Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness

Abstract

General anesthesia (GA) is a reversible drug-induced state of altered arousal required for more than 60,000 surgical procedures each day in the United States alone. Sedation and unconsciousness under GA are associated with stereotyped electrophysiological oscillations that are thought to reflect profound disruptions of activity in neuronal circuits that mediate awareness and cognition. Computational models make specific predictions about the role of the cortex and thalamus in these oscillations. In this paper, we provide in vivo evidence in rats that alpha oscillations (10-15 Hz) induced by the commonly used anesthetic drug propofol are synchronized between the thalamus and the medial prefrontal cortex. We also show that at deep levels of unconsciousness where movement ceases, coherent thalamocortical delta oscillations (1-5 Hz) develop, distinct from concurrent slow oscillations (0.1-1 Hz). The structure of these oscillations in both cortex and thalamus closely parallel those observed in the human electroencephalogram during propofol-induced unconsciousness. During emergence from GA, this synchronized activity dissipates in a sequence different from that observed during loss of consciousness. A possible explanation is that recovery from anesthesiainduced unconsciousness follows a "boot-up" sequence actively driven by ascending arousal centers. The involvement of medial prefrontal cortex suggests that when these oscillations (alpha, delta, slow) are observed in humans, self-awareness and internal consciousness would be impaired if not abolished. These studies advance our understanding of anesthesia-induced unconsciousness and altered arousal and further establish principled neurophysiological markers of these states.anesthesia | prefrontal cortex | thalamus | coherence | propofol G eneral anesthesia (GA) is a reversible drug-induced state consisting of unconsciousness, analgesia, amnesia, akinesia, and physiological stability (1). In the United States nearly 60,000 surgical procedures are conducted under GA every day, making GA one of the most common manipulations of the brain and central nervous system in medicine (1). The molecular mechanisms by which anesthetic drugs alter brain function have been well characterized (2, 3). Detailed analyses of neural circuitand systems-level mechanisms of GA are more recent (1, 4, 5). Understanding the system-wide effects of anesthetic drugs is necessary in order to understand how these drugs produce states of altered arousal and unconsciousness.One of the most commonly used anesthetic drugs is 2,6-diisopropylphenol (propofol), a GABA-A receptor agonist (6). Electroencephalogram (EEG) recordings in humans during gradual induction of unconsciousness with propofol show the appearance of frontal β oscillations (15-30 Hz) at the onset of sedation, followed by the appearance of coherent frontal α (8-12 Hz) oscillations (7-10) and widespread slow (0.1-1 Hz) and δ (1-4 Hz) oscillations (7, 11, 12) when subjects no longer respond to sensory stimuli. Biophysical models of neuronal dy...

Dynamic changes in rhythmic and arrhythmic neural signatures in the subthalamic nucleus induced by anaesthesia and intubation

“…The dynamic changes in the power law exponent correlated with fluctuation of broadband high-frequency activity. Our finding coincides with previous computational modelling and animal studies showing increased frontal corticothalamic alpha coherence associated with consciousness 13,39 . Our results are also consistent with the previous study showed reduced beta band activity in STN during general anaesthesia 19 .…”

“…Numerous neuroimaging studies have also shown that several subcortical brain structures are involved in altered arousal and unconsciousness [7][8][9] , and it is suggested that the disruption of communication between the cortical and subcortical structures play a crucial role in anaesthetic-induced unconsciousness 8,10,11 . Therefore, investigating subcortical changes and neuronal network-level effects induced by anaesthetic drugs has become compelling and necessary for better understanding the neuronal mechanism of how general anaesthetics cause loss of consciousness [12][13][14] .…”

Novel neuroactive steroid with hypnotic and T‐type calcium channel blocking properties exerts effective analgesia in a rodent model of post‐surgical pain

“…Our data reveals that Ca V 3.2 isoform of T‐channels is relevant for the induction but not for the maintenance of 3β‐OH hypnotic effect. These channels are expressed in cortex and reticular thalamic nucleus (Talley et al, ), brain structures heavily involved in the induction of anaesthesia (Flores et al, ; Lewis et al, ). Furthermore, our previous finding revealed that Ca V 3.2 KO mice exhibited delayed onset of isoflurane anaesthesia (Orestes et al, ).…”

Monitoring the brain strikes a discordant note for anesthesiologists

“…3 To this end, there are useful online educational resources 18,19 and informative journal articles. 20,21 As we learn more about general anesthesia, from the molecular to the systems neuroscience level, [22][23][24] we will be able to design a new generation of brain monitors with everstronger scientific foundations that will accord more accurately with different neurological states and depths of anesthesia.…”

“…• 20,21 Au fur et à mesure que nous en saurons plus sur l'anesthésie générale, du niveau moléculaire jusqu'au niveau des neurosciences sur le système, [22][23][24] nous pourrons concevoir une nouvelle génération de moniteurs cérébraux avec disposant de bases scientifiques toujours plus solides qui refléteront plus précisément les différents états neurologiques et les profondeurs de l'anesthésie.…”