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PubMed2005

Long-term monitoring of pulmonary arterial pressure in conscious, unrestrained mice.

INTRODUCTION: The ability to genetically engineer specific gene 'knock-out' mice has provided a powerful tool for investigating the various mechanisms that contribute to the pathogenesis of pulmonary arterial hypertension (PAH). Yet, so far there have been no reports describing the measurement of pulmonary arterial pressure (PAP) in the conscious wild type mouse-an essential requirement for monitoring dynamic changes associated with the pathogenesis of PAH. Therefore, in this study we describe a new technique for long-term measurement of PAP in conscious unrestrained mice using telemetry. METHODS: In five male C57BL/6 mice (B.W. 25-30 g), the sensing catheter of a telemetric transmitter was inserted into the right ventricle and advanced into the pulmonary artery. The transmitter body was positioned either within the abdominal cavity or subcutaneously on the back. During recovery from surgery, mean PAP was recorded daily for 1 week. Subsequently, the PAP responses to acute hypoxia (8% O2 for 10 min) and L-NAME (50 mg/kg, s.c.) were tested in three mice. RESULTS: By 1-week post surgery, all mice had fully recovered from surgery and baseline MPAP was stable at 14.9+/-0.7 mm Hg. Additionally, the pulmonary vascular stimulants acute hypoxia and L-NAME provoked a 63% and 86% increase MPAP, respectively. DISCUSSION: In summary, this study has demonstrated the ability to accurately measure PAP by telemetry in conscious, unrestrained mice. One important application of this technique for future studies is the possibility to assess the relative contribution of specific genes (using 'knock-out' mice) during the chronic development of pulmonary pathological conditions.

Animals↗

PubMed2006

From unilateral neglect to the brain basis of consciousness.

According to the dominant focus model, the differential activation of the thalamocortical network is a sufficient condition for the diversity of states of consciousness to occur, and coherent patterns of interactive forebrain activation peaks are sufficient to generate specific conscious figures against ground. These minimal assumptions are consonant with the known properties of unilateral neglect. It becomes unnecessary to suppose that consciousness is an independent entity, occupies a dedicated location in the brain, is contingent on a minimal level of neural complexity, plays a causal role in enabling perception or action, or evolved because it plays any such role.

Attention↗

PubMed1995

Effects of ryanodine on cardiac contraction, excitation-contraction coupling and "Treppe" in the conscious dog.

The effects of ryanodine on left ventricular (LV) function and hemodynamics were studied in 16 conscious dogs, chronically instrumented for measurements of LV pressures and dimensions. Systemic infusion of ryanodine (0.5-4 micrograms/kg i.v.) resulted in a dose-dependent depression of cardiac contraction. For example, ryanodine, 4 micrograms/kg i.v., decreased LV fractional shortening by 30.5 +/- 4.1%, LV dP/dt by 41.5 +/- 4.0% and Vcfc by 37.8 +/- 4.1%, while increasing the isovolumic relaxation time constant, tau, from 23.1 +/- 1.4 to 34.1 +/- 3.6 ms without a major effect on preload or afterload. Ryanodine also depressed (P < 0.05) the plateau phase of the mechanical restitution and post-extrasystolic potentiation responses, indicating a direct effect on excitation-contraction coupling. The heart rate dependent positive staircase ("Treppe") was significantly enhanced (P < 0.05) after ryanodine infusion, i.e. LV dP/dt rose by 43.1 +/- 4.7% with an increase in heart rate from 150 to 240 beats/min in the presence of ryanodine 4 micrograms/kg, but by only 7.5 +/- 2.1% without ryanodine. The more pronounced "Treppe" in the conscious dog under the condition of impaired SR calcium release caused by ryanodine, supports the concept that the classical Bowditch "Treppe" reflects either a state of myocardial depression due to alteration in SR calcium handling, or enhanced availability of trans-sarcolemmal Ca2+ influx. This finding may help to understand the discrepancy in the importance of the "Treppe" between conscious animals and more isolated preparations.

Animals↗

PubMed2005

A neurophilosophical slant on consciousness research.

Explaining the nature and mechanisms of conscious experience in neurobiological terms seems to be an attainable, if yet unattained, goal. Research at many levels is important, including research at the cellular level that explores the role of recurrent pathways between thalamic nuclei and the cortex, and research that explores consciousness from the perspective of action. Conceptually, a clearer understanding of the logic of expressions such as "causes" and "correlates", and about what to expect from a theory of consciousness are required. The logic of some terms, such as "qualia" and "reductionism", continues to generate misunderstandings about the scientific possibilities and limits. Experimentally, a deeper understanding of the role of the thalamus in coordinating activity across cortical levels, and a readiness to reconsider the orthodox approach to thalamocortical organization are also required.

Animals↗

PubMed2005

Posterior cingulate, precuneal and retrosplenial cortices: cytology and components of the neural network correlates of consciousness.

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.

Animals↗

PubMed2005

Two aspects of impaired consciousness in Alzheimer's disease.

Alzheimer's disease (AD) is a degenerative dementia characterized by different aspects of impaired consciousness. For example, there is a deficit of controlled processes that require conscious processing of information. Such an impairment is indexed by decreased performances at controlled cognitive tasks, and it is related to reduced brain metabolic activity in a network of frontal, posterior associative, and limbic regions. Another aspect of impaired consciousness is that AD patients show variable levels of anosognosia concerning their cognitive deficits. A discrepancy score between patient's and caregiver's assessment of cognitive functions is one of the most frequently used measures of anosognosia. A high discrepancy score has been related to impaired activity in the superior frontal sulcus and the parietal cortex in AD. Anosognosia for cognitive deficits in AD could be partly explained by impaired metabolism in parts of networks subserving self-referential processes (e.g., the superior frontal sulcus) and perspective-taking (e.g., the temporoparietal junction). We hypothesize that these patients are impaired in the ability to see themselves with a third-person perspective (i.e., being able to see themselves as other people see them).

Agnosia↗

PubMed2003

An investigation into asymmetrical cortical regulation of salivary S-IgA in conscious man using transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) can activate discrete areas of the cerebral cortex through the intact skull of healthy conscious volunteers. A magnetic coil generates a brief and focused magnetic field that penetrates the skull to activate the specific area of cerebral cortex beneath. This non-invasive procedure is painless, well tolerated by participants and now widely used to explore brain function. We used TMS to investigate asymmetrical cortical regulatory influences on one aspect of immune function: secretion of the antibody immunoglobulin A (S-IgA) into saliva. The right and left temporo-parietal-occipital cortex of 16 healthy, conscious subjects was stimulated on two different occasions, at least 1 week apart. There was an immediate increase in S-IgA concentration following both right and left stimulation. Saliva volume was reduced immediately post-right but not left stimulation. When secretion (microg/min) of S-IgA was calculated (controlling for changing saliva volume) an increase was apparent following left but not right hemisphere stimulation. Furthermore, a significant difference between the relationship between S-IgA concentration and volume of saliva post-left and right stimulation was observed. We conclude that TMS can be used as a tool to investigate cortical regulation of autonomic and immune function in healthy, conscious human subjects and that secretion of saliva and S-IgA is differentially affected by stimulation of the left and right cerebral cortex.

Analysis of Variance↗

PubMed2004

A TMS study of the ventral projections from V1 with implications for the finding of neural correlates of consciousness.

The study of subliminal perception in normal and brain lesioned subjects has long been of interest to scholars studying the neural mechanisms behind conscious vision. Using brief durations and a developed methodology of introspective reporting, we present an experiment with visual stimuli that gives rise to little or no subliminal perception under normal viewing conditions. Coupled with transcranial magnetic stimulation, however, we find a dissociation between correctness and conscious awareness. Furthermore, we find support for the hypothesis that the ventral projection streams from V1 are necessary for visual consciousness.

Adult↗

PubMed1998

An interdisciplinary approach towards a theory of consciousness.

Instead of attacking the difficult problem of consciousness or self-consciousness directly, the theory is based on the more basic concept of reflection. A concept of reflection is suggested on four levels (recursion, reflective thinking, self-reflection, intersubjective reflection). We propose the glial-neuronal interaction as a neurobiological substrate for reflection processes. It is assumed that glia have a boundary-setting function (scaffolding, compartmentalization) in the spatio-temporal interaction with the neurons. This function could be a possible mechanism of 'dividing' the brain into different self-systems each with their own capacity of self-organization. Although the brain's different self-systems are normally integrated, they may disintegrate and show themselves in special states of the brain (e.g. multiple personality disorder). A tree of reflection consisting of a number of places (ontological loci) on which reflection processes of varying complexity take place, is suggested as the formal model. Finally, the problem of self-conscious qualitative experience (Qualia) is discussed in terms of the reflection model.

Animals↗

PubMed1998

Conscious experience and information.

Conscious experience, our main source of information, has special properties. Primary among them is privacy, or privileged access by persons to their own conscious states. The consequent theoretical and practical problems for research on both consciousness and information are delineated.

Cognition↗

PubMed2003

Selective attentional bias, conscious awareness and the fear of pain.

It has been suggested that healthy individuals with a high fear of pain possess a selective attentional bias in favour of pain-related material. However, evidence is limited since only a few studies have been conducted to date. In addition, these studies have not yet examined whether such attentional biases are relatively automatic, and so are outside conscious control. We, therefore, conducted a study with unmasked (conscious) and masked (preconscious) versions of the visual dot-probe task, and examined the effect of pain fearfulness on performance. In the masked trials, we confirmed that individuals with a low fear of pain seem to orient away from pain-related material. Furthermore, we also found that when stimuli were masked, this bias was reversed. Neither effect was found amongst participants high in the fear of pain. Together, these findings suggest that the ability to orient away from pain-related stimuli may be under conscious control in low fearful people, whereas such a mechanism does not seem to exist in those high in the fear of pain.

Adolescent↗

PubMed1997

Consciousness in waking and dreaming: the roles of neuronal oscillation and neuromodulation in determining similarities and differences.

State-dependent aspects of consciousness are explored with particular attention to waking and dreaming. First, those phenomenological differences between waking and dreaming that have been established through subjective reports are reviewed. These differences are robustly expressed in most aspects of consciousness including perception, attention, memory, emotion, orientation, and thought. Next, the roles of high frequency neuronal oscillation and neuromodulation are explored in waking and rapid eye movement sleep, the stage of sleep with which the most intense dreaming is associated. The high frequency neuronal oscillations serve similar functions in the wake and rapid eye movement states sleep but neuromodulation is very different in the two states. The collective high frequency oscillatory activity gives coherence to spatially separate neurons but, because of the different neuromodulation, the binding of sensory input in the wake state is very different from the binding of internally perceived input during rapid eye movement sleep. An explanatory model is presented which states that neuromodulation, as well as input source and brain activation level differentiate states of the brain, while the self-organized collective neuronal oscillations unify consciousness via long range correlations.

Consciousness↗

PubMed2001

Cortical networks for working memory and executive functions sustain the conscious resting state in man.

The cortical anatomy of the conscious resting state (REST) was investigated using a meta-analysis of nine positron emission tomography (PET) activation protocols that dealt with different cognitive tasks but shared REST as a common control state. During REST, subjects were in darkness and silence, and were instructed to relax, refrain from moving, and avoid systematic thoughts. Each protocol contrasted REST to a different cognitive task consisting either of language, mental imagery, mental calculation, reasoning, finger movement, or spatial working memory, using either auditory, visual or no stimulus delivery, and requiring either vocal, motor or no output. A total of 63 subjects and 370 spatially normalized PET scans were entered in the meta-analysis. Conjunction analysis revealed a network of brain areas jointly activated during conscious REST as compared to the nine cognitive tasks, including the bilateral angular gyrus, the left anterior precuneus and posterior cingulate cortex, the left medial frontal and anterior cingulate cortex, the left superior and medial frontal sulcus, and the left inferior frontal cortex. These results suggest that brain activity during conscious REST is sustained by a large scale network of heteromodal associative parietal and frontal cortical areas, that can be further hierarchically organized in an episodic working memory parieto-frontal network, driven in part by emotions, working under the supervision of an executive left prefrontal network.

Adult↗

PubMed2003

Reversible altered consciousness with brain atrophy caused by valproic acid.

A 5-year-old female developed alteration of consciousness during 3 days of long-term treatment with valproic acid for localization-related epilepsy. Computed tomography revealed cerebral atrophy, and electroencephalography presented slow background activity. Consciousness cleared only 12 hours after valproic acid was discontinued, and normal electroencephalography results were evident 1 week later. Cerebral atrophy was nonexistent 2 months later. This rapidly developing but reversible alteration of consciousness in parallel with brain atrophy is recognized as a rare idiosyncratic adverse effect of valproic acid.

Atrophy↗

PubMed2001

Theta synchronization during episodic retrieval: neural correlates of conscious awareness.

The neural correlates of conscious awareness during successful memory retrieval were examined. In a recognition test, subjects indicated whether they consciously recalled the event in which a word was earlier presented (Remembering), or whether they recognized it on the basis that it was familiar in the absence of recollection (Knowing). An early EEG synchronization in the theta band predicted knowing, and a later remembering. Moreover, early and late event-related potentials were also found to predict knowing and remembering, respectively. The results indicate that the temporal dynamics of theta synchronization are related to the particular conscious experiences associated with memory retrieval.

Adult↗

PubMed2002

Increased dopamine tone during meditation-induced change of consciousness.

This is the first in vivo demonstration of an association between endogenous neurotransmitter release and conscious experience. Using 11C-raclopride PET we demonstrated increased endogenous dopamine release in the ventral striatum during Yoga Nidra meditation. Yoga Nidra is characterized by a depressed level of desire for action, associated with decreased blood flow in prefrontal, cerebellar and subcortical regions, structures thought to be organized in open loops subserving executive control. In the striatum, dopamine modulates excitatory glutamatergic synapses of the projections from the frontal cortex to striatal neurons, which in turn project back to the frontal cortex via the pallidum and ventral thalamus. The present study was designed to investigate whether endogenous dopamine release increases during loss of executive control in meditation. Participants underwent two 11C-raclopride PET scans: one while attending to speech with eyes closed, and one during active meditation. The tracer competes with endogenous dopamine for access to dopamine D2 receptors predominantly found in the basal ganglia. During meditation, 11C-raclopride binding in ventral striatum decreased by 7.9%. This corresponds to a 65% increase in endogenous dopamine release. The reduced raclopride binding correlated significantly with a concomitant increase in EEG theta activity, a characteristic feature of meditation. All participants reported a decreased desire for action during meditation, along with heightened sensory imagery. The level of gratification and the depth of relaxation did not differ between the attention and meditation conditions. Here we show increased striatal dopamine release during meditation associated with the experience of reduced readiness for action. It is suggested that being in the conscious state of meditation causes a suppression of cortico-striatal glutamatergic transmission. To our knowledge this is the first time in vivo evidence has been provided for regulation of conscious states at a synaptic level.

Adult↗

PubMed1997

The state of consciousness and very high frequency signalling in the serotonergic neuronal system.

The attributes of consciousness are briefly discussed and matched to the known characteristics of the serotonergic neuronal system. In particular sleep, the action of agonist drugs, the regulatory role and monitoring components, together with the receptor areas for serotonergic activity, are identified as significant correlates of consciousness. Fröhlich-like phenomena are attributed to the topology of the serotonergic cell which is posited to produce excitations in the gigaHz or very high frequency range. Coding by discrete channel frequency and propagation throughout the vast microtubule cytoskeletal structure of serotonergic activity is proposed as the biophysical basis of consciousness in higher mammals, particularly humans.

Animals↗

PubMed1999

Interaction modeling of propofol and sufentanil on loss of consciousness.

STUDY OBJECTIVES: To examine the possible pharmacodynamic interaction of propofol and sufentanil with respect to the induction of loss of consciousness. DESIGN: Prospective, randomized, double-blinded study. SETTING: University hospital. PATIENTS: 30 female, ASA physical status I and II patients undergoing elective gynecologic surgery. INTERVENTIONS: Patients were allocated randomly to receive an individual combination of propofol (1, 2, 3, 4, 5, or 6 micrograms/ml) and sufentanil (0.1, 0.2, 0.3, 0.5, or 1.0 ng/ml) target blood concentrations using target-controlled infusions. MEASUREMENTS AND MAIN RESULTS: Study endpoint was loss of consciousness, which was tested by response to verbal commands and classified as responder or nonresponder, as assessed by the anesthetist, who was blinded to the drugs' target blood concentrations. Nonlinear association (interaction) of both drugs was accomplished with logistic regression analysis using the maximum likelihood method, based principally on the hypothesis of interaction: In [p/(1-p)] = beta 0 + beta 1 x Cprop + beta 2 x Csuf + beta 3 x Cprop x Csuf with a p-value < 0.05 for coefficient estimates considered significant. In the logistic regression model, sufentanil and propofol showed no supra-additive interaction regarding loss of consciousness (p = 0.5916). CONCLUSIONS: Our results give no evidence of additional hypnotic properties of sufentanil compared to the other fentanyl congeners, although logistic regression may be of limited value in modeling interaction of hypnotic-analgesic combinations.

Adult↗