Yanyang Zhang1, Tao Zhou1, Shiyu Feng1, Wenxin Wang2, Hailong Liu1, Peng Wang1, Zhiqiang Sha3, Xinguang Yu4. 1. Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, PR China. 2. Department of Radiology, The First Medical Center of Chinese PLA General Hospital, Beijing, PR China. 3. Department of Psychiatry, Western Psychiatric Institute and Clinic, , University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: sha.zhiqiang@163.com. 4. Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, PR China. Electronic address: yuxinguang_301@163.com.
Abstract
BACKGROUND: Cortisol has long been considered to play a crucial role in the pathogenesis of stress-related disorders. Cushing's disease (CD) provides an excellent "hyperexpression model" to investigate the chronic effects of cortisol on brain physiology and cognition. Previous studies have shown that cortisol is associated with neurophysiological alterations in animal models, which has also been examined by neural activity and cerebral blood flow (CBF) in human studies. However, the manner in which cortisol affects the coupling between brain activity and metabolic demand remains largely unknown. METHODS: Here we used functional magnetic resonance imaging and arterial-spin-labeling imaging to investigate neurophysiological coupling by examining the ratio of CBF and functional connectivity strength (FCS) in 100 participants (47 CD patients and 53 healthy controls). RESULTS: The results showed that CD was associated with lower CBF-FCS coupling predominantly in regions involving cognitive processing, such as the left dorsolateral prefrontal cortex and precuneus, as well as greater CBF-FCS coupling in subcortical structures, including the bilateral thalamus, right putamen, and hippocampus (P < 0.05, false discovery rate corrected). Moreover, regions with disrupted CBF-FCS coupling were associated with cortisol dosage and cognitive decline in CD patients. CONCLUSIONS: Together, these findings elucidate the effect of cortisol excess on cerebral microenvironment regulation and associated cognitive disturbances in the human brain.
BACKGROUND:Cortisol has long been considered to play a crucial role in the pathogenesis of stress-related disorders. Cushing's disease (CD) provides an excellent "hyperexpression model" to investigate the chronic effects of cortisol on brain physiology and cognition. Previous studies have shown that cortisol is associated with neurophysiological alterations in animal models, which has also been examined by neural activity and cerebral blood flow (CBF) in human studies. However, the manner in which cortisol affects the coupling between brain activity and metabolic demand remains largely unknown. METHODS: Here we used functional magnetic resonance imaging and arterial-spin-labeling imaging to investigate neurophysiological coupling by examining the ratio of CBF and functional connectivity strength (FCS) in 100 participants (47 CD patients and 53 healthy controls). RESULTS: The results showed that CD was associated with lower CBF-FCS coupling predominantly in regions involving cognitive processing, such as the left dorsolateral prefrontal cortex and precuneus, as well as greater CBF-FCS coupling in subcortical structures, including the bilateral thalamus, right putamen, and hippocampus (P < 0.05, false discovery rate corrected). Moreover, regions with disrupted CBF-FCS coupling were associated with cortisol dosage and cognitive decline in CD patients. CONCLUSIONS: Together, these findings elucidate the effect of cortisol excess on cerebral microenvironment regulation and associated cognitive disturbances in the human brain.