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PubMed1999

Assessment of command-following in minimally conscious brain injured patients.

OBJECTIVE: To develop a method for establishing the presence of command-following in individuals with traumatic brain injury, based on the principles of single-subject experimental design. DESIGN: A series of single-subject experiments, individualized to the particular command-following question about a particular patient. SETTING: An inpatient rehabilitation hospital with a specialized program for vegetative and minimally conscious brain injured patients. PATIENTS: Eight individuals with serious brain injury of traumatic or nontraumatic origin, presenting in vegetative or minimally conscious states. INTERVENTIONS: The frequency of performance of the behavior in question was assessed in response to commands and in relation to appropriate control conditions. Data were analyzed with chi2 or Fisher's exact test, as well as measures derived from signal detection theory. MAIN OUTCOME MEASURES: The frequency of performance of a specific behavior in the presence of a command and in relevant contrasting conditions. RESULTS: This method identified whether a specific behavior was being performed in response to command and whether the reliability of this behavior was changing over time either spontaneously or in response to treatment. CONCLUSIONS: Quantitative assessment of command-following based on principles of single-subject experimental design can determine whether patients are capable of following commands and whether this ability changes over time or in response to treatment.

Adult↗
PubMed2001

Cardiorespiratory and metabolic responses to injection of bicuculline into the hypothalamic paraventricular nucleus (PVN) of conscious rats.

Stimulation of the PVN increases mean arterial pressure (MAP) and heart rate (HR). However, little is known about its role in modulating ventilation. We tested the hypothesis that the stimulation of the PVN by microinjection of bicuculline methiodide (BMI), a gamma-aminobutyric acid (GABA)(A) receptor antagonist, increases ventilation in conscious rats. Oxygen consumption was also evaluated to determine if the ventilatory responses were associated with increases in metabolic rate. Male Sprague--Dawley rats were instrumented with femoral catheters to measure MAP and HR and cannulae were implanted 1 mm above the PVN. After 5 to 7 days of recovery, metabolic, ventilatory, and cardiovascular responses to artificial cerebrospinal fluid (aCSF) and BMI were evaluated. Rats were given a 50 nl unilateral microinjection of aCSF (the vehicle control) followed by 50 n1 of BMI (1 mM) into the other side. Microinjection of BMI significantly increased MAP compared to aCSF (145+/-4 vs. 124+/-5 mmHg, P<0.02), HR to 460+/-17 from 362+/-22 breaths/min (P<0.01). Ventilation increased by 300% (P=0.01) by stimulating frequency of breathing (176+/-14 compared to 79+/-12 breaths/min, P<0.005) and increasing tidal volume. Concomitantly, O(2) consumption doubled (P<0.006). These data suggest that in the PVN GABA receptors may be important regulators of cardiopulmonary and metabolic function in conscious rats.

Animals↗
PubMed2003

Effects of head-down tilt on the intracranial pressure in conscious rabbits.

Head-down tilt (HDT) causes a fluid shift towards the upper body, which increases intracranial pressure (ICP). In the present study, the time course of ICP changes during prolonged exposure to HDT was investigated in conscious rabbits through a catheter chronically implanted into the subarachnoid space. The production of cerebrospinal fluid (CSF) after exposure to 7-days HDT was also examined by a ventriculo-cisternal perfusion method. The ICP increased from 4.3+/-0.4 (mean+/-S.E.M.) mmHg to 8.0+/-0.8 mmHg immediately after the onset of 45 degrees HDT, reached a peak value of 15.8+/-1.9 mmHg at 11 h, and then decreased to 10.4+/-1.1 mmHg at 24 h. During 7-days HDT, it also increased from 4.8+/-0.9 mmHg to 9.2+/-1.6 mmHg immediately after the onset of 45 degrees HDT, reached a peak value of 12.8+/-2.5 mmHg at 12 h of HDT, and then decreased gradually towards the pre-HDT baseline value for 7 days. The rate of CSF production was 10.1+/-0.6 microl/min in rabbits exposed to 7-days HDT, and 9.7+/-0.5 microl/min in control rabbits. These results suggest that the rabbits begin to adapt to HDT within a few days and that the production of CSF is preserved after exposure to 7-days HDT. The time course of ICP changes during HDT in conscious rabbits seems to be considerably different from that in anesthetized rabbits.

Animals↗
PubMed2003

A PET study following treatment with a pharmacological stressor, FG7142, in conscious rhesus monkeys.

FG7142 is a benzodiazepine partial inverse agonist, which is known as a pharmacological stressor. Several reports demonstrated that FG7142 produced anxiety in humans, non-human primates, and rodents, and impaired working memory in non-human primates and rodents. In this study, we examined the effect of FG7142 on cerebral blood flow and glucose metabolism using positron emission tomography (PET) in conscious rhesus monkeys. Male rhesus monkeys were intramuscularly treated with FG7142 (0.2 or 1.0 mg/kg, n=5, respectively), and regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of glucose (rCMRglc) were measured by PET 20 min and 40 min after treatment, respectively. During PET measurement, physiological parameters and plasma cortisol levels were monitored. FG7142 significantly decreased rCBF in the thalamus and rCMRglc in all brain regions examined in a dose-dependent manner without changes in physiological parameters. FG7142 also significantly increased plasma cortisol levels. The present study may provide an important insight into the understanding of the pathophysiology of anxiety and stress-related disorders in humans, and strongly suggesting that prevention of anxiety or stress is important when measuring conscious brain function.

Animals↗
PubMed1997

Cardiovascular effects of central administration of clonidine in conscious cats.

The effects on arterial blood pressure and heart rate after an intracerebroventricular (i.c.v.) administration of clonidine were investigated using conscious normotensive cats. Injection of clonidine (5-10 microg; 5 microl; i.c.v.) elicited a decrease in mean arterial pressure (MAP) and heart rate (HR) in a dose-dependent manner. The highest dose of 10 microg of clonidine decreased MAP and HR by 39 +/- 3 mmHg and 74 +/- 5 b.p.m., respectively (n = 7). Pretreatment with yohimbine, the alpha2-adrenoceptor antagonist (8 microg; 5 microl; i.c.v.) blocked the cardiovascular responses to a subsequent i.c.v. injection of 10 microg clonidine (n = 7). Furthermore, preadministration of cimetidine (100 microg; 5 microl; i.c.v.), the H2 histamine receptor antagonist with imidazoline receptor activating properties, prevented the decreases in MAP and HR to a subsequent i.c.v. injection of 10 microg clonidine (n = 7). By contrast, pretreatment with the specific I1 imidazoline receptor blocker, efaroxan (100-500 microg; 5 microl; i.c.v.), failed to inhibit the cardiovascular effects of an i.c.v. administration of 10 microg clonidine (n = 7). These results suggest that the effects of centrally administered clonidine on MAP and HR are probably not mediated through activation of the I1 subtype of imidazoline receptors in conscious cats. However, the cardiovascular effects elicited by i.c.v. administration of clonidine appear to result from stimulation of central alpha2-adrenergic or the H2 histaminergic-like receptors.

Adrenergic alpha-Antagonists↗
PubMed2004

Cognition in dyschiria: Edoardo Bisiach's theory of spatial disorders and consciousness.

An overview of Bisiach's theory of mental representations and consciousness is presented. Neuropsychological observations on space disorders led Bisiach to consider analogical representations (and not only symbolic representations) as truly 'cognitive', insofar as they are necessary for the normal functioning of linguistic processes. Bisiach's approach to the scientific study of consciousness, conceived both as the private aspect of phenomenal experience and as a monitoring process, is also discussed.

Body Image↗
PubMed2005

The conscious self: ontology, epistemology and the mirror quest.

Here we address the notion of the self as the subject of experience, in contrast with its other popular meanings of a state of self-awareness, a body image, or a narrative center. In this perspective, the main player is not consciousness per se (the famous "hard problem"), but its subject. We start by showing that the self as the subject of immediate self-awareness cannot be conceived as an illusion. Then we formulate axioms of the self-concept based on the framework that Chalmers initially developed for consciousness. Using a thought experiments (the "mirror quest"), we show that this framework may require corrections in order to accommodate the subject. We analyze several possibilities that lead to a novel doctrine of "subjective nonreductive functionalism". As an epistemological model, this position has further important implications for brain sciences.

Awareness↗
PubMed2005

The right hemisphere and the dark side of consciousness.

Self-awareness and Theory of Mind comprise the main elements of higher-order consciousness. In attempting to localize these abilities, it appears that regions of the right hemisphere including fronto-temporal regions are capable of sustaining a sense of self-awareness. The right hemisphere appears dominant for tasks involving Theory of Mind as well as deception, which may be important for understanding the brain and laterality in terms of evolution. These findings are critical for our understanding of hemispheric differences in terms of higher-order consciousness.

Awareness↗
PubMed2000

Hemodynamic effects of MF 10058, a new cardioselective muscarinic M(2) receptor antagonist, in conscious dogs.

The 5-¿4-[4-(diethylamino)butyl]-1-piperidinyl¿acetyl-5H-dibenz[b, f]-azepine (MF 10058) is a new potent and selective muscarinic M(2) receptor antagonist. The hemodynamic effects of MF 10058 were investigated in conscious freely moving dogs. Placebo and three doses of MF 10058 (2, 4 and 8 mg/kg) were orally administered according to a randomised four-way crossover design. Heart rate, cardiac conduction times, systolic and diastolic blood pressure were telemetrically recorded for 12-24 h after dosing. After placebo administration, a consistent reduction over time in heart rate was observed during the night-time period (-15%, P=0.019). MF 10058 administration antagonised the nocturnal bradycardia and shortened QT interval. The effect of the drug reached statistically significance, compared to placebo, with the highest dose of 8 mg/kg (+19% on heart rate, P=0.013; -4% on QT interval, P=0.049). The effect on heart rate lasted for the entire 24-h observation period (+16%, P=0.030). Nocturnal systolic and diastolic blood pressure were not significantly affected by MF 10058. No other signs of peripheral or central cholinergic block were observed at any dose. The results of this study demonstrated that oral administration of MF 10058 produces long-lasting hemodynamic effects in the conscious dog. The drug has a therapeutic potential for the treatment of bradycardic disorders.

Animals↗
PubMed2001

Cardiovascular action of a cardioselective Ca(2+)channel blocker AH-1058 in conscious dogs assessed by telemetry.

AH-1058, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2-propenyl]piperidine hydrochloride, is a novel Ca(2+)channel blocker exerting cardioselective action in isolated or anesthetized canine heart preparations. To clarify the cardiac and hemodynamic action of AH-1058 in conscious dogs, we assessed the effects of the drug on the hemodynamic parameters continuously recorded by telemetry in conscious unrestrained beagle dogs, and its cardiovascular effects were compared with those of verapamil, disopyramide and atenolol. Oral administration of AH-1058 (0.15, 0.3 and 0.6 mg/kg) reduced the systolic blood pressure and maximal upstroke velocity of the left ventricular pressure (LVdP/dt(max)), increased heart rate and prolonged the QA interval in a dose-dependent manner whereas the drug did not affect diastolic blood pressure. Verapamil at 10 mg/kg reduced systolic and diastolic blood pressure with little effect on heart rate, LVdP/dt(max) and QA interval. Disopyramide at 20 mg/kg increased systolic and diastolic blood pressure, decreased LVdP/dt(max) and prolonged the QA interval with little changes in heart rate. Atenolol at 10 mg/kg decreased LVdP/dt(max) and prolonged the QA interval with little changes in systolic blood pressure, diastolic blood pressure and heart rate. The time course of the cardiohemodynamic action of AH-1058 was longer than those of the other drugs. These results suggest that AH-1058 is a long-acting cardiodepressive drug, and its hemodynamic profile is obviously different from that of disopyramide and atenolol. This unique cardiovascular profile may be beneficial for the treatment of certain pathological processes in which selective inhibition of the ventricular Ca(2+)channels would be the target of drug therapy.

Animals↗
PubMed2002

Amiloride inhibits proximal tubular reabsorption in conscious euvolemic rats.

Based on the results of micropuncture studies, it is generally assumed that amiloride inhibits Na+ (and Li+) reabsorption in the distal nephron, without affecting proximal tubular reabsorption. This is the basis for the use of amiloride to test for distal nephron Li+ reabsorption. We have examined the validity of this assumption by administering amiloride in doses of 0, 0.02, 0.07, 0.2 and 2.0 mg x kg(-1) x h(-1) to conscious, chronically instrumented rats fed a diet with a normal Na+ and K+ content. Na+ and water homeostasis was maintained by servo-controlled replacement in order to avoid any effect of volume depletion on proximal tubular reabsorption. The effects of the two highest doses of amiloride were also examined without Na+ and water replacement. In the servo-controlled rats, the two highest doses of amiloride increased the fractional excretion of both Na+ (FE(Na)) and Li+ (FE(Li)), whereas the two lowest doses affected only FE(Na). In the rats without servo-control, FE(Li) also rose in response to amiloride infusion, but the increase was significantly lower than that observed in the servo-controlled animals. Since distal Li+ reabsorption is absent or negligible in rats fed a diet with a normal Na+ and K+ content, the large increase in FE(Li) following the highest doses of amiloride (15-18% of the filtered load in servo-controlled rats) indicates inhibition of proximal tubular reabsorption. We conclude that amiloride, in doses usually employed to detect distal Li+ reabsorption, inhibits proximal tubular reabsorption in conscious euvolemic rats.

Absorption↗
PubMed1997

Breath timing, volume and drive to breathe in conscious rats: comparative aspects.

In conscious animals, respiratory frequency (f) and tidal volume (VT) vary breath to breath. Examining the average value of variables associated with specific bins of another variable, such as breath f, provides a unique tool to examine respiratory behaviour. In conscious Sprague-Dawley rats respiratory breath timing, tidal volume (VT) and drive (VT/TI) were characterized using a plethysmograph. In the majority of rats at low breath f, expiratory time (TE) exceeded inspiratory time (TI) and these times became equal as f exceeded 150 breaths/min; there was no evidence for TI greater than TE at higher f, as observed in cats and dogs. When VT is normalized per kg, rat breath VT and VT/TI, binned by breath f, are continuous with those for the cat and non-panting dog at the lowest breath f. Relative to breath f, breath VT and VT/TI in rats are greater than in normothermic panting dogs (20 degrees C), but only slightly greater than those variables in panting dogs in the heat (30 degrees C). Lower values of breath VT/TI, binned by breath f or V, in cats and dogs are compensated for by a greater TI relative to the duration of a given breath. This comparative analysis suggests continuities of respiratory pattern generation among species.

Animals↗
PubMed2005

Skill, corporality and alerting capacity in an account of sensory consciousness.

We suggest that within a skill-based, sensorimotor approach to sensory consciousness, two measurable properties of perceivers' interaction with the environment, "corporality" and "alerting capacity", explain why sensory stimulation is experienced as having a "sensory feel", unlike thoughts or memories. We propose that the notions of "corporality" and "alerting capacity" make possible the construction of a "phenomenality plot", which charts in a principled way the degree to which conscious phenomena are experienced as having a sensory quality.

Attention↗
PubMed2005

Genes and experience shape brain networks of conscious control.

One aspect of consciousness involves voluntary control over thoughts and feelings, often called will. Progress in neuroimaging and in sequencing the human genome makes it possible to think about voluntary control in terms of a specific neural network that includes midline and lateral frontal areas. A number of cognitive tasks involving conflict as well as the control of emotions have been shown to activate these brain areas. Studies have traced the development of this network in the ability to regulate cognition and emotion from about 2.5 to 7 years of age. Individual differences in this network have been related to parental reports of the ability of children to regulate their behavior, to delay reward and to develop a conscience. In adolescents these individual differences predict the propensity for antisocial behavior. Differences in specific genes are related to individual efficiency in performance of the network, and by neuroimaging, to the strength of its activation of this network. Future animal studies may make it possible to learn in detail how genes influence the common pattern of development of self-regulation made possible by this network. Moreover, a number of neurological and psychiatric pathologies involving difficulties in awareness and volition show deficits in parts of this network. We are now studying whether specific training experiences can influence the development of this network in 4-year-old children and if so, for whom it is most effective. Voluntary control is also important for the regulation of conscious input from the sensory environment. It seems likely that the same network involved in self-regulation is also crucial for focal attention to the sensory world.

Brain↗
PubMed2005

The locked-in syndrome : what is it like to be conscious but paralyzed and voiceless?

The locked-in syndrome (pseudocoma) describes patients who are awake and conscious but selectively deefferented, i.e., have no means of producing speech, limb or facial movements. Acute ventral pontine lesions are its most common cause. People with such brainstem lesions often remain comatose for some days or weeks, needing artificial respiration and then gradually wake up, but remaining paralyzed and voiceless, superficially resembling patients in a vegetative state or akinetic mutism. In acute locked-in syndrome (LIS), eye-coded communication and evaluation of cognitive and emotional functioning is very limited because vigilance is fluctuating and eye movements may be inconsistent, very small, and easily exhausted. It has been shown that more than half of the time it is the family and not the physician who first realized that the patient was aware. Distressingly, recent studies reported that the diagnosis of LIS on average takes over 2.5 months. In some cases it took 4-6 years before aware and sensitive patients, locked in an immobile body, were recognized as being conscious. Once a LIS patient becomes medically stable, and given appropriate medical care, life expectancy increases to several decades. Even if the chances of good motor recovery are very limited, existing eye-controlled, computer-based communication technology currently allow the patient to control his environment, use a word processor coupled to a speech synthesizer, and access the worldwide net. Healthy individuals and medical professionals sometimes assume that the quality of life of an LIS patient is so poor that it is not worth living. On the contrary, chronic LIS patients typically self-report meaningful quality of life and their demand for euthanasia is surprisingly infrequent. Biased clinicians might provide less aggressive medical treatment and influence the family in inappropriate ways. It is important to stress that only the medically stabilized, informed LIS patient is competent to consent to or refuse life-sustaining treatment. Patients suffering from LIS should not be denied the right to die - and to die with dignity - but also, and more importantly, they should not be denied the right to live - and to live with dignity and the best possible revalidation, and pain and symptom management. In our opinion, there is an urgent need for a renewed ethical and medicolegal framework for our care of locked-in patients.

Consciousness↗
PubMed2000

Schizophrenia and the mechanisms of conscious integration.

This article considers the possibility that defective interactions among distributed brain areas may underlie certain dysfunctions of conscious integration such as those seen in schizophrenia. Recent experimental evidence obtained using whole-head magnetoencephalography during binocular rivalry is first reviewed. The results outline a cortical network that underlies conscious integration in the normal brain. This network is not localized to a small part of the brain but it is distributed over frontal, parietal, temporal, and occipital areas. Large-scale simulations of the dynamics of thalamocortical integration are then examined. These studies indicate that several factors can affect the rapid integration of the activity of distributed thalamocortical regions and the resulting behavioral performance. These simulations show that an altered dynamics of corticothalamic and corticocortical re-entrant circuits can result from increased conduction delays, blockade of voltage-dependent connections, reduced synaptic density, and disruptions of the local connectivity within a single cortical area. It can also result from alterations in the activity of diffuse ascending systems that lead to defective reinforcement of integrated activity patterns. Finally, the article briefly reviews theoretical measures of the integration of multiple brain areas, such as measures of functional clustering. These measures have been applied to PET data obtained from schizophrenic subjects and controls while performing cognitive tasks. The results show a change in the functional interactions among distributed brain areas in schizophrenics despite the absence of a change in activation patterns. The possibility is raised that disruption of re-entrant interactions among cortical areas may contribute to the pathophysiology of schizophrenia.

Brain↗
PubMed1997

Real-time extracellular measurement of neurotransmitters in conscious sheep.

Measurements of neurotransmitters in conscious animals have been restrictive in real-time. The use of specific enzymes within an amperometric probe, based upon a microdialysis membrane, may overcome some of these problems. I report the use of such a probe, with different perfusions of enzymes, to allow real-time measurement of glutamate, catecholamines and indoleamines, in conscious animals. At an adjacent site microdialysis sample collections were made concurrently and neurotransmitters measured in the dialysate. Both probes were positioned within the somatosensory cortex. Values obtained by amperometric probes were similar to those in dialysate samples for glutamate, catecholamines and indoleamines during basal and stimuli related collections. Amperometric measurements showed higher peak concentrations and better time resolution than dialysate sampling. This reflects sampling differences. Application of external stimuli increased extracellular concentrations of glutamate, catecholamines and indoleamines, in both forms of sampling. Dopamine measurements did not correlate well between the two forms of sampling. This may reflect the non-specificity of the enzyme (dopamine-beta-hydroxylase) used in the amperometric probe. This combination, of microdialysis and amperometry, offers a useful tool for real-time neurotransmitter studies in vivo.

Animals↗
PubMed2000

Compensatory vasoconstrictor effects of sodium pentobarbital on the hindquarters of conscious normotensive control and lumbar-sympathectomized Wistar rats.

The aim of this study was to compare the vasoconstrictor effect of sodium pentobarbital on the hindquarter resistance of intact control Wistar rats with the effect on lumbar-sympathectomized rats. For this purpose, mean arterial pressure (MAP) and hindquarter (supplied terminal aorta) flow (HQF) were simultaneously measured in these conscious rats with an arterial in dwelling cannula and electromagnetic flow probe implanted around the terminal aorta. Hindquarter resistance (HQR) was calculated as MAP divided by HQF. In the intact control conscious rats, subsequent pentobarbital anesthesia (30 mg/kg, i.v.) caused an increase in HQR (+43.5 +/- 7.4%, mean +/- S.E.M.) and a decrease in MAP (-17.0 +/- 3.2%). After pentobarbital anesthesia, subsequent ganglionic blockade with hexamethonium bromide (C6; 25 mg, i.v.) induced a significant decrease in HQR (-30.9 +/- 3.0%) with a further lowering of MAP (-20.9 +/- 1.6%). However, in rats not anesthetized with sodium pentobarbital, C6 alone induced almost no change in HQR (-3.4 +/- 5.3%), even when MAP was lowered (-24.2 +/- 2.5%). In the lumbar-sympathectomized rats, pentobarbital anesthesia produced almost no change in HQR (-11.7 +/- 4.4%), although MAP decreased significantly (-24.3 +/- 2.2%). These findings suggest that: (1) sodium pentobarbital anesthesia newly generates a compensatory vasoconstrictor tone in the hindquarters acting against the depressor effect, and (2) the vasocompensator tone is controlled by the efferent fibers, including those in the lumbar sympathetic nerves.

Anesthesia↗