`Funda-Mentality': is the conscious mind subtly linked to a basic level of the universe?

Age-old battle lines over the puzzling nature of mental experience are shaping a modern resurgence in the study of consciousness. On one side are the long-dominant `physicalists' who view consciousness as an emergent property of the brain's neural networks. On the alternative, rebellious side are those who see a necessary added ingredient: proto-conscious experience intrinsic to reality, perhaps understandable through modern physics (panpsychists, pan-experientialists, `funda-mentalists'). It is argued here that the physicalist premise alone is unable to solve completely the difficult issues of consciousness and that to do so will require supplemental panpsychist/pan-experiential philosophy expressed in modern physics. In one scheme proto-conscious experience is a basic property of physical reality accessible to a quantum process associated with brain activity. The proposed process is Roger Penrose's `objective reduction' (OR), a self-organizing `collapse' of the quantum wave function related to instability at the most basic level of space-time geometry. In the Penrose-Hameroff model of `orchestrated objective reduction' (Orch OR), OR quantum computation occurs in cytoskeletal microtubules within the brain's neurons. The basic thesis is that consciousness involves brain activities coupled to self-organizing ripples in fundamental reality.

Doxepin effects on chronic pain, depression and plasma opioids.

Thirty patients with chronic low back or cervical pain combined with clinical depression were studied in a six-week, randomized, double-blind comparison of doxepin and placebo. Dependent variables included Hamilton Depression Scores, the Clinical Global Assessment Scale, and Profile of Mood States (POMS), and subjective ratings (visual analogue scales) of pain severity, percent of time pain felt, and effect of pain on activity, muscle tension, sleep, mood, and analgesic drug consumption. Plasma levels of doxepin, desmethyldoxepin, beta-endorphin, and enkephalin-like activity were also measured. Significant improvements in the doxepin-treated group compared to the placebo group were seen in Hamilton scores, Global Assessment Scale, Profile of Mood States, percent of time pain felt, and effect of pain on sleep, muscle tension, and mood. Some improvement was observed after 1 week, although most improvement occurred at 6 weeks, when the mean doxepin dose was 2.5 mg/kg and plasma doxepin and desmethyldoxepin averaged 70 ng/ml. Nonspecific enkephalin-like activity (but not beta-endorphins) increased for the treatment group and decreased for the placebo group. The efficacy of doxepin compared with that of placebo was thus documented in several depressive and pain parameters, indicating that doxepin is a valuable treatment for patients with chronic pain and depression.

Doxepin's effects on chronic pain and depression: a controlled study.

Sixty patients with chronic pain of the low back or cervical spine concomitant with clinical depression were studied in a 6-week, randomized, double-blind comparison of doxepin and placebo. Significant improvements in the doxepin-treated group compared to placebo or to baseline values were seen on Hamilton depression scores, Global Assessment Scale scores, pain severity, percent of time pain felt, and effect of pain on activity, sleep, and muscle tension. Some improvements were observed after 1 week of treatment; the most improvement occurred at 6 weeks, when the mean doxepin dosage was approximately 200 mg/day and plasma doxepin and nordoxepin averaged 80 ng/ml. No significant harmful effects were observed. Neither plasma beta-endorphin nor enkephalin-like activity demonstrated significant differences from baseline. These data indicate that doxepin is a valuable treatment for patients with chronic pain and depression.

Transdermal fentanyl: pharmacokinetics and preliminary clinical evaluation.

A new transdermal drug-delivery system that administers the synthetic opioid fentanyl through intact skin was evaluated for 24 hours postoperatively in eight patients who had undergone orthopedic surgery. Plasma samples were obtained over a 72-hour period for pharmacokinetic analysis in five patients. The patients were also evaluated intensively for adequacy of analgesia, frequency of nausea and sedation, and occurrence of ventilatory depression. A median lag time of 2.25 hours after application of the transdermal system was observed before the appearance of fentanyl in the blood. Median peak concentration and time to peak were 1.0 ng/ml and 22 hours, respectively. The apparent elimination of fentanyl after transdermal administration is prolonged relative to previously reported values. Absorption analysis indicates zero-order fentanyl administration, and in addition, suggests deposition of drug in an epidermal site, with the resultant prolonged absorption process giving the appearance of slow elimination. No significant toxicities were observed. Four patients required no additional analgesia. No consistent correlations among fentanyl concentration and any clinical values were observed. Transdermal administration of fentanyl appears to be a viable alternative to conventional routes of narcotic administration and warrants further study.

Effect of hyperbaric oxygen therapy or dimethyl sulfoxide on cerebral ischemia in unanesthetized gerbils.

To determine whether treatment with hyperbaric oxygen (HBO) or dimethyl sulfoxide (DMSO) could mitigate the fatal effects of cerebral ischemia, we anesthetized 68 gerbils with ketamine, ligated the right carotid artery (CA), and placed a snare occluder around the left CA. After 48 hours, 30 gerbils that were neurologically normal or had suffered only mild deficits were subjected to left CA occlusion without anesthesia for periods of 2 to 60 minutes. The onset of circling, posturing, falling, and lethargy began immediately; seizures and coma ensued 4 to 5 minutes later and persisted until release of the left CA occluder. All gerbils recovered after 2-minute staged bilateral CA occlusions. The mortality rate was 33% after both 5- and 10-minute occlusions and 100% after 20- and 60-minute bilateral occlusions. Twelve gerbils were placed in an HBO chamber (100% oxygen at 1.5 atmospheres) for 15 minutes during 20-minute bilateral occlusion; only 2 died (16% mortality rate). Thus, HBO therapy conferred significant protection against death from untreated ischemia (P less than 0.001). Histological examination showed that the extent of patchy bilateral ischemic neuronal damage was much less in surviving gerbils that received HBO therapy than in those that died after 20-minute occlusions. Fourteen gerbils were treated with DMSO, 2.5 g/kg intraperitoneally, during 5- or 10-minute bilateral CA occlusion; 12 died (86% mortality rate). Thus, DMSO provided no protection against fatal cerebral infarction; in fact, the results in the 10-minute reperfusion group suggest that DMSO may have a deleterious effect.

Effect of alterations in frequency, inspiratory time, and airway pressure on gas exchange during high frequency jet ventilation in dogs with normal lungs.

High frequency jet ventilation (HFJV) is becoming increasingly useful for providing respiratory support in patients with normal lungs during operative procedures, and also has been advocated as a technique for ventilating patients during cardiopulmonary resuscitation. We studied the effect of frequency, percent inspiratory time (I/E ratio), peak airway pressure, and airway pressure difference (peak-PEEP) during HFJV as operational variables on the efficacy of gas exchange in dogs with normal lungs. We observed that at a constant peak airway pressure and percent inspiratory time, PaCO2 generally increases as frequency rises above 100/min. In contrast, PaCO2 generally decreases as percent inspiratory time is reduced at a constant frequency and peak airway pressure. In addition, increasing peak airway pressure and airway pressure difference are associated with lower levels of PaCO2. Arterial oxygenation was adversely affected by frequencies above 300/min, but was otherwise not influenced by alterations in frequency, percent inspiratory time, or airway pressure.

Quantum computation in brain microtubules: decoherence and biological feasibility.

The Penrose-Hameroff orchestrated objective reduction (orch. OR) model assigns a cognitive role to quantum computations in microtubules within the neurons of the brain. Despite an apparently "warm, wet, and noisy" intracellular milieu, the proposal suggests that microtubules avoid environmental decoherence long enough to reach threshold for "self-collapse" (objective reduction) by a quantum gravity mechanism put forth by Penrose. The model has been criticized as regards the issue of environmental decoherence, and a recent report by Tegmark finds that microtubules can maintain quantum coherence for only 10(-13) s, far too short to be neurophysiologically relevant. Here, we critically examine the decoherence mechanisms likely to dominate in a biological setting and find that (1) Tegmark's commentary is not aimed at an existing model in the literature but rather at a hybrid that replaces the superposed protein conformations of the orch. OR theory with a soliton in superposition along the microtubule; (2) recalculation after correcting for differences between the model on which Tegmark bases his calculations and the orch. OR model (superposition separation, charge vs dipole, dielectric constant) lengthens the decoherence time to 10(-5)-10(-4) s; (3) decoherence times on this order invalidate the assumptions of the derivation and determine the approximation regime considered by Tegmark to be inappropriate to the orch. OR superposition; (4) Tegmark's formulation yields decoherence times that increase with temperature contrary to well-established physical intuitions and the observed behavior of quantum coherent states; (5) incoherent metabolic energy supplied to the collective dynamics ordering water in the vicinity of microtubules at a rate exceeding that of decoherence can counter decoherence effects (in the same way that lasers avoid decoherence at room temperature); (6) microtubules are surrounded by a Debye layer of counterions, which can screen thermal fluctuations, and by an actin gel that might enhance the ordering of water in bundles of microtubules, further increasing the decoherence-free zone by an order of magnitude and, if the dependence on the distance between environmental ion and superposed state is accurately reflected in Tegmark's calculation, extending decoherence times by three orders of magnitude; (7) topological quantum computation in microtubules may be error correcting, resistant to decoherence; and (8) the decohering effect of radiative scatterers on microtubule quantum states is negligible. These considerations bring microtubule decoherence into a regime in which quantum gravity could interact with neurophysiology.

Cytoskeletal logic: a model for molecular computation via Boolean operations in microtubules and microtubule-associated proteins.

Adaptive behaviors and dynamic activities within living cells are organized by the cytoskeleton: intracellular networks of interconnected protein polymers which include microtubules (MTs), actin, intermediate filaments, microtubule associated proteins (MAPs) and other protein structures. Cooperative interactions among cytoskeletal protein subunit conformational states have been used to model signal transmission and information processing. In the present work we present a theoretical model for molecular computing in which Boolean logic is implemented in parallel networks of individual MTs interconnected by MAPs. Conformational signals propagate on MTs as in data buses and in the model MAPs are considered as Boolean operators, either as bit-lines (like MTs) where a signal can be transported unchanged between MTs ('BUS-MAP'), or as bit-lines where a Boolean operation is performed in one of the two MAP-MT attachments ('LOGIC-MAP'). Three logic MAPs have been defined ('NOT-MAP, 'AND-MAP', 'XOR-MAP') and used to demonstrate addition, subtraction and other arithmetic operations. Although our choice of Boolean logic is arbitrary, the simulations demonstrate symbolic manipulation in a connectionist system and suggest that MT-MAP networks can perform computation in living cells and are candidates for future molecular computing devices.

Quantum optical coherence in cytoskeletal microtubules: implications for brain function.

'Laser-like,' long-range coherent quantum phenomena may occur biologically within cytoskeletal microtubules. This paper presents a theoretical prediction of the occurrence in biological media of the phenomena which we term 'superradiance' and 'self-induced transparency'. Interactions between the electric dipole field of water molecules confined within the hollow core of microtubules and the quantized electromagnetic radiation field are considered, and microtubules are theorized to play the roles of non-linear coherent optical devices. Superradiance is a specific quantum mechanical ordering phenomenon with characteristic times much shorter than those of thermal interaction. Consequently, optical signalling (and computation) in microtubules would be free from both thermal noise and loss. Superradiant optical computing in networks of microtubules and other cytoskeletal structures may provide a basis for biomolecular cognition and a substrate for consciousness.

Phase space electroencephalography (EEG): a new mode of intraoperative EEG analysis.

Intraoperative monitoring of electroencephalography (EEG) data can help assess brain integrity and/or depth of anesthesia. We demonstrate a computer generated technique which provides a visually robust display of EEG data plotted as 'phase space trajectories' and a mathematically derived parameter ('dimensionality') which may correlate with depth of anesthesia. Application of nonlinear mathematical analysis, used to describe complex dynamical systems, can characterize 'phase space' EEG patterns by identifying attractors (geometrical patterns in phase space corresponding to specific ordered EEG data subjects) and by quantifying the degree of order and chaos (calculation of dimensionality). Dimensionality calculations describe the degree of complexity in a signal and may generate a clinically useful univariate EEG descriptor of anesthetic depth. In this paper we describe and demonstrate phase space trajectories generated for sine waves, mixtures of sine waves, and white noise (random chaotic events). We also present EEG phase space trajectories and dimensionality calculations from a patient undergoing surgery and general anesthesia in 3 recognizable states: awake, anesthetized, and burst suppression. Phase space trajectories of the three states are visually distinguishable, and dimensionality calculations indicate that EEG progresses from 'chaos' (awake) to progressively more 'ordered' attractors (anesthetized and burst suppression).

Effects of halothane and fentanyl anesthesia on plasma beta-endorphin immunoreactivity during cardiac surgery.

We studied the effects of halothane anesthesia (n = 6) and fentanyl anesthesia (n = 9; 50-100 micrograms/kg) on plasma beta-endorphin immunoreactivity as a measure of stress response during coronary artery bypass grafting, including cardiopulmonary bypass. Plasma levels of beta-endorphin immunoreactivity measured prior to induction, after induction, after intubation, after skin incision, during cardiopulmonary bypass, and on leaving the operating room were significantly higher in patients given halothane during cardiopulmonary bypass and on leaving the operating room than they were in patients given fentanyl.

Fentanyl preloading for rapid-sequence induction of anesthesia.

Protecting the patient's airway is of paramount importance in the induction of general anesthesia. For the patient at risk of regurgitation of stomach contents, the rapid-sequence (crash) induction provides protection, but at the expense of increased stress response to laryngoscopy and intubation. This stress response is especially dangerous for the patient at risk for myocardial ischemia. The purpose of this study was to examine the efficacy of using low-dose fentanyl (5 micrograms/kg) to reduce cardiovascular and neuroendocrine stress responses to rapid-sequence induction. Thirty patients were randomly assigned to a rapid-sequence induction protocol either with or without fentanyl preloading. Fentanyl-preloaded patients (fentanyl group) received 2 mg/kg of thiopental whereas patients who were not preloaded with fentanyl (control group) received 4 mg/kg of thiopental. Data collected as indices of the stress response included heart rate, systolic, diastolic, and mean blood pressures, and plasma concentrations of catecholamines (epinephrine, norepinephrine, dopamine) and beta-endorphin. Electrocardiograms (modified V5 lead) were monitored for dysrhythmias and ST segment depression. Control patients had higher systolic, diastolic, and mean blood pressures after intubation than did patients given fentanyl (P less than 0.05). Although the incidence of dysrhythmias was decreased by fentanyl (20% vs 42%), this difference was not statistically significant. Plasma concentrations of beta-endorphin and norepinephrine increased significantly in control patients but not in patients given fentanyl (P less than 0.05). Low-dose fentanyl (5 micrograms/kg) reduces some aspects of the stress response to rapid-sequence induction of anesthesia.

Comparison of bupivacaine, etidocaine, and saline for trigger-point therapy.

Injections of local anesthetics, saline, "dry needling," or other stimuli at specific, tender loci (trigger or acupuncture points) are reportedly efficacious in treatment of chronic pain syndromes. In a randomized, double-blind crossover study, subjective responses of 15 patients with myofascial syndrome to trigger-point injections of either bupivacaine 0.5%, etidocaine 1%, or physiologic saline without preservative were compared. Responses in six pain-related categories were determined before treatment and 15 minutes, 24 hours, and 7 days after treatment. Trigger-point injections with bupivacaine and etidocaine were generally preferred over saline in several pain-tested categories. Implications and possible mechanisms are discussed.

Acute cardiovascular effects of dimethylsulfoxide.

Dimethylsulfoxide (DMSO) has been advocated as a central nervous system (CNS) protectant against ischemia and trauma. The present study was performed to evaluate acute cardiovascular effects of DMSO which might complicate the clinical treatment of CNS compromised patients. Intravenously administered DMSO in doses which reportedly provide CNS protection, 2 g/kg, were infused in 6 dogs; hemodynamic variables were measured and compared to infusion of equal volumes of 0.9% sodium chloride. Immediately after infusion, DMSO caused increases in cardiac index, heart rate, pulmonary capillary wedge pressures (WP), and pulmonary arterial (systolic, mean, and diastolic) pressures which were significantly greater than changes induced by saline. DMSO decreased systematic diastolic pressure and systemic vascular resistance at the end of infusion. Most DMSO induced changes returned toward pre-infusion values 10 min after the end of infusion. These results suggest transient DMSO effects different from equal volumes of saline, possibly due to hyperosmotic expansion of plasma volume. A decrease in systemic vascular resistances was also observed. Although neither CNS production, intracranial pressure or blood flow were studied, these data suggest that DMSO used for CNS protection would not have adverse acute hemodynamic consequences. This may be particularly relevant in traumatized, hypovolemic patients.

General anesthetics directly inhibit electron mobility: dipole dispersion theory of anesthetic action.

A model system of gaseous electron mobility, excitation, and plasma activity was used to study direct effects of six gases, including four general anesthetics, in oxygen. Helium increased, and nitrogen had minimal effects on gaseous excitation. Nitrous oxide, as well as the potent anesthetics halothane, enflurane, and isoflurane, inhibited gaseous excitation, nitrous oxide having the weakest anesthetic effect. The data are compatible with the view that anesthetic inhibition is mediated by Van der Waals dipole dispersion interactions among anesthetic molecules (e.g., halogenated hydrocarbons) and electrons accelerated by the applied field. Dipole dispersion interactions may also mediate anesthetic effects on synaptic protein conformational control.

High-frequency alternating lung ventilation.

A new mode, high-frequency alternating lung ventilation (HFALV) is described and demonstrated in which the lungs are alternately pulsed. A fluidic oscillator may be used to deliver two pulsed gas streams, 180 degrees out of phase, to bronchial catheters placed via a double lumen endobronchial tube. Inspiratory phase of one lung thus coincides with expiratory phase in the other, and characteristic lateral rocking chest movements is observed. In six dogs, HFALV was compared to simultaneous pulsing of both lungs with comparable flow (18.5 l/min), frequency (144 min-1), and pulse wave shape. Arterial PCO2 was significantly lower (P less than 0.001) with HFALV. Arterial PCO2 was also found to increase linearly (r = -0.862, P less than 0.001) with distance of the catheters' distal tips from the dogs' carinae. Theoretical mechanisms and possible applications of HFALV are discussed.