Minocycline Synergizes with N-Acetylcysteine and Improves Cognition and Memory Following Traumatic Brain Injury in Rats

Background: There are no drugs presently available to treat traumatic brain injury (TBI). A variety of single drugs have failed clinical trials suggesting a role for drug combinations. Drug combinations acting synergistically often provide the greatest combination of potency and safety. The drugs examined (minocycline (MINO), N-acetylcysteine (NAC), simvastatin, cyclosporine A, and progesterone) had FDA-approval for uses other than TBI and limited brain injury in experimental TBI models. Methodology/Principal Findings: Drugs were dosed one hour after injury using the controlled cortical impact (CCI) TBI model in adult rats. One week later, drugs were tested for efficacy and drug combinations tested for synergy on a hierarchy of behavioral tests that included active place avoidance testing. As monotherapy, only MINO improved acquisition of the massed version of active place avoidance that required memory lasting less than two hours. MINO-treated animals, however, were impaired during the spaced version of the same avoidance task that required 24-hour memory retention. Coadministration of NAC with MINO synergistically improved spaced learning. Examination of brain histology 2 weeks after injury suggested that MINO plus NAC preserved white, but not grey matter, since lesion volume was unaffected, yet myelin loss was attenuated. When dosed 3 hours before injury, MINO plus NAC as single drugs had no effect on interleukin-1 formation; together they synergistically lowered interleukin-1 levels. This effect on interleukin-1 was not observed when th

MnemoCity Task: Assessment of Childrens Spatial Memory Using Stereoscopy and Virtual Environments

[EN] This paper presents the MnemoCity task, which is a 3D application that introduces the user into a totally 3D virtual environment to evaluate spatial short-term memory. A study has been carried out to validate the MnemoCity task for the assessment of spatial short-term memory in children, by comparing the children s performance in the developed task with current approaches. A total of 160 children participated in the study. The task incorporates two types of interaction: one based on standard interaction and another one based on natural interaction involving physical movement by the user. There were no statistically significant differences in the results of the task using the two types of interaction. Furthermore, statistically significant differences were not found in relation to gender. The correlations between scores were obtained using the MnemoCity task and a traditional procedure for assessing spatial short-term memory. Those results revealed that the type of interaction used did not affect the performance of children in the MnemoCity task.This work was funded mainly by the Spanish Ministry of Economy and Competitiveness (MINECO) through the CHILDMNEMOS project (TIN2012-37381-C02-01) and confinanced by the European Regional Development Fund (FEDER). Other financial support was received from the Gobierno de Aragon (Departamento de Industria e Innovacion), and Fondo Social Europeo for Aragon.Rodríguez-Andrés, D.; Juan, M.; Mendez Lopez, M.; Pérez Hernández, E.; Lluch Crespo, J. (2016). MnemoCity Task: Assessment of Childrens Spatial Memory Using Stereoscopy and Virtual Environments. PLoS ONE. 11(8):1-28. https://doi.org/10.1371/journal.pone.0161858S12811

Augmented Reality for the assessment of children's spatial memory in real settings

Short-term memory can be defined as the capacity for holding a small amount of information in mind in an active state for a short period of time. There are no available, specific, and adapted instruments to study the development of memory and spatial orientation in people while they are moving. In this paper, we present the ARSM (Augmented Reality Spatial Memory) task, the first Augmented Reality task that involves a user's movement to assess spatial short-term memory in healthy children. The experimental procedure of the ARSM task was designed to assess the children s skill to retain visuospatial information. They were individually asked to remember the real place where augmented reality objects were located. The children (N=76) were divided into two groups: preschool (5-6 year olds) and primary school (7-8 year olds). We found a significant improvement in ARSM task performance in the older group. The correlations between scores for the ARSM task and traditional procedures were significant. These traditional procedures were the Dot Matrix subtest for the assessment of visuospatial short-term memory of the computerized AWMA-2 battery and a parent s questionnaire about a child s everyday spatial memory. Hence, we suggest that the ARSM task has high verisimilitude with spatial short-term memory skills in real life. In addition, we evaluated the ARSM task s usability and perceived satisfaction. The study revealed that the younger children were more satisfied with the ARSM task. This novel instrument could be useful in detecting visuospatial short-term difficulties that affect school academic achievementFunded by the Spanish Government (MINECO) and European Regional Development Fund (FEDER) in the CHILDMNEMOS project TIN2012-37381-C02-01, Gobierno de Aragon (Dpt. Industria e Innovacion), Fondo Social Europeo, Fundacion Universitaria Antonio Gargallo and Obra Social Ibercaja. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Juan, M.; Mendez Lopez, M.; Pérez Hernández, E.; Albiol Pérez, S. (2014). Augmented Reality for the assessment of children's spatial memory in real settings. PLoS ONE. 9(12):113751-113771. https://doi.org/10.1371/journal.pone.0113751S113751113771912Linn, M. C., & Petersen, A. C. (1985). Emergence and Characterization of Sex Differences in Spatial Ability: A Meta-Analysis. Child Development, 56(6), 1479. doi:10.2307/1130467Simmons, F. R., Willis, C., & Adams, A.-M. (2012). Different components of working memory have different relationships with different mathematical skills. Journal of Experimental Child Psychology, 111(2), 139-155. doi:10.1016/j.jecp.2011.08.011Alloway, T. P., & Alloway, R. G. (2010). Investigating the predictive roles of working memory and IQ in academic attainment. Journal of Experimental Child Psychology, 106(1), 20-29. doi:10.1016/j.jecp.2009.11.003Bavin, E. L., Wilson, P. H., Maruff, P., & Sleeman, F. (2005). Spatio‐visual memory of children with specific language impairment: evidence for generalized processing problems. International Journal of Language & Communication Disorders, 40(3), 319-332. doi:10.1080/13682820400027750Szucs, D., Devine, A., Soltesz, F., Nobes, A., & Gabriel, F. (2013). Developmental dyscalculia is related to visuo-spatial memory and inhibition impairment. Cortex, 49(10), 2674-2688. doi:10.1016/j.cortex.2013.06.007Mammarella, I. C., & Cornoldi, C. (2013). An analysis of the criteria used to diagnose children with Nonverbal Learning Disability (NLD). Child Neuropsychology, 20(3), 255-280. doi:10.1080/09297049.2013.796920Alloway TP (2007) Automated Working Memory Assessment. London: The Psychological Corporation.Oades, R. D., & Isaacson, R. L. (1978). The development of food search behavior by rats: The effects of hippocampal damage and haloperidol. Behavioral Biology, 24(3), 327-337. doi:10.1016/s0091-6773(79)90184-6Morris, R. (1984). Developments of a water-maze procedure for studying spatial learning in the rat. Journal of Neuroscience Methods, 11(1), 47-60. doi:10.1016/0165-0270(84)90007-4Olton, D. S. (1987). The radial arm maze as a tool in behavioral pharmacology. Physiology & Behavior, 40(6), 793-797. doi:10.1016/0031-9384(87)90286-1Méndez-López, M., Méndez, M., López, L., & Arias, J. L. (2009). Sexually dimorphic c-Fos expression following spatial working memory in young and adult rats. Physiology & Behavior, 98(3), 307-317. doi:10.1016/j.physbeh.2009.06.006Munoz M, Morris RGM (2009) Episodic memory in animals. In:Squire LR editor. New Encyclopedia of Neuroscience. Oxford: Academic Press. pp.1173–1182.SHORE, D. I., STANFORD, L., MACINNES, W. J., KLEIN, R. M., & BROWN, R. E. (2001). Of mice and men: Virtual Hebb-Williams mazes permit comparison of spatial learning across species. Cognitive, Affective, & Behavioral Neuroscience, 1(1), 83-89. doi:10.3758/cabn.1.1.83Astur, R. S., Taylor, L. B., Mamelak, A. N., Philpott, L., & Sutherland, R. J. (2002). Humans with hippocampus damage display severe spatial memory impairments in a virtual Morris water task. Behavioural Brain Research, 132(1), 77-84. doi:10.1016/s0166-4328(01)00399-0Astur, R. S., Tropp, J., Sava, S., Constable, R. T., & Markus, E. J. (2004). Sex differences and correlations in a virtual Morris water task, a virtual radial arm maze, and mental rotation☆. Behavioural Brain Research, 151(1-2), 103-115. doi:10.1016/j.bbr.2003.08.024Sturz, B. R., & Bodily, K. D. (2010). Encoding of variability of landmark-based spatial information. Psychological Research, 74(6), 560-567. doi:10.1007/s00426-010-0277-4Cánovas, R., García, R. F., & Cimadevilla, J. M. (2011). Effect of reference frames and number of cues available on the spatial orientation of males and females in a virtual memory task. Behavioural Brain Research, 216(1), 116-121. doi:10.1016/j.bbr.2010.07.026Cimadevilla, J. M., Cánovas, R., Iribarne, L., Soria, A., & López, L. (2011). A virtual-based task to assess place avoidance in humans. Journal of Neuroscience Methods, 196(1), 45-50. doi:10.1016/j.jneumeth.2010.12.026Cheng, K. (1986). A purely geometric module in the rat’s spatial representation. Cognition, 23(2), 149-178. doi:10.1016/0010-0277(86)90041-7Burgess, N., Maguire, E. A., Spiers, H. J., & O’Keefe, J. (2001). A Temporoparietal and Prefrontal Network for Retrieving the Spatial Context of Lifelike Events. NeuroImage, 14(2), 439-453. doi:10.1006/nimg.2001.0806Burgess, N., Maguire, E. A., & O’Keefe, J. (2002). The Human Hippocampus and Spatial and Episodic Memory. Neuron, 35(4), 625-641. doi:10.1016/s0896-6273(02)00830-9Passolunghi, M. C., & Mammarella, I. C. (2011). Selective Spatial Working Memory Impairment in a Group of Children With Mathematics Learning Disabilities and Poor Problem-Solving Skills. Journal of Learning Disabilities, 45(4), 341-350. doi:10.1177/0022219411400746Thomas, E., Reeve, R., Fredrickson, A., & Maruff, P. (2011). Spatial memory and executive functions in children. Child Neuropsychology, 17(6), 599-615. doi:10.1080/09297049.2011.567980SPOONER, D., & PACHANA, N. (2006). Ecological validity in neuropsychological assessment: A case for greater consideration in research with neurologically intact populations. Archives of Clinical Neuropsychology, 21(4), 327-337. doi:10.1016/j.acn.2006.04.004Juan, M. C., Alcaniz, M., Monserrat, C., Botella, C., Banos, R. M., & Guerrero, B. (2005). Using Augmented Reality to Treat Phobias. IEEE Computer Graphics and Applications, 25(6), 31-37. doi:10.1109/mcg.2005.143Furió, D., González-Gancedo, S., Juan, M.-C., Seguí, I., & Costa, M. (2013). The effects of the size and weight of a mobile device on an educational game. Computers & Education, 64, 24-41. doi:10.1016/j.compedu.2012.12.015Juan MC, Furió D, Alem L, Ashworth P, Cano J (2011) ARGreenet and BasicGreenet: Two mobile games for learning how to recycle. Proceedings of the 19th International Conference on Computer Graphics, Visualization and Computer Vision. pp.25–32.Furió, D., González-Gancedo, S., Juan, M.-C., Seguí, I., & Rando, N. (2013). Evaluation of learning outcomes using an educational iPhone game vs. traditional game. Computers & Education, 64, 1-23. doi:10.1016/j.compedu.2012.12.001Albrecht, U.-V., Folta-Schoofs, K., Behrends, M., & von Jan, U. (2013). Effects of Mobile Augmented Reality Learning Compared to Textbook Learning on Medical Students: Randomized Controlled Pilot Study. Journal of Medical Internet Research, 15(8), e182. doi:10.2196/jmir.2497Liu, P.-H. E., & Tsai, M.-K. (2012). Using augmented-reality-based mobile learning material in EFL English composition: An exploratory case study. British Journal of Educational Technology, 44(1), E1-E4. doi:10.1111/j.1467-8535.2012.01302.xBaddeley AD (1986) Working memory. Oxford: Clarendon Press.Alloway TP (2012) Working Memory Assessment. Second Edi. London: Pearson Assessment.Kamphaus KW, Perez-Hernandez E, Sanchez-Sanchez F (2014) Cuestionario de Evaluación Clínica de la Memoria. In press. Madrid: TEA Ediciones.Smith, A. D., Gilchrist, I. D., & Hood, B. M. (2005). Children’s Search Behaviour in Large-Scale Space: Developmental Components of Exploration. Perception, 34(10), 1221-1229. doi:10.1068/p5270Piccardi, L., Palermo, L., Leonzi, M., Risetti, M., Zompanti, L., D’Amico, S., & Guariglia, C. (2014). The Walking Corsi Test (WalCT): A Normative Study of Topographical Working Memory in a Sample of 4- to 11-Year-Olds. The Clinical Neuropsychologist, 28(1), 84-96. doi:10.1080/13854046.2013.863976Gathercole, S. E., Pickering, S. J., Ambridge, B., & Wearing, H. (2004). The Structure of Working Memory From 4 to 15 Years of Age. Developmental Psychology, 40(2), 177-190. doi:10.1037/0012-1649.40.2.177Best, J. R., & Miller, P. H. (2010). A Developmental Perspective on Executive Function. Child Development, 81(6), 1641-1660. doi:10.1111/j.1467-8624.2010.01499.xBianchini, F., Incoccia, C., Palermo, L., Piccardi, L., Zompanti, L., Sabatini, U., … Guariglia, C. (2010). Developmental topographical disorientation in a healthy subject. Neuropsychologia, 48(6), 1563-1573. doi:10.1016/j.neuropsychologia.2010.01.025Iaria, G., & Barton, J. J. S. (2010). Developmental topographical disorientation: a newly discovered cognitive disorder. Experimental Brain Research, 206(2), 189-196. doi:10.1007/s00221-010-2256-9Lowe, P. A., Mayfield, J. W., & Reynolds, C. R. (2003). Gender differences in memory test performance among children and adolescents. Archives of Clinical Neuropsychology, 18(8), 865-878. doi:10.1093/arclin/18.8.865Barnfield, A. M. C. (1999). Development of Sex Differences in Spatial Memory. Perceptual and Motor Skills, 89(1), 339-350. doi:10.2466/pms.1999.89.1.339Alloway, T. P., Gathercole, S. E., Kirkwood, H., & Elliott, J. (2009). The working memory rating scale: A classroom-based behavioral assessment of working memory. Learning and Individual Differences, 19(2), 242-245. doi:10.1016/j.lindif.2008.10.003Injoque-Ricle, I., Calero, A. D., Alloway, T. P., & Burin, D. I. (2011). Assessing working memory in Spanish-speaking children: Automated Working Memory Assessment battery adaptation. Learning and Individual Differences, 21(1), 78-84. doi:10.1016/j.lindif.2010.09.012Jones, A., Scanlon, E., Tosunoglu, C., Morris, E., Ross, S., Butcher, P., & Greenberg, J. (1999). Contexts for evaluating educational software. Interacting with Computers, 11(5), 499-516. doi:10.1016/s0953-5438(98)00064-2Mayes, J. ., & Fowler, C. . (1999). Learning technology and usability: a framework for understanding courseware. Interacting with Computers, 11(5), 485-497. doi:10.1016/s0953-5438(98)00065-4Squires, D., & Preece, J. (1999). Predicting quality in educational software: Interacting with Computers, 11(5), 467-483. doi:10.1016/s0953-5438(98)00063-0Sun, P.-C., Tsai, R. J., Finger, G., Chen, Y.-Y., & Yeh, D. (2008). What drives a successful e-Learning? An empirical investigation of the critical factors influencing learner satisfaction. Computers & Education, 50(4), 1183-1202. doi:10.1016/j.compedu.2006.11.007Lee, S. J., Srinivasan, S., Trail, T., Lewis, D., & Lopez, S. (2011). Examining the relationship among student perception of support, course satisfaction, and learning outcomes in online learning. The Internet and Higher Education, 14(3), 158-163. doi:10.1016/j.iheduc.2011.04.001Lyons KE, Zelazo PD (2011) Monitoring, metacognition, and executive function: elucidating the role of self-reflection in the development of self-regulation. In:Benson Jeditor. Advances in Child Development and Behavior. Burlington: Academic Press. pp.379–412

BEDYN: development of a methodology to characterize the behaviour of composite structures under dynamic loading

The methodology of design of polymer-based composite structures under static loadings, and even fatigue loads, is quite mature and well stablished. However, for intermediate and high dynamic loading conditions, the methods are still under development and often limited to academic research levels, without any type of standardization. It is crucial to understand how the materials used in the aerospace sector behave under dynamic loadings. Composite materials may exhibit strain rate effects and the analysis tools based on static formulations could be far away from the actual material and structural response, therefore robust and industrial dedicated dynamic tests, analysis and modelling methods are then necessary to design and certify composite airframe structures. This is what the proposed project will deal with. The aim of BEDYN project is to address a methodology to properly characterize the dynamic behaviour up to rupture of thermoset polymer-based composite structures submitted to dynamic loading. BEDYN is a European granted Clean Sky 2 Joint Undertaking (JU).&nbsp

Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation

Adult hippocampal neurogenesis is a unique form of neural circuit plasticity that results in the generation of new neurons in the dentate gyrus (DG) throughout life 1, 2. Adult-born neurons exhibit heightened synaptic plasticity during their maturation 3 and can account for up to ten percent of the entire granule cell population 4. Moreover, levels of adult hippocampal neurogenesis are elevated by interventions associated with beneficial effects on cognition and mood such as learning 5, environmental enrichment 6, exercise 6 and chronic antidepressant treatment 7–10. Together, these properties of adult neurogenesis suggest that it may be harnessed to improve hippocampal functions. However, despite a substantial number of studies demonstrating that adult-born neurons are necessary for mediating specific cognitive functions 11 and some of the behavioural effects of antidepressants 8–10, 12, 13, it is unknown whether increasing adult hippocampal neurogenesis is sufficient to improve cognition and mood. Here we show that inducible genetic expansion of the population of adult-born neurons by enhancing their survival improves performance in a specific cognitive task in which an animal must distinguish between two similar contexts. Mice with increased adult hippocampal neurogenesis show normal object recognition, spatial learning, contextual fear conditioning and extinction learning but are more efficient in differentiating between overlapping contextual representations, suggestive of enhanced pattern separation. Furthermore, stimulation of adult hippocampal neurogenesis, when combined with an intervention such as voluntary exercise, produces a robust increase in exploratory behaviour. In contrast, increasing adult hippocampal neurogenesis, on its own, does not produce an anxiolytic or antidepressant-like behavioural response. Together, our findings suggest that strategies designed to specifically increase adult hippocampal neurogenesis, by targeting cell death of adult-born neurons or other means, may have therapeutic potential for reversing impairments in pattern separation such as that seen during normal aging 14, 15