Enhancing and advancing the understanding and study of dreaming and memory consolidation: Reflections, challenges, theoretical clarity, and methodological considerations.

Empirical investigations that search for a link between dreaming and sleep-dependent memory consolidation have focused on testing for an association between dreaming of what was learned, and improved memory performance for learned material. Empirical support for this is mixed, perhaps owing to the inherent challenges presented by the nature of dreams, and methodological inconsistencies. The purpose of this paper is to address critically prevalent assumptions and practices, with the aim of clarifying and enhancing research on this topic, chiefly by providing a theoretical synthesis of existing models and evidence. Also, it recommends the method of Targeted Memory Reactivation (TMR) as a means for investigating if dream content can be linked to specific cued activations. Other recommendations to enhance research practice and enquiry on this subject are also provided, focusing on the HOW and WHY we search for memory sources in dreams, and what purpose (if any) they might serve.

Workforce preparation for delivery of nurturing care in low- and middle-income countries: Expert consensus on critical multisectoral training needs.

BACKGROUND: Services to support nurturing care through early childhood development (ECD) in low- and middle-income countries are hampered by significant workforce challenges. The global early childhood workforce is both diverse and complex, and it supports the delivery of a wide range of services in extremely diverse geographical and social settings. In the context of contemporary global goals for the universal provision of quality early childhood provision, there is an urgent need to build appropriate platforms for strengthening and supporting this workforce. However, the evidence base to support this work is severely limited. METHODS: To contribute to evidence on how to strengthen the ECD workforce in low- and middle-income countries, this study used a Delphi methodology involving three rounds of data collection with 14 global experts, to reach consensus on the most critical training needs of three key early childhood workforce groups: (i) health; (ii) community-based paraprofessionals, and (iii) educational professionals working across ECD programmes. RESULTS: The study identified a comprehensive set of shared, as well as distinct, training needs across the three groups. Shared training needs include the following: (i) nurturing dispositions that facilitate work with children and families in complex settings; (ii) knowledge and skills to support responsive, adaptable delivery of ECD programmes; and (iii) systems for ECD training and professional pathways that prioritise ongoing mentoring and support. CONCLUSIONS: The study's detailed findings help to address a critical gap in the evidence on training needs for ECD workers in low-resource contexts. They provide insights into how to strengthen content, systems, and methods of training to support intersectoral ECD work in resource-constrained contexts.

The neurocognition of dreaming: key questions and foci.

Until recently, understanding the neurobiology of dreaming has relied upon on correlating a subjective dream report with a measure of brain activity or function sampled from a different occasion. As such, most assumptions about dreaming come from the neuroscience of rapid eye-movement (REM) sleep from which many, but not all, dream reports are recalled. Core features of REM sleep (intense emotional activation, a reduction in activity in most frontal regions, particularly the dorsolateral prefrontal cortex, along with increased dopamine, acetylcholine, cholinergic activation) align with typical dream characteristics (characterised by fear, reduced reality monitoring, increased bizarreness and hyperassociativity, respectively). The default mode network offers a way of understanding the nature of dreaming more independently from a REM sleep context, and electroencephalography methods paired with serial awakenings to elicit dream reports demonstrate how high-frequency activity in posterior regions may be associated with dreaming. Nevertheless, all measures of dreaming rely fundamentally on recall processes, so our understanding of dreaming must embrace and address memory's crucial involvement in dream report production.

Consciousness across Sleep and Wake: Discontinuity and Continuity of Memory Experiences As a Reflection of Consolidation Processes.

The continuity hypothesis (1) posits that there is continuity, of some form, between waking and dreaming mentation. A recent body of work has provided convincing evidence for different aspects of continuity, for instance that some salient experiences from waking life seem to feature in dreams over others, with a particular role for emotional arousal as accompanying these experiences, both during waking and while asleep. However, discontinuities have been somewhat dismissed as being either a product of activation-synthesis, an error within the consciousness binding process during sleep, a methodological anomaly, or simply as yet unexplained. This paper presents an overview of discontinuity within dreaming and waking cognition, arguing that disruptions of consciousness are as common a feature of waking cognition as of dreaming cognition, and that processes of sleep-dependent memory consolidation of autobiographical experiences can in part account for some of the discontinuities of sleeping cognition in a functional way. By drawing upon evidence of the incorporation, fragmentation, and reorganization of memories within dreams, this paper proposes a model of discontinuity whereby the fragmentation of autobiographical and episodic memories during sleep, as part of the consolidation process, render salient aspects of those memories subsequently available for retrieval in isolation from their contextual features. As such discontinuity of consciousness in sleep is functional and normal.

Metaphor and hyperassociativity: the imagination mechanisms behind emotion assimilation in sleep and dreaming.

In this paper we propose an emotion assimilation function of sleep and dreaming. We offer explanations both for the mechanisms by which waking-life memories are initially selected for processing during sleep, and for the mechanisms by which those memories are subsequently transformed during sleep. We propose that emotions act as a marker for information to be selectively processed during sleep, including consolidation into long term memory structures and integration into pre-existing memory networks; that dreaming reflects these emotion assimilation processes; and that the associations between memory fragments activated during sleep give rise to measureable elements of dream metaphor and hyperassociativity. The latter are a direct reflection, and the phenomenological experience, of emotional memory assimilation processes occurring during sleep. While many theories previously have posited a role for emotion processing and/or emotional memory consolidation during sleep and dreaming, sleep theories often do not take enough account of important dream science data, yet dream research, when conducted systematically and under ideal conditions, can greatly enhance theorizing around the functions of sleep. Similarly, dream theories often fail to consider the implications of sleep-dependent memory research, which can augment our understanding of dream functioning. Here, we offer a synthesized view, taking detailed account of both sleep and dream data and theories. We draw on extensive literature from sleep and dream experiments and theories, including often-overlooked data from dream science which we believe reflects sleep phenomenology, to bring together important ideas and findings from both domains.

Autobiographical memory and hyperassociativity in the dreaming brain: implications for memory consolidation in sleep.

In this paper we argue that autobiographical memory (AM) activity across sleep and wake can provide insight into the nature of dreaming, and vice versa. Activated memories within the sleeping brain reflect one's personal life history (autobiography). They can appear in largely fragmentary forms and differ from conventional manifestations of episodic memory. Autobiographical memories in dreams can be sampled from non-REM as well as REM periods, which contain fewer episodic references and become more bizarre across the night. Salient fragmented memory features are activated in sleep and re-bound with fragments not necessarily emerging from the same memory, thus de-contextualizing those memories and manifesting as experiences that differ from waking conceptions. The constructive nature of autobiographical recall further encourages synthesis of these hyper-associated images into an episode via recalling and reporting dreams. We use a model of AM to account for the activation of memories in dreams as a reflection of sleep-dependent memory consolidation processes. We focus in particular on the hyperassociative nature of AM during sleep.

Memory sources of dreams: the incorporation of autobiographical rather than episodic experiences.

The present study aimed to explore autobiographical memories (long-lasting memories about the self) and episodic memories (memories about discrete episodes or events) within dream content. We adapted earlier episodic memory study paradigms and reinvestigated the incorporation of episodic memory sources into dreams, operationalizing episodic memory as featuring autonoetic consciousness, which is the feeling of truly re-experiencing or reliving a past event. Participants (n = 32) recorded daily diaries and dream diaries, and reported on wake-dream relations for 2 weeks. Using a new scale, dreams were rated for their episodic richness, which categorized memory sources of dreams as being truly episodic (featuring autonoetic consciousness), autobiographical (containing segregated features of experiences that pertained to waking life) or otherwise. Only one dream (0.5%) was found to contain an episodic memory. However, the majority of dreams (>80%) were found to contain low to moderate incorporations of autobiographical memory features. These findings demonstrate the inactivity of intact episodic memories, and emphasize the activity of autobiographical memory and processing within dreams. Taken together, this suggests that memories for personal experiences are experienced fragmentarily and selectively during dreaming, perhaps in order to assimilate these memories into the autobiographical memory schema.

Bear phalanx traumatically introduced into a living human: Prehistoric evidence.

Traumatically induced skeletal injuries are common and can be ascribed to a normal range of events occurring in an individual's lifetime. A subset of these trauma-induced injuries provides enhanced insight into cultural history. Such cases might include those referable to medico-surgical and religious/ritualistic practices. We describe prehistoric evidence and cultural implications of the traumatic insertion of an Ursus manual phalanx into the elbow of a living human. The injury healed and the phalanx remained in situ until death. The individual derives from the Ellis Landing shellmound and dates to a subphase of the Middle Period (≈500BC-300AD) in the California cultural sequence. The remains are of a 30-40 year-old female. Comparative data on arm morphology and pathological conditions present were collected (n=159). Three Ursus subspecies (n=15) were examined to identify the taxon represented by the phalanx. The described individual was probably wearing bear paw ornaments at the time she was crushed by a heavy object. During this event, a bear claw was driven into her cubital fossa, the basal phalangeal tubercle being impressed into the humerus. The wound healed completely. The presence of Ursus body parts indicates an elevated societal role for this female; most likely she was a shaman or healer.

Color changes in modern and fossil teeth induced by synchrotron microtomography.

Studies using synchrotron microtomography have shown that this radiographic imaging technique provides highly informative microanatomical data from modern and fossil bones and teeth without the need for physical sectioning. The method is considered to be nondestructive; however, researchers using the European Synchrotron Radiation Facility have reported that color changes sometimes occur in teeth during submicron scanning. Using the Advanced Light Source, we tested for color changes during micron-level scanning and for postexposure effects of ultraviolet light. We exposed a 2.0-mm wide strip (band) to synchrotron light in 32 specimens, using multiple energy levels and scan durations. The sample included modern and fossilized teeth and bone. After scanning, the specimens were exposed to fluorescent and direct ultraviolet light. All teeth showed color changes caused by exposure to synchrotron radiation. The resulting color bands varied in intensity but were present even at the lowest energy and shortest duration of exposure. Color bands faded during subsequent exposure to fluorescent and ultraviolet light, but even after extensive ultraviolet exposure, 67% (8/12) of UV-exposed teeth retained some degree of induced color. We found that the hydroxyapatite crystals, rather than the organic component, are the targets of change, and that diagenesis appears to impact color retention. Color changes have significance beyond aesthetics. They are visible indicators of ionization (chemical change) and, therefore, of potential physical damage. It is important for researchers to recognize that synchrotron microtomography may damage specimens, but adopting suitable safeguards and procedures may moderate or eliminate this damage.

A systematic survey of the response of a model NF-κB signalling pathway to TNFα stimulation.

White's lab established that strong, continuous stimulation with tumour necrosis factor-α (TNFα) can induce sustained oscillations in the subcellular localisation of the transcription factor nuclear factor κB (NF-κB). But the intensity of the TNFα signal varies substantially, from picomolar in the blood plasma of healthy organisms to nanomolar in diseased states. We report on a systematic survey using computational bifurcation theory to explore the relationship between the intensity of TNFα stimulation and the existence of sustained NF-κB oscillations. Using a deterministic model developed by Ashall et al. in 2009, we find that the system's responses to TNFα are characterised by a supercritical Hopf bifurcation point: above a critical intensity of TNFα the system exhibits sustained oscillations in NF-kB localisation. For TNFα below this critical value, damped oscillations are observed. This picture depends, however, on the values of the model's other parameters. When the values of certain reaction rates are altered the response of the signalling pathway to TNFα stimulation changes: in addition to the sustained oscillations induced by high-dose stimulation, a second oscillatory regime appears at much lower doses. Finally, we define scores to quantify the sensitivity of the dynamics of the system to variation in its parameters and use these scores to establish that the qualitative dynamics are most sensitive to the details of NF-κB mediated gene transcription.

Interactions among oscillatory pathways in NF-kappa B signaling.

BACKGROUND: Sustained stimulation with tumour necrosis factor alpha (TNF-alpha) induces substantial oscillations--observed at both the single cell and population levels--in the nuclear factor kappa B (NF-kappa B) system. Although the mechanism has not yet been elucidated fully, a core system has been identified consisting of a negative feedback loop involving NF-kappa B (RelA:p50 hetero-dimer) and its inhibitor I-kappa B-alpha. Many authors have suggested that this core oscillator should couple to other oscillatory pathways. RESULTS: First we analyse single-cell data from experiments in which the NF-kappa B system is forced by short trains of strong pulses of TNF-alpha. Power spectra of the ratio of nuclear-to-cytoplasmic concentration of NF-kappa B suggest that the cells' responses are entrained by the pulsing frequency. Using a recent model of the NF-kappa B system due to Caroline Horton, we carried out extensive numerical simulations to analyze the response frequencies induced by trains of pulses of TNF-alpha stimulation having a wide range of frequencies and amplitudes. These studies suggest that for sufficiently weak stimulation, various nonlinear resonances should be observable. To explore further the possibility of probing alternative feedback mechanisms, we also coupled the model to sinusoidal signals with a wide range of strengths and frequencies. Our results show that, at least in simulation, frequencies other than those of the forcing and the main NF-kappa B oscillator can be excited via sub- and superharmonic resonance, producing quasiperiodic and even chaotic dynamics. CONCLUSIONS: Our numerical results suggest that the entrainment phenomena observed in pulse-stimulated experiments is a consequence of the high intensity of the stimulation. Computational studies based on current models suggest that resonant interactions between periodic pulsatile forcing and the system's natural frequencies may become evident for sufficiently weak stimulation. Further simulations suggest that the nonlinearities of the NF-kappa B feedback oscillator mean that even sinusoidally modulated forcing can induce a rich variety of nonlinear interactions.

Physiological levels of TNFalpha stimulation induce stochastic dynamics of NF-kappaB responses in single living cells.

Nuclear factor kappa B (NF-kappaB) signalling is activated by cellular stress and inflammation and regulates cytokine expression. We applied single-cell imaging to investigate dynamic responses to different doses of tumour necrosis factor alpha (TNFalpha). Lower doses activated fewer cells and those responding showed an increasingly variable delay in the initial NF-kappaB nuclear translocation and associated IkappaBalpha degradation. Robust 100 minute nuclear:cytoplasmic NF-kappaB oscillations were observed over a wide range of TNFalpha concentrations. The result is supported by computational analyses, which identified a limit cycle in the system with a stable 100 minute period over a range of stimuli, and indicated no co-operativity in the pathway activation. These results suggest that a stochastic threshold controls functional all-or-nothing responses in individual cells. Deterministic and stochastic models simulated the experimentally observed activation threshold and gave rise to new predictions about the structure of the system and open the way for better mechanistic understanding of physiological TNFalpha activation of inflammatory responses in cells and tissues.

The self and dreams during a period of transition.

The content of dreams and changes to the self were investigated in students moving to University. In study 1, 20 participants completed dream diaries and memory tasks before and after they had left home and moved to university, and generated self images, "I am..." statements (e.g. I am an undergraduate), reflective of their current self. Changes in "I ams" were observed, indicating a newly-formed 'university' self. These self, images and related autobiographical knowledge were found to be incorporated into recent dreams but not into dreams from other periods. Study 2 replicated these findings in a different sample (N=55). We suggest that these data reflect a period of self-consolidation in which new experiences and self images are incorporated into autobiographical memory knowledge structures representing personal goals during sleep.

Pulsatile stimulation determines timing and specificity of NF-kappaB-dependent transcription.

The nuclear factor kappaB (NF-kappaB) transcription factor regulates cellular stress responses and the immune response to infection. NF-kappaB activation results in oscillations in nuclear NF-kappaB abundance. To define the function of these oscillations, we treated cells with repeated short pulses of tumor necrosis factor-alpha at various intervals to mimic pulsatile inflammatory signals. At all pulse intervals that were analyzed, we observed synchronous cycles of NF-kappaB nuclear translocation. Lower frequency stimulations gave repeated full-amplitude translocations, whereas higher frequency pulses gave reduced translocation, indicating a failure to reset. Deterministic and stochastic mathematical models predicted how negative feedback loops regulate both the resetting of the system and cellular heterogeneity. Altering the stimulation intervals gave different patterns of NF-kappaB-dependent gene expression, which supports the idea that oscillation frequency has a functional role.

Single live-cell imaging for systems biology.

Understanding how mammalian cells function requires a dynamic perspective. However, owing to the complexity of signalling networks, these non-linear systems can easily elude human intuition. The central aim of systems biology is to improve our understanding of the temporal complexity of cell signalling pathways, using a combination of experimental and computational approaches. Live-cell imaging and computational modelling are compatible techniques which allow quantitative analysis of cell signalling pathway dynamics. Non-invasive imaging techniques, based on the use of various luciferases and fluorescent proteins, trace cellular events such as gene expression, protein-protein interactions and protein localization in cells. By employing a number of markers in a single assay, multiple parameters can be measured simultaneously in the same cell. Following acquisition using specialized microscopy, analysis of multi-parameter time-lapse images facilitates the identification of important qualitative and quantitative relationships-linking intracellular signalling, gene expression and cell fate.