Different anesthetics are known to modulate different types of membrane-bound receptors. Their common mechanism of action is expected to alter the mechanism for consciousness. Consciousness is hypothesized as the integral of all the units of internal sensations induced by reactivation of inter-postsynaptic membrane functional LINKs during mechanisms that lead to oscillating potentials. The thermodynamics of the spontaneous lateral curvature of lipid membranes induced by lipophilic anesthetics can lead to the formation of non-specific inter-postsynaptic membrane functional LINKs by different (...) mechanisms. These include direct membrane contact by excluding the inter-membrane hydrophilic region and readily reversible partial membrane hemifusion. The constant reorganization of the lipid membranes at the lateral edges of the postsynaptic terminals (dendritic spines) resulting from AMPA receptor-subunit vesicle exocytosis and endocytosis can favor the effect of anesthetic molecules on lipid membranes at this location. Induction of a large number of non-specific LINKs can alter the conformation of the integral of the units of internal sensations that maintain consciousness. Anesthetic requirement is reduced in the presence of dopamine that causes enlargement of dendritic spines. Externally applied pressure can transduce from the middle ear through the perilymph, cerebrospinal fluid, and the recently discovered glymphatic pathway to the extracellular matrix space, and finally to the paravenular space. The pressure gradient reduce solubility and displace anesthetic molecules from the membranes into the paravenular space, explaining the pressure reversal of anesthesia. Changes in membrane composition and the conversion of membrane hemifusion to fusion due to defects in the checkpoint mechanisms can lead to cytoplasmic content mixing between neurons and cause neurodegenerative changes. The common mechanism of anesthetics presented here can operate along with the known specific actions of different anesthetics. (shrink)

Several general anesthetics produce their sedative effect by activating endogenous sleep pathways. We propose that general anesthesia is a two‐step process targeting sleep circuits at low doses, and synaptic release mechanisms across the entire brain at the higher doses required for surgery. Our hypothesis synthesizes data from a variety of model systems, some which require sleep (e.g. rodents and adult flies) and others that probably do not sleep (e.g. adult nematodes and cultured cell lines). Non‐sleeping systems can be made (...) insensitive (or hypersensitive) to some anesthetics by modifying a single pre‐synaptic protein, syntaxin1A. This suggests that the synaptic release machinery, centered on the highly conserved SNARE complex, is an important target of general anesthetics in all animals. A careful consideration of SNARE architecture uncovers a potential mechanism for general anesthesia, which may be the primary target in animals that do not sleep, but a secondary target in animals that sleep. (shrink)

This paper discusses the ways in which anesthetic agents can be used to investigate the role of awareness in learning and memory. It reviews research into learning during light, subclinical anesthesia, termedhypesthesia.This research suggests that the effects of anesthetics on implicit and explicit memory are roughly comparable, although implicit memory for simple stimuli may resist the effects of very low doses of anesthetic. In addition, this paper reports experimental data demonstrating that long-term retention of information is prevented by doses (...) of anesthetic that are low enough to permit awareness and even short-term memory of auditory stimuli. Overall, these findings are consistent with the hypothesis that frontal lobe function is particularly sensitive to anesthetics. They raise theoretical and practical questions about the necessity of consciousness for learning and about interpretation of the evidence for learning during surgery under general anesthesia. (shrink)

It is argued here that the practice of medical students performing pelvic exams on women who are under anesthetic and have not consented is immoral and indefensible. This argument begins by laying out the ethical justification for the practice of informed consent, which can be found in autonomy and basic rights. Foregoing the process of consent within medicine can result in violations of both autonomy and basic rights, as well as trust, forming the basis of the wrong of unauthorized pelvic (...) examinations. Several objections to this argument are considered, all of which stem from the idea that this practice constitutes an exception to the general requirement of informed consent. These objections suggest that nonconsensual pelvic examinations on women under anesthetic are ethically acceptable on utilitarian grounds, in that they offer benefits either to the patient or to society, or on the grounds of triviality, in that consent is already presumed, or the practice is insignificant. Each of these objections is rejected and the practice is deemed indefensible. (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)

A unifying theory of general anesthetic-induced unconsciousness must explain the common mechanism through which various anesthetic agents produce unconsciousness. Functional-brain-imaging data obtained from 11 volunteers during general anesthesia showed specific suppression of regional thalamic and midbrain reticular formation activity across two different commonly used volatile agents. These findings are discussed in relation to findings from sleep neurophysiology and the implications of this work for consciousness research. It is hypothesized that the essential common neurophysiologic mechanism underlying anesthetic-induced unconsciousness is, as with (...) sleep-induced unconsciousness, a hyperpolarization block of thalamocortical neurons. A model of anesthetic-induced unconsciousness is introduced to explain how the plethora of effects anesthetics have on cellular functioning ultimately all converge on a single neuroanatomic/neurophysiologic system, thus providing for a unitary physiologic theory of narcosis related to consciousness. (shrink)

Evidence coming from several studies into memory and awareness during general anesthesia suggests that in surgical patients who seem to be adequately anesthetized , some form of cognitive functioning is preserved. This finding has important implications both for clinical practice and for memory research. In order to give the methodological background of the present situation in this field of research, this article deals, on the basis of recent experiments, with important methodological aspects of studies into perception and memory during general (...) anesthesia. (shrink)

Possible systemic effects of general anesthetic agents on neural information processing are discussed in the context of the thalamocortical suppression hypothesis presented by Drs. Alkire, Haier, and Fallon (this issue) in their PET study of the anesthetized state. Accounts of the neural requisites of consciousness fall into two broad categories. Neuronal-specificity theories postulate that activity in particular neural populations is sufficient for conscious awareness, while process-coherence theories postulate that particular organizations of neural activity are sufficient. Accounts of anesthetic narcosis, on (...) the other hand, explain losses of consciousness in terms of neural signal-suppressions, transmission blocks, and the disruptions of signal interpretation. While signal-suppression may account for the actions of some anesthetic agents, the existence of anesthetics, such as choralose, that cause both loss of consciousness and elevated discharge rates, is problematic for a general theory of narcosis that is based purely on signal suppression and transmission-block. However, anesthetic agents also alter relative firing rates and temporal discharge patterns that may disrupt the coherence of neural signals and the functioning of the neural networks that interpret them. It is difficult at present, solely on the basis of regional brain metabolic rates, to test process-coherence hypotheses regarding organizational requisites for conscious awareness. While these pioneering PET studies have great merit as panoramic windows of mind-brain correlates, wider ranges of theory and empirical evidence need to be brought into the formulation of truly comprehensive theories of consciousness and anesthesia. (shrink)

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)

I propose that primary conscious awareness arises from synchronized activity in dendrites of neurons in dorsal thalamic nuclei, mediated particularly by inhibitory interactions with thalamic reticular neurons. In support, I offer four evidential pillars: consciousness is restricted to the results of cortical computations; thalamus is the common locus of action of brain injury in vegetative state and of general anesthetics; the anatomy and physiology of the thalamus imply a central role in consciousness; neural synchronization is a neural correlate of (...) consciousness. (shrink)

Neuronal aggregates involved in conscious awareness are not evenly distributed throughout the CNS but comprise key components referred to as the neural network correlates of consciousness (NNCC). A critical node in this network is the posterior cingulate, precuneal, and retrosplenial cortices. The cytological and neurochemical composition of this region is reviewed in relation to the Brodmann map. This region has the highest level of cortical glucose metabolism and cytochrome c oxidase activity. Monkey studies suggest that the anterior thalamic projection likely (...) drives retrosplenial and posterior cingulate cortex metabolism and that the midbrain projection to the anteroventral thalamic nucleus is a key coupling site between the brainstem system for arousal and cortical systems for cognitive processing and awareness. The pivotal role of the posterior cingulate, precuneal, and retrosplenial cortices in consciousness is demonstrated with posterior cingulate epilepsy cases, midcingulate lesions that de-afferent this region and are associated with unilateral sensory neglect, observations from stroke and vegetative state patients, alterations in blood flow during sleep, and the actions of general anesthetics. Since this region is critically involved in self reflection, it is not surprising that it is similarly a site for the NNCC. Interestingly, information processing during complex cognitive tasks and during aversive sensations such as pain induces efforts to terminate self reflection and result in decreased processing in posterior cingulate and precuneal cortices. (shrink)

One of the most essential characteristics of living material—indeed, according to many, its most essential characteristic—is the fact that it is irritable. A living cell responds to sudden environmental changes, and typically a cell of a given sort responds in a definite and particular way no matter what the nature of the stimulation. Thus when a muscle cell is exposed to sudden heat, to sudden cold, to a sharp mechanical impact, to ultraviolet radiation, or to an electric current, it shortens. (...) Similarly, a nerve fiber responds in its own characteristic way, and this response is independent of the nature of the stimulation. In general, mechanical impacts, ultraviolet radiation, electric shocks, and certain types of chemical substances are stimulating agents for many diverse types of protoplasm and they serve to arouse it to activity. The response of protoplasm to stimulation may be prevented by anesthetics. These are substances which nullify the effect of a stimulus without killing or seriously injuring the protoplasm. The remarkable fact is that there are general anesthetics, substances which in much the same concentration can prevent protoplasmic activity in widely different protoplasmic systems. Many fat solvents, such as ether, are general anesthetics. Magnesium salts also behave as anesthetics for many different types of cells. (shrink)

There is evidence from neuropsychological and psychophysical measurements that conscious sensory information is processed in discrete time segments. The segmentation process may be described as neuronal activity at a frequency of 40 Hz. Stimulus-induced neuronal activities of this frequency are found in the middle latency range of the auditory evoked potential . First, we have studied the effects of different general anesthetics on MLAEP and auditory evoked 40-Hz activity. Second, we investigated MLAEP and explicit and implicit memory for information (...) presented during cardiac anesthesia. In the awake patients peak latencies of the MLAEP were in the normal range. An auditory evoked 40-Hz activity was present 20–100 ms poststimulus. Under nonspecific anesthetics MLAEP and the 40-Hz activity were suppressed, and under receptor-specific agents MLAEP and the 40-Hz activity were partly preserved. None of the cardiac patients had conscious explicit recall of the intraoperative events, whereas some patients showed unconscious implicit memory for an intraoperative tape message. The implicit memory could be related to midlatency auditory evoked potentials. No implicit memory was detectable when MLAEP and the primary cortical processing of the auditory stimuli and 40-Hz activity were blocked. Implicit memory could be detected in more than 50% of the cases when MLAEP, a 30-Hz activity, and the primary cortical stimulus processing were preserved. In conclusion, our observations support the view that a high frequency oscillatory mechanisms, recorded as a grouped neuronal activity in the MLAEP, may be part of a basic neuronal program for conscious sensory information processing. (shrink)

Kierkegaard's relation to Luther and Lutheranism varied drastically according to his different authorial goals. In general, Kierkegaard employed Luther and the Lutheran doctrines of justification by grace and kenosis positively when he wanted to comfort believers or to prod partially sympathetic devout individuals toward a more authentic faith. However, he sharply critiqued Luther when he intended to challenge the basic premises of a spiritually anesthetized Christendom that took grace for granted. Consequently, the dialectic of rigor and leniency that Kierkegaard sometimes (...) discerned in Luther was reflected in Kierkegaard's own appropriation of Luther. (shrink)

Unconsented intimate exams on men and women are known to occur for training purposes and diagnostic reasons, mostly during gynecological surgeries but also during prostate examinations and abdominal surgeries. UIEs most often occur on anesthetized patients but have also been reported on conscious patients. Over the last 30 years, several parties—both within and external to medicine—have increasingly voiced opposition to these exams. Arguments from medical associations, legal scholars, ethicists, nurses, and some physicians have not compelled meaningful institutional change. Opposition is (...) escalating in the form of legislative bans and whistleblower reports. Aspiring to professional and scientific detachment, institutional consent policies make no distinction between intimate exams and exams on any other body part, but patients do not think of their intimate regions in a detached or neutral way and believe intimate exams call for special protections. UIEs are found to contribute to moral erosion and moral distress of medical students and compromise the sacred trust between the medical community and the general public. This paper refutes the main arguments in favor of the status quo, identifies a series of harms related to continuing the current practice, and proposes an explicit consent policy for intimate exams along with specific changes to medical school curriculum and institutional culture. Because patients are the rights-holders of their bodies, consent practices should reflect and uphold patient values which call for explicit consent for intimate exams. (shrink)

BackgroundA patient who fulfils the due diligence requirements for euthanasia, and is medically suitable, is able to donate his organs after euthanasia in Belgium, the Netherlands and Canada. Since 2012, more than 70 patients have undergone this combined procedure in the Netherlands. Even though all patients who undergo euthanasia are suffering hopelessly and unbearably, some of these patients are nevertheless willing to help others in need of an organ. Organ donation after euthanasia is a so-called donation after circulatory death (DCD), (...) Maastricht category III procedure, which takes place following cardiac arrest, comparable to donation after withdrawal of life sustaining therapy in critically ill patients. To minimize the period of organ ischemia, the patient is transported to the operating room immediately after the legally mandated no-touch period of 5 min following circulatory arrest. This means that the organ donation procedure following euthanasia must take place in the hospital, which appears to be insurmountable to many patients who are willing to donate, since they already spent a lot of time in the hospital. Case presentationThis article describes the procedure of organ donation after euthanasia starting at home (ODAEH) following anesthesia in a former health care professional suffering from multiple system atrophy. This case is unique for at least two reasons. He spent his last conscious hours surrounded by his family at home, after which he underwent general anaesthesia and was intubated, before being transported to the hospital for euthanasia and organ donation. In addition, the patient explicitly requested the euthanasia to be performed in the preparation room, next to the operating room, in order to limit the period of organ ischemia due to transport time from the intensive care unit to the operating room. The medical, legal and ethical considerations related to this illustrative case are subsequently discussed.ConclusionsOrgan donation after euthanasia is a pure act of altruism. This combined procedure can also be performed after the patient has been anesthetized at home and during transportation to the hospital. (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 lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 11.1 (2001) 91-112 [Access article in PDF] Scope Note 40 Animals in Research and Education: Ethical Issues Laura Jane Bishop and Anita Lonnes Nolen Scientific enquiry is inexorably tied to animal experimentation in the popular imagination and human history. Many, if not most, of the spectacular innovations in the medical understanding and treatment of today's human maladies have been based on research using animals. (...) However, the use of animals in research and experimentation has been debated, defended, and protested by both individuals and organizations at various levels. Responses range from personal lifestyle decisions and fervent philosophical treatises to strident arguments, violent demonstrations, and direct action. The continuum of attitudes about animals and the human relationship with animals spans the range between those who support no regulation of the human use of animals and those who advocate absolute animal liberation from all human use (see II, Orlans 1993, p. 22). History The first recorded experimentation on animals occurred in ancient Rome, but not until the Renaissance did scholars begin serious study of how the body works. Leonardo da Vinci (1452-1519) and other artists and anatomists pursued anatomical investigations of muscle and bone structure. William Harvey (1578-1657) discovered the circulation of the blood via his experiments on live deer. During this period, much live animal experimentation both in England and France was based on the view of French philosopher René Descartes (1596-1650) that animals are incapable of feeling pain. Jeremy Bentham (1748-1832), the English utilitarian philosopher, thought otherwise. In his "Introduction to the Principles of Morals and Legislation" in 1789, Bentham declared, "The question is not, can they reason? Nor, can they talk? But can they suffer? Despite Bentham and others, the belief that animals could not perceive pain persisted in many quarters into the twentieth century. Nineteenth century French physiologist Claude Bernard [End Page 91] (1813-1878)-and his teacher, François Magendie (1783-1855)-conducted wide-ranging animal experiments including surgery, use of drugs, and removal of body parts from many species. Bernard argued that while no amount of benefit could justify any harm to human research subjects, even extreme harm and pain for animal research subjects could be justified by the potential benefit to human beings. Although he did use anesthetics in his work after their discovery in 1847, even Bernard's later work was controversial because of the numbers of animals used and the repetitive nature of his research. The experiments of Magendie and Bernard both laid the foundations for animal experimentation as a practice for scientific advance and contributed in large measure to the emergence of the anti-vivisection movement. Public protests over animal experiments conducted in France and the fear that these might come to England led to the passage of the first law controlling animal experimentation, the "1876 Cruelty to Animals Act" in England. This history and the dynamic tension between scientific inquiry and public concern set the stage for the activism and scholarship of the twentieth century.Since the 1960s, the amount of attention, activism, and scholarship related to animal use has increased at a rapid pace. The modern animal protection movement, led by the Australian philosopher Peter Singer in his book, Animal Liberation (II, 1975), based its advocacy on animals' ability to experience pain and suffering (Bentham's argument). Singer's book and other investigations into animal research, such as LIFE magazine's photojournalism piece on pet theft, animal cruelty, and animal experimentation (Concentration Camps for Dogs. LIFE (4 February 1966), pp. 22-29), brought the use of animals in research, testing, and education to the attention of the general public. Activists, advocates, laypersons, scientists, lawmakers, and animals themselves, have created the interesting, complicated, and complex history of animal rights and animal welfare over the last several decades. Current Statistics Worldwide, approximately 35 million animals are used in research each year; the United States alone uses 12 million animals annually--more than any other country. In 1998, the official number of research animals recorded in the United States was 1... (shrink)

Le général André Bach dans une réflexion sur l’« horizon de mort dans la violence de guerre » part d’une approche anthropologique du phénomène de violence et de la peur (quasiment biologique) qu’il engendre en soulignant les difficultés des sociétés occidentales à penser la mort. C’est l’État qui donne à la guerre un sens politique et sacré et qui crée les catégories fonctionnelles de la guerre (les concepts de paix et de guerre ne sont pas en eux-mêmes opérationnels). Dans le (...) cadre d’une réflexion clausewitzienne sur la montée aux extrêmes, l’« extrême » pour le soldat est toujours sa propre mort (plus que celle de l’ennemi). Les notions de barbarisation et humanisation ne peuvent en ce sens rendre compte de la violence et de la peur radicales présentes dans toute guerre où le rôle du commandement est toujours de mettre en œuvre un degré de violence supérieur à celui de l’adversaire, sans aucune considération de « proportionnalité » de cette violence. La mise à distance technique ne diminue pas la violence mais l’augmente à proportion de l’éloignement de la peur. Seul le politique peut et doit mettre des limites à cette violence militaire par nature illimitée. La modernisation des armes ne relève jamais d’une humanisation du combat mais d’une recherche d’une violence plus efficace. L’entraînement du soldat en temps de paix n’est jamais entraînement à la violence mais apprentissage de savoir-faire et effort de constitution d’un groupe soudé, doté d’un bon moral. L’ordre et la formation tentent de limiter la sauvagerie mais il existe une constitution endogène de comportements propres au soldat, que la hiérarchie tente de canaliser dans une symbolique guerrière fondée sur le sentiment de l’honneur (destiné à compenser la peur d’être une proie vouée à mourir et à faire préférer la lutte au coude à coude sur l’instinct de conservation). Le couple violence/honneur fait que l’armée dépourvue de contrat social n’est pas soluble dans le politique (aujourd’hui dans les écoles militaires on ne parle plus d’« honneur » mais d’« éthique »…, mais pour dire la même chose). La conscription fut une rupture de la logique endogène de l’armée et introduisit une brèche dans ce système archaïque. Mais religion (au Moyen Âge) ou logique démocratique (de nos jours) s’avèrent surtout des « béquilles idéologiques » qui, en définitive, sont souvent plus efficaces pour accroître la barbarisation que pour l’éviter (exemple de la colonisation algérienne où une armée de paix, fonctionnarisée et rigoureusement canalisée, appartenant à une génération n’ayant jamais connu de violence de guerre, développe des massacres de masse). (shrink)

(2010). Remaining True to Our Values – Reflections on Military Ethics in Trying Times. Journal of Military Ethics: Vol. 9, No. 3, pp. 183-194. doi: 10.1080/15027570.2010.510850.

Écriture sans écriture, critique sans discours : il s’agit de traquer et de faire ressortir l’obsession du « projet » et de son idéologie dans la trame d’un appel à contrats doctoraux. Ctrl+B chaque fois (et elles sont très nombreuses) où le petit mot est réitéré.