Graph Theoretical Analysis of Sedation's Effect on Whole Brain Functional System in School-Aged Children

Abstract

The neurophysiological mechanism underlying sedation, especially in school-aged children, remains largely unknown. The recently emerged resting-state functional magnetic resonance imaging (rsfMRI) technique, capable of delineating brain's functional interaction pattern among distributed brain areas, proves to be a unique and powerful tool to study sedation-induced brain reorganization. Based on a relatively large school-aged children population (n=28, 10.3±2.6 years, range 7-15 years) and leveraging rsfMRI and graph theoretical analysis, this study aims to delineate sedation-induced changes in brain's information transferring property from a whole brain system perspective. Our results show a global deterioration in brain's efficiency properties (p=0.0085 and 0.0018, for global and local efficiency, respectively) with a locally graded distribution featuring significant disruptions of key consciousness-related regions. Moreover, our results also indicate a redistribution of brain's information-processing hubs characterized by a right and posterior shift as consistent with the reduced level of consciousness during sedation. Overall, our findings inform a sedation-induced functional reorganization pattern in school-aged children that greatly improve our understanding of sedation's effect in children and may potentially serve as reference for future sedation-related experimental studies and clinical applications.

Network Properties in Transitions of Consciousness during Propofol-induced Sedation

“…We calculated the global efficiency, local efficiency, and small-worldness. These indices are crucial for understanding the information sharing, integration, and segregation among the brain system 58 . Global efficiency represents the total capacity for parallel processing of information and integrated processing 59 .…”

Assessing Cerebral White Matter Microstructure in Children With Congenital Sensorineural Hearing Loss: A Tract-Based Spatial Statistics Study

“…Nevertheless, we recognize that sedation may affect brain structure and function. A brain connectivity analysis of resting-state functional MRI study examined the effect of chloral hydrate-induced light sedation in school-aged children (Wei et al, 2013). Their study showed a global detrimental effect of sedation on the functional interactions of the brain, especially on the information-processing properties.…”

Biomarkers, designs, and interpretations of resting‐state fMRI in translational pharmacological research: A review of state‐of‐the‐Art, challenges, and opportunities for studying brain chemistry

“…Anesthetics have often been used to gain a better understanding of the clinical relevance of resting‐state fMRI biomarkers (see “Methods Validation and Calibration” for details). Derivative biomarkers such as network properties, coherence or spectral power, have been used to study the global effects of drugs on the brain, in terms of the reconfiguration of resting‐state networks under sedation with propofol [Gili et al, ; Jordan et al, ; Monti et al, ; Schroter et al, ; Schrouff et al, ], chloral hydrate [Wei et al, ] and sevoflurane [Peltier et al, ; Qiu et al, ].…”

“…Anesthetics have often been used to gain a better understanding of the clinical relevance of resting-state fMRI biomarkers (see "Methods Validation and Calibration" for details). Derivative biomarkers such as network properties, coherence or spectral power, have been used to study the global effects of drugs on the brain, in terms of the reconfiguration of resting-state networks under sedation with propofol [Gili et al, 2013;Jordan et al, 2013;Monti et al, 2013;Schroter et al, 2012;Schrouff et al, 2011], chloral hydrate [Wei et al, 2013] and sevoflurane [Peltier et al, 2005;Qiu et al, 2008]. As will be discussed in "Challenges and Limitations," dose/response evaluation, also known as pharmacokinetic/pharmacodynamic (PK/PD) modeling is one of the most challenging, but also most important goals of pharmacological neuroimaging.…”

“…As will be discussed in “Pharmacological Probing of Neural Networks,” pharmacological studies involving anesthetics have been critical in validation of these graph metrics, by finding association between their features and states of conscious mental activity. For example, reduced local and global efficiency of cortical regions are detected during light chloral hydrate sedation in children [Wei et al, ] and during loss of consciousness in propofol sedation in adults [Monti et al, ], indicating that global network efficiency can serve as a biomarker of the state of consciousness. Although these global effects may reflect the global state of consciousness and metabolism, the regional network properties do not change in a single direction.…”