Anesthesiology
February 7, 2012
Robert D. Sanders, Giulio Tononi, Steven Laureys et al.
478 citations
Consciousness—subjective experience—persists during sleep and anesthesia, as evidenced by dreaming. A defining feature of dreaming is disconnection from the environment. Anesthesia aims to prevent the experience of surgery (connected consciousness) by inducing either unconsciousness or disconnection. The isolated forearm technique reveals that consciousness, connectedness, and responsiveness can uncouple during anesthesia; under clinical conditions, a median 37% of patients demonstrate connected consciousness. Potential neurobiological constructs explain this: during light anesthesia, subcortical mechanisms for spontaneous behavioral responsiveness are disabled, but information integration within the corticothalamic network continues producing consciousness, while unperturbed norepinephrinergic signaling maintains connectedness. These concepts emphasize the need for anesthetic regimens and depth-of-anesthesia monitors targeting mechanisms of consciousness, connectedness, and responsiveness.
Trends in Anaesthesia and Critical Care
March 22, 2014
Jamie Sleigh, Martyn Harvey, Logan J. Voss et al.
441 citations
Ketamine has been used clinically for over 50 years, but its mechanisms remain largely unclear. Its hypnotic effects are mainly mediated by blocking NMDA and HCN1 receptors, while cholinergic, aminergic, and opioid systems modulate sedation and analgesia. Ketamine's effects on chronic pain and depression outlast drug levels, likely due to a secondary increase in synaptic connectivity triggered by a neuronal response to a hyper-glutamatergic state.
British Journal of Anaesthesia
February 4, 2018
Jamie Sleigh, Catherine E. Warnaby, Irene Tracey
35 citations
Selfhood depends on brain processes that allow a person to experience being a distinct, capable agent. It includes a hierarchy of components: core self (awareness of existence), embodied self (sentience), executive self (agency), and higher-order cognition. Consciousness and selfhood are related but not identical; understanding selfhood helps explain partial consciousness during anesthesia. Brain-imaging and EEG studies show that anesthetic drugs selectively impair self-related networks, especially the anterior insula and salience network, causing depersonalization at moderate doses while preserving disembodied self-awareness. Unlike natural sleep, where loss of agency and sentience tracks with decreasing self-awareness, anesthesia maintains posterior brain connectivity even at high concentrations, possibly marking a core self involved in reduced energy homeostasis.
Human Brain Mapping
December 6, 2019
Anna Forsyth, Rebecca McMillan, Doug Campbell et al.
19 citations
The validity of fMRI functional connectivity as a drug biomarker was tested by comparing seven preprocessing pipelines and by simultaneously measuring EEG and fMRI in a placebo-controlled, three-way crossover study with ketamine and midazolam. Independent components analysis (ICA)-denoising produced stronger reductions in connectivity after ketamine and weaker increases after midazolam than pipelines using physiological noise modelling or averaged signals from cerebrospinal fluid or white matter. This indicates that pipeline decisions should match a drug's unique noise structure; when unknown, extensive ICA denoising may sacrifice some signal but increase confidence in remaining results. No significant relationship was found between changes in electrophysiological and hemodynamic correlation structures, cautioning against cross-modal comparisons of pharmacologically-modulated functional connectivity.
Journal of visualized experiments : JoVE
January 13, 2018
Andria Pelentritou, Levin Kuhlmann, John Cormack et al.
Inhaling the gaseous anesthetics nitrous oxide (N2O) and xenon (Xe) allows study of brain activity during unconsciousness via simultaneous magnetoencephalography (MEG) and electroencephalography (EEG). Healthy male participants received step-wise increasing concentrations of Xe (8, 16, 24, 42%) and N2O (16, 32, 47%) in a repeated measures cross-over design. An auditory continuous performance task tracked responsiveness. The protocol, refined over multiple sessions, details subject recruitment, equipment setup, data collection, and basic analysis. Results show sensor-level raw data, spectral topography, minimal head movements, and level-dependent effects on auditory evoked responses. The method can be adapted for volatile and intravenous anesthetics to advance understanding of macro-scale anesthesia mechanisms.