Van Maldegem Milan, Vohryzek Jakub, Atasoy Selen, Alnagger Naji, Cardone Paolo, Bonhomme Vincent, Vanhaudenhuyse Audrey, Demertzi Athena, Jaquet Oceane, Bahri Mohamed Ali, Nunez Pablo, Kringelbach Morten L, Stamatakis Emmanuel A, Luppi Andrea I
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK; Division of Anaesthesia, University of Cambridge, Cambridge, UK.
Centre for Eudaimonia and Human Flourishing, Department of Psychiatry, University of Oxford, Oxford, UK; Centre for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain.
Br J Anaesth. 2025 Apr;134(4):1088-1104. doi: 10.1016/j.bja.2024.12.036. Epub 2025 Feb 10.
Ketamine, in doses suitable to induce anaesthesia in humans, gives rise to a unique state of unresponsiveness accompanied by vivid experiences and sensations, making it possible to disentangle the correlated but distinct concepts of conscious awareness and behavioural responsiveness. This distinction is often overlooked in the study of consciousness.
The mathematical framework of connectome harmonic decomposition (CHD) was used to view functional magnetic resonance imaging (fMRI) signals during ketamine-induced unresponsiveness as distributed patterns across spatial scales. The connectome harmonic signature of this particular state was mapped onto signatures of other states of consciousness for comparison.
An increased prevalence of fine-grained connectome harmonics was found in fMRI signals obtained during ketamine-induced unresponsiveness, indicating higher granularity. After statistical assessment, the ketamine sedation harmonic signature showed alignment with signatures of LSD-induced (fixed effect =0.0113 [0.0099, 0.0127], P<0.001) or ketamine-induced (fixed effect =0.0087 [0.0071, 0.0103], P<0.001) psychedelic states, and misalignment with signatures seen in unconscious individuals owing to propofol sedation (fixed effect =-0.0213 [-0.0245, -0.0181], P<0.001) or brain injury (fixed effect =-0.0205 [-0.0234, -0.0178], P<0.001).
The CHD framework, which only requires resting-state fMRI data and can be applied retrospectively, has the ability to track alterations in conscious awareness in the absence of behavioural responsiveness on a group level. This is possible because of ketamine's unique property of decoupling these two facets, and is important for consciousness and anaesthesia research.
氯胺酮在适合诱导人类麻醉的剂量下,会引发一种独特的无反应状态,同时伴有生动的体验和感觉,这使得区分意识觉知和行为反应性这两个相关但不同的概念成为可能。在意识研究中,这种区别常常被忽视。
采用连接组谐波分解(CHD)的数学框架,将氯胺酮诱导的无反应状态下的功能磁共振成像(fMRI)信号视为跨空间尺度的分布模式。将这种特定状态的连接组谐波特征映射到其他意识状态的特征上进行比较。
在氯胺酮诱导的无反应状态下获得的fMRI信号中,发现细粒度连接组谐波的患病率增加,表明粒度更高。经过统计评估,氯胺酮镇静谐波特征与LSD诱导(固定效应=0.0113[0.0099,0.0127],P<0.001)或氯胺酮诱导(固定效应=0.0087[0.0071,0.0103],P<0.001)的迷幻状态特征一致,与因丙泊酚镇静(固定效应=-0.0213[-0.0245,-0.0181],P<0.001)或脑损伤(固定效应=-0.0205[-0.0234,-0.0178],P<0.001)导致的无意识个体的特征不一致。
CHD框架仅需要静息态fMRI数据且可回顾性应用,能够在群体水平上追踪无行为反应时意识觉知的变化。这之所以可能,是因为氯胺酮具有将这两个方面解耦的独特特性,对意识和麻醉研究具有重要意义。