Physiology, REM Sleep

Sleep is a reversible state of disconnection from the environment, including reduced consciousness, skeletal muscle mobility, and metabolism. All forms of sensory responses are markedly decreased to varying degrees depending on the sleep cycle stage. Although this phenomenon is observed in all species that have been studied and occupies a significant fraction of the human lifespan, the purpose and function of sleep remain poorly understood. Sleep is measured primarily by polysomnography (PSG) which is considered the gold standard for diagnosing sleep disorders.. PSG reveals that sleep architecture has several distinct stages that vacillate between the non-rapid eye movement (NREM) stages and rapid eye movement (REM) stages. The REM stage is of particular interest due to its association with various pathological, psychological, and physiological phenomena. The wide variety of medical and psychiatric pathologies, as well as common pharmacotherapies that can disrupt normal sleep, are summarized in this article. With more than 50 million Americans affected by sleep loss, the treatment of sleep disorders is becoming an increasingly more specialized and interprofessional field with a significant impact on patient health in both acute and chronic settings

Neurobiology and clinical implications of lucid dreaming

Several lines of evidence converge to the idea that rapid eye movement sleep (REMS) is a good model to foster our understanding of psychosis. Both REMS and psychosis course with internally generated perceptions and lack of rational judgment, which is attributed to a hyperlimbic activity along with hypofrontality. Interestingly, some individuals can become aware of dreaming during REMS, a particular experience known as lucid dreaming (LD), whose neurobiological basis is still controversial. Since the frontal lobe plays a role in self-consciousness, working memory and attention, here we hypothesize that LD is associated with increased frontal activity during REMS. A possible way to test this hypothesis is to check whether transcranial magnetic or electric stimulation of the frontal region during REMS triggers LD. We further suggest that psychosis and LD are opposite phenomena: LD as a physiological awakening while dreaming due to frontal activity, and psychosis as a pathological intrusion of dream features during wake state due to hypofrontality. We further suggest that LD research may have three main clinical implications. First, LD could be important to the study of consciousness, including its pathologies and other altered states. Second, LD could be used as a therapy for recurrent nightmares, a common symptom of depression and post-traumatic stress disorder. Finally, LD may allow for motor imagery during dreaming with possible improvement of physical rehabilitation. In all, we believe that LD research may clarify multiple aspects of brain functioning in its physiological, altered and pathological states

Light-dark cycle synchronization of circadian rhythm in blind primates

BACKGROUND: Recently, several papers have shown that a small subset of retinal ganglion cells (RGCs), which project to the suprachiasmatic nucleus (SCN) and contain a new photopigment called melanopsin, are the photoreceptors involved in light-dark entrainment in rodents. In our primate colony, we found a couple of common marmosets (Callithrix jacchus) that had developed progressive and spontaneous visual deficiency, most likely because of retinal degeneration of cones and/or rods. In this study, we evaluated the photoresponsiveness of the circadian system of these blind marmosets. METHODS: Two blind and two normal marmosets were kept in cages with a controlled light-dark cycle (LD) to study photoentrainment, masking, and phase response to a dark pulse. RESULTS: Blind marmosets were entrained with the new LD cycle when light onsets were delayed and advanced by 6 hours. In constant light conditions, blind marmosets free-ran with a period of 23.2 hours, while normal animals free-ran with a period of 23.6 hours. All marmosets responded to dark pulses in the early subjective day with phase delays and with phase advances in the late subjective day. CONCLUSION: Our results demonstrate that light can synchronize circadian rhythms of blind marmosets and consequently, that this species could be a good primate model for circadian photoreception studies

Scaling of Reaction Zones in the A+B->0 Diffusion-Limited Reaction

We study reaction zones in three different versions of the A+B->0 system. For a steady state formed by opposing currents of A and B particles we derive scaling behavior via renormalization group analysis. By use of a previously developed analogy, these results are extended to the time-dependent case of an initially segregated system. We also consider an initially mixed system, which forms reaction zones for dimension d<4. In this case an extension of the steady-state analogy gives scaling results characterized by new exponents.Comment: 4 pages, REVTeX 3.0 with epsf, 2 uuencoded postscript figures appended, OUTP-94-33

Neurobiology and clinical implications of lucid dreaming

Article history: a b s t r a c t Several lines of evidence converge to the idea that rapid eye movement sleep (REMS) is a good model to foster our understanding of psychosis. Both REMS and psychosis course with internally generated perceptions and lack of rational judgment, which is attributed to a hyperlimbic activity along with hypofrontality. Interestingly, some individuals can become aware of dreaming during REMS, a particular experience known as lucid dreaming (LD), whose neurobiological basis is still controversial. Since the frontal lobe plays a role in self-consciousness, working memory and attention, here we hypothesize that LD is associated with increased frontal activity during REMS. A possible way to test this hypothesis is to check whether transcranial magnetic or electric stimulation of the frontal region during REMS triggers LD. We further suggest that psychosis and LD are opposite phenomena: LD as a physiological awakening while dreaming due to frontal activity, and psychosis as a pathological intrusion of dream features during wake state due to hypofrontality. We further suggest that LD research may have three main clinical implications. First, LD could be important to the study of consciousness, including its pathologies and other altered states. Second, LD could be used as a therapy for recurrent nightmares, a common symptom of depression and post-traumatic stress disorder. Finally, LD may allow for motor imagery during dreaming with possible improvement of physical rehabilitation. In all, we believe that LD research may clarify multiple aspects of brain functioning in its physiological, altered and pathological states

Understanding and predicting a complex behaviour using n-of-1 methods : Photoprotection in xeroderma pigmentosum

Acknowledgements: We would like to thank Lesley Foster (research nurse) for all her work in setting up the n-of-1 study with patients; the XP national clinical team (Hiva Fassihi, Tanya Henshaw, Sally Turner, Isabel Garrood, Alan Lehmann) and members of the PPI panel (Cathy Coleman, Ben Fowler, Sandra Webb, Ros Tobin) for input into design of materials. Funding: This research is funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research (RP-PG- 1212-20009). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS, or the Department of Health.Peer reviewedPostprin

The biological effects of subacute inhalation of diesel exhaust following addition of cerium oxide nanoparticles in atherosclerosis-prone mice

AbstractBackgroundCerium oxide (CeO2) nanoparticles improve the burning efficiency of fuel, however, little is known about health impacts of altered emissions from the vehicles.MethodsAtherosclerosis-prone apolipoprotein E knockout (ApoE−/−) mice were exposed by inhalation to diluted exhaust (1.7mg/m3, 20, 60 or 180min, 5 day/week, for 4 weeks), from an engine using standard diesel fuel (DE) or the same diesel fuel containing 9ppm cerium oxide nanoparticles (DCeE). Changes in hematological indices, clinical chemistry, atherosclerotic burden, tissue levels of inflammatory cytokines and pathology of the major organs were assessed.ResultsAddition of CeO2 to fuel resulted in a reduction of the number (30%) and surface area (10%) of the particles in the exhaust, whereas the gaseous co-pollutants were increased (6–8%). There was, however, a trend towards an increased size and complexity of the atherosclerotic plaques following DE exposure, which was not evident in the DCeE group. There were no clear signs of altered hematological or pathological changes induced by either treatment. However, levels of proinflammatory cytokines were modulated in a brain region and liver following DCeE exposure.ConclusionsThese results imply that addition of CeO2 nanoparticles to fuel decreases the number of particles in exhaust and may reduce atherosclerotic burden associated with exposure to standard diesel fuel. From the extensive assessment of biological parameters performed, the only concerning effect of cerium addition was a slightly raised level of cytokines in a region of the central nervous system. Overall, the use of cerium as a fuel additive may be a potentially useful way to limit the health effects of vehicle exhaust. However, further testing is required to ensure that such an approach is not associated with a chronic inflammatory response which may eventually cause long-term health effects

A new ghost cell/level set method for moving boundary problems:application to tumor growth

In this paper, we present a ghost cell/level set method for the evolution of interfaces whose normal velocity depend upon the solutions of linear and nonlinear quasi-steady reaction-diffusion equations with curvature-dependent boundary conditions. Our technique includes a ghost cell method that accurately discretizes normal derivative jump boundary conditions without smearing jumps in the tangential derivative; a new iterative method for solving linear and nonlinear quasi-steady reaction-diffusion equations; an adaptive discretization to compute the curvature and normal vectors; and a new discrete approximation to the Heaviside function. We present numerical examples that demonstrate better than 1.5-order convergence for problems where traditional ghost cell methods either fail to converge or attain at best sub-linear accuracy. We apply our techniques to a model of tumor growth in complex, heterogeneous tissues that consists of a nonlinear nutrient equation and a pressure equation with geometry-dependent jump boundary conditions. We simulate the growth of glioblastoma (an aggressive brain tumor) into a large, 1 cm square of brain tissue that includes heterogeneous nutrient delivery and varied biomechanical characteristics (white matter, gray matter, cerebrospinal fluid, and bone), and we observe growth morphologies that are highly dependent upon the variations of the tissue characteristics—an effect observed in real tumor growth

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio