute, the Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, 3Guangdong Academy of Medical Science, Guangdong General Hospital, Guangdong Mental Health Center, Guangzhou, 4Department of Radiology of the Second Xiangya Hospital, Central South University, Changsha, 5Shenzhen Kangning Hospital of Guangdong Province, Shenzhen, People’s Republic of China*These authors contributed equally to this workBackground: Recent research suggests that variability in brain signal provides important information about brain function in health and disease. However, it is unknown whether blood oxygen level-dependent (BOLD) signal variability is altered in post-traumatic stress disorder (PTSD). We aimed to identify the BOLD signal variability changes of PTSD patients during symptom provocation and compare the brain patterns of BOLD signal variability with those of brain activation.Methods: Twelve PTSD patients and 14 age-matched controls, who all experienced a mining accident, underwent clinical assessment as well as fMRI scanning while viewing trauma-related and neutral pictures. BOLD signal variability and brain activation were respectively examined with standard deviation (SD) and general linear model analysis, and compared between the PTSD and control groups. Multiple regression analyses were conducted to explore the association between PTSD symptom severity and these two brain measures across all subjects as well as in the PTSD group.Results: PTSD patients showed increased activation in the middle occipital gyrus compared with controls, and an inverse correlation was found between PTSD symptom severity and brain activation in the hippocampus and anterior cingulate cortex/medial prefrontal cortex. Brain variability analysis revealed increased SD in the insula, anterior cingulate cortex/medial prefrontal cortex, and vermis, and decreased SD in the parahippocapal gyrus, dorsolateral prefrontal cortex, somatosensory cortex, and striatum. Importantly, SD alterations in several regions were found in both traumatic and neutral conditions and were stratified by PTSD symptom severity.Conclusion: BOLD signal variability may be a reliable and sensitive biomarker of PTSD, and combining brain activation and brain variability analysis may provide complementary insight into the neural basis of this disorder.Keywords: brain variability, general linear model, insula, functional magnetic resonance imaging