Risk factors for the occurrence of electroencephalogram abnormalities during induction of anesthesia with sevoflurane in nonepileptic patients

BACKGROUND: The aim of this prospective study was to determine the risk factors of epileptiform discharge during induction with sevoflurane in healthy adult patients. METHODS: Forty adult patients with American Society of Anesthesiologists physical status I were randomly allocated to one of four groups. Group A: Patients breathed 8% sevoflurane in oxygen (8 l/min) via a prefilled circuit. End-tidal sevoflurane was maintained at 4%. Tracheal intubation was performed at the third minute after cisatracurium injection. Group B: The anesthesia protocol was similar, but a vital capacity technique was performed. Group C: Patients were anesthetized as in group A but were hyperventilated. Group D: Patients were anesthetized as in group A, but end-tidal sevoflurane was maintained at 2%. An electroencephalogram was recorded before and during induction up to 11 min after the start of induction. Statistical analysis was performed with Statview 5.0 (SAS Institute Inc., Cary, NC) for multivariate analysis. RESULTS: Twelve patients experienced epileptiform discharges. Risk factors were female sex (odds ratio, 12.60; 95% confidence interval, 1.46-135), delay to the occurrence of beta waves (odds ratio, 0.92; 95% confidence interval, 0.86-0.99), and end-tidal sevoflurane (odds ratio, 8.78; 95% confidence interval, 1.12-69). Epileptiform discharges were not associated with significant hemodynamic or Bispectral Index variations. CONCLUSION: Induction with sevoflurane may result in epileptiform electroencephalographic activity. Only electroencephalographic monitoring allows the diagnosis. Risk factors are mainly female sex, short delay to onset of anesthesia, and high alveolar sevoflurane concentration. Induction with high sevoflurane concentration is controversial mainly in women.     

Developing an interstitial ultrasound applicator for thermal ablation in liver: results of animal experiments

BACKGROUND: In this project, an interstitial ultrasound applicator was developed for the treatment of primary and secondary cancers of the liver. Experiments on animals were used to check the destructive capabilities of this probe within the hepatic parenchyma of the pig in vivo, with a study of the physical parameters of the ultrasound treatment. In parallel, the possibility of visualizing the lesions induced by means of ultrasound imaging was also studied. MATERIALS AND METHODS: Thirteen pigs were used in this project, which had received the prior approval of the ethics committee of Lyon Veterinary School. Ultrasound lesions were performed by varying the physical parameters of the treatment (acoustic intensity and shot time) with the aim of obtaining larger and larger areas of destruction. An operative device was developed to ensure precision in treatments. Two types of lesions were performed: elementary lesions corresponding to single shots at 40 degrees to 50 degrees rotation intervals, and cylindrical lesions obtained by a continuous rotary deployment of the probe. The effect of hepatic pedicle clamping on the size of ultrasound lesions was studied. The aspect and dimension of the lesions were analyzed by means of operative ultrasound imaging and macroscopic examination. Histological analysis showed the impact of the treatment on the hepatic parenchyma. RESULTS: This work made it possible to study the elementary ultrasound lesions produced by our probe. Seventy elementary ultrasound lesions were analyzed. Treatments could be performed on all pigs without any difficulty. There were no operative incidents. The ultrasound-induced elementary lesions showed complete necrosis, with lesion length of up to 37 mm obtained without resort to pedicle clamping; this must be considered as a radius of the final lesion obtained over a complete rotary deployment (360 degrees ), then a diameter of 7 cm of thermal ablation can theoretically be obtained. The effect of pedicle clamping was studied and showed improvement of the lesion length. Results of continuous rotary deployment of the probe were encouraging. Operative ultrasound imaging proved to be a simple tool for directing and positioning the applicator in the target zone on the one hand and which, on the other hand, enabled accurate, real-time visualization of the ultrasound lesions. On histological analysis, the ultrasound-induced necrosis was complete and well defined. CONCLUSION: This work shows that it is feasible to treat cancers of the liver using interstitial ultrasound probe. Thermal damage obtained on the hepatic parenchyma of pigs in vivo is complete and can be monitored using simple diagnostic ultrasound. The ultrasound parameters can be adapted to obtain destruction of variable size.     

Refractoriness of hepatitis C virus internal ribosome entry site to processing by Dicer in vivo

Background  

Hepatitis C virus (HCV) is a positive-strand RNA virus harboring a highly structured internal ribosome entry site (IRES) in the 5' nontranslated region of its genome. Important for initiating translation of viral RNAs into proteins, the HCV IRES is composed of RNA structures reminiscent of microRNA precursors that may be targeted by the host RNA silencing machinery.     

Selection of Polymorphic Peptides from GRA6 and GRA7 Sequences of Toxoplasma gondii Strains To Be Used in Serotyping

The evaluation of Toxoplasma gondii isolates obtained from geographical environments other than Europe and North America revealed the existence of atypical strains that are not included in the three archetypal clonal lineages (lineages I, II, and III). GRA6 and GRA7 are polymorphic genes that have been used for the genotyping of Toxoplasma. The coding regions of GRA6 and GRA7 from 49 nonarchetypal strains were sequenced and compared with the sequences of type I, II, and III reference strains. Eighteen and 10 different amino acid sequences were found for GRA6 and GRA7, respectively. The polymorphisms found between the different sequences were analyzed, with the objective of defining peptides to be used for the serotyping of Toxoplasma infections. Two peptides specific for clonal lineages I and III (peptides GRA7I and GRA7III, respectively) were selected from the GRA7 locus. Three peptides specific for some atypical strains (peptides Am6, Af6, and Am7) were selected from both the GRA6 and the GRA7 loci. Serum samples from humans infected with Toxoplasma strains of known genotypes were serotyped with the selected peptides. Peptide GRA7III seems to be a good candidate for the serotyping of infections caused by type III strains. Peptide GRA7I had a very low sensitivity. Peptides Am6 and Af6 had low specificities, since they reacted with serum samples from patients infected with strains belonging to the three archetypal lineages. Although peptide Am7 was specific, it had low sensitivity.The vast majority of Toxoplasma gondii isolates from human patients and domestic animals in Europe and North America belong to three archetypal clonal lineages, namely, types I, II, and III (1, 11, 30). However, nonarchetypal strains with atypical genotypes have recently been described in unusual hosts such as sea otters (10, 42, 43) and in tropical areas such as South America and Africa (2, 32, 39, 46, 54). Genotyping studies that distinguish different types of strains are important to gain knowledge of the biodiversity of the parasite in order to understand the molecular epidemiology of Toxoplasma and to highlight the correlation between the genotype of the parasite and the pathogenesis of human toxoplasmosis.The dense granules (GRA) are parasitic organelles involved in cell invasion and in the intracellular survival of the parasite. GRA proteins are expressed by the three stages of T. gondii: the tachyzoite, bradyzoite (38), and sporozoite (55) stages. GRA6 is a GRA antigen of 32 kDa described for the first time by Lecordier et al. (38). In extracellular parasites, GRA6 exists in dense secretor granules mostly as soluble proteins. Like the other GRA proteins, GRA6 is involved in host cell invasion. GRA6 is a glycine-rich protein and behaves like an integral membrane protein within the parasitophorous vacuole (36, 41). GRA6 is considered a good marker of acute infection (27, 28, 52). However, the immune response to GRA6 is very heterogeneous (25).GRA7 is a GRA antigen of 29 kDa (26, 31). Like GRA6, it is involved in host cell invasion. This protein is associated with the parasite membrane complex, the tubular elements of the intravacuolar network, and the parasitophorous vacuolar membrane. It migrates from the GRA to the parasitophorous vacuolar membrane through the intravacuolar network during host cell invasion (9). GRA7 is an antigen characteristic of the acute phase of the infection (27, 49, 51) and a target antigen in the intracerebral immune response during the chronic phase of infection (23, 45). These immunogenic properties make this antigen a good marker for serodiagnostic studies (5, 6, 7, 50).GRA6 and GRA7 are polymorphic loci. The coding region of the GRA6 locus has been used as a marker for the genotyping of Toxoplasma (8, 15-20, 24, 33, 34, 40, 43, 47, 53). Sequencing of GRA6 detected a high degree of polymorphism (24, 57). Single nucleotide polymorphisms (SNP) in the region encoding GRA6 can be detected by methods based on PCR followed by restriction fragment length polymorphism (PCR-RFLP): digestion of the amplification products with a single endonuclease (MseI) can differentiate genotypes I, II, and III (24). Another method based on GRA6 polymorphisms is pyrosequencing (21). This technique allows the analysis of short DNA sequences and SNP. Two SNP located at positions 162 and 171 of the GRA6 gene allow the differentiation of types I, II, and III. GRA7 has been less explored as a marker for the genotyping of Toxoplasma. Preliminary results (I. Villena, unpublished data) showed that GRA7 allows the discrimination between genotypes I, II, and III and some atypical strains by PCR-RFLP.Kong et al. (35) first proposed the use of the GRA6 and GRA7 proteins for serotyping. Basically, serotyping consists of a serological test with polymorphic peptides from Toxoplasma immunogens to detect strain-specific antibodies. Different peptides were proposed on the basis of the sequences of these antigens (35, 48, 53). However, the available peptides can differentiate only type II from non-type II infections. Infections due to nonarchetypal strains are misclassified as type II strains or type I or III strains, since GRA6 C-terminal peptides specific for type II and type I or III strains cross-react with serum samples from patients with infections caused by nonarchetypal strains (53).We proposed to determine polymorphic regions of GRA6 and GRA7 with the objective of defining possible polymorphic peptides that could be used to distinguish type I from type III infections and infections due to atypical strains by serotyping. Some of the defined peptides were tested in order to evaluate their utility as serotyping markers.     

Dual Role of CCR2 in the Constitution and the Resolution of Liver Fibrosis in Mice

Inflammation has been shown to induce the progression of fibrosis in response to liver injury. Among inflammatory cells, macrophages and lymphocytes play major roles in both the constitution and resolution of liver fibrosis. The chemokine receptor CCR2 is involved in the recruitment of monocytes to injury sites, and it is known to be induced during the progression of fibrosis in humans. However, its specific role during this process has not yet been unveiled. We first demonstrated that, compared with wild-type mice, CCR2 knockout animals presented a delay in liver injury after acute CCl₄ injection, accompanied by a reduction in infiltrating macrophage populations. We then induced fibrosis using repeated injections of CCl₄ and observed a significantly lower level of fibrotic scars at the peak of fibrosis in mutant animals compared with control mice. This diminished fibrosis was associated with a reduction in F4/80⁺CD11b⁺ and CD11c⁺ populations at the sites of injury. Subsequent analysis of the kinetics of the resolution of fibrosis showed that fibrosis rapidly regressed in wild-type, but not in CCR2^−/− mice. The persistence of hepatic injury in mutant animals was correlated with sustained tissue inhibitor of metalloproteinase-1 mRNA expression levels and a reduction in matrix metalloproteinase-2 and matrix metalloproteinase-13 expression levels. In conclusion, these findings underline the role of the CCR2 signaling pathway in both the constitution and resolution of liver fibrotic scars.Liver fibrosis and its progression toward cirrhosis is the consequence of chronic liver aggressions provoked by various agents such as viruses, bile acids, or alcohol. It is characterized by an accumulation of extracellular matrix mainly secreted by activated myofibroblasts and hepatic stellate cells (HSCs).^1,2 Although originally considered as an irreversible process, cirrhosis has now been shown to be potentially reversible, provided that the causative agent is removed.³ Current evidence suggests that the process of hepatic fibrosis is driven primarily by the development of an inflammatory reaction in response to parenchymal injury. In agreement with this hypothesis, deletion of specific components of the inflammatory response modifies or attenuates the fibrotic scar in vivo. It has been demonstrated that Kupffer cell inactivation,⁴ B lymphocyte deficiency,⁵ or macrophage depletion⁶ result in lower scarring and reduced activation of HSCs.Molecular mechanisms responsible for reversibility of liver fibrosis are only now starting to be deciphered. Experimental depletion of macrophages at the onset of fibrosis resolution retards extracellular matrix degradation and the loss of activated hepatic stellate cells.⁶ Therefore, macrophages seem to be crucial in both processes: fibrogenesis and fibrosis resolution.Chemokines are known to be critical mediators of inflammatory cell trafficking into sites of injury. Monocyte chemoattractant proteins (MCPs) attract cells through activation of their cognate receptor. MCP-1 is expressed by hepatocytes, endothelial cells, Kupffer cells, and HSCs in response to injury. CC chemokine receptor 2 (CCR2), which is expressed on monocytes/macrophages and on a subpopulation of T lymphocytes, has been found progressively up-regulated during the progression of liver fibrosis in humans.⁷ Moreover, comparison of serial sections of liver biopsies from patients with various degrees of necroinflammatory activity showed that infiltration with monocytes/macrophages is directly correlated with the expression of MCP-1,⁸ for which CCR2 is the main receptor.We hypothesized that signaling through CCR2 is involved in inflammatory cell recruitment during fibrogenesis and/or regression of fibrosis. To test this hypothesis, we compared the establishment and resolution of fibrosis after chronic liver aggression in CCR2-deficient mice versus wild-type mice. Our data show that the absence of CCR2 has opposite consequences during the constitution and the resolution of fibrosis.     

Efficacy of a Vaccine Based on Protective Antigen and Killed Spores against Experimental Inhalational Anthrax

Protective antigen (PA)-based anthrax vaccines acting on toxins are less effective than live attenuated vaccines, suggesting that additional antigens may contribute to protective immunity. Several reports indicate that capsule or spore-associated antigens may enhance the protection afforded by PA. Addition of formaldehyde-inactivated spores (FIS) to PA (PA-FIS) elicits total protection against cutaneous anthrax. Nevertheless, vaccines that are effective against cutaneous anthrax may not be so against inhalational anthrax. The aim of this work was to optimize immunization with PA-FIS and to assess vaccine efficacy against inhalational anthrax. We assessed the immune response to recombinant anthrax PA from Bacillus anthracis (rPA)-FIS administered by various immunization protocols and the protection provided to mice and guinea pigs infected through the respiratory route with spores of a virulent strain of B. anthracis. Combined subcutaneous plus intranasal immunization of mice yielded a mucosal immunoglobulin G response to rPA that was more than 20 times higher than that in lung mucosal secretions after subcutaneous vaccination. The titers of toxin-neutralizing antibody and antispore antibody were also significantly higher: nine and eight times higher, respectively. The optimized immunization elicited total protection of mice intranasally infected with the virulent B. anthracis strain 17JB. Guinea pigs were fully protected, both against an intranasal challenge with 100 50% lethal doses (LD₅₀) and against an aerosol with 75 LD₅₀ of spores of the highly virulent strain 9602. Conversely, immunization with PA alone did not elicit protection. These results demonstrate that the association of PA and spores is very much more effective than PA alone against experimental inhalational anthrax.Bacillus anthracis is a gram-positive, aerobic, facultatively anaerobic, spore-forming, rod-shaped bacterium and is the etiologic agent of anthrax. B. anthracis resides in the soil as a dormant spore that is highly resistant to adverse conditions and can remain viable for years. The spore typically enters herbivores through ingestion; although anthrax is predominantly a disease of herbivores, humans can be infected through incidental exposure during handling of animals or animal products. In humans, the disease may take three forms—cutaneous, gastrointestinal, or pulmonary—depending on the site of entry. The most common human form is cutaneous anthrax, typically caused by spores infecting open wounds or skin abrasions. The mortality of cutaneous anthrax is near 20% if untreated (21). Gastrointestinal anthrax may in some cases extend to neuromeningitidis and generally leads to fatal systemic disease if untreated (5, 21). Naturally acquired pulmonary anthrax is very unusual. However, the mortality of pulmonary anthrax is almost 100% if not treated very early (80). Inhalational anthrax manifests as the rapid development of nonspecific, flulike symptoms that, if untreated, progress quickly to shock, respiratory distress, and death (21, 80).Inhaled spores are deposited in alveolar spaces where they are ingested by macrophages (39, 66) and by dendritic cells (DCs) (9, 15). Then, the intracellular spores germinate into nascent bacilli that escape from the macrophage, multiply extracellularly in the lymphatic system and spread into the bloodstream, where rapid multiplication continues (38, 39); alternatively, phagocytized spores are transported by migrating macrophages to the mediastinal and peribronchial lymph nodes, where they germinate into bacilli (66). DCs may be central to this step of the infection (15). Anthrax disease appears to result from a two-step process involving overwhelming bacterial replication and subsequent toxin production. Nevertheless, the fate of spores within macrophages, the resistance of macrophages to anthrax toxins and the role of macrophages in B. anthracis dissemination all remain controversial (19, 20, 38, 39, 83). An alternative mechanism has been recently described, suggesting that inhaled spores establish an initial infection in nasally associated lymphoid tissues where they germinate. The bacteria then disseminate first to the draining lymph nodes, then to the spleen and lungs, and finally to the blood (37).B. anthracis has two major virulence determinants. One is a tripartite protein complex toxin composed of lethal factor (LF), edema factor (EF), and protective antigen (PA) all encoded by plasmid pXO1. The other is antiphagocytic poly-γ-d-glutamic acid (γPDGA) capsule encoded by plasmid pXO2. EF and LF combine with PA to form the edema toxin (ET) and lethal toxin (LT), respectively, which both impair host immune defenses and probably act synergistically in vivo to cause edema formation and death (58, 75). The PA-LF/PA-EF complex is internalized by receptor-mediated endocytosis and, after acidification of the endosome, the toxin is translocated into the host cell cytosol, where it exerts cytotoxic effects (89). LT is a zinc metalloprotease that inactivates mitogen-activated protein kinase kinases, leading to toxic effects on susceptible macrophages (3, 18, 24, 54) and impairment of the bactericidal activity of alveolar macrophages, thus facilitating B. anthracis survival (35, 65). ET is a calmodulin-dependent adenylate cyclase that catalyzes the production of cyclic AMP from host ATP, perturbing water homeostasis, which in turn causes massive edema (55). ET is also cytotoxic in a cell-dependent manner and may contribute to the disease through directly killing cells, leading to tissue necrosis (79) and multiorgan failure, resulting in host death (28). LT and ET cooperatively inhibit activation of both DCs (14, 76) and T cells (57), thereby suppressing both the innate immune response and the priming of adaptive immune responses. Therefore, preventing either the entry of the toxin complex into the host cell or its translocation into the cytosol would make a major contribution to protection.The PDGA capsule is a poorly immunogenic polypeptide but seems to be vital for the dissemination of B. anthracis in the bodies of infected animals (12). The in vivo synthesis of capsule determines the outcome of infection (22, 49), and capsule degradation enhances both in vitro macrophage phagocytosis and neutrophil killing of encapsulated B. anthracis (68).The potential use of B. anthracis spores as a weapon of biological warfare or as inhaled weapons of bioterrorism has increased the need for a safe and effective vaccine to protect humans against inhalational anthrax (6, 31).The current United Kingdom licensed anthrax vaccine, anthrax vaccine precipitate, is an alum-precipitated filtrate of B. anthracis 34F2 Sterne strain culture consisting mainly of PA (77). The U.S. licensed anthrax vaccine absorbed (AVA/Biothrax) also consists mainly of PA, in this case extracted from cultures of the unencapsulated, toxin-producing strain of B. anthracis V770-NP1-R adsorbed onto aluminum hydroxide (33). Both vaccines contain small amounts of EF and LF and probably other components that presumably contribute to vaccine efficacy (33, 77, 88).These vaccines have the major disadvantage of inducing only a limited duration of protection and require frequent booster injections if sufficient immunity is to be maintained (32). Furthermore, such PA-based vaccines, acting on toxins, are less effective than live attenuated vaccines such as the Sterne strain, suggesting that additional antigens may contribute in a significant manner to protective immunity (4, 16, 42, 51, 59, 85).Various animal models have been used for testing the protective activities of vaccines against anthrax infection, including mice (10, 30, 86), rats (46), guinea pigs (10, 26, 46, 70), hamsters (27), rabbits (26, 50, 60, 61), and nonhuman primates (26, 40, 44, 60). These studies emphasize the large differences of protection between species. For instance, PA-based vaccines confer better protection to guinea pigs, rabbits, and nonhuman primates than to mice, probably because the γPDGA capsule is the primary virulence factor in mice (87). Indeed, many reports suggest that capsule antigen(s) (13, 47, 64, 67, 81) and spore antigen(s) (10, 16, 23) might confer additional protection. An immunodominant glycoprotein antigen of the spore surface (BclA) has been identified among the various surface proteins of the exosporium and may contribute to protective immunity (72, 74). Sera from animals immunized with living spores of the toxinogenic unencapsulated STI-1 strain of B. anthracis have been reported to express both antitoxin and antispore activities, the latter involving inhibition of spore germination, which was attributed by some authors to both anti-PA and anti-LF antibodies (73). Furthermore, PA-based vaccines induce antispore activity characterized by stimulation of phagocytosis of opsonized spores by murine macrophages in vitro and by inhibition of spore germination. As a consequence, anti-PA antibody-specific immunity may contribute to impeding the early stages of infection with B. anthracis spores (84).Brossier et al. demonstrated that the addition of formaldehyde-inactivated spores (FIS) of B. anthracis to PA antigen (PA-FIS) elicits total protection of mice and guinea pigs against subcutaneous (s.c.) challenge with a virulent B. anthracis strain (10). However, vaccines that are effective for the s.c. route of infection may not be so against the pulmonary route (30).Several studies have demonstrated that either live spore-based vaccines or PA-based vaccines may confer variable protection against different B. anthracis strains and isolates in both mice and guinea pigs (26, 43, 51, 82, 85). Therefore, we used two different B. anthracis challenge strains in our study, namely, strains 9602 and 17JB from the Institut Pasteur collection. Although both strains are encapsulated and toxinogenic (cap⁺ tox⁺), harboring both pXO1 and pXO2 plasmids, they differ in virulence, as shown by the 50% lethal doses (LD₅₀) (s.c. route), estimated to be about 50 and 500 spores per mouse, respectively (10). Strain 9602 is as virulent as the Ames strain (10, 43); strain 17JB (the atypical Pasteur vaccine strain 2-17JB (78), harboring both pXO1 and pXO2 (cap+ tox+), is very similar to the so-called “Carbosap” strain used in Italy for immunization against ovine and bovine anthrax (25). It has residual pathogenicity characteristics that cause death in mice and guinea pigs but expresses no virulence in rabbits (25). Adone et al. demonstrated that the attenuation of the Carbosap vaccine strain is not due to the lack of virulence genes (cya, lef, and pagA), of regulatory genes (atxA and pagR), or of the gerX operon involved in germination within macrophages, or to divergence of the sequences of these genes from those of a wild-type virulent B. anthracis strain (1). Indeed, sophisticated advanced molecular analysis has been unable to identify the genetic differences accounting for differences in virulence between Carbosap and virulent strains (48).There are various possible causes of these differences in virulence and pathogenesis, including (i) involvement of unknown virulence factors and/or mechanisms involved in attenuation, (ii) differences in expression and activity of the known virulence factors and their regulators (48), and (iii) differences in pXO2 plasmid copy number (17). Nevertheless, like the Vollum strain, 17JB remains a relevant model for the study of vaccine efficacy: it is less pathogenic than wild-type strains such as 9602 or Ames but is nevertheless cap⁺ tox⁺.In summary, despite obvious efficacy in nonhuman primates, the currently licensed anthrax vaccines have shortcomings, such as a limited duration of protection and the need for frequent booster injections. Moreover, trace amounts of LF, EF, and probably other components are likely to have contributed to the efficacy of the vaccine in the reported studies. For instance, AVA provides partial protection in a guinea pig model of inhalational anthrax, whereas a recombinant anthrax PA from B. anthracis (rPA)-based vaccine elicits no protection (53). Furthermore, PA-based vaccines may confer variable protection against different B. anthracis strains and isolates, and large differences in the level of protection afforded are observed between animal species. These limitations have stimulated interest in the development of improved anthrax vaccines. The data discussed above suggest that other antigens in addition to PA are required for full protection.The aim of the present study was to optimize the PA-FIS vaccine immunization protocol so as to elicit protection against inhalational anthrax in an experimental model of lung infection. We assessed the systemic and mucosal immune response to PA-FIS in mice and guinea pigs, immunized either through the s.c. or the intranasal (i.n.) route or both. Second, we assessed the protection afforded in an experimental model of inhalational anthrax of mice and guinea pigs infected by nasal instillation or an aerosol.     

A TPM3 mutation causing cap myopathy

Cap disease is a rare congenital myopathy associated with skeletal malformations and respiratory involvement. Abnormally arranged myofibrils taking the appearance of a “cap” are the morphological hallmark of this entity. We report a case of cap disease concerning a 42-year-old man, without any family history and presenting a p.Arg168His mutation on the TPM3 gene. His first biopsy at 7 years had only shown selective type I hypotrophy. Mutations of TPM3 gene have been found in nemaline myopathy, congenital fiber type disproportion, but never before in cap disease.     

Neural correlates of subjective awareness and unconscious processing: an ERP study

The aim of the present study was to dissociate the ERP (Event Related Potentials) correlates of subjective awareness from those of unconscious perception. In a backward masking paradigm, participants first produced a forced-choice response to the location of a liminal target presented for an individually calibrated duration, and then reported on their subjective awareness of the target's presence. We recorded (Event-Related Potentials) ERPs and compared the ERP waves when observers reported being aware vs. unaware of the target but localized it correctly, thereby isolating the neural correlates of subjective awareness while controlling for differences in objective performance. In addition, we compared the ERPs when participants were subjectively unaware of the target's presence and localized it correctly versus incorrectly, thereby isolating the neural correlates of unconscious perception. All conditions involved stimuli that were physically identical and were presented for the same duration. Both behavioral measures were associated with modulation of the amplitude of the P3 component of the ERP. Importantly, this modulation was widely spread across all scalp locations for subjective awareness, but was restricted to the parietal electrodes for unconscious perception. These results indicate that liminal stimuli that do not affect performance undergo considerable processing and that subjective awareness is associated with a late wave of activation with widely distributed topography.