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Consciousness and disturbances of consciousness.

The problem of consciousness is discussed briefly, including the contrary views of consciousness as a transcendental phenomenon and as an animistic fiction. Measurement of consciousness is possible only indirectly by means of quantitative assessment of accompanying behavioral deficits. Knowledge of the structural basis of consciousness is incomplete. The ascending reticular activating system (ARAS) is necessary for the maintenance of the state of consciousness. The monoamine and a great number of descending projections modulate the ARAS. The contents of consciousness depend also on telencephalic structures, primarily on the telencephalic cortex. Certain localized telencephalic lesions bring about disturbances of consciousness. The role of the corpus callosum in the problem of consciousness is discussed (one brain--two minds hypothesis). Then a classification of the various disturbances of consciousness is proposed. The term "disturbances of vigilance" is used for all disturbances of consciousness which are caused by a lesion in or a functional disorder of the ARAS or any of its modulating subsystems. The term "disturbances of the contents of consciousness" refers to disturbances of consciousness due to global or localized lesions or functional disorders of telencephalic structures. A list of characteristic features is given for each class of disturbances of consciousness.

Attention

Reversal of central nervous system effects by flumazenil after intravenous conscious sedation with midazolam: report of a multicenter clinical study. The Flumazenil in Intravenous Conscious Sedation with Midazolam Multicenter Study Group I.

Flumazenil, a benzodiazepine antagonist, reverses the residual central nervous system effects of benzodiazepines. In this US double-blind, multicenter study, the efficacy of flumazenil was compared with that of placebo in antagonizing the effects of midazolam, a benzodiazepine used to induce intravenous conscious sedation. The mean dose of flumazenil was 0.7 mg, administered intravenously. At 5 minutes posttreatment, 82% of 131 flumazenil-treated patients, compared with 15% of 65 placebo-treated patients, demonstrated complete reversal of sedation. In 85% of patients who responded to flumazenil, this reversal of sedation was maintained throughout the 180-minute observation period. Psychomotor performance returned to prestudy levels 5 minutes posttreatment in 87% of the flumazenil-treated patients, compared with 28% of the placebo-treated patients. At the doses administered, flumazenil was less effective in reversing midazolam-induced amnesia, with only 60% of patients demonstrating partial recovery of memory. It was, nevertheless, more effective than placebo. Flumazenil was well tolerated. Dizziness (10%) and nausea (9%) were the most frequently reported adverse effects. Results of this study demonstrate that flumazenil antagonizes the central nervous system effects of midazolam after intravenous conscious sedation.

Adolescent

Reversal of central benzodiazepine effects by flumazenil after conscious sedation produced by intravenous diazepam. The Flumazenil in Intravenous Conscious Sedation with Diazepam Multicenter Study Group I.

Flumazenil is a competitive benzodiazepine antagonist that rapidly reverses the residual effects of benzodiazepines following intravenous conscious sedation. In a double-blind, multicenter study, postoperative patients who had been sedated with intravenous diazepam were randomly allocated to receive intravenous doses of flumazenil (0.4 mg to 1 mg) or placebo. Levels of sedation and psychomotor impairment were evaluated prestudy, at baseline, and at 6 intervals from 5 to 180 minutes posttreatment. A global evaluation of effectiveness was made at the 5-minute assessment, and memory was assessed at the 180-minute assessment. Flumazenil (mean dose: 0.73 mg [7.3 ml]) was significantly more effective than placebo (mean dose: 8.9 ml) in reversing sedation, psychomotor impairment, and amnesia within 5 minutes after the start of administration. At the 5-minute posttreatment assessment, 84% of 102 flumazenil-treated patients (compared with 42% of 52 placebo-treated patients) experienced complete reversal of sedation. Ninety-two percent of 93 flumazenil-treated patients (compared with 41% of 46 placebo-treated patients) had normal psychomotor function. Reversal of amnesia at the 5-minute assessment was achieved in 75% of 101 flumazenil-treated patients and in 20% of 51 placebo-treated patients. Statistically significant differences between flumazenil and placebo were also observed at the 15-minute assessment. Thereafter there were no significant differences between the two treatment groups. Most (70%) flumazenil-treated patients exhibited no recurrence of sedation during the 180-minute assessment period. The most frequent adverse reaction in the flumazenil group was dizziness (6%). There were no serious adverse experiences related to the test drug. Flumazenil provided prompt, controlled reversal of residual effects, especially sedation, in the majority (84%) of patients recovering from intravenous conscious sedation induced by diazepam. For most (70%) of these flumazenil-treated patients, the reversal was maintained throughout the 180-minute assessment.

Adolescent

Reversal of central benzodiazepine effects by intravenous flumazenil after conscious sedation with midazolam and opioids: a multicenter clinical study. The Flumazenil in Intravenous Conscious Sedation with Midazolam Multicenter Study Group II.

The efficacy and safety of flumazenil in antagonizing the central effects of the benzodiazepine midazolam was demonstrated in patients in whom conscious sedation was induced with midazolam plus an opioid (fentanyl, meperidine, or morphine). In a double-blind, multicenter study, 240 patients were administered flumazenil postoperatively at an average intravenous dose of 0.7 mg (7 ml) and 114 patients were administered an average dose of 9 ml placebo. Complete reversal of sedation was observed in 80% of flumazenil-treated patients and 30% of placebo-treated patients 5 minutes posttreatment. In 87% of patients who responded to flumazenil, the level of alertness was maintained throughout the 180-minute observation period. Midazolam-impaired psychomotor performance returned to normal 5 minutes posttreatment in 80% of the flumazenil-treated patients and 28% of the placebo-treated patients. Flumazenil was less effective in reversing midazolam-induced amnesia, with only 70% of flumazenil-treated patients (and 15% of placebo-treated patients) able to recall the picture shown them at the 5-minute assessment, and fewer patients able to recall pictures shown at later times. Flumazenil was well tolerated, although adverse effects were reported slightly more often than in the placebo group. The most frequent adverse events in both groups were dizziness and nausea. Vital signs were not affected.

Adolescent

Reversal of central benzodiazepine effects by flumazenil after intravenous conscious sedation with diazepam and opioids: report of a double-blind multicenter study. The Flumazenil in Intravenous Conscious Sedation with Diazepam Multicenter Study Group II.

The efficacy and safety of a new benzodiazepine antagonist, flumazenil, were assessed in a double-blind multicenter study. Flumazenil (mean dose, 0.76 mg) or placebo (mean dose, 8.9 ml) was administered intravenously to 130 and 67 patients, respectively, who had been given diazepam in conjunction with an opioid (fentanyl, meperidine, or morphine) for the induction and maintenance of intravenous conscious sedation for diagnostic or therapeutic surgical procedures. The group assessable for efficacy comprised 122 patients treated with flumazenil and 64 patients given placebo. After 5 minutes, 80/115 (70%) flumazenil-treated patients, compared with 21/63 (33%) placebo-treated patients, were completely awake and alert, as indicated by a score of 5 on the Observer's Assessment of Alertness/Sedation Scale. Ninety-five percent of patients in each group who attained a score of 5 at the 5-minute assessment showed no loss of alertness throughout the 180-minute assessment period. Flumazenil-treated patients also performed significantly better on the Finger-to-Nose Test and the recall of pictures shown at the 5-minute assessment. Flumazenil was well tolerated, with no serious adverse effects reported. Thirty-nine (30%) of flumazenil-treated patients, compared with 17 (25%) of placebo-treated patients had one or more drug-related adverse experiences. The most common adverse effects were nausea and vomiting in the flumazenil group and nausea and injection-site pain in the placebo group. Flumazenil was found to promptly reverse sedation induced by diazepam in the presence of opioids.

Adolescent

The action of angiotensin II on the baroreflex response of the conscious ewe and the conscious fetus.

1. In conscious non-pregnant and pregnant ewes and in chronic fetal lamb preparations, the beat by beat relationship between pulse interval and systolic pressure was studied during acute elevations in arterial pressure induced by phenylephrine. Baroreflex sensitivity, which was defined as the slope of the pressure-pulse interval relationship when phenylephrine was used to raise pressure, was abolished by atropine and increased by propranolol. Baroreflex sensitivity was less in pregnant ewes and in foetal lambs compared with non-pregnant ewes. 2. These findings suggest that the vagus nerve is responsible for the reflex bradycardia that occurs in the foetus and the ewe when arterial pressure is increased. 3. In both fetal and adult sheep, actue hypertension due to I.V. injection of angiotensin II was not associated with a consistent and progressive bradycardia, such as was seen with acute hypertension caused by phenylephrine. Angiotensin II has no direct chronotropic effect on heart rate in either the adult or the fetus. 4. No linear relationship between arterial pressure and pulse interval was seen when angiotensin II was used to raise pressure in sheep which were treated with propranolol. Therefore the lack of cardiac slowing with pressor doses of angiotensin II was not due to concomitant activation of the sympathoadrenal system. 5. It is concluded that in both fetal and adult sheep angiotensin II reduces the increase in vagal tone which is responsible for slowing of heart rate in response to acute rises in arterial pressure.

Angiotensin II

Three types of consciousness.

It is useful to distinguish three senses of the word 'consciousness'. 'Minimal' consciousness is the occurrence of any mental activity, whether or not the subject is aware of this activity. 'Perceptual' consciousness is perceptual activity. Minimal and perceptual consciousness may be present, yet 'introspective' consciousness be lacking. Introspective consciousness is conceived as it was by Locke and Kant: as perception-like awareness of the subject's own current mental states and activities. It includes introspective consciousness of introspective consciousness itself. A useful model for demystifying and naturalizing introspective consciousness is the subject's proprioceptive awareness of bodily states and activities. Introspective consciousness may be further subdivided into 'reflex' introspective consciousness and 'introspection proper'. The distinction is one of degree: the degree of attention involved. We attach a quite special importance to introspective consciousness and are particularly unwilling to identify it with a purely physical process in the brain. It is suggested, however, that this springs from (a) the fact that what is introspected is taken to be a state or activity of a single thing, the self; and (b) the fact that event-memory is generally only possible if the event remembered was the object of introspective consciousness at the time. Without introspective consciousness, therefore, awareness of a self and the past history of that self is lacking.

Adolescent

The tasks of consciousness: how could the brain do them?

According to Darwin's theory of evolution by natural selection, the existence of mental operations proves their usefulness. Darwin called himself a mental materialist. This is one scientific theory of consciousness. Human consciousness has three useful aspects: awareness, intentionality and sharing with others. All have simple equivalents in animals. The latter two are neglected in neurophysiology and experimental psychology. Developmental, neuroanatomical and neuropsychological evidence shows that the human brain has innate structures of awareness, intentionality and interpersonal sharing. Human life depends on interpersonal cooperation. We may have a conscious self, but consciousness of others is essential in us. Studies of commissurotomy patients demonstrate the elaborate interconnected neural organization of consciousness and provide evidence of underlying and necessary levels of motivation, perception and motor integration below consciousness. Additionally, they show that awareness may be split into two different modes. These regulate one another during development and are complementary in culturally sophisticated adult life. One hemisphere, usually the left, has responsibility for expressing ideas and purposes in language. The other responds to the phenomenal context and the subjective situation. Both have human experiences and purposes. Both still collaborate in a unified intentional system after commissurotomy. Infant studies reveal that language develops out of an interpersonal mental process. This seems to control development of thinking. Thus notions of the newborn as an isolated amoral id, and of the infant as an egocentric discoverer of the object concept, must be rejected. Cultivation of moral awareness and a sense of purpose guided by meanings and values depends on innate organization of the human brain for interpersonal consciousness.

Awareness

Neurophysiological mechanisms and consciousness.

Consciousness may be understood as a behavioural state and thus levels of consciousness may be distinguished. But consciousness as we understand it is an experience. Any critical reasoning about it will lead to a dualistic formula. A neurophysiological mechanism may exist for this. In the neocortex various aspects of the world and of the physical and social relationships of the individuum to the world are represented through thalamocortical projection systems. There is no unified representation of the world in any single cortical area. All neocortical outputs feed into action systems of the brain. The synthesis of the distributed cortical representations of the world is thus realized through the action elicited by their combination. The action systems of the midbrain-cerebellum and the basal ganglia feed back into neocortical areas (internal loops). The action itself changes the relationship of the individual to the outside world and thus its representation in the brain (external loops). The role of the basal ganglia in the normal functioning of processes in consciousness and in the synthesis of cortical representations is described, which further emphasizes the intricate connections between motor performance and consciousness. The function of the reticular substance and related structures is seen as a gating mechanism for the (thalmic) access gates to the cortex and thus to mechanisms of conscious experience. The basis for the experience of consciousness is the symbolic representation of the world and of the individual to that individual's brain. This self-representation is based on the linguistic competence of the brain in a broad sense and is therefore possible only for brains with such a competence. The symbolic self-representation is called the reflective loop and its conditons are briefly discussed.

Basal Ganglia

Microinjection of L-glutamate into the nucleus tractus solitarii increases arterial pressure in conscious rats.

Microinjection of L-glutamate into the nucleus tractus solitarii (NTS) of anesthetized rats produces a fall in mean arterial pressure (MAP) similar to that observed during activation of baroreceptor afferents. In the present study we examined the effect of bilateral microinjections of L-glutamate through chronically implanted cannulae in the NTS of conscious freely moving rats. Group I (n = 6) was studied under conscious conditions and 24 h later the rats were anesthetized with urethane and the effects of L-glutamate re-examined. In conscious rats, L-glutamate (30 pmol to 5 nmol/100 nl) produced dose-dependent increases in MAP (+37 +/- 7 mmHg, 5 nmol), whereas under urethane anesthesia falls in MAP were observed (-11 +/- 3 mmHg, 5 nmol). Group II (n = 7) was studied under conscious conditions and 1 h later the rats were anesthetized with chloralose and the effects of L-glutamate re-examined. In this group of conscious rats L-glutamate (300 pmol to 5 nmol/100 nl) also produced dose-dependent increases in MAP (+37 +/- 5 mmHg, 5 nmol), whereas under chloralose anesthesia a dose-dependent depressor response was observed (-33 +/- 6 mmHg, 5 nmol). Saline microinjections into the NTS of conscious and anesthetized rats produced negligible effects. These data demonstrate that microinjection of L-glutamate into the NTS of rats produces a pressor response in conscious animals in contrast to depressor responses in animals anesthetized with chloralose or urethane.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General

Evolution of consciousness.

The hypothesis of the origin of consciousness is built upon the unique properties of the mammalian neocortex. The apical dendrites of the pyramidal cells bundle together as they ascend to lamina I to form neural receptor units of approximately 100 apical dendrites plus branches receiving hundreds of thousands of excitatory synapses, the collective assemblage being called a dendron. It is proposed that the whole world of consciousness, the mental world, is microgranular, with mental units called psychons, and that in mind-brain interaction one psychon is linked to one dendron through quantum physics. The hypothesis is that in mammalian evolution dendrons evolved for more effective integration of the increased complexity of sensory inputs. These evolved dendrons had the capacity for interacting with psychons that came to exist, so forming the mental world and giving the mammal conscious experiences. In Darwinian evolution, consciousness would have occurred initially some 200 million years ago in relation to the primitive cerebral cortices of evolving mammals. It would give global experiences of a surrounding world for guiding behavior beyond what is given by the unconscious operation of sensory cortical areas per se. So conscious experiences would give mammals evolutionary advantage over the reptiles, which lack a neocortex giving consciousness. The Wulst of the avian brain needs further investigation to discover how it could give birds the consciousness that they seem to have.

Animals

Orthostatic hypotension occurs following alpha 2-adrenoceptor blockade in chronic prazosin-pretreated conscious spontaneously hypertensive rats.

1. Studies were performed to evaluate whether chronic prazosin treatment alters the alpha 2-adrenoceptor function for orthostatic control of arterial blood pressure in conscious spontaneously hypertensive rats (SHR). 2. Conscious SHR (male 300-350 g) were subjected to 90 degrees head-up tilts for 60 s following acute administration of prazosin (0.1 mg kg-1 i.p.) or rauwolscine (3 mg kg-1 i.v.). Orthostatic hypotension was determined by the average decrease (%) in mean arterial pressure (MAP femoral) over the 60-s tilt period. The basal MAP of conscious SHR was reduced to a similar extent by prazosin (-23%(-)-26% MAP) and rauwolscine (-16%(-)-33% MAP). However, the head-up tilt induced orthostatic hypotension in the SHR treated with prazosin (-16% MAP, n = 6), but not in the SHR treated with rauwolscine (less than +2% MAP, n = 6). 3. Conscious SHR were treated for 4 days with prazosin at 2 mg kg-1 day-1 i.p. for chronic alpha 1-adrenoceptor blockade. MAP in conscious SHR after chronic prazosin treatment was 14% lower than in the untreated SHR (n = 8). Head-up tilts in these rats did not produce orthostatic hypotension when performed either prior to or after acute dosing of prazosin (0.1 mg kg-1 i.p.). Conversely, administration of rauwolscine (3 mg kg-1 i.v.) in chronic prazosin treated SHR decreased the basal MAP by 12-31% (n = 4), and subsequent tilts induced further drops of MAP by 19-23% in these rats. 4. The pressor responses and bradycardia to the alpha 1-agonist cirazoline (0.6 and 2 micrograms kg-1 i.v.), the alpha 2-agonist Abbott-53693 (1 and 3 micrograms kg-1 i.v.), and noradrenaline (0.1 and 1.0 micrograms kg-1 i.v.) were determined in conscious SHR with and without chronic prazosin pretreatment. Both the pressor and bradycardia effects of cirazoline were abolished in chronic prazosin treated SHR (n = 4) as compared to the untreated SHR (n = 4). On the other hand, the pressor effects of Abbott-53693 were similar in both groups of SHR, but the accompanying bradycardia was greater in SHR with chronic prazosin treatment than without such treatment. Furthermore, the bradycardia that accompanied the noradrenaline-induced pressor effect in SHR was similar with and without chronic prazosin treatment despite a 47-71% reduction of the pressor effect in chronic alpha 1-receptor blocked SHR.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Agonists

Role of the descending pressor pathway in the conscious and pentobarbital-anesthetized dog.

Resting cardiovascular parameters and the responses to bilateral carotid occlusions (BCO) were monitored in pentobarbital-anesthetized and conscious dogs before and after placing lesions in the dorsolateral funiculi at C7-C8 and after spinal transections at C7. Pre- and postlesion blood pressure (BP) and heart rate (HR) responses to exercise were also monitored. The lesions significantly attenuated the responses to BCO and decreased resting BP in anesthetized dogs. Yet neither resting HR in anesthetized or conscious dogs nor the resting BP in conscious dogs was affected by the lesions. Subsequent spinal transections significantly decreased resting HR and BP and the responses to BCO but did not affect the BP response to BCO in anesthetized dogs as compared with corresponding postlesion parameters. BP responses to exercise were significantly attenuated by the lesions, but HR responses were not affected. Since stimulation and BP studies indicated that the descending pressor pathway had been ablated, the data suggest that the pathway mediates BP and HR responses to BCO in pentobarbital-anesthetized and conscious dogs. It does not maintain resting HR in anesthetized or conscious animals, and the resting BP in conscious dogs. This pathway is important for BP responses to exercise but is not necessary for HR responses. Finally, other spinal pathways are involved in cardiovascular control.

Animals

Contribution of prostaglandins to the renal circulation in conscious, anesthetized, and laparotomized dogs.

The effects of an inhibitor of prostaglandin (PG) synthetase, indomethacin, were studied on renal blood flow (RBF) and mean aortic blood pressure (MABP) and related to changes in concentrations of PGs in renal venous blood under widely different experimental conditions. Although levels of PGE-like material ("PGE") in renal venous blood of the chloralose-anesthetized-laparotomized dog were 8-fold greater than in conscious dogs, viz., 0.39 vs. 0.05 ng/ml of blood, respectively, RBF and MABP were similar for each group. Indomethacin in doses as high as 10 mg/kg, iv, affected neither RBF, MABP, nor PG levels either in the conscious dog or in the anesthetized dog. However, in the anesthetized-laparotomized dog, smaller doses of indomethacin (2 mg/kg, iv) decreased RBF by more than 40% and increased MABP by 15%. This was associated with a decline in concentration of renal venous PGs to those levels observed in conscious dogs. The principal renal PG varied according to the experimental conditions. The venous levels of "PGF" were greater than "PGE" in conscious dogs, whereas in acutely stressed dogs the renal venous concentrations of "PGE" were more than 2-fold those of "PGF". Plasma renin activity was highly correlated with "PGE" levels in renal venous blood, but not with "PGF" levels. Thus, in the acutely stressed dog, the renal circulation is supported by a major PG component, withdrawal of which results in a decline in RBF. In contrast, in the conscious dog at rest, renal PGs do not appear to contribute significantly to RBF. The significance of the small basal release of PGs into the renal venous effluent of the conscious dog, which is not affected by indomethacin, remains to be determined.

Anesthesia

Correlates of self-consciousness.

Examined the relationship between the three subscales of the Self-Consciousness Scale and a variety of other personality dimensions, including measures of reflectivity, self-regulation, and social desirability. Data from six geographically diverse samples (total N = 1395) were presented. In general, both the construct validity and discriminant validity of the subscales were supported. First, private self-consciousness significantly correlated with the Guilford-Zimmerman Thoughtfulness Scale and the Paivio Imagery Scale. Second, all of the self-consciousness subscales were shown to be relatively independent of the social desirability response set. Third, less than 6% of the variance in each self-consciousness subscale was shared with scores on the Self-Monitoring Scale. Finally, the minimal relationships between the self-consciousness subscales and measures of emotionality and test anxiety reported by Carver and Glass (1976) were in general replicated. The low magnitude of the correlations obtained was interpreted as supporting the distinctive contribution of the Self-Consciousness Scale to personality assessment.

Anxiety