Learning and memory consolidation processes in children and adults: a<p>neurophysiological and neuropsychological investigation.<p><p>Sleep is a complex and active state of the brain, associated with essential functional changes<p>[1]. Accumulated evidence in the adult population indicates that sleep participates in the<p>consolidation of declarative (i.e. memory for facts and episodes) and procedural (i.e. skills<p>and habits) memory, allowing novel information to be integrated for the long term in cerebral<p>networks [2]. Whether sleep supports memory consolidation in children likewise and to the<p>same extent than in adults remains disputed. In this framework, I have developed<p>experiments aimed at investigating sleep-dependent consolidation processes both in children<p>and adults, using behavioral and neurophysiological techniques (magneto-encephalography<p>[MEG]; electro-encephalography [EEG]; functional magnetic resonance imaging [fMRI]). To<p>sum up, researches conducted during my PhD thesis have contributed to start unraveling<p>neurophysiological mechanisms participating in sleep-dependent consolidation processes.<p>On the one hand, I report that despite a lack of detectable behavioral differences, posttraining<p>sleep plays a role in reshaping the cerebral networks subtending implicit motor<p>sequence learning in adults [3]. I also showed using a motor adaptation task [4] that sleep<p>contributes to the consolidation of procedural memory in children [5]. On the other hand, I<p>have evidenced neuromagnetic correlates of learning novel semantic representations in<p>children [6-7], and is currently finalizing the analysis of the effect of a post-training nap on the<p>consolidation of these representations. Finally, I showed in epileptic children that interictal<p>epileptic discharges (IED) during sleep impairs declarative memory consolidation processes<p>[8-9], and that this phenomenon is reversible upon pharmacological treatment suppressing<p>IED. Altogether, these findings advocate the need to explore further memory consolidation<p>and its neurophysiological basis in children, both healthy and suffering from various brain<p>pathologies [10].<p>[1] Urbain C. Peigneux, P. & Schmitz R. Sleep and the Brain. (to appear). In The Oxford Handbook of<p>Sleep and Sleep Disorders. C. M. Morin and C. A. Espie (Eds.). Oxford University Press, Oxford, NY.<p>[2] Peigneux P. Schmitz R. & Urbain C. Sleep and Forgetting. In Forgetting. S. Della Sala (Ed.).<p>Psychology Press, Hove, UK. 2010. (pp. 165-184).<p>[3] Urbain C. Schmitz R. Schmidt C. Cleeremans A. Van Bogaert P. Maquet P. and Peigneux P.<p>(submitted). Neuroanatomical Sleep-Dependent Processing in the Probabilistic Serial Reaction Time<p>Task.<p>[4] Huber, R. Ghilardi, M.F. Massimini, M. And Tononi, G. Local sleep and learning. Nature, 2004,<p>430, 78-84.<p>[5] Urbain C. Houyoux E. Albouy G. Peigneux P. (in preparation). Sleep-dependent consolidation of<p>procedural learning in children.<p>[6] Urbain C. Schmitz R. Op De Beeck M. Bourguignon M. Galer S. X. De Tiège, Van Bogaert P.<p>and Peigneux P. (in preparation). How learning new meanings about novel objects modulates cerebral<p>activity in children: A MEG Study.<p>[7] Urbain C. Schmitz R. Bourguignon M. Op De Beeck M. Galer S, De Tiège X. Van Bogaert P.<p>Peigneux P. (2011). Learning and Fast-Mapping Meanings to Novel Object in Children: A MEG Study.<p>17th Annual Meeting of the Organization for Human Brain Mapping [HBM], 26-30 June 2011, Québec<p>City, Canada<p>[8] Urbain C. et al. Is sleep-related consolidation impaired in focal idiopathic epilepsies of childhood?<p>A pilot study, Epilepsy and Behavior, 2011, 22(2), 380-384.<p>[9] Van Bogaert P. Urbain C. Galer S. Ligot N. Peigneux P. and De Tiège X. Impact of focal<p>interictal epileptiform discharges on behaviour and cognition in children. Neurophysiologie<p>Clinique/Clinical Neurophysiology, 2012, 42(1–2), 53-58. / Doctorat en Sciences Psychologiques et de l'éducation / info:eu-repo/semantics/nonPublished

Indiana University-Purdue University Indianapolis (IUPUI) / Down syndrome (DS), a genetic disorder that affects ~1 in 700 live births, is caused by trisomy of human chromosome 21 (Hsa21). Individuals with DS are affected by a wide spectrum of phenotypes which vary in severity and penetrance. However, cognitive and skeletal impairments can be commonly observed in all individuals with DS. To study these phenotypes, we utilized the Ts65Dn mouse model that carries three copies of approximately half the gene orthologs found on Hsa21 and exhibit similar phenotypes as observed in humans with DS. Individuals with DS and Ts65Dn mice have deficits in bone mineral density (BMD), bone architecture, bone strength, learning and memory. Over-expression of DYRK1A, a serine-threonine kinase encoded on Hsa21, has been linked to deficiencies in DS bone homeostasis and cognition. Epigallocatechin-3-gallate (EGCG), an aromatic polyphenol found in high concentrations in green tea, is a selective inhibitor of DYRK1A activity. Normalization of DYRK1A activity by EGCG therefore may have the potential to ameliorate skeletal and cognitive deficits. We hypothesized that supplements containing EGCG obtained from health food stores/ online vendors will not be as effective as EGCG from a chemical company in correcting bone deficits associated with DS. Our results suggest that EGCG improves the bone mineral density of trisomic femurs significantly better than the supplements while the EGCgNOW supplement from NOW FOODS improves trabecular and cortical bone structure. The results from HPLC analysis of supplements showed the presence of other catechins in EGCgNOW and degradation analysis revealed the rapid degradation of supplements. Therefore we hypothesize that the presence of EGCG degradation products and other green tea catechins in supplements may play a role in the differential skeletal effects we observed. We further hypothesized that a three week treatment of adolescent mice with EGCG will lead to an improvement in the learning and memory deficits that are observed in trisomic animals in comparison to control mice. However, our results indicate that three weeks of low-dose EGCG treatment during adolescence is insufficient to improve hippocampal dependent learning and memory deficits of Ts65Dn mice. The possibility remains that a higher dose of EGCG that begins at three weeks but lasts throughout the behavioral test period may result in improvement in learning and memory deficit of Ts65Dn mice.

Indiana University-Purdue University Indianapolis (IUPUI) / The purpose of the current study was to investigate the impact of emotionality on the memory of children with an autism spectrum disorder. Although emotional events enhance memory in adults and children without an autism spectrum disorder, there are different memory patterns among individuals on the autism spectrum. Specifically, individuals with autism may show a decreased advantage in memory for emotional content and may have deficits in memory for information that is not presented visually. Currently, however, there are no studies that look at how emotional content affects memory specifically in children with autism. In the current study, children with and without autism were presented with stimuli contrasting emotional and neutral content using one of two modalities, auditory and visual, and then completed memory recognition tasks for the stimuli. Results indicate that children with an autism spectrum disorder did not demonstrate enhanced memory for emotional information. Rather, they were equally able to remember emotional and neutral stimuli. Additionally, individuals on the spectrum demonstrated better memory for visual stimuli compared to their neurotypical peers. These results support the notion that individuals with an autism spectrum disorder may learn and remember material differently than those without the disorder and that educators need to acknowledge these differences as children with autism spectrum disorders continue to be integrated into classroom settings.

Indiana University-Purdue University Indianapolis (IUPUI) / Methamphetamine (MA) is a widely abused psychostimulant that has been shown to evoke an array of neurobiological abnormalities and cognitive deficits in humans and in rodent models (Marshall & O'Dell, 2012). Alterations in cognitive function after repeated drug use may lead to impaired decision-making, a lack of behavioral control, and ultimately the inability to abstain from drug use. Human studies have shown that alterations in neurobiology resulting from prolonged MA use may lead to a number of cognitive deficits, including impairments in executive function, learning, memory, and impulsivity. These impairments, specifically those that engage the prefrontal cortex (PFC) or hippocampus (HC), may persist or recover based on the duration of abstinence. In rodents, repeated intermittent injections of MA yield protracted changes in neurobiology and behavior, which have been shown to effectively model a number of the biological and cognitive abnormalities observed in addiction. In order to assess the temporal evolution of impaired cognitive function throughout abstinence, sensitization was first induced in rats (7 x 5.0 mg/kg MA over 14 days). MA-treated rats initially exhibited a robust increase in locomotion that transitioned to stereotypy as the induction phase progressed. Then, the effects of MA sensitization on social interaction (SI), temporal order recognition (TOR) and novel object recognition (NOR) was assessed at one-day and 30-days post induction. No differences were observed in SI in either group or after a single injection of MA. However, an acute injection of 5.0 mg/kg of MA 30-minutes prior to testing dramatically reduced SI time. Impairments in TOR and NOR were observed in MA-treated rats after one day of abstinence, and impairments in TOR, but not NOR, were observed on day 30 of abstinence. No differences in TOR and NOR after a single injection of MA or saline were observed. These data establish that after 30 days of abstinence from a sensitizing regimen of MA, the ability to recall the temporal sequence that two stimuli were encountered was impaired and that was not attributable to impaired novelty detection. These data also suggest that at least some of the neurocognitive abnormalities caused by chronic MA administration may normalize after prolonged abstinence, since the ability to detect novelty recovered after 30 days of abstinence. These data provide compelling support that, since MA-sensitization caused temporal deficits in memory, PFC and HC function may be differentially impaired throughout the time course of abstinence.