Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, School of Psychology, Center for Studies of Psychological Application, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, Guangdong 510631, China.
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200433, China; Neurosurgical Institute of Fudan University, Shanghai Clinical Medical Center of Neurosurgery, Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai 200433, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200433, China.
Neuroimage Clin. 2022;33:102951. doi: 10.1016/j.nicl.2022.102951. Epub 2022 Jan 30.
The neural mechanism that enables the recovery of consciousness in patients with unresponsive wakefulness syndrome (UWS) remains unclear. The aim of the current study is to characterize the cortical hub regions related to the recovery of consciousness. In the current fMRI study, voxel-wise degree centrality analysis was adopted to identify the cortical hubs related to the recovery of consciousness, for which a total of 27 UWS patients were recruited, including 13 patients who emerged from UWS (UWS-E), and 14 patients who remained in UWS (UWS-R) at least three months after the experiment performance. Furthermore, other recoverable unconscious states were adopted as validation groups, including three independent N3 sleep datasets (n = 12, 9, 9 respectively) and three independent anesthesia datasets (n = 27, 14, 6 respectively). Spatial similarity of the hub characteristic with the validation groups between the UWS-E and UWS-R was compared using the dice coefficient. Finally, with the cortical regions persistently shown as hubs across UWS-E and validation states, functional connectivity analysis was further performed to explore the connectivity patterns underlying the recovery of consciousness. The results identified four cortical hubs in the UWS-E, which showed significantly higher degree centrality for UWS-E than UWS-R, including the anterior precuneus, left inferior parietal lobule, left inferior frontal gyrus, and left middle frontal gyrus, of which the degree centrality value also positively correlated with the patients' Glasgow Outcome Scale (GOS) score that assessed global brain functioning outcome after a brain injury. Furthermore, the anterior precuneus was found with significantly higher similarity of hub characteristics as well as functional connectivity patterns between UWS-E and the validation groups. The results suggest that the recovery of consciousness may be relevant to the integrity of cortical hubs in the recoverable unconscious states, especially the anterior precuneus. The identified cortical hub regions could serve as potential treatment targets for patients with UWS.
意识恢复的神经机制在无反应性觉醒综合征(UWS)患者中仍不清楚。本研究旨在描述与意识恢复相关的皮质中枢区域。在当前的 fMRI 研究中,采用体素度中心度分析来识别与意识恢复相关的皮质中枢,共招募了 27 名 UWS 患者,其中包括 13 名从 UWS 中苏醒的患者(UWS-E)和 14 名在实验表现后至少三个月仍处于 UWS 的患者(UWS-R)。此外,还采用了其他可恢复的无意识状态作为验证组,包括三个独立的 N3 睡眠数据集(n=12、9、9 分别)和三个独立的麻醉数据集(n=27、14、6 分别)。使用 Dice 系数比较 UWS-E 和 UWS-R 之间验证组中中枢特征的空间相似性。最后,对 UWS-E 和验证状态下始终表现为中枢的皮质区域进行功能连接分析,以探讨意识恢复的连接模式。结果在 UWS-E 中确定了四个皮质中枢,这些皮质中枢的 UWS-E 度中心度明显高于 UWS-R,包括前楔前叶、左顶下小叶、左额下回和左额中回,其度中心度值也与患者的格拉斯哥预后量表(GOS)评分呈正相关,该评分评估脑损伤后大脑整体功能的预后。此外,还发现前楔前叶与 UWS-E 和验证组之间的中枢特征和功能连接模式具有显著更高的相似性。结果表明,意识恢复可能与可恢复无意识状态的皮质中枢的完整性有关,尤其是前楔前叶。所确定的皮质中枢区域可以作为 UWS 患者的潜在治疗靶点。