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At least 343 records · Page 19Linked to original sources
PubMed2005

Assessment of drug-induced QT interval prolongation in conscious rabbits.

INTRODUCTION: Most preclinical trials are designed to identify potential torsadogenicity test only for surrogates of torsade de pointes, most commonly prolongation of the heart rate corrected QT interval (QTc). This study was conducted to determine which correction method best accounts for the effects of changes in the RR interval on the QT interval of conscious rabbits. This study was also conducted to validate the use of conscious, sling-trained rabbits to assess the QTc interval, and to evaluate the reliability and accuracy of this preparation in predicting drug-induced QTc prolongation in humans. METHODS: ECGs were recorded via bipolar transthoracic ECG leads in 7 conscious rabbits previously trained to rest quietly in slings. The heart rate was slowed with 2.0 mg/kg zatebradine to assess the effects of heart rate on the QT interval. The same ECG and sling preparation was used to evaluate the effects in of three drugs known to be torsadogenic in humans (cisapride, dofetilide and haloperidol), two drugs known to be non-torsadogenic in humans (propranolol and enalaprilat) and a control article (vehicle). All of the test articles were administered intravenously to 4 rabbits, and both RR and QT intervals were measured and the corrected QT values were calculated by an investigator blinded to the test article, utilizing our own algorithm (QTc=QT/(RR)(0.72)) which permitted the least dependency of QTc on RR interval. RESULTS: The following regression equations were obtained relating QT to RR: QT=2.4RR(0.72), r(2)=0.79, with RR intervals varying between 210 and 350 ms. QTc lengthened significantly in all conscious rabbits given intravenous cisapride, dofetilide and haloperidol (p<0.05), and QTc did not change with DMSO (vehicle control), propranolol or enalaprilat. DISCUSSION: Results indicate that a bipolar transthoracic ECG recorded in conscious, sling-trained rabbits may provide an easy and economical methodology useful in predicting QTc lengthening of novel pharmacological entities.

Animals↗
PubMed2001

Consciousness and the brainstem.

In the first part of this article we summarize a theoretical framework and a set of hypotheses aimed at accounting for consciousness in neurobiological terms. The basic form of consciousness, core consciousness is placed in the context of life regulation; it is seen as yet another level of biological processing aimed at ensuring the homeostatic balance of a living organism; and the representation of the current organism state within somato-sensing structures is seen as critical to its development. Core consciousness is conceived as the imaged relationship of the interaction between an object and the changed organism state it causes. In the second part of the article we discuss the functional neuroanatomy of nuclei in the brainstem reticular formation because they constitute the basic set of somato-sensing structures necessary for core consciousness and its core self to emerge. The close relationship between the mechanisms underlying cortical activation and the bioregulatory mechanisms outlined here is entirely compatible with the classical idea that the reticular formation modulates the electrophysiological activity of the cerebral cortex. However, in the perspective presented here, that modulation is placed in the setting of the organism's homeostatic regulation.

Brain Stem↗
PubMed2001

Paradox and cross purposes in recent work on consciousness.

Functionalists about consciousness identify consciousness with a role; physicalists identify consciousness with an implementer of that role. The global workspace theory of consciousness fits the functionalist perspective, but the physicalist sees consciousness as a biological phenomenon that implements global accessibility.

Brain↗
PubMed2003

Expertise and the evolution of consciousness.

This paper argues that expertise can be used as an indicator of consciousness in humans and other animals. The argument is based on the following observations: (1) expertise and skill acquisition require deliberate practice; and (2) the characteristics of deliberate practice such as performance evaluation against a more proficient model, retention of voluntary control over actions, self-monitoring, goal-setting, error-detection and correction, and the construction of hierarchically organized retrieval structures are outside of the currently understood bounds of unconscious processing. Thus, to the extent that evidence of expertise exists in an organism, evidence of conscious experience is also present. Two important implications arise from this conclusion: (1) evidence of expertise can be used as the basis for cross-species comparisons of consciousness; and (2) the evolution of human consciousness can be assessed using fossil evidence of skilled behavior as a measure of consciousness.

Animals↗
PubMed2004

[The cerebral substrate of visual consciousness: a neurological approach].

Since the last thirty Years, scientific study of the cerebral substrate of consciousness has been marked by significant achievements, resulting in part from a rich interaction between the exploration of cognition in both brain-damaged patients and healthy subjects. Several neuropsychological syndromes contain spectacular dissociations which permit to identify principles related to the neurophysiology of consciousness. The generality of those principles can then be evaluated in the healthy subject using the combination of experimental psychology paradigms, and functional brain-imaging tools. In this paper, we review some of the recent results relevant to visual phenomenal consciousness, which is the most scientifically investigated aspect of consciousness. We isolate several of those general principles through the exploration of neuropsychological syndromes such as "blindsight", visual agnosias and neglect, and expose how their generality has been demonstrated in the healthy subject using conditions such as visual illusions or subliminal perception. Finally, we describe the bases of a scientific model of consciousness, based on the concept of a "global workspace", which takes into account the data reviewed.

Attention↗
PubMed2005

Visual phenomenal consciousness: a neurological guided tour.

The scientific study of the cerebral substrate of consciousness has been marked by significant recent achievements, resulting partially from an interaction between the exploration of cognition in both brain-damaged patients and healthy subjects. Several neuropsychological syndromes contain marked dissociations that permit the identification of principles related to the neurophysiology of consciousness. The generality of these principles can then be evaluated in healthy subjects using a combination of experimental psychology paradigms, and functional brain-imaging tools. In this chapter, I review some of the recent results relevant to visual phenomenal consciousness, which is an aspect of consciousness most frequently investigated in neuroscience. Through the exploration of neuropsychological syndromes such as "blindsight," visual form agnosia, optic ataxia, visual hallucinations, and neglect, I highlight four general principles and explain how their generality has been demonstrated in healthy subjects using conditions such as visual illusions or subliminal perception. Finally, I describe the bases of a scientific model of consciousness on the basis of the concept of a "global workspace," which takes into account the data reviewed.

Brain↗
PubMed1989

Duration of impaired consciousness in relation to side of lesion after severe head injury. NIH Traumatic Coma Data Bank Research Group.

The relation between hemispheric lateralisation of intracerebral lesion and duration of impaired consciousness was investigated in 43 survivors of severe closed head injury. Duration of impaired consciousness, defined as the time from injury until the obeying of commands, was significantly longer in patients with left hemisphere than right hemisphere lesions. However, the side of intracerebral lesion had no effect on duration of impaired consciousness defined as time from injury until localisation to pain. Use of verbal methods to assess level of consciousness may be responsible for the observation that lesions of the language dominant hemisphere produce greater disturbance of consciousness than similar insults to the right hemisphere.

Age Factors↗
PubMed2002

The neurophysics of consciousness.

Consciousness combines information about attributes of the present multimodal sensory environment with relevant elements of the past. Information from each modality is continuously fractionated into distinct features, processed locally by different brain regions relatively specialized for extracting these disparate components and globally by interactions among these regions. Information is represented by levels of synchronization within neuronal populations and of coherence among multiple brain regions that deviate from random fluctuations. Significant deviations constitute local and global negative entropy, or information. Local field potentials reflect the degree of synchronization among the neurons of the local ensembles. Large-scale integration, or 'binding', is proposed to involve oscillations of local field potentials that play an important role in facilitating synchronization and coherence, assessed by neuronal coincidence detectors, and parsed into perceptual frames by cortico-thalamo-cortical loops. The most probable baseline levels of local synchrony, coherent interactions among brain regions, and frame durations have been quantitatively described in large studies of their age-appropriate normative distributions and are considered as an approximation to a conscious 'ground state'. The level of consciousness during anesthesia can be accurately predicted by the magnitude and direction of reversible multivariate deviations from this ground state. An invariant set of changes takes place during anesthesia, independent of the particular anesthetic agent. Evidence from a variety of neuroscience areas supporting these propositions, together with the invariant reversible electrophysiological changes observed with loss and return of consciousness, are used to provide a foundation for this theory of consciousness. This paper illustrates the increasingly recognized need to consider global as well as local processes in the search for better explanations of how the brain accomplishes the transformation from synchronous and distributed neuronal discharges to seamless global subjective awareness.

Brain↗
PubMed1996

How can we find the neural correlate of consciousness?

There are two concepts of consciousness, access consciousness and phenomenal consciousness. But just as the concepts of water and H2O are different concepts of the same thing, so the two concepts of consciousness might come to the same thing in the brain. Some recent papers by Crick and Koch raise issues that suggest that these two concepts of consciousness might have different (though overlapping) neural correlates, despite Crick and Koch's implicit rejection of this idea.

Animals↗
PubMed1997

Breathing patterns and levels of consciousness in children during administration of nitrous oxide after oral midazolam premedication.

PURPOSE: The combination of midazolam and nitrous oxide is commonly used to achieve sedation and analgesia during pediatric oral procedures, yet there are few, if any, data that illustrate the ventilatory effects of N2O in children, especially when used in combination with additional central nervous system (CNS) depressants. It was hypothesized that the addition of N2O inhalation to oral midazolam premedication would enhance the sedative effects of the midazolam and add analgesia without causing significant respiratory depression. The purpose of this study was to test this hypothesis. MATERIALS AND METHODS: Thirty-four healthy children about to undergo restorative dental treatment under general anesthesia were premedicated with oral midazolam, 0.7 mg/kg, and were then exposed to 40% N2O for 15 minutes after a 5-minute control period. The effect of adding N2O on SpO2, respiratory rate, PETCO2, VT, and VT/TI was examined and the levels of consciousness (conscious vs deep sedation) before and during N2O inhalation were determined. RESULTS: During the course of the study, no child developed hypoxemia (SpO2 < 92%) nor clinically significant upper airway obstruction. Four children who did not develop hypoventilation (defined as PETCO2 > 45 mm Hg) during the control period did so after initiation of N2O. Overall, there were no significant differences in SpO2, PETCO2, VT, or VT/TI between the control and study periods. However, respiratory rates were significantly higher in the first 10 minutes of N2O inhalation when compared with the control period. Before starting N2O administration, 14 children were not clinically sedated, 19 children met the criteria for conscious sedation, and one child met the criteria for deep sedation. At the end of 15 minutes of N2O inhalation, 12 children were not clinically sedated, 17 children met the definition of conscious sedation, three were deeply sedated, and one child had no response to IV insertion, implying a state of general anesthesia. There were no differences in sedation scores between the control and study periods (P = .6). Overall, seven children had an increase in their sedation score while breathing N2O, four had a decrease in their sedation score, and 22 had no change. CONCLUSIONS: The addition of 40% N2O to oral midazolam, 0.7 mg/kg, did not result in clinically meaningful respiratory depression nor upper airway obstruction, but did, in some children, cause an increase in the level of sedation beyond simple conscious sedation.

Adjuvants, Anesthesia↗
PubMed2002

S-100 protein as early predictor of regaining consciousness after out of hospital cardiac arrest.

BACKGROUND AND PURPOSE: Patients resuscitated from cardiac arrest (CA) have a high mortality rate. Prognostic evaluation based on clinical observations is uncertain and would benefit from the use of biochemical markers of hypoxic brain damage. The purpose of the study was to validate the use of the serum astroglial protein S-100 levels at admission with regard to regaining consciousness after out of hospital CA. METHODS: Fifty-eight patients resuscitated from out-of-hospital CA were followed up until they regained consciousness or until their death or permanent vegetative state occurred. Serum samples for measurement of S-100, using an immunoradiometric assay, were obtained at admission. RESULTS: At admission, the mean value+/-standard error of the mean of serum S-100 protein was significantly higher in patients who did not regain consciousness compared with patients who regained consciousness, respectively 4.66+/-0.61 microg/l and 0.84+/-0.21 microg/l. A serum S-100 value of >0.7 microg/l at admission was found to be a predictor that consciousness would not be regained, with a specificity of 85%, a sensitivity of 66.6%, a positive predictive value of 84%, a negative predictive value of 78% and an accuracy of 77.6%. CONCLUSIONS: Serum S-100 protein at admission gives reliable and independent information concerning the short term neurological outcome after resuscitation; and could be a good marker of brain cell damage.

Aged↗
PubMed2003

High density ERP indices of conscious and unconscious semantic priming.

The existence of differential brain mechanisms of conscious and unconscious processing is a matter of debate nowadays. The present experiment explores whether conscious and unconscious semantic priming in a lexical decision task at a long prime-target stimulus onset asynchrony (SOA) correlate with overlapping or different event related potential (ERP) effects. Results show that the N400 effect, which appeared when words were consciously perceived, completely disappeared when primes were masked at a level where the ability of participants to detect the prime was near chance. Instead, a rather different set of ERP effects was found to index unconscious semantic priming. This suggests that the processes at the basis of conscious and unconscious semantic analyses can under some circumstances be rather different. Moreover, our results support the notion that conscious and unconscious processes are at least partially separable in the brain.

Adult↗
PubMed2003

Level and contents of consciousness in connection with partial epileptic seizures.

The present study introduces concepts and methods that can be used in the systematic psychological study of a seizure, to gain more insight into the seizure as it is experienced by the patient and the significant other. Fourteen patients reported 40 descriptions of their subjective experiences during complex partial seizures. We analyzed the descriptions with respect to the temporal progression of the seizure and the level and contents of consciousness. There were three main findings: (1). We identified an impairment of the voluntary control of attention ("forced attention") that seems to characterize the early stages of the seizure in all patients. (2). Although most patients reported the total absence of consciousness, we identified a subgroup of patients with a fluctuating level of consciousness during the seizure. (3). The patients who reported some contents of consciousness during the seizure were found to usually experience internal mental images rather than other contents of consciousness (e.g., sensations or perceptions). We propose that use of a qualitative methodology for the psychological assessment of seizures could lead to a better understanding of seizures as experienced from the patient's perspective and thereby to improvements in the treatment of seizures.

Adult↗
PubMedDate not supplied

Changes in level of consciousness and association with hyperglycemia as tool for predicting and preventing re-bleeding after spontaneous subarachnoid hemorrhage.

INTRODUCTION: It is crucial to predict and prevent re-bleeding from ruptured intracranial aneurysms in patients with subarachnoid hemorrhage (SAH). During the prehospital period and on arrival to the hospital, blood glucose and serum potassium levels, as well as changes in levels of consciousness were assessed in patients in the acute stage of spontaneous subarachnoid hemorrhage. These assessments were analyzed as possible risk factors for re-bleeding and as potential contributors to the prevention of re-bleeding, both in prehospital care and after hospital admission. METHODS: Upon the arrival of 202 patients with spontaneous subarachnoid hemorrhage, the following indications were examined retrospectively: (1) presence/absence of re-bleeding; (2) time interval between the onset of SAH and re-bleeding; (3) level of consciousness using the Glasgow Coma Scale (GCS) score before and on arrival; (4) amount and distribution of subarachnoid blood using Fisher's Computerized Tomography Classification; (5) blood pressure; (6) blood glucose concentration; and (7) serum potassium concentration. The patients were hospitalized in the Yokohama City University Critical Care and Emergency Center (Yokohama, Japan) between January 1991 and December 2000. The re-bleeding rate was analyzed using the chi-square (chi2 test, and the averages and standard deviations of hematological data were compared using the Mann-Whitney U-test. The level of statistical significance was set at p < 0.05. RESULTS: The overall re-bleeding rate was 20.8%. Among 119 patients with a GCS score of 3-7 before arrival, 42 (35.3%) had re-bleeding, but none of the 83 patients with a GCS score of 8-15 before arrival had re-bleeding. Of 105 patients with a GCS score of 13-15 on arrival, 14 (51.8%) of 27 patients whose consciousness level was a GCS score of 3-7 before arrival experienced re-bleeding. The re-bleeding rate of this group was high. Moreover, this rebleeding group had a significantly higher blood glucose concentration than did the patients whose GCS score was 13-15 both before and on arrival. Between the patients with or without re-bleeding, there was no significant difference in the blood pressure on arrival or in distribution according to Fisher's Computerized Tomography Classification CONCLUSION: Since the re-bleeding rate is high in patients who have hyperglycemia and a history of a level of consciousness as low as a GCS score of 3-7, a detailed assessment of level of consciousness and blood glucose tests performed on arrival provide important information that will contribute to predicting and preventing re-bleeding. This may be extended to the prehospital phase, because blood glucose tests are simple and safe when performed by paramedics.

Consciousness↗
PubMed2005

Timing of the brain events underlying access to consciousness during the attentional blink.

In the phenomenon of attentional blink, identical visual stimuli are sometimes fully perceived and sometimes not detected at all. This phenomenon thus provides an optimal situation to study the fate of stimuli not consciously perceived and the differences between conscious and nonconscious processing. We correlated behavioral visibility ratings and recordings of event-related potentials to study the temporal dynamics of access to consciousness. Intact early potentials (P1 and N1) were evoked by unseen words, suggesting that these brain events are not the primary correlates of conscious perception. However, we observed a rapid divergence around 270 ms, after which several brain events were evoked solely by seen words. Thus, we suggest that the transition toward access to consciousness relates to the optional triggering of a late wave of activation that spreads through a distributed network of cortical association areas.

Adolescent↗
PubMed2000

Designing a bridge for consciousness: are criteria for a unification of approaches feasible?

Different intrinsic rules of functioning for body and mind are overemphasized by the mutually exclusive methods of investigation in both consciousness and the sciences. Classical science, alternative and complementary healing, quantum physics, and metaphysics all take drastically different approaches to consciousness research. A bridge is needed to restore the conceptual unity of mind-body. However, the construction of such a bridge paradoxically must rely on consciousness for information. The construction company (Consciousness, Inc.) therefore becomes means and end in the design of the bridge. This piece argues that the methods of each discipline contain research tools and resources to create a bridge that satisfies a unified multidimensional and multidisciplinary conception. The piece further suggests that the framework of the bridge must place consciousness as a partner to physiology in the evolutionary trajectory of life, since problems of survival are a primary consideration in the activity of both. Finally, the piece develops six criteria by which to evaluate the effectiveness of any construction design.

Consciousness↗
PubMed1997

Consciousness and attention.

This article addresses the relationship between attention and consciousness. I take consciousness to refer, at least in an approximate sense, to those thoughts, memories, sensations, and actions of which one is aware, whereas attention refers to those processes that modulate neuronal activity. This modulation may be achieved by virtue of linking or binding distinct neuronal populations or by selecting information for further processing. Thus, consciousness and attention are different but closely related in that attention provides the glue that binds processes and representations to the prevailing cognitive set, thereby rendering them conscious. In this context, then, attention may be viewed as a control process. A number of neurologic syndromes in which disorders of attention result in the fragmentation of consciousness are discussed. Finally, the anatomic bases of attention, both cortical and subcortical, are reviewed.

Attention↗
PubMed2006

Nonconscious semantic processing of emotional words modulates conscious access.

Whether masked words can be processed at a semantic level remains a controversial issue in cognitive psychology. Although recent behavioral studies have demonstrated masked semantic priming for number words, attempts to generalize this finding to other categories of words have failed. Here, as an alternative to subliminal priming, we introduce a sensitive behavioral method to detect nonconscious semantic processing of words. The logic of this method consists of presenting words close to the threshold for conscious perception and examining whether their semantic content modulates performance in objective and subjective tasks. Our results disclose two independent sources of modulation of the threshold for access to consciousness. First, prior conscious perception of words increases the detection rate of the same words when they are subsequently presented with stronger masking. Second, the threshold for conscious access is lower for emotional words than for neutral ones, even for words that have not been previously consciously perceived, thus implying that written words can receive nonconscious semantic processing.

Consciousness↗