Dávila Diego G, McKinstry-Wu Andrew, Kelz Max B, Proekt Alex
Departments of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
J Neurosci. 2025 May 14;45(20):e1545242025. doi: 10.1523/JNEUROSCI.1545-24.2025.
During wakefulness, external stimuli elicit conscious experiences. In contrast, dreams and drug-induced dissociated states are characterized by vivid internally generated conscious experiences and reduced ability to perceive external stimuli. Understanding the physiological distinctions between normal wakefulness and dissociated states may therefore disambiguate signatures of responsiveness to external stimuli from those that underlie conscious experience. The hypothesis that conscious experiences are associated with brain criticality has received considerable theoretical and experimental support. Consistent with this hypothesis, statistical signatures of criticality are similar in normal wakefulness and dissociative states but are abolished in dreamless sleep and under anesthesia. Thus, while statistical measures of criticality are associated with the ability to have conscious experience, they do not readily distinguish between perception of the external world from internally generated percepts. Here, we investigate distinct, dynamical, signatures of criticality during escalating ketamine doses in high-density EEG in human male volunteers. We show that during normal wakefulness, EEG is found at a critical point between damped and exploding oscillations. With increasing doses of ketamine, as dissociative symptoms intensify, activity is progressively stabilized-most prominently at higher frequencies. We also show that stabilization is a more reliable marker of the effects of ketamine than conventional measures such as power spectra. These findings suggest that stabilization of cortical dynamics correlates with decreased ability to respond to and perceive external stimuli rather than the ability to have conscious experiences per se. Altogether, these results suggest that combining statistical and dynamical criticality measures may distinguish wakefulness, dissociation, and unconsciousness.
在清醒状态下，外部刺激会引发有意识的体验。相比之下，梦境和药物诱发的分离状态的特点是有生动的内在产生的有意识体验，以及感知外部刺激的能力下降。因此，了解正常清醒状态和分离状态之间的生理差异，可能会区分对外部刺激的反应特征与构成有意识体验的基础特征。有意识体验与大脑临界性相关的假设已获得了大量的理论和实验支持。与这一假设一致的是，临界性的统计特征在正常清醒状态和分离状态中相似，但在无梦睡眠和麻醉状态下则消失。因此，虽然临界性的统计测量与有意识体验的能力相关，但它们并不能轻易地区分对外界的感知和内在产生的感知。在此，我们在人类男性志愿者的高密度脑电图中，研究了氯胺酮剂量增加过程中不同的、动态的临界性特征。我们发现，在正常清醒状态下，脑电图处于阻尼振荡和爆发振荡之间的临界点。随着氯胺酮剂量的增加，随着分离症状的加剧，活动逐渐稳定——最明显的是在较高频率。我们还表明，与功率谱等传统测量方法相比，稳定化是氯胺酮效应更可靠的指标。这些发现表明，皮层动力学的稳定化与对外界刺激的反应和感知能力下降相关，而不是与有意识体验本身的能力相关。总之，这些结果表明，结合统计和动态临界性测量方法可能有助于区分清醒、分离和无意识状态。
