The cognitive unbinding paradigm suggests that the synthesis of neural information is attenuated by general anesthesia. Here, we analyzed the functional organization of brain activities in the conscious and anesthetized states, based on functional segregation and integration. Electroencephalography recordings were obtained from 14 subjects undergoing induction of general anesthesia with propofol. We quantified changes in mean information integration capacity in each band of the EEG. After induction with propofol, mean information integration capacity was reduced most prominently in the (...) γ band of the EEG . Furthermore, we demonstrate that loss of consciousness is reflected by the breakdown of the spatiotemporal organization of γ waves. We conclude that induction of general anesthesia with propofol reduces the capacity for information integration in the brain. These data directly support the information integration theory of consciousness and the cognitive unbinding paradigm of general anesthesia. (shrink)

Human consciousness is widely understood to be underpinned by rich and diverse functional networks, whose breakdown results in unconsciousness. Candidate neural correlates of anesthetic-induced unconsciousness include: (1) disrupted frontoparietal functional connectivity; (2) disrupted brain network hubs; and (3) reduced spatiotemporal complexity. However, emerging counterexamples have revealed that these markers may appear outside of the state they are associated with, challenging both their inclusion as markers of conscious level, and the theories of consciousness that rely on their evidence. In this study, (...) we present a case series of three individuals in disorders of consciousness (DOC) who exhibit paradoxical brain responses to exposure to anesthesia. High-density electroencephalographic data were recorded from three patients with unresponsive wakefulness syndrome (UWS) while they underwent a protocol of propofol anesthesia with a targeted effect site concentration of 2 μg/ml. Network hubs and directionality of functional connectivity in the alpha frequency band (8–13 Hz), were estimated using the weighted phase lag index (wPLI) and directed phase lag index (dPLI). The spatiotemporal signal complexity was estimated using three types of Lempel-Ziv complexity (LZC). Our results illustrate that exposure to propofol anesthesia can paradoxically result in: (1) increased frontoparietal feedback-dominant connectivity; (2) posterior network hubs; and (3) increased spatiotemporal complexity. The case examples presented in this paper challenge the role of functional connectivity and spatiotemporal complexity in theories of consciousness and for the clinical evaluation of levels of human consciousness. (shrink)

Closed-loop administration of propofol for the control of hypnosis in anesthesia has evidenced an outperformance when comparing it with manual administration in terms of drug consumption and post-operative recovery of patients. Unlike other systems, the success of this strategy lies on the availability of a feedback variable capable of quantifying the current hypnotic state of the patient. However, the appearance of anomalies during the anesthetic process may result in inaccurate actions of the automatic controller. These anomalies may come from (...) the monitors, the syringe pumps, the actions of the surgeon or even from alterations in patients. This could produce adverse side effects that can affect the patient postoperative and reduce the safety of the patient in the operating room. Then, the use of anomaly detection techniques plays a significant role to avoid this undesirable situations. This work assesses different one-class intelligent techniques to detect anomalies in patients undergoing general anesthesia. Due to the difficulty of obtaining real data from anomaly situations, artificial outliers are generated to check the performance of each classifier. The final model presents successful performance. (shrink)

Healthcare professionals are currently working under extreme pressure as they respond to the pandemic outbreak of COVID-19. At the time of writing, there is currently no effective vaccine or anti-viral treatment. The pandemic is fast-moving, relatively unpredictable and of uncertain duration. In many countries, it is placing an enormous stress on healthcare resources and providing care to existing standards is proving difficult. Unfortunately, in some countries, health services have been overwhelmed. The impact of the pandemic on resource-poor countries is of (...) particular concern. This extraordinary situation is raising, or has the potential to raise, many ethical challenges for doctors delivering care to patients. It is possible, for example, that there may be points in this pandemic where decisions need to be made about who should have access to finite specialised intensive care beds, drugs and equipment. This has happened in some countries and, despite efforts by the UK Government to reduce demand and increase supply, it is still possible that this could happen in the UK. Some hospital trusts in the UK are already reporting concerningly low supplies of oxygen and vital medicines such as propofol and alfentanil.1 In these circumstances, where not everyone can be treated, difficult ethical decisions will have to made. For example, can some patients be prioritised over others? How should a doctor decide on which patients to treat? Can treatment be withdrawn from patients who are currently being treated, but are not responding, in order to offer treatment to those who may have a better chance of benefiting? The UK is also reporting concerningly low supplies of vital personal protective equipment for frontline workers, raising the question - what are a doctor’s obligations to treat patients, in circumstances that present a high …. (shrink)

Continuous recordings of brain electrical activity were obtained from a group of 176 patients throughout surgical procedures using general anesthesia. Artifact-free data from the 19 electrodes of the International 10/20 System were subjected to quantitative analysis of the electroencephalogram (QEEG). Induction was variously accomplished with etomidate, propofol or thiopental. Anesthesia was maintained throughout the procedures by isoflurane, desflurane or sevoflurane (N = 68), total intravenous anesthesia using propofol (N = 49), or nitrous oxide plus narcotics (N = 59). (...) A set of QEEG measures were found which reversibly displayed high heterogeneity of variance between four states as follows: (1) during induction; (2) just after loss of consciousness (LOC); (3) just before return of consciousness (ROC); (4) just after ROC. Homogeneity of variance across all agents within states was found. Topographic statistical probability images were compared between states. At LOC, power increased in all frequency bands in the power spectrum with the exception of a decrease in gamma activity, and there was a marked anteriorization of power. Additionally, a significant change occurred in hemispheric relationships, with prefrontal and frontal regions of each hemisphere becoming more closely coupled, and anterior and posterior regions on each hemisphere, as well as homologous regions between the two hemispheres, uncoupling. All of these changes reversed upon ROC. Variable resolution electromagnetic tomography (VARETA) was performed to localize salient features of power anteriorization in three dimensions. A common set of neuroanatomical regions appeared to be the locus of the most probable generators of the observed EEG changes. (shrink)

Information processing that subserves conscious cognitive functions is thought to involve recurrent signaling through feedforward and feedback loops among hierarchically arranged functional regions of the cerebral cortex. In the current issue of Consciousness and Cognition, Lee et al. report that loss of consciousness, as produced by a bolus injection of the general anesthetic propofol to human volunteers, was accompanied by a decrease in wide-band EEG feedback connectivity from frontal cortex to parietal cortex, confirming a prediction from previous experimental studies. (...) Interestingly, frontoparietal feedback connectivity did not fully recover after the anesthetic effect wore off and the subjects first opened their eyes in response to a verbal command. Possible interpretations of the results and their implications with respect to the neural correlates of consciousness and unconsciousness are discussed. (shrink)

Frontoparietal connectivity has been suggested to be important in conscious processing and its interruption is thought to be one mechanism of general anesthesia. Data in animals demonstrate that feedforward processing of information may persist during the anesthetized state, while feedback processing is inhibited. We investigated the directionality and functional organization of frontoparietal connectivity in 10 human subjects anesthetized with propofol on two separate occasions. Multichannel electroencephalography and a computational method of assessing directed functional connectivity were employed. We demonstrate that (...) directed feedback connectivity is diminished with loss of consciousness and returns with responsiveness to verbal command. We also applied the Dendrogram classification method to assess the global organization of directed functional connectivity during consciousness and anesthesia. We demonstrate a state-specific hierarchy and subject-specific subhierarchy in functional organization. These data support the hypothesis that specific states of human consciousness are defined by specific states of frontoparietal connectivity. (shrink)

In August 2012, the drug manufacturer, Fresenius Kabi, barred the sale of the anaesthetic, propofol, for use in lethal injections. The company announced that it would not accept orders for the drug from US departments of correction, and put in place similar requirements on all its wholesalers and distributors.1Propofol is one of the world's most widely used anaesthetics. Earlier in 2012, US states began to use propofol in executions following shortages of other drugs which had previously been used (...) in lethal injections. In May 2012, the state of Missouri decided to move to a one-drug protocol, using propofol alone for lethal injections, in place of the three-drug protocol that had been used by most states carrying out the death penalty. Missouri took this decision when supplies of thiopental sodium and pentobarbital, drugs used in the three-drug protocol, became unavailable.2Fresenius Kabi said that it had imposed the restrictions in order to ‘prevent Propofol from being used for purposes other than its approved medical indications’ and to ensure that ‘the immediate access to Propofol needed by medical professionals’ was not hindered. The company said that it objected to the use of its products in any manner that was not in full accordance with the medical indications for which they have been approved by health authorities.3 All forms of Fresenius Kabi propofol are manufactured in Europe. A European Union Council regulation prevents products that may reasonably be expected to be used in executions from being exported from the EU. The company said that, should propofol begin to be used in executions in the USA, inadequate access to the drug in the country was a likely consequence. At the time of writing, the US Food and Drug Administration was reporting shortages of the drug in the USA for …. (shrink)

Emerging technologies raise the possibility that we may be able to treat trauma victims by pharmaceutically dampening factual or emotional aspects of their memories. Such technologies raise a panoply of legal and ethical issues. While many of these issues remain off in the distance, some have already arisen. In this brief commentary, I discuss a real-life case of memory erasure. The case reveals why the contours of our freedom of memory—our limited bundle of rights to control our memories and be (...) free of outside control—already merit some attention. (shrink)

In October 2013, Missouri officials abandoned a plan to execute a convicted murderer using a novel method—an injection of propofol. The name of this drug became a household word after propofol played a role in singer Michael Jackson's death, but this has been a popular therapeutic drug for many years. Clinicians use it in intensive care, surgery, and common procedures like colonoscopy. After deciding to halt the execution, Missouri governor Jay Nixon told corrections officials to come up with (...) a different lethal injection protocol. But that was not a simple assignment. Missouri had proposed using propofol because officials had faced barriers to obtaining the drugs previously used for executions. Corrections officials in death penalty states are finding it harder to secure drugs for lethal injection. (shrink)