High-Field Magnetic Resonance Department, Max Planck Institute for Biological Cybernetics, Tuebingen, 72076, Germany; Graduate Training Centre of Neuroscience, International Max Planck Research School, University of Tuebingen, Tuebingen, 72074, Germany.
Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital, Boston, MA, 02114, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.
Neuroimage. 2019 Apr 1;189:615-630. doi: 10.1016/j.neuroimage.2019.01.060. Epub 2019 Jan 29.
Despite the association between brainstem lesions and coma, a mechanistic understanding of coma pathogenesis and recovery is lacking. We developed a coma model in the rat mimicking human brainstem coma, which allowed multimodal analysis of a brainstem tegmentum lesion's effects on behavior, cortical electrophysiology, and global brain functional connectivity. After coma induction, we observed a transient period (∼1h) of unresponsiveness accompanied by cortical burst-suppression. Comatose rats then gradually regained behavioral responsiveness concurrent with emergence of delta/theta-predominant cortical rhythms in primary somatosensory cortex. During the acute stage of coma recovery (∼1-8h), longitudinal resting-state functional MRI revealed an increase in functional connectivity between subcortical arousal nuclei in the thalamus, basal forebrain, and basal ganglia and cortical regions implicated in awareness. This rat coma model provides an experimental platform to systematically study network-based mechanisms of coma pathogenesis and recovery, as well as to test targeted therapies aimed at promoting recovery of consciousness after coma.
尽管脑干部位病变与昏迷存在关联,但对于昏迷发病机制和恢复的机制理解仍存在不足。我们在大鼠中建立了一种模拟人脑干部位昏迷的昏迷模型,该模型允许对脑干部位被盖损伤对行为、皮质电生理学和全脑功能连接的影响进行多模态分析。在昏迷诱导后,我们观察到短暂的无反应期(约 1 小时),伴有皮质爆发抑制。随后,昏迷大鼠逐渐恢复行为反应,同时初级体感皮层出现以 delta/theta 为主的皮质节律。在昏迷恢复的急性期(约 1-8 小时),纵向静息态功能 MRI 显示丘脑、基底前脑和基底神经节的皮质下觉醒核与意识相关的皮质区域之间的功能连接增加。该大鼠昏迷模型为系统研究昏迷发病机制和恢复的网络机制以及测试旨在促进昏迷后意识恢复的靶向治疗提供了一个实验平台。