Immobilization of cells by electrostatic droplet generation: a model system for potential application in medicine

The process of electrostatic extrusion as a method for cell immobilization was investigated that could be used for potential applications in medicine. An attempt was made to assess the effects of cell addition and polymer concentration on the overall entrapment procedure, ie, on each stage of immobilization: polymer-cell suspension rheological characteristics, electrostatic extrusion process, and the process of gelation. The findings should contribute to a better understanding of polymer–cell interactions, which could be crucial in possible medical treatments. Alginate–yeast was used as a model system for carrier-cells. The electrostatic extrusion was considered as a complex two-phase flow system and the effects of cell and alginate concentrations on the resulting microbead size and uniformity were assessed. Under investigated conditions, microbeads 50–600 μm in diameter were produced and the increase in both alginate and cell concentrations resulted in larger microbeads with higher standard deviations in size. We attempted to rationalize the findings by rheological characterization of the cell–alginate suspensions. Rheological characterization revealed non-Newtonian, pseudoplastic behavior of cell-alginate suspensions with higher viscosities at higher alginate concentrations. However, the presence of cells even at high concentrations (5×108 and 1×109 cells/mL) did not significantly affect the rheological properties of Na-alginate solution. Lastly, we investigated the kinetics of alginate gelation with respect to the quantity of Ca2+ ions and cell presence. The gelation kinetics were examined under conditions of limited supply with Ca2+ ions, which can be essential for immobilization of highly sensitive mammalian cells that require minimal exposure to CaCl2 solution. The molar ratio of G units to Ca2+ ions of 3.8:1 provided complete crosslinking, while the increase in alginate concentration resulted in prolonged gelation times but higher strength of the resulting gel. The cell presence decreased the rate of network formation as well as the strength of the obtained Ca-alginate hydrogel

Overnight consolidation aids the transfer of statistical knowledge from the medial temporal lobe to the striatum

Sleep is important for abstraction of the underlying principles (or gist) which bind together conceptually related stimuli, but little is known about the neural correlates of this process. Here, we investigate this issue using overnight sleep monitoring and functional magnetic resonance imaging (fMRI). Participants were exposed to a statistically structured sequence of auditory tones then tested immediately for recognition of short sequences which conformed to the learned statistical pattern. Subsequently, after consolidation over either 30min or 24h, they performed a delayed test session in which brain activity was monitored with fMRI. Behaviorally, there was greater improvement across 24h than across 30min, and this was predicted by the amount of slow wave sleep (SWS) obtained. Functionally, we observed weaker parahippocampal responses and stronger striatal responses after sleep. Like the behavioral result, these differences in functional response were predicted by the amount of SWS obtained. Furthermore, connectivity between striatum and parahippocampus was weaker after sleep, whereas connectivity between putamen and planum temporale was stronger. Taken together, these findings suggest that abstraction is associated with a gradual shift from the hippocampal to the striatal memory system and that this may be mediated by SWS

Increased Sleep Fragmentation Leads to Impaired Off-Line Consolidation of Motor Memories in Humans

A growing literature supports a role for sleep after training in long-term memory consolidation and enhancement. Consequently, interrupted sleep should result in cognitive deficits. Recent evidence from an animal study indeed showed that optimal memory consolidation during sleep requires a certain amount of uninterrupted sleep

Time- but not sleep-dependent consolidation promotes the emergence of cross-modal conceptual representations

Conceptual knowledge about objects comprises a diverse set of multi-modal and generalisable information, which allows us to bring meaning to the stimuli in our environment. The formation of conceptual representations requires two key computational challenges: integrating information from different sensory modalities and abstracting statistical regularities across exemplars. Although these processes are thought to be facilitated by offline memory consolidation, investigations into how cross-modal concepts evolve offline, over time, rather than with continuous category exposure are still missing. Here, we aimed to mimic the formation of new conceptual representations by reducing this process to its two key computational challenges and exploring its evolution over an offline retention period. Participants learned to distinguish between members of two abstract categories based on a simple one-dimensional visual rule. Underlying the task was a more complex hidden indicator of category structure, which required the integration of information across two sensory modalities. In two experiments we investigated the impact of time- and sleep-dependent consolidation on category learning. Our results show that offline memory consolidation facilitated cross-modal category learning. Surprisingly, consolidation across wake, but not across sleep showed this beneficial effect. By demonstrating the importance of offline consolidation the current study provided further insights into the processes that underlie the formation of conceptual representations

The consolidation of implicit sequence memory in obstructive sleep apnea

Obstructive Sleep Apnea (OSA) Syndrome is a relatively frequent sleep disorder characterized by disrupted sleep patterns. It is a well-established fact that sleep has beneficial effect on memory consolidation by enhancing neural plasticity. Implicit sequence learning is a prominent component of skill learning. However, the formation and consolidation of this fundamental learning mechanism remains poorly understood in OSA. In the present study we examined the consolidation of different aspects of implicit sequence learning in patients with OSA. We used the Alternating Serial Reaction Time task to measure general skill learning and sequence-specific learning. There were two sessions: a learning phase and a testing phase, separated by a 10-hour offline period with sleep. Our data showed differences in offline changes of general skill learning between the OSA and control group. The control group demonstrated offline improvement from evening to morning, while the OSA group did not. In contrast, we did not observe differences between the groups in offline changes in sequence-specific learning. Our findings suggest that disrupted sleep in OSA differently affects neural circuits involved in the consolidation of sequence learning

Cross-Modal Transfer of Statistical Information Benefits from Sleep

Extracting regularities from a sequence of events is essential for understanding our environment. However, there is no consensus regarding the extent to which such regularities can be generalised beyond the modality of learning. One reason for this could be the variation in consolidation intervals used in different paradigms, also including an opportunity to sleep. Using a novel statistical learning paradigm in which structured information is acquired in the auditory domain and tested in the visual domain over either 30min or 24hr consolidation intervals, we show that cross-modal transfer can occur, but this transfer is only seen in the 24hr group. Importantly, the extent of cross-modal transfer is predicted by the amount of SWS obtained. Additionally, cross-modal transfer is associated with the same pattern of decreasing MTL and increasing striatal involvement which has previously been observed to occur across 24 hours in unimodal statistical learning. We also observed enhanced functional connectivity after 24 hours in a network of areas which have been implicated in cross-modal integration including the precuneus and the middle occipital gyrus. Finally, functional connectivity between the striatum and the precuneus was also enhanced, and this strengthening was predicted by SWS. These results demonstrate that statistical learning can generalise to some extent beyond the modality of acquisition, and together with our previously published unimodal results, support the notion that statistical learning is both domain-general and domain-specific

Sleep’s Role in Schema Learning and Creative Insights

Purpose of Review A recent resurgence of interest in schema theory has influenced research on sleep-dependent memory consolidation and led to a new understanding of how schemata might be activated during sleep and play a role in the reorganisation of memories. This review aims to synthesise recent findings into a coherent narrative and draw overall conclusions. Recent Findings Rapid consolidation of schematic memories has been shown to benefit from an interval containing sleep. These memories have shown reduced reliance on the hippocampus following consolidation in both humans and rodents. Using a variety of methodologies, notably including the DRM paradigm, it has been shown that activation of a schema can increase the rate of false memory as a result of activation of semantic associates during slow wave sleep (SWS). Memories making use of a schema have shown increased activity in the medial prefrontal cortex, which may reflect both the schematic activation itself and a cognitive control component selecting an appropriate schema to use. SWS seems to be involved in assimilation of new memories within existing semantic frameworks and in making memories more explicit, while REM sleep may be more associated with creating entirely novel associations while keeping memories implicit. Summary Sleep plays an important role in schematic memory consolidation, with more rapid consolidation, reduced hippocampal involvement and increased prefrontal involvement as the key characteristics. Both SWS and REM sleep may have a role to play