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PubMed2006

Affirming the right to care, preserving the right to die: disorders of consciousness and neuroethics after Schiavo.

In this article, I attempt to untangle some of the cultural, philosophical, and ethical currents that informed the Schiavo case. My objective is to better apprehend what the Schiavo case means for end-of-life care in general and to assert that our discourse about the ethical issues attendant to brain injury will be impoverished if we limit our discussions about disorders of consciousness solely to the vegetative state. If we ignore emerging developments in neuroscience that are helping to elucidate the nature of these disorders and fail to broaden the conversation about brain injury, beyond the unmitigated futility of the permanent vegetative state, we will imperil others who might improve and be helped. Through such efforts we can help mitigate the tragedy of the Schiavo case and overcome the rhetoric that marked the national discourse in March 2005. Once the complexity of disorders of consciousness is appreciated, rhetorical statements about a right to die or a right to life are exposed as being incompatible with the challenge of providing care to such patients. This is especially true as neuroscience brings greater diagnostic refinement to their assessment and management, a topic addressed in this article, which specifically focuses on the clinical and ethical implications of the recently described minimally conscious state. Instead of staking out ideological positions that do not meet the needs of patients or families, we should strive to both preserve the right to die for those who are beyond hope while affirming the right to care to those who might benefit from coming advances in neuroscience. If we can achieve that delicate balance, we will be able to transcend the partisan debate that shrouded the life and death of Theresa Marie Schiavo and begin to articulate a palliative neuroethics of care for those touched by severe brain injury and disorders of consciousness.

Brain Damage, Chronic↗

PubMed2001

Self-consciousness and Alzheimer's disease.

OBJECTIVES: To propose a neuropsychological study of the various aspects of self-consciousness (SC) in Alzheimer's disease. METHODS: Forty-five patients with probable mild or moderate AD were included in the study. Severity of their dementia was assessed by the Mini Mental State (MMS). Fourteen questions were prepared to evaluate SC. RESULTS: No significant correlations were found between SC score and educational level, age, and duration of disease. A significant correlation was found between SC score and the severity of dementia, whereas frontal disturbances were just short of the significance threshold. The various aspects of SC were not impaired to the same degree. The most disturbed ones were awareness of cognitive deficiencies, moral judgements and prospective memory. The least disturbed aspects were awareness of identity and of mental representation of the body. Items relating to anosognosia and moral judgements were significantly correlated with the MMS score, whereas affective state, body representation disorders, prospective memory, and capacities for introspection were not related to the severity of the dementia. Consciousness of identity was sound, regardless of MMS score. CONCLUSIONS: AD clearly induces an heterogeneous impairment of SC. SC requires a convergence of many neural networks. In AD, neuronal alterations involve many cortical areas and information sent to the associative frontal cortex from memory, language and visuospatial areas is lacking or disturbed. Thus, the sequential order of successive stimuli cannot be maintained by the heteromodal associative cortex (dorsal convexity of the prefrontal cortex), and the supramodal associative cortex (located rostrally in the frontal lobes) is unable to provide reliable monitoring and assessment of simultaneous neural cognitive networks carrying insufficient and inadequate input. The core deficiency in AD patients might be impaired SC equated with the disability to maintain sequential and simultaneous "attention to life". The Self-Consciousness Questionnaire, a clinical scale providing multidimensional measurement, indicates that different aspects of consciousness are not correlated with overall cognitive deficiency as determined by the MMSE.

Aged↗

PubMed1998

On the development of conscious and unconscious memory.

The distinction between conscious and unconscious memory, which is central to modern theories of cognition, has received only limited scrutiny in developmental research. One reason is a need for developmental methodologies that allow age variability in conscious and unconscious memory to be quantified. A simple paradigm (called conjoint recognition) and model are presented that quantify conscious and unconscious memory for learned materials and for the types of unlearned materials that have been found to induce false memories in children. A validation study showed that the model gave excellent accounts of the performance of 7- and 10-year-olds and that conscious and unconscious memory parameters reacted in appropriate ways to 3 manipulations (age, meaningfulness of distractors and targets, and priming).

Child↗

PubMed1985

Individual differences in phenomenological experience: states of consciousness as a function of absorption.

State manifestations of the trait of absorption--a trait associated with differential responsivity to hypnosis, meditation, marijuana intoxification, and electromyograph (EMG) biofeedback--were assessed to determine (a) if absorption correlates with various (sub)dimensions of phenomenological experience, and (b) if individuals of differing absorption ability experience different states of consciousness. In two experiments 249 and 304 participants completed Tellegen's absorption scale and experienced several stimulus conditions. Each condition's phenomenological state was assessed by means of a retrospective self-report questionnaire and quantified in terms of intensity and pattern parameters. The results indicated that absorption correlated with increased and more vivid imagery, inward and absorbed attention, and positive affect; decreased self-awareness; and increased alterations in state of consciousness and various aspects of subjective experience. In addition, individuals of high absorption ability, relative to lows, experienced a different state of consciousness during ordinary, waking consciousness that became an altered state with eye closure and an hypnoticlike induction. The usefulness of the results for understanding altered-state induced procedures such as hypnosis is discussed.

Attention↗

PubMed2006

A first examination of the relationships between primed subconscious goals, assigned conscious goals, and task performance.

The authors conducted 2 studies of subconscious goal motivation. First, the authors ran a pilot study to establish the effects of priming of subconscious goals on a performance task frequently used in goal setting research. Second, the authors conducted the main study in which the authors examined the effects of both priming of subconscious goals and assigned conscious goals on the same performance task. The authors found significant main effects of both manipulations and a significant interaction between subconscious and conscious goals. The effects of conscious difficult and do-best goals were enhanced by subconscious goals, although conscious easy goals were not affected. All effects from the main study still held after 1 day.

Adult↗

PubMed1989

Effects of MK-801 upon local cerebral glucose utilisation in conscious rats and in rats anaesthetised with halothane.

The effects of MK-801 (0.5 mg/kg i.v.), a non-competitive N-methyl-D-aspartate (NMDA) antagonist, upon local cerebral glucose utilisation were examined in conscious, lightly restrained rats and in rats anaesthetised with halothane in nitrous oxide by means of the quantitative autoradiographic [14C]-2-deoxyglucose technique. In the conscious rats, MK-801 produced a heterogenous pattern of altered cerebral glucose utilisation with significant increases being observed in 12 of the 28 regions of gray matter examined and significant decreases in 6 of the 28 regions. Pronounced increases in glucose use were observed after MK-801 in the olfactory areas and in a number of brain areas in the limbic system (e.g., hippocampus molecular layer, dentate gyrus, subicular complex, posterior cingulate cortex, and mammillary body). In the cerebral cortices, large reductions in glucose use were observed after administration of MK-801, whereas in the extrapyramidal and sensory-motor areas, glucose use remained unchanged after MK-801 administration in conscious rats. In the halothane-anaesthetised rats, the pattern of altered glucose use after MK-801 differed qualitatively and quantitatively from that observed in conscious rats. In anaesthetised rats, significant reductions in glucose use were noted after MK-801 in 10 of the 28 regions examined, with no area displaying significantly increased glucose use after administration of the drug. In halothane-anaesthetised rats, MK-801 failed to change the rates of glucose use in the olfactory areas, the hippocampus molecular layer, and the dentate gyrus.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

PubMed1999

Renal function in chronically catheterized conscious diabetic rats using constant and servo-controlled infusion.

1. Infusion experiments were performed on chronically catheterized conscious rats to assess kidney function before and after the induction of diabetes mellitus with streptozotocin. 2. Two infusion regimens were used, a conventional constant-infusion protocol and a novel computer-driven, servo-controlled fluid replacement technique. The latter enables body fluid status to be maintained throughout a study occasion by servo-controlled replacement of spontaneous urinary fluid losses. 3. The chronically catheterized conscious rat infused using a servo-controlled system appears to be the optimum model for a study of diabetic renal function. The conscious preparation circumvents problems associated with anaesthesia and acute surgery. The servo-controlled infusion protocol maintains the altered fluid status of the diabetic condition. Both hyperfiltration and polyuria, characteristics of human diabetes often absent in anaesthetized and/or constantly infused diabetic rats, were seen in all conscious servo-controlled diabetic animals. 4. The new regimen enables a more accurate assessment of renal function in experimental diabetes than with previous protocols. It should prove useful in future studies, particularly those assessing the role of anti-diabetic drugs on the kidney.

Animals↗

PubMed1995

Differential effects of chloral hydrate and pentobarbital sodium on a cocaine level and its catecholamine response in the medial prefrontal cortex: a comparison with conscious rats.

Adult male Sprague-Dawley rats anesthetized with chloral hydrate and pentobarbital sodium were used as two different treatment groups. Conscious rats were used as a control group. By using baseline (precocaine) concentration as 100%, after cocaine administration (3.0 mg/kg i.v.), the maximal dopamine (DA) increase occurring at the first microdialysis collection period (20 min) in the medial prefrontal cortex was 299 +/- 46% for the chloral hydrate group, 168 +/- 12% for the pentobarbital sodium group, and 325 +/- 23% for the conscious group. At the same time, norepinephrine (NA) increases reached a maximum and were 162 +/- 20%, 100 +/- 5%, and 141 +/- 17%, respectively. The maximal changes of DA and NA in the chloral hydrate group and in the control group were both significantly higher than that in the pentobarbital sodium group. Meanwhile, the cocaine concentration was higher over a 100-min period of time in the chloral hydrate group when compared with the pentobarbital group and the control group. The peak cocaine concentration in dialysate occurred in the same time slot of maximal DA and NA responses, which were 0.65 +/- 0.08, 0.30 +/- 0.02, and 0.41 +/- 0.05 microM, respectively. Anesthetics suppress the pharmacologic response of neurons, which may explain the difference in catecholamine response between the pentobarbital sodium and the conscious groups. Conversely, because there was no significant difference in DA and NA response between the chloral hydrate group and the conscious group, it may possible be due to the balancing effect between the higher existing cocaine concentration and the anesthetic suppression on pharmacological response of neurons in the chloral hydrate group. The effect of guide cannula implantation on the cocaine-induced catecholamine response was also evaluated.

Anesthesia↗

PubMed2002

BIS monitoring during midazolam and midazolam-ketamine conscious intravenous sedation for oral surgery.

OBJECTIVE: The purpose of this study was to determine whether the bispectral index scale (BIS) would provide added benefit to established methods of monitoring conscious sedation with midazolam (M group) or midazolam supplemented with ketamine (MK group). STUDY DESIGN: BIS was prospectively and blindly examined in 22 patients receiving outpatient oral surgery with conscious sedation supplemented with local anesthesia. RESULTS: The average midazolam dose in the midazolam group over the treatment period was 0.01 mg/kg/h, and the average midazolam plus ketamine dose was 0.01 and 0.05 mg/kg/h, respectively. Mean BIS values throughout the sedation study period were 90 for the midazolam group and 94 for the midazolam plus ketamine group. The addition of ketamine did not lower BIS. BIS values did not alter significantly over time except for an expected transient drop after the midazolam bolus induction. CONCLUSION: BIS levels remained close to baseline levels, suggesting that BIS would not provided any additional benefit to currently established methods of monitoring patient consciousness during conscious sedation for oral surgery.

Adult↗

PubMed2003

Temporal changes in ventricular function assessed echocardiographically in conscious and anesthetized mice.

The mouse is an important model system for cardiovascular biology, with echocardiography a critical tool for noninvasive measurement of cardiac morphology and function. The feasibility and short-term temporal consistency of repeated echocardiographic measurements in conscious mice has not been previously evaluated. We performed serial 2-dimensional guided M-mode transthoracic echocardiographic measurements at 5- to 10-minute intervals over 60 minutes in conscious mice and in mice treated with 1 of 3 anesthetic regimens: ketamine and acepromazine (n = 14); pentobarbital (n = 14); and ketamine and xylazine (n = 13). Unanesthetized mice received intraperitoneal saline (n = 6) or no injection (n = 7). In sequentially repeated measurements over 1 hour in conscious mice, none of the measured or derived echocardiographic parameters differed from baseline, whereas all 3 anesthetic regimens produced significant, prolonged, and temporally variable decreases in heart rate and fractional shortening. The relationship between heart rate and fractional shortening was not altered by anesthetic choice. Serial echocardiographic assessments of cardiac function, dimension, and mass can be performed with high reproducibility in conscious mice.

Acepromazine↗

PubMed2006

Relative blindsight in normal observers and the neural correlate of visual consciousness.

By using a paradigm based on metacontrast masking, we created experimental conditions in which the subjective report of consciousness differs but the objectively measured ability to discriminate visual targets does not. This approach allowed us to study the neural correlate of consciousness while having performance levels carefully matched in healthy human subjects. A comparison of the neural activity associated with these conditions as measured by functional MRI showed that conscious perception is associated with spatially specific activity in the mid-dorsolateral prefrontal cortex (area 46). Further analysis confirms that this activation is not only free from any performance confound, but is also not driven by differences in the timing of the physical stimuli. Our results suggest that the prefrontal cortex is important for the essentially subjective aspects of conscious perception.

Consciousness↗

PubMed1995

Parameters affecting conscious versus unconscious visual discrimination with damage to the visual cortex (V1).

When the visual (striate) cortex (V1) is damaged in human subjects, cortical blindness results in the contralateral visual half field. Nevertheless, under some experimental conditions, subjects demonstrate a capacity to make visual discriminations in the blind hemifield (blindsight), even though they have no phenomenal experience of seeing. This capacity must, therefore, be mediated by parallel projections to other brain areas. It is also the case that some subjects have conscious residual vision in response to fast moving stimuli or sudden changes in light flux level presented to the blind hemifield, characterized by a contentless kind of awareness, a feeling of something happening, albeit not normal seeing. The relationship between these two modes of discrimination has never been studied systematically. We examine, in the same experiment, both the unconscious discrimination and the conscious visual awareness of moving stimuli in a subject with unilateral damage to V1. The results demonstrate an excellent capacity to discriminate motion direction and orientation in the absence of acknowledged perceptual awareness. Discrimination of the stimulus parameters for acknowledged awareness apparently follows a different functional relationship with respect to stimulus speed, displacement, and stimulus contrast. As performance in the two modes can be quantitatively matched, the findings suggest that it should be possible to image brain activity and to identify the active areas involved in the same subject performing the same discrimination task, both with and without conscious awareness, and hence to determine whether any structures contribute uniquely to conscious perception.

Adult↗

PubMed1999

Neuroimaging of genesis and satiation of thirst and an interoceptor-driven theory of origins of primary consciousness.

There are defined hypothalamic functions in the genesis of thirst, but little is known of the cortical processes subserving consciousness of thirst notwithstanding the medical disorders that occur in psychiatric illness, addiction, and the attested decline of thirst with aging. In 10 adult males, positron emission tomography scans were made (i) during genesis of moderate thirst by infusion of i.v. hypertonic saline 0.51 M, (ii) after irrigation of the mouth with water to remove the sensation of dryness, and (iii) 3, 14, 45, and 60 minutes after drinking water to fully satiate thirst. The correlation of regional cerebral blood flow with thirst score showed the major activation to be in the posterior cingulate. Maximum thirst sensation evoked 13 highly significant activations and 9 deactivations in cingulate and parahippocampal gyri, insula, thalamus, amygdala, and mesencephalon. It is possible that cingulate sites (Brodmann's areas 32, 24, and 31) that persisted with wet mouth but disappeared immediately after drinking to satiation may have an important role in the consciousness of thirst. Consciousness of thirst, a primal vegetative emotion, and satiation of thirst appear to be subserved by phylogenetically ancient brain regions. This is salient to current discussion on evolutionary emergence of primary consciousness.

Adult↗

PubMedDate not supplied

Assessing level of consciousness and cognitive changes from vegetative state to full recovery.

Although investigations addressing cognitive recovery from the vegetative state have been reported, to date there have been no detailed studies of these patients combining both neuropsychology and functional imaging to monitor and record the recovery of consciousness. This paper describes the recovery of a specific vegetative state (VS) case. The patient (OG) remained in the vegetative state for approximately two months, increasing her level of awareness to a minimally conscious state, where she continued for approximately 70 days. In the course of the ensuing 18 months, she was able to reach an acceptable level of cognitive functioning, with partial levels of independence. Throughout this two year period, she received continuous cognitive evaluation, for which several different tools were applied including coma and low functioning scales, full cognitive batteries, and structural and functional magnetic resonance imaging (MRI). We present here preliminary data on fMRI using a word presentation paradigm before and after recovery; we also discuss the difficulty of how to determine level of consciousness using the tools currently available, and the subsequent improvement in different cognitive domains. We confirm that accurate diagnosis and proper cognitive assessment are critical for the rehabilitation of patients with disorders of consciousness.

Adult↗

PubMed1994

Propofol infusion and the suppression of consciousness: the EEG and dose requirements.

We have used Median Power Frequency (MPF) to study changes in the electroencephalogram during propofol infusions in 52 women about to undergo gynaecological surgery. Patients were allocated to receive propofol by one of nine different manually-controlled infusion schemes designed to achieve and maintain a stable blood propofol concentration between 1.0 and 6.0 micrograms ml-1, covering a range of states between conscious sedation and full anaesthesia. We recorded the changes in MPF and the response to clinical signs of loss of consciousness at these different doses and concentrations of propofol. Using probit analysis, we derived MPF values corresponding to 50% and 95% suppression of response to verbal (9.3 Hz and 6.8 Hz), eyelash (8.9 Hz and 6.7 Hz) and venepuncture (5.7 Hz and 3.0 Hz) stimuli. Likewise, we obtained dose and concentration requirements for propofol to suppress these stimuli. The mean (95% confidence intervals) ED50 (5.8 (3.5-6.8) mg kg-1 h-1) and ED95 (8.3 (7.1-16.9) mg kg-1 h-1) propofol doses for suppression of consciousness were similar to the values for suppression of the eyelash reflex (6.2 (5.3-6.8) mg kg-1 h-1 and 8.6 (7.8-10.8) mg kg-1 h-1, respectively). The EC50 for loss of consciousness was a propofol concentration of 2.3 (1.8-2.7) micrograms ml-1 and for 50% suppression of MPF was 3.1 (2.7-3.5) micrograms ml-1. The dose required for 50% suppression of MPF was 7.1 (6.2-8.0) mg kg-1 h-1. After 30 min, at blood propofol concentrations > 4.0 micrograms ml-1, consistent with stable anaesthesia, the mean MPF was 5.6 (4.5-6.3) Hz.

Adolescent↗

PubMed2001

Biphasic EEG changes in relation to loss of consciousness during induction with thiopental, propofol, etomidate, midazolam or sevoflurane.

The time course of four EEG effect variables, amplitude in the 2-5 Hz and in the 11-15 Hz band, spectral edge frequency 95% (SEF95), and bispectral index (BIS), in response to increasing concentrations of thiopental, propofol, etomidate, midazolam, or sevoflurane during a 10 min induction of anaesthesia was studied in 25 patients to determine the existence of a biphasic effect and to study the relationship of the EEG effect to the moment of loss of consciousness. A biphasic effect, that is, an initial increase of the effect variable followed by a decrease at higher concentrations, during the transition from consciousness to unconsciousness was found in EEG amplitude (both frequency bands) and in SEF95 for all anaesthetics except midazolam. There was a concentration-related decrease in BIS for all anaesthetics. There was no consistent relationship between the time of occurrence of the peak EEG effect, or the value of the EEG variable and the moment of loss of consciousness. With rapidly changing drug concentrations during the induction of anaesthesia, none of these EEG effect variables could be correlated to the moment of loss of consciousness.

Adolescent↗

PubMed2003

Schizophrenia, consciousness, and the self.

In recent years, there has been much focus on the apparent heterogeneity of schizophrenic symptoms. By contrast, this article proposes a unifying account emphasizing basic abnormalities of consciousness that underlie and also antecede a disparate assortment of signs and symptoms. Schizophrenia, we argue, is fundamentally a self-disorder or ipseity disturbance (ipse is Latin for "self" or "itself") that is characterized by complementary distortions of the act of awareness: hyperreflexivity and diminished self-affection. Hyperreflexivity refers to forms of exaggerated self-consciousness in which aspects of oneself are experienced as akin to external objects. Diminished self-affection or self-presence refers to a weakened sense of existing as a vital and self-coinciding source of awareness and action. This article integrates recent psychiatric research and European phenomenological psychiatry with some current work in cognitive science and phenomenological philosophy. After introducing the phenomenological approach along with a theoretical account of normal consciousness and self-awareness, we turn to a variety of schizophrenic syndromes. We examine positive, then negative, and finally disorganization symptoms-attempting in each case to illuminate shared distortions of consciousness and the sense of self. We conclude by discussing the possible relevance of this approach for identifying early schizophrenic symptoms.

Affect↗

PubMed1998

The effect of the interaction of propofol and alfentanil on recall, loss of consciousness, and the Bispectral Index.

UNLABELLED: The Bispectral Index (BIS) correlates well with the level of consciousness with single anesthetic drugs. We studied the effect of the interaction of propofol with alfentanil on propofol concentration and BIS associated with 50% probability of loss of consciousness and lack of recall (Cp50 and BIS50, respectively). We studied 40 consenting volunteers at two institutions who were randomly assigned to receive stepped increases of propofol (10 subjects at each site), propofol plus alfentanil 50 ng/mL (10 subjects at Emory site), or propofol plus alfentanil 100 ng/mL (10 subjects at Duke site) by using a target-controlled infusion device. Measures of sedation, BIS, deltaBIS (absolute change of BIS after a painful stimulus), memory, and drug concentration were obtained at each target drug concentration. The relation among BIS, measured drug concentration, sedation score, and presence or absence of recall was determined by linear and logistic regression for different drug regimens, and the prediction probability (Pk) was calculated. The addition of alfentanil in increasing doses did not significantly affect the BIS50 and propofol Cp50 values for loss of consciousness and lack of recall. DeltaBIS was significantly decreased by both an increase in the concentration of propofol and the presence of alfentanil. The Pk for BIS was >0.93 with all drug regimens, better than those of the target and measured propofol concentrations. We conclude that BIS correlated well with the hypnotic component of anesthesia independent of the presence of an opioid. Moreover, the level of consciousness, and, therefore, the BIS index, is affected by a painful stimulus, and this response is ablated either by opioids or increasing propofol concentration. IMPLICATIONS: In volunteers, the sedation and changes in memory function produced by propofol correlated well with changes in the Bispectral Index. This relationship was not altered by the addition of an analgesic (alfentanil). However, in moderately sedated patients who received a painful stimulus, the Bispectral Index increased, but this response was blocked by the analgesic or increasing propofol concentrations.

Adult↗