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Vertical information flow in the brain: on neuronal micro events and consciousness.

The consciousness problem and its relation to theories of spontaneous brain activity are discussed. It is argued that an evolutionary perspective suggests an interactionist solution of the consciousness problem, i.e., mental events interact with physical brain events. A specification of the physical events assumed to be associated with mental events is proposed to make the discussion of mind-brain theories more fruitful. An interactionist solution of the consciousness problem requires random spontaneous brain activity. A mechanism for such activity is proposed on the basis of experimental findings. Some new results from patch-clamp experiments on intact tissue (the hippocampal slice preparation) are presented. The results indicate that single channel events may cause random spontaneous neuronal activity, illustrating the phenomenon of micro events inducing macro or global brain events, and also the central theme of vertical information flow. The findings highlight the importance of understanding the stochastic nature of channel gating.

Brain↗

Intrathecal kynurenate reduces arterial pressure, heart rate and baroreceptor-heart rate reflex in conscious rats.

In the present study, an excitatory amino acid (EAA) pathway in the spinal cord which maintains sympathetic vasomotor tone in conscious rats has been investigated. To this end, the cardiovascular effects of an intrathecally administered EAA antagonist, kynurenate (KYN), were studied in conscious rats. KYN (0.5 mumol in 10 microliters) caused a dramatic reduction in mean arterial pressure (MAP) and heart rate (HR) that persisted for 2-3 h, and also resulted in extensor paralysis of the hindlimbs. The time courses of fall in MAP and HR and hindlimb paralysis were similar. Baroreceptor-HR reflex activity was also markedly impaired after KYN, suggesting functional diminution of sympathetic outflow at the level of the spinal cord after blockade of EAA receptors by KYN. Xanthurenate, a metabolite of KYN without EAA antagonistic properties, produced negligible effects at the same dose of KYN. While these findings do not identify the putative EAA pathway, they do provide the first demonstration that this system is tonically active in conscious rats.

Animals↗

Transient phase-locking of 40 Hz electrical oscillations in prefrontal and parietal human cortex reflects the process of conscious somatic perception.

Electrical potential oscillations in the range of 35-45 Hz (gamma waves) have recently been shown to occur rather ubiquitously in the brain of awake humans. During selective somatic attention, we demonstrate a transient phase-locking of the gamma waves generated in the contralateral prefrontal and parietal cortical areas that we had previously shown to be involved in such selective attention tasks. In line with other microphysiological evidence obtained on mammalian visual cortex, this selective functional synchronization between critical human brain areas (as far as about 9 cm apart) is proposed to reflect the transient 'binding' of discrete cognitive features that are processed in distributed neuronal assemblies of the brain whereby the conscious perception of an object or event can be achieved. On this basis we emphasize that the conscious function of the brain is neither epiphenomenal nor delayed, but operates transiently to integrate relevant perceptual features at the time of target object identification and of conscious behavioural decision.

Adult↗

Allodynia evoked by intrathecal administration of prostaglandin E2 to conscious mice.

We recently reported that intrathecal (i.t) administration of prostaglandin (PG) F2 alpha to conscious mice induced allodynia that was elicited by non-noxious brushing of the flanks. In the presents study, we demonstrate that i.t. administration of PGD2 and PGE2 to conscious mice also results in allodynia. Dose dependency of PGD2 for allodynia showed a skewed bell-shaped pattern (0.1 ng-2.5 micrograms/mouse), and the maximal allodynic effect was observed with 1.0 microgram at 15 min after intrathecal injection. PGD2-induced allodynia showed a time course and dose dependency similar to that induced by PGF2 alpha, but with lower scores. On the other hand, dose dependency of PGE2 for allodynia showed a bell-shaped pattern over a wide range of dosage from 10 fg to 2.0 micrograms/mouse. The maximal allodynic effect was observed with 0.01-0.1 microgram at 5 min after i.t. injection, and the response gradually decreased over the experimental period of 50 min. Intrathecally administered strychnine and the GABAA antagonist bicuculline also induced allodynia in conscious mice. The time courses of allodynia evoked by strychnine and bicuculline coincided with those by PGE2 and PGF2 alpha, respectively. PGE2-induced allodynia was dose-dependently relieved by the strychnine-sensitive glycine receptor agonist taurine, the NMDA receptor antagonist ketamine, and a high dose of the alpha 2-adrenergic agonist clonidine, but not by the GABAA agonist muscimol or by the GABAB agonist baclofen. In contrast, PGF2-induced allodynia was dramatically inhibited by clonidine and baclofen, but not by taurine, ketamine or muscimol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evidence of direct positive inotropic and chronotropic actions by PGE1 not mediated by cyclic AMP in conscious sheep.

The underlying mechanism for the cardiac responses to PGE1 has not yet been fully elucidated. In order to investigate a possible role for cyclic AMP in the positive inotropic and chronotropic actions of prostaglandin E1 (PGE1) in conscious sheep, theophylline-ethylenediamine was used to inhibit phosphodiesterase activity. Any significant potentiation or the lack of potentiation of the measured cardiac response to PGE1 was then used as a criterion to establish whether the cardiac actions of PGE1 were produced by an alteration in the intracellular levels of cyclic AMP. The results suggest that PGE1 produced positive inotropic and chronotropic actions in conscious sheep, which is neither caused by the autonomic nervous system (baroreflexes) nor by changes in intracellular cyclic AMP levels. Further research seems warranted to establish whether a relationship exists between Ca2+ and the contractile response of PGE1. Such a relationship could then possibly explain the positive inotropic action of PGE1 in conscious sheep.

Animals↗

Factors influencing self-esteem and self-consciousness in adolescents with spina bifida.

PURPOSE: To identify the demographic, personal, familial, attitudinal, and social factors that influence the self-esteem of adolescents with spina bifida. METHODS: A structured face-to-face interview, that included the Rosenberg Self-Esteem Inventory, was conducted with 107 adolescents with spina bifida. Discriminant analyses were performed to identify the factors that discriminate between adolescents with spina bifida who have low vs. high self-esteem and low vs. high self-consciousness. The discriminant functions included variables from the following domains: sociodemographics, personal biography, family interaction, peer relationships and activities, school and work experiences, attitudes toward spina bifida, sexuality and sexual education, and future aspirations. RESULTS: The factors contributing most positively to adolescents' self-esteem were age-appropriate treatments by parents and parental permissiveness in social participation, as perceived by the adolescents. Factors negatively associated with self-esteem included school problems, a perception of disability by others, and living in a medium-sized town (i.e., population 10,000-49,999). The discriminant models correctly identified 57.8% of adolescents who had low self-esteem and 50.4% of those with high self-consciousness, and accurately classified 92.6% and 88.4% of those who had high self-esteem and low self-consciousness, respectively. CONCLUSION: Parents' relationships with their adolescents have important associations with the self-image of the youth.

Adolescent↗

Measurement of cardiac left ventricular pressure in conscious rats using a fluid-filled catheter.

A fluid-filled catheter consisting of 100 cm of PE50 polyethylene tubing welded to 7 cm of PE10 polyethylene tubing (PE50/PE10) was constructed for the purpose of measuring the rate of left ventricular pressure development (+dP/dt) in conscious, freely moving rats. Prior to in vivo experiments, four PE50/PE10 catheters were randomly selected, and their natural frequencies and damping ratios were determined using a square wave impact. The mean (n = 4), natural frequency of these catheters was shown to be 35.0 +/- 5.5 Hz, and the mean damping ratio was 0.83 +/- 0.10. Natural frequency plotted against increasing PE50 tubing length was shown to have a slope of -0.44 Hz/cm with a correlation coefficient of 0.99. The effect of the 7-cm PE10 tubing segment on the catheter damping ratio was also demonstrated. One of the four PE50/PE10 type catheters exhibited a damping ratio of 0.74 +/- 0.09. When the 7-cm PE10 tube was removed, the damping ratio was reduced to 0.31 +/- 0.04. Left ventricular +dP/dt obtained in conscious rats with a PE50/PE10 catheter (n = 7; 6300 +/- 300 mmHg/sec) was significantly less than the +dP/dt obtained using a 100-cm PE50 catheter (n = 6; 9400 +/- 400 mmHg/sec). The results of this study make it clear that the PE50/PE10 catheter is suitable for the measurement of left ventricular +dP/dt in the conscious rat, and that catheter design has a profound influence on both the catheter natural frequency and damping ratio.

Animals↗

Fearful and sexual pictures not consciously seen modulate the startle reflex in human beings.

BACKGROUND: Animal and human studies consistently have demonstrated that the startle reflex elicited by intense auditory stimulation is enhanced by the previous presentation of fear-evoking stimuli. There is also growing and varied evidence of the nonconscious processing of fear stimuli in human beings eliciting brain and autonomic fear responses. METHODS: We report two studies using the startle probe paradigm and the backward-masking procedure to examine the modulation of the eye-blink component of the startle reflex by consciously and nonconsciously presented emotional pictures. RESULTS: Conscious and nonconscious presentation of fearful pictures amplified the magnitude of the startle reflex in both studies. The opposite tendency was observed for conscious and nonconscious presentation of sexually attractive pictures in the second study. CONCLUSIONS: These findings support the notion that negative (and possibly positive) biologically relevant stimuli can be nonconsciously processed, presumably via amygdala activation, and can affect behavioral responding.

Acoustic Stimulation↗

The effects of self-focused attention, performance demand, and dispositional sexual self-consciousness on sexual arousal of sexually functional and dysfunctional men.

Sexually functional (N=26) and sexually dysfunctional heterosexual men with psychogenic erectile disorder (N=23) viewed two sexually explicit videos. Performance demand was manipulated through verbal instruction that a substantial genital response was to be expected from the videos. Self-focused attention was manipulated by introducing a camera pointed at the participant. Dispositional self-consciousness was assessed by questionnaire. Performance demand was found to independently inhibit the genital response. No main effect of self-focus was found. Self-focus inhibited genital response in men scoring high on general and sexual self-consciousness traits, whereas it enhanced penile tumescence in low self-conscious men. Inhibition effects were found in both volunteers and patients. No interaction effects of performance demand and self-focus were found. Subjective sexual arousal in sexually functional men was highest in the self-focus condition. In sexually dysfunctional men, subjective sexual response proved dependent on locus of attention as well as presentation order.

Adult↗

Tolerable infusion rate of citrate based on clinical signs and the electrocardiogram in conscious dogs.

BACKGROUND & AIMS: The possible clinical significance of the toxic effects of citrate has not yet been fully clarified. This study was therefore conducted to confirm the toxicity and determine the tolerable infusion rate of citrate administered by rapid intravenous infusion to conscious dogs. METHODS: Citrate solutions were infused via the cephalic vein of 4 conscious dogs at 0.33, 0.67, or 1.33mmol/kg/h up to 1.33mmol/kg. Clinical signs and the electrocardiogram were observed during and after infusion. Serum citrate and ionized calcium levels were also measured. RESULTS: Although the mean citrate level increased in accordance with the infusion rate, the calcium level decreased. No significant changes in clinical signs or the electrocardiogram were observed during infusion at 0.33mmol/kg/h despite an increase in the serum citrate level to 1.22+/-0.11mmol/l (pre-infusion value: 0.38+/-0.01mmol/l) and a decrease in the serum calcium level to 1.28+/-0.03mmol/l (pre-infusion value: 1.50+/-0.05mmol/l). Vomiting and QTc prolongation were observed at 0.67mmol/kg/h or higher. Salivation and tachycardia were observed at 1.33mmol/kg/h. CONCLUSIONS: Based on clinical signs and the electrocardiogram, the tolerable infusion rate of citrate in conscious dogs is concluded to be 0.33mmol/kg/h.

Animals↗

Comparison of conscious sedation for oocyte retrieval between low-anxiety and high-anxiety patients.

STUDY OBJECTIVE: To investigate the correlation among the level of anxiety, the intravenous propofol requirement for conscious sedation, and recovery profile in in vitro fertilization patients. DESIGN: Prospective, randomized, double-blinded study. SETTING: Operating room of tertiary-care university hospital. PATIENTS: One hundred fifty consecutive women scheduled for oocyte retrieval under conscious sedation. INTERVENTIONS: Anxiety scores were separately measured by an anesthesiologist who was not involved in sedation. The patients were divided into 2 groups, high-anxiety and low-anxiety, as determined by using the median of anxiety VAS scoring for assessment of preoperative anxiety (4.0 cm). The subjects were collected, 76 in high-anxiety group and 74 in low-anxiety group. MEASUREMENTS: An infusion of propofol with a preset target concentration of 2.5 microg/mL(-1) was started until the patient had reached and maintained a sedation level of 3 on a 5-point sedation scale. Hemodynamic variables were recorded by using standard monitors. The scorings of sedation, operability, and satisfaction were assessed by one of the investigator-anesthesiologists. Data of induction quality and concentration of propofol were obtained from Target-Controlled Infusion system that runs on a microcomputer connected to an infusion pump (Becton-Dickinson infusion system, Le Grande chemin, France). Recovery data were measured in the recovery room. MAIN RESULTS: The high-anxiety group required more for the induction of sedation and a larger amount of total dosage of propofol for sedation, as compared with the low-anxiety group. The concentrations of propofol on the Target-Controlled Infusion at sedation level 3 of the high-anxiety group were significantly higher than those of the low-anxiety group. Context-sensitive half time of high-anxiety group was also longer than that of the low-anxiety group. The postoperative pain score of the high-anxiety group was higher than that of the low-anxiety group. Increased preoperative anxiety was significantly correlated with postoperative wound pain (r = 0.240, P = 0.009) and previously experienced pain on same procedure (r = 0.252, P = 0.031), but not with pain on propofol injection (r = -0.05, P = 0.58). CONCLUSIONS: The high-anxiety group needs more sedative requirement of propofol for conscious sedation than the low-anxiety group. Thus, we suggest that propofol dose for such sedation must take into account the individual patient's anxiety level when propofol is administered by an anesthesiologist for oocyte retrieval.

Adult↗

Reversible vagal blockade in conscious rats using a targeted delivery device.

Reversible methods of nerve blockade greatly aid neurophysiological and behavioral studies. We have developed an implantable device for the local delivery of anesthetics to the area surrounding the vagal nerve in rats. The device consists of a thick silicone tube for insulating the nerves from the surrounding tissue, and a thin silicone tube for the infusion of anesthetics into the insulating tube. The in vivo performance of the device was tested electrophysiologically, and cardiovascular responses to vagal stimulation were measured in conscious animals. Nerve conductivity was completely blocked by injection of a small amount (<20 microl) of 1% lidocaine, with conductivity subsequently recovering gradually after 10-40 min. Electrical stimulation of the right vagus nerve in conscious rats increased arterial pressure while decreasing heart rate. The local blockade of afferent fibers abolished the arterial pressure response but preserved the bradycardic response to vagal nerve stimulation. The targeted delivery device was useful for reversible vagal blockade in conscious rats.

Anesthetics, Local↗

Effortless control: executive attention and conscious feeling of mental effort are dissociable.

Recruitment of executive attention is normally associated to a subjective feeling of mental effort. Here we investigate the nature of this coupling in a patient with a left mesio-frontal cortex lesion including the anterior cingulate cortex (ACC), and in a group of comparison subjects using a Stroop paradigm. We show that in normal subjects, subjective increases in effort associated with executive control correlate with higher skin-conductance responses (SCRs). However, our patient experienced no conscious feeling of mental effort and showed no SCR, in spite of exhibiting normal executive control, and residual right anterior cingulate activity measured with event-related potentials (ERPs). Finally, this patient demonstrated a pattern of impaired behavior and SCRs in the Iowa gambling task-elaborated by Damasio, Bechara and colleagues-replicating the findings reported by these authors for other patients with mesio-frontal lesions. Taken together, these results call for a theoretical refinement by revealing a decoupling between conscious cognitive control and consciously reportable feelings. Moreover, they reveal a fundamental distinction, observed here within the same patient, between the cognitive operations which are depending on normal somatic marker processing, and those which are withstanding to impairments of this system.

Adult↗

Bilateral dorsolateral thalamic lesions disrupts conscious recollection.

In an earlier study we disputed the claim that the mediodorsal thalamic nucleus is critical for familiarity. We reported patient (QX) who showed a severe deficit in conscious recollection, and behavioural problems (disinhibition, emotional lability) with relative sparing of familiarity-aware memory following a left mediodorsal thalamic lesion. More recent MR imaging has revealed that QX's lesions are more extensive than previously reported and involve both dorsolateral thalamic nuclei, and whilst there is evidence of left mediodorsal thalamic damage, it is not the main focus of damage. This paper reports a full analysis of QX's thalamic pathology alongside a more detailed investigation of his recognition memory, using yes/no and forced-choice procedures, and executive function. The results revealed impairments in yes/no recognition and conscious recollection rates of famous, artist and unknown names. In addition to the previously noted behavioural disinhibition and emotional lability, a deficit in spontaneous planning ability was evident on the Zoo Map Test (subtest of the Bahavioural Assessment of the Dysexecutive Syndrome). Forced-choice recognition, familiarity estimates and remote memory showed higher levels of preservation. The findings indicate that the dorsolateral thalamus is part of the extended hippocampal circuit which is causally critical only for recall and conscious recollection of complex associations rather than for the more automatic processes linked with novelty detection.

Brain Injuries↗

Imaging kidney in conscious rats with high-frequency ultrasound and detection of two cases of unilateral congenital hydronephrosis.

A quick noninvasive screen of laboratory animal organ phenotype by high-resolution ultrasound is useful in biomedical research and new drug discovery. During new drug testing, imaging animal at the conscious state avoiding anaesthesia does not only speed up the screening process, but also avoids the potential compounding interaction of anaesthetic agents with the new drugs. The feasibility of imaging kidney in conscious rats with high-frequency ultrasound was explored in this study. Two operators were involved with the procedure, with one operator holding the rat and the other operator doing the imaging process. A VisualSonics ultrasound system was used, with a 30 MHz central frequency probe at the resolution of 115 x 55 microm. It was feasible to hold the conscious rats still, allowing ultrasound imaging of kidneys, without causing stress to the animals. In a group of 12 male Han Wistar rats (Charles River, UK), two cases of unilateral congenital hydronephrosis of the right kidney were identified. The right kidneys with hydronephrosis showed an echolucent dilated pelvis and overall parenchymal hypotrophy.

Animals↗

Computed tomography-guided, resistance-based, percutaneous radiofrequency ablation of renal malignancies under conscious sedation at two years of follow-up.

OBJECTIVES: To evaluate the use of computed tomography-guided, resistance-based, percutaneous radiofrequency ablation of renal malignancies using conscious sedation. METHODS: Twenty-three patients with a mean age of 74 years underwent 27 PRFA treatments, using only conscious sedation, for enhancing renal masses, with a mean renal mass of 2.69 cm. All patients had multiple medical comorbidities that precluded standard operative management. Patients were followed up postoperatively at 3-month intervals with renal function studies and enhanced imaging. Successful ablation was defined as a lack of enhancement or resolution of the renal mass. RESULTS: Of the 23 patients, 16 (80%) had successful ablation with a single treatment, 4 had initial failure, and 3 were lost to follow-up. Of the 4 patients with initial failure, 2 underwent reablation successfully, 1 patient elected watchful waiting, and 1 patient died of metastatic renal cell carcinoma. The overall cancer-free survival rate was 90% (18 of 20 patients) at a mean follow-up of 24 months. The exclusion of 2 patients who underwent four sessions for renal masses greater than 4 cm improved the survival rate to 94% (17 of 18). No statistically significant difference was found between the preoperative and postoperative serum creatinine levels (P = 0.46), even in the patients with a preoperative creatinine level greater than 1.5 (P = 0.51). Our only complication was a single perinephric hematoma that resolved spontaneously. CONCLUSIONS: We have demonstrated promising oncologic results for computed tomography-guided percutaneous radiofrequency ablation of tumors in select patients with small renal masses. The procedure was well tolerated under conscious sedation. None of the patients demonstrated significant changes in renal function.

Aged↗

A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation derived from the effects of terfenadine, cisapride and E-4031 in the conscious chronic av node--ablated, His bundle-paced dog.

INTRODUCTION: Terfenadine, cisapride, and E-4031, three drugs that prolong ventricular repolarization, were selected to evaluate the sensitivity of the conscious chronic atrioventricular node--ablated, His bundle-paced Dog for defining drug induced cardiac repolarization prolongation. A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation was generated from these data. METHODS: Three male beagle dogs underwent radiofrequency AV nodal ablation, and placement of a His bundle-pacing lead and programmable pacemaker under anesthesia. Each dog was restrained in a sling for a series of increasing dose infusions of each drug while maintained at a constant heart rate of 80 beats/min. RT interval, a surrogate for QT interval in His bundle-paced dogs, was recorded throughout the experiment. RESULTS: E-4031 induced a statistically significant RT prolongation at the highest three doses. Cisapride resulted in a dose-dependent increase in RT interval, which was statistically significant at the two highest doses. Terfenadine induced a dose-dependent RT interval prolongation with a statistically significant change occurring only at the highest dose. The relationship between drug concentration and RT interval change was described by a sigmoid E(max) model with an effect site. Maximum RT change (E(max)), free drug concentration at half of the maximum effect (EC(50)), and free drug concentration associated with a 10 ms RT prolongation (EC(10 ms)) were estimated. A linear correlation between EC(10 ms) and HERG IC(50) values was identified. DISCUSSION: The conscious dog with His bundle-pacing detects delayed cardiac repolarization related to I(Kr) inhibition, and detects repolarization change induced by drugs with activity at multiple ion channels. A clinically relevant sensitivity and a linear correlation with in vitro HERG data make the conscious His bundle-paced dog a valuable tool for detecting repolarization effect of new chemical entities.

Animals↗

Monitoring i.v. conscious sedation, the legal scope of practice.

Registered nurses who are not CRNAs and are undertaking the administration and/or monitoring of patients receiving IV conscious sedation should consult their state board of nursing, undertake and document the additional education or training to monitor IV conscious sedation patients safety and document the successful achievement of competency in these services, and work with nursing, surgery, and anesthesia staff members to develop written protocols and policies. Written policies must include the provisions, if any, as prescribed by the state's board of nursing. The provisions of other state boards of nursing could be considered for possible inclusion. Policies should reflect nursing practice as described in the professional literature. Professional association position statements, such as those issued by the ANA and endorsed by AORN and other specialty associations and those issued by AANA, should be consulted. AORN's "Recommended practices for monitoring patients receiving intravenous conscious sedation" in the 1993 edition of AORN Standards and Recommended Practices for Perioperative Nursing should be incorporated into the institution policy as appropriate.

Procedural Sedation↗