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PubMed2001

Conscious recollection and illusory recognition: an event-related fMRI study.

In this event-related functional magnetic resonance imaging (fMRI) study we examined the neuronal correlates of the subprocesses underlying recognition memory. In an explicit memory task, participants had to discriminate studied ('old') words from semantically related and unrelated 'new' (unstudied) words. We examined whether the correct rejection of semantically related words which were similar to old words, which had elicited correct responses, was based on conscious recollection of study phase information. In this task, false-positive responses to semantically related new words can be assumed to result from the assessment of the semantic similarity between test words and studied words with minimal recollection. For correct identification of old words and correct rejection of new related words we found common activation in a variety of brain areas that have been shown to be involved in conscious recollection, among them the left middle frontal gyrus, the precuneus, the retrosplenial cortex, the left parahippocampal gyrus and the thalamus. For correct responses to old words, the frontomedian wall, the posterior cingulate cortex and the nucleus accumbens were additionally activated, suggesting an emotional contribution to these judgements. Correct rejections of related new words were associated with additional activation of the right middle frontal gyrus, suggesting higher monitoring demands for these more difficult recognition judgements. False-positive responses to semantically related new words were associated with enhanced activation in the frontomedian wall. The results point to an important role of the prefrontal cortex as well as medial temporal and medial parietal regions of the brain in successful memory retrieval and conscious recollection.

Adult↗
PubMed2001

Effects of losartan, prazosin and a vasopressin V1-receptor antagonist on renal and femoral blood flow in conscious sheep.

The regulation of blood flow to different organs is determined by the autonomic nervous system and systemic and/or local vasoactive substances. Although the cardiovascular effects of the renin-angiotensin system (RAS), the sympathoadrenal system and vasopressin (AVP) have been thoroughly studied, there are relatively few investigations on these systems with concomitant measurements of systemic haemodynamics and regional blood flow in conscious unstressed individuals. We therefore studied effects of pharmacological blockade of AVP V1-, angiotensin II (ANG II) AT1-and adrenergic alpha-receptors on central and regional (renal and femoral blood flow) haemodynamics in adult conscious ewes. Eight adult cross-bred ewes were chronically intrumented with peri-vascular ultrasonic flow probes implanted unilaterally around the renal and the femoral artery. While standing in their habitual environment, systemic and regional haemodynamics were measured before and after the following treatments as single intravenous injections. Animals in group A (n = 6) were given isotonic saline (NaCl) followed by the AT1-receptor blocker losartan (LOS, 10 mg kg-1) 30 min later; group B (n = 6) animals were given the alpha-adrenoceptor blocker prazosin (PRAZ, 0.2 mg kg-1); and group C (n = 6) the vasopressin V1 receptor antagonist [d(CH2)5Tyr(Me)AVP] (AVP-a, 10 microg kg-1). PRAZ reduced mean arterial pressure (MAP) by 11% concomitant with an increase in heart rate (HR) (32%), whereas the other substances where without effect on those variables. Femoral blood flow (FBF) was enhanced (increased by 82%) by injection of PRAZ only. Administration of LOS increased the renal blood flow (RBF) by 11% while the other drugs were without effect on that parameter. We conclude that basal renal vascular tone in conscious unstressed sheep is dependent on angiotensinergic mechanism and that blockade of this influence causes a local increase in flow without concomitant effects on systemic haemodynamics.

Angiotensin Receptor Antagonists↗
PubMed2001

Coronary artery baroreceptor-mediated changes in arterial pressure: a pilot study in conscious and anaesthetized sheep.

1. Evidence suggesting the presence of coronary artery baroreceptors on coronary arteries has existed for over 30 years. 2. Evidence that activation of ventricular mechanoreceptors can elicit cardiovascular changes has been challenged, with those changes now thought to be due to coronary artery mechanoreceptors. 3. Studies have suggested that coronary artery mechanoreceptors act as coronary baroreceptors with a role in cardiovascular regulation. However, all evidence to date has been obtained in anaesthetized animal models in physiologically compromised intra-operative states. 4. The purpose of the present study was to design an ovine model that would allow the discrete stretch of coronary arteries without causing ischaemia or changing flow or intra-arterial pressure and that would confirm results seen in previous studies. In addition, the possibility that the technique could be used for studies of coronary artery baroreflexes in conscious sheep was investigated. 5. Controlled stretch of the proximal left anterior descending coronary artery elicited decreases in arterial pressure without changes in heart rate or electrocardiographic activity in halothane-anaesthetized sheep. Similar results were demonstrated in conscious sheep after surgical recovery of up to 2 weeks. 6. The present study supports the possibility that coronary artery baroreceptors exist and likely have a role in cardiovascular regulation. The results of the present study in anaesthetized sheep are in agreement with previous results in anaesthetized animals, but also provide the first demonstration of coronary baroreceptor activity in a conscious animal model, underscoring the potential use of the model in the study of coronary artery baroreceptors in the intact animal.

Anesthesia↗
PubMed2004

Depth of consciousness and deep sedation attained in children as administered by nonanaesthesiologists in a children's hospital.

BACKGROUND: Sedation of children is administered by nonanaesthesiologists in a variety of locations within our children's hospital. The purpose of this study was to assess the depth of sedation administered to children in four locations using the Bispectral Index (BIS) and the University of Michigan Sedation Scale (UMSS). METHODS: Eighty-six children under the age of 12 years undergoing procedures with conscious or deep sedation were enrolled. The study included patients undergoing cardiac catheterization, computerized tomography imaging, gastrointestinal endoscopy, and dental procedures. Sedation for each procedure was based on departmental protocols and preferences; the study did not dictate choice or dose of drugs. An independent observer applied the UMSS sedation scale at 10 min intervals for 1 h. The observer and the personnel administering sedation were blinded to the BIS score, which was recorded continuously. RESULTS: The goal of either conscious or deep sedation was attained in 53% (BIS) and 72% (UMSS) of patients. Depth consistent with general anaesthesia was observed in 35% (BIS) and 0% (UMSS), and an awake state was observed in 12% (BIS) and 28% (UMSS). About 8% of patients experienced desaturation and airway events associated with deeper levels of sedation. CONCLUSIONS: Our data demonstrate wide variations in depth of sedation attained in the hospital. The goal of either conscious or deep sedation was not achieved in a significant number of children. This is a therapeutic failure that requires reassessment of sedation protocols and investigation of new approaches.

Anesthesia, General↗
PubMed2001

Involvement of the thalamocortical system in epileptic loss of consciousness.

Experiments on putative neuronal mechanisms underlying absence seizures as well as clinical observations are critically reviewed for their ability to explain apparent "loss of consciousness." It is argued that the initial defect in absences lies with corticothalamic (CT) neuronal mechanisms responsible for selective attention and/or planning for action, rather than with those establishing either the states or the contents of consciousness. Normally, rich thalamocortical (TC)-CT feedback loops regulate the flow of information to the cortex and help its neurons to organize themselves in discrete assemblies, which through high-frequency (>30 Hz) oscillations bind those distributed processes of the brain that are considered important, so that we are able to focus on what is needed from moment to moment and be aware of this fact. This ability is transiently lost in absence seizures, because large numbers of CT loops are recruited for seconds in much stronger, low-frequency ( approximately 3 Hz) oscillations of EPSP/IPSP sequences, which underlie electroencephalographic (EEG) spike-and-wave discharges (SWDs). These oscillations probably result from a transformation of the normal EEG rhythm of sleep spindles on an abnormal increase of cortical excitability that results in strong activation of inhibitory neurons in the cortex and in nucleus reticularis thalami. The strong general enhancement of CT feedback during SWDs may disallow the discrete feedback, which normally selects specific TC circuits for conscious perception and/or motor reaction. Such a mechanism of SWD generation allows variability in the extent to which different TC sectors are engaged in the SWD activity and thus explains the variable ability of some patients to respond during an absence, depending on the sensory modality examined.

Animals↗
PubMed2001

Runner-up in the young physician's section of the Gowers' prize 2000. Epilepsy and the physical basis of consciousness.

The issue of human consciousness, in both its popular and neuroscientific sense, is considered from a clinical perspective. The ictal semiologies of the various epilepsies, together with associated clinical features, are demonstrated to highlight certain neuroanatomical and neurophysiological facets of consciousness. It is suggested that further insights into consciousness, even those bordering on the philosophical, may be led by clinical neurological phenomena and emerging neuroinvestigative techniques.

Awards and Prizes↗
PubMed2000

Cardiovascular pharmacological studies on JTV-506, a new potassium channel opener. 2nd communication: effects on blood pressure in conscious animals.

The effects of JTV-506 ((-)-(3S,4R)-2,2-bis(methoxymethyl)-4-[(1,6-dihydro-1-methyl-6-oxo-3- pyridazinyl)amino]-3-hydroxychroman-6-carbonitrile hemihydrate, CAS 170148-29-5), a novel coronary vasodilator, on blood pressure were evaluated in conscious dogs and rats. In conscious dogs, JTV-506 (0.01-1 mg/kg p.o.), levcromakalim (0.01-1 mg/kg p.o.) and nifedipine (3-30 mg/kg p.o.) elicited an increase in double product, whereas nicorandil (1-10 mg/kg p.o.) did not affect the double product. The JTV-506-induced increase in double product was abolished by a beta-blocker, propranolol, suggesting that this increase in double product may be due to augumentation of heart rate by sympathetic nerves which mediate the baroreflex. The doses at which JTV-506 increased coronary blood flow in a previous study were lower than the doses required to increase the double product. JTV-506 did not have a crucial influence on electrocardiogram. In conscious rats, orally administered JTV-506, levcromakalim, nicorandil and nifedipine reduced blood pressure and increased heart rate dose dependently. These effects were more remarkable in hypertensive rats than in normotensive rats. JTV-506, a new potassium channel opener, seems to be relatively free of any hemodynamic effects.

Animals↗
PubMed1996

[Severe metabolic alkalosis with a consciousness disorder].

HISTORY AND CLINICAL FINDINGS: A 47-year-old man in a reduced general condition, presumed to be a chronic alcoholic, was hospitalised in a sleepy state and impaired level of consciousness (Glasgow Coma Scale 8). There were no focal neurological deficits, but all proprioceptor reflexes were weak. Body temperature was 36.8 degrees C, blood pressure 90/60 mm Hg, and heart rate 80/min. INVESTIGATIONS: Biochemical tests showed sodium concentration reduced to 121 mmol/l, potassium to 1.83 mmol/l, chloride to 55 mmol/l and, on the next day, phosphate to 0.11 mmol/l. Blood gas analysis demonstrated a noncompensated respiratory alkalosis (pH 7.69, bicarbonate 39.5 mmol/l and a base excess of 20 mmol/l. TREATMENT AND COURSE: The impaired consciousness was thought to be due to the marked alkalosis in combination with hypophosphataemia. The alkalosis was completely removed within 48 hours by administration of Ringer's solution and potassium chloride concentrate, without sodium chloride Phosphate deficit was neutralised with KH2PO4 infusion. Normal consciousness was restored. CONCLUSIONS: Even severe hypochloraemic alkalosis can be quickly reversed with infusion of chloride without sodium Successful treatment with chloride alone excludes alkalosis induced by mineralocorticoids.

Acute Disease↗
PubMed2003

A neuronal network model linking subjective reports and objective physiological data during conscious perception.

The subjective experience of perceiving visual stimuli is accompanied by objective neuronal activity patterns such as sustained activity in primary visual area (V1), amplification of perceptual processing, correlation across distant regions, joint parietal, frontal, and cingulate activation, gamma-band oscillations, and P300 waveform. We describe a neuronal network model that aims at explaining how those physiological parameters may cohere with conscious reports. The model proposes that the step of conscious perception, referred to as access awareness, is related to the entry of processed visual stimuli into a global brain state that links distant areas including the prefrontal cortex through reciprocal connections, and thus makes perceptual information reportable by multiple means. We use the model to simulate a classical psychological paradigm: the attentional blink. In addition to reproducing the main objective and subjective features of this paradigm, the model predicts an unique property of nonlinear transition from nonconscious processing to subjective perception. This all-or-none dynamics of conscious perception was verified behaviorally in human subjects.

Adult↗
PubMed1994

Attention: the mechanisms of consciousness.

A number of recent papers and books discuss theoretical efforts toward a scientific understanding of consciousness. Progress in imaging networks of brain areas active when people perform simple tasks may provide a useful empirical background for distinguishing conscious and unconscious information processing. Attentional networks include those involved in orienting to sensory stimuli, activating ideas from memory, and maintaining the alert state. This paper reviews recent findings in relation to classical issues in the study of attention and anatomical and physical theories of the nature of consciousness.

Animals↗
PubMed2004

Differential time and related appearance of signs, indicating improvement in the state of consciousness in vegetative state traumatic brain injury (VS-TBI) patients after initiation of dopamine treatment.

OBJECTIVE: The goal of the study was to look for the response of treatment with increasing doses of dopaminergic medication on the recovery of vegetative state patients post-TBI. DESIGN: A prospective study of eight patients aged 25-50 years in vegetative state (VS) of mean duration of 104 days following traumatic brain injury (TBI) was performed by investigating changes of their state of consciousness while they were treated with levodopa/carbidopa. RESULTS: Initial improvement was observed in all patients within a mean of 13 days after onset of treatment. Seven patients recovered consciousness after a mean time of 31 days of treatment. The remaining patient showed only slight improvement to minimally conscious state. The sequence of symptoms leading to recovery was the same in all patients; the first to appear was moving a limb on a request, which appeared at a mean time of 13 days. Gradual increase of dose leads to the appearance of better-organized responses like reacting to more than one command, than opening the mouth and appearance of a reciprocal contact. The only side effect was visual hallucinations in one patient, which disappeared after decreasing the dosage. CONCLUSIONS: Clinical awareness to the structured order of responses and to the effect of dosage can help clinicians in early assessment of response to dopaminergic treatment in VS patients.

Adult↗
PubMedDate not supplied

Human nature and the nature of reality: conceptual challenges from consciousness research.

Holotropic states (a large special subgroup of nonordinary states of consciousness) have been the focus of many fields of modern research, such as experiential psychotherapy, clinical and laboratory work with psychedelic substances, field anthropology, thanatology, and therapy with individuals undergoing psychospiritual crises ("spiritual emergencies"). This research has generated a plethora of extraordinary observations that have undermined some of the most fundamental assumptions of modern psychiatry, psychology, and psychotherapy. Some of these new findings seriously challenge the most basic philosophical tenets of Western science concerning the relationship between matter, life, and consciousness. This article summarizes the most important major revisions that would have to be made in our understanding of consciousness and of the human psyche in health and disease to accommodate these conceptual challenges. These areas of changes include: a new understanding and cartography of the human psyche; the nature and architecture of emotional and psychosomatic disorders; therapeutic mechanisms and the process of healing; the strategy of psychotherapy and self-exploration; the role of spirituality in human life; and the nature of reality.

Consciousness↗
PubMed2000

Dissociation of cerebral glucose metabolism and level of consciousness during the period of metabolic depression following human traumatic brain injury.

Utilizing [18F]fluorodeoxyglucose positron emission tomography (FDG-PET), we studied the correlation between CMRglc and the level of consciousness within the first month following human traumatic brain injury. Forty-three FDG-PET scans obtained on 42 mild to severely head-injured patients were quantitatively analyzed for the determination of regional cerebral metabolic rate of glucose (CMRglc). Reduction of cerebral glucose utilization, defined as a CMRglc of < or =4.9 mg/100 g/min, was present regionally in 88% of the studies. The prevalence of global cortical CMRglc reduction was higher in severely head-injured patients (86% versus 67% mild-moderate), although the absolute magnitude was similar across the injury severity spectrum (mean CMRglc 3.9 +/- 0.6 mg/100 g/min). The level of consciousness, as measured by the Glasgow Coma Scale, correlated poorly with the global cortical CMRglc value (r = 0.08; p = 0.63). With regards to severity of head injury, this correlation was worst for the severely injured (r = -0.11; p = 0.58) and better for the mildly injured patients (r = 0.50; p = 0.07). In most cases, intraparenchymal hemorrhagic lesions were associated with either focal CMRglc reduction or elevation. It is concluded that the etiologies of CMRglc reduction are likely multifactorial given the complex nature of traumatic brain injury and that the reduction of CMRglc represents a fundamental pathobiologic state following head injury that is not tightly coupled to level of consciousness.

Adult↗
PubMed2001

Quantitative EEG changes associated with loss and return of consciousness in healthy adult volunteers anaesthetized with propofol or sevoflurane.

Significant changes in topographic quantitative EEG (QEEG) features were documented during induction and emergence from anaesthesia induced by the systematic administration of sevoflurane and propofol in combination with remifentanil. The goal was to identify those changes that were sensitive to alterations in the state of consciousness but independent of anaesthetic protocol. Healthy paid volunteers were anaesthetized and reawakened using propofol/remifentanil and sevoflurane/remifentanil, administered in graded steps while the level of arousal was measured. Alterations in the level of arousal were accompanied by significant QEEG changes, many of which were consistent across anaesthetic protocols. Light sedation was accompanied by decreased posterior alpha and increased frontal/central beta power. Frontal power predominance increased with deeper sedation, involving alpha and, to a lesser extent, delta and theta power. With loss of consciousness, delta and theta power increased further in anterior regions and also spread to posterior regions. These changes reversed with return to consciousness.

Adult↗
PubMed2006

Level of consciousness affects the excitability of spinal motor neurones during propofol sedation in humans.

BACKGROUND: To investigate the relationship between the depression of spinal motor neuronal excitability and the sedative level induced by propofol infusion, we simultaneously analysed the suppressive effect of propofol on the F wave and the sedative level during propofol infusion. METHODS: After spinal anaesthesia, sedation was achieved using a propofol target-controlled infusion (TCI) system to achieve a score of 4 on the Wilson sedation scale. The excitability of spinal motor neurones was determined by measuring the left median nerve F wave. F-wave persistence and the F/M ratio were recorded at pre-sedation as the control, during sedation, at arousal by mild physical stimulation and at post-sedation. RESULTS: Wilson sedation scores increased significantly corresponding to the increase in the target propofol concentration (Cpt), and a Cpt-producing Wilson sedation scale 4 ranged between 1.2 and 1.8 microg ml(-1). The F-wave persistence and F/M ratio before propofol infusion were 80.7 (8.6)% and 9.5 (3.9)%, respectively. At Wilson sedation scale 4, F-wave persistence and F/M ratio were 17.6 (12.8)% (0-37.5%) and 4.3 (4.1)%, and, at return of consciousness by mild physical stimulation, significantly increased to 71.3 (7.9)% and 10.0 (5.0)%, respectively. CONCLUSION: We demonstrated that the excitability of spinal motor neurones was suppressed during sedation by propofol TCI, but this suppressive effect vanished at return of consciousness by mild physical stimulation even at a constant Cpt. Our data suggested that the effect of propofol on the excitability of spinal motor neurones might be affected by consciousness level rather than propofol Cpt in humans.

Adult↗
PubMed2000

The neural correlates of 'deaf-hearing' in man: conscious sensory awareness enabled by attentional modulation.

Attentional modulation of normal sensory processing has a two-fold impact on human brain activity: activation of a network of localized brain regions is associated with paying attention, and activation of specific sensory regions is enhanced relative to passive stimulation. The mechanisms underlying attentional modulation of perception in patients with lesions of sensory cortices are less well understood. Here we report a unique patient suffering from extensive bilateral destruction of the auditory cortices (including the primary auditory fields) who demonstrated conscious perception of the onset and offset of sounds only when selectively attending to the auditory modality. This is the first description of such an attentively modulated 'deaf-hearing' phenomenon and its neural correlates, using H(2)(15)O-PET. Increases in cerebral blood flow associated with conscious awareness of sound that was achieved by listening attentively (compared with identical auditory stimulation presented when the patient was inattentive) were found bilaterally in the lateral (pre)frontal cortices, the spared middle temporal cortices and the cerebellar hemispheres. We conclude that conscious awareness of sounds may be achieved in the absence of the primary auditory cortex, and that selective, 'top-down' attention, associated with prefrontal systems, exerts a crucial modulatory effect on auditory perception within the remaining auditory system.

Acoustic Stimulation↗
PubMed2002

The process of awakening: a PET study of regional brain activity patterns mediating the re-establishment of alertness and consciousness.

Awakening from sleep entails rapid re-establishment of consciousness followed by the relatively slow (20-30 min later) re-establishment of alertness--a temporal dissociation that facilitates specification of the physiological underpinnings of each of these facets of the awakening process. H(2)(15)O PET was used to assess changes in regional cerebral blood flow (rCBF) upon awakening from stage 2 sleep. Cerebral blood flow (CBF) was most rapidly re-established in centrencephalic regions (e.g. brainstem and thalamus), suggesting that the reactivation of these regions underlies the re-establishment of conscious awareness. Across the ensuing 15 min of wakefulness, further increases in CBF were evident primarily in anterior cortical regions, suggesting that the dissipation of sleep inertia effects (post-awakening performance and alertness deficits) is effected by reactivation of these regions. Concomitant shifts in correlation patterns of regional brain activity across the post-awakening period [in particular, a waning negative correlation between prefrontal cortex and mesencephalic reticular formation (RF) activity, and a waxing positive correlation between prefrontal cortex and ventromedial caudate nucleus (CAUD) activity] suggest that the post-awakening reversal of sleep inertia effects may be mediated by more than mere reactivation--it may also involve the functional reorganization of brain activity. Conversely, stable post-awakening correlations--such as those found between the anterior cingulate cortex (ACC) and most other brain regions--may denote the pattern of functional connectivity that underlies consciousness itself.

Adult↗
PubMed2005

Visuo-spatial consciousness and parieto-occipital areas: a high-resolution EEG study.

Conscious and unconscious visuo-spatial processes are mainly related to parieto-occipital cortical activation. In this study, the working hypothesis was that a specific pattern of parieto-occipital activation is induced by conscious, as opposed to unconscious, visuo-spatial processes. Electroencephalographic data (128 channels) were recorded in 12 normal adults during a visuo-spatial task. A cue stimulus appeared on the right or the left (equal probability) monitor side for a 'threshold time' inducing approximately 50% of correct recognitions. It was followed (after 2 s) by visual go stimuli at spatially congruent or incongruent positions with reference to the cue location. The left (right) mouse button was clicked if the go stimulus appeared on the left (right) monitor side. Subjects were required to say 'seen' if they had detected the cue stimulus or 'not seen' if they missed it (self-report). 'Seen' and 'not seen' electroencephalographic trials were averaged separately to form visual evoked potentials. Sources of these potentials were estimated by LORETA software. Reaction time to go stimuli was shorter during spatially congruent than incongruent 'seen' trials, possibly due to covert attention on cue for self-report. It was also shorter during spatially congruent than incongruent 'not seen' trials, as an objective sign of unconscious processes. Cue stimulus evoked parieto-occipital potentials which has the same peak latencies in the 'seen' and 'not seen' cases. Sources of these potentials were located in occipital area 19 and parietal area 7. Source strength was significantly stronger in 'seen' than 'not seen' cases at approximately +300 ms post-stimulus. These results may unveil features of parieto-occipital activation accompanying visuo-spatial consciousness.

Adult↗