A cluster-randomised, controlled trial of the impact of Cogmed Working Memory Training on both academic performance and regulation of social, emotional and behavioural challenges.

BACKGROUND: We explored whether school-based Cogmed Working Memory Training (CWMT) may optimise both academic and psychological outcomes at school. Training of executive control skills may form a novel approach to enhancing processes that predict academic achievement, such as task-related attention, and thereby academic performance, but also has the potential to improve the regulation of emotion, social problems and behavioural difficulties. METHODS: Primary school children (Mean age = 12 years, N = 148) were cluster-randomised to complete active CWMT, a nonadaptive/placebo version of CWMT, or no training. RESULTS: No evidence was found for training effects on task-related attention when performing academic tasks, or performance on reading comprehension and mathematics tasks, or teacher-reported social, emotional and behavioural difficulties. CONCLUSIONS: CWMT did not improve control of attention in the classroom, or regulation of social, emotional and behavioural difficulties.

From scientific theory to classroom practice.

The importance of neuroscience in education is becoming widely recognized by both neuroscientists and educators. However, to date, there has been little effective collaboration between the two groups, resulting in the spread of ideas in education poorly based on neuroscience. For their part, educators are often too busy to develop sufficient scientific literacy, and neuroscientists are put off collaborations with risk of overinterpretation of their work. We designed and led a successful 6-month collaborative project between educators and neuroscientists. The project consisted of a series of seminars on topics chosen by both parties such as the neuroscience of attention, learning, and memory and aimed to create a dialog between the two. Here, we report that all teachers found the seminars relevant to their practice and that the majority felt the information was presented in an accessible manner. Such was the success of the project that teachers felt there were direct changes in their classroom practice as a consequence and that the course should be more widely available. We suggest that this format of co-constructed dialog allows for lucrative collaborations between neuroscientists and educators and may be a step to bridging the waters that separate these intrinsically linked disciplines.

Impact of detergents on the activity of acetylcholinesterase and on the effectiveness of its inhibitors.

Acetylcholinesterase (AChE) plays a central role in the development of Alzheimer's disease: AChE inhibition for preventing the characteristic dwindling of acetylcholine levels constitutes the current standard treatment for the disorder. Amongst the diverse risk factors contributing to the degenerative process, high cholesterol causes a reduction in the effectiveness of the otherwise therapeutic inhibitors of AChE. Our biochemical study on the activity of AChE elucidates the effect of amphiphilic molecules on the activity and kinetics of AChE, and sheds light onto the nature of the impact of these amphiphilic molecules on enzyme-inhibitor interactions. Using kinetic studies we discovered that detergents alter the enzymatic activity of AChE through an uncompetitive mechanism. Additional experiments using AChE inhibitors (amphiphilic procaine hydrochloride, hydrophobic tetrabutylammonium bromide) in the absence or presence of detergent further illustrate the detergent-enzyme-solvent interactions. The results contribute to the understanding of the importance of hydrophobic-lipophilic interactions for the correct function of AChE and its inhibitors. We present a model system for the study of lipid-related alterations in the activity of isolated AChE in the central nervous system. This model may also be used to assess and predict the effectiveness of AChE inhibitors, which are traditionally used for the treatment of cognitive impairment, under pathological (high-cholesterol) conditions.

Methylphenidate amplifies long-term plasticity in the hippocampus via noradrenergic mechanisms.

Methylphenidate treatment is used for Attention Deficit Hyperactivity Disorder and can improve learning and memory. Previously, improvements were considered a by-product of increased attention; however, we hypothesize that methylphenidate directly alters mechanisms underlying learning and memory, and therefore examined its effects on hippocampal long-term potentiation and long-term depression. Methylphenidate enhanced both mechanisms in the absence of presynaptic changes and in a noradrenalin beta-receptor-dependent manner. These findings can explain both the improved learning and memory and decreased learning selectivity found with methylphenidate treatment and constitute the first demonstration of direct actions of methylphenidate on mechanisms implicated in cognition.

Selective enhancement of the activity of C-terminally truncated, but not intact, acetylcholinesterase.

Acetylcholinesterase (AChE) is one of the fastest enzymes approaching the catalytic limit of enzyme activity. The enzyme is involved in the terminal breakdown of the neurotransmitter acetylcholine, but non-enzymatic roles have also been described for the entire AChE molecule and its isolated C-terminal sequences. These non-cholinergic functions have been attributed to both the developmental and degenerative situation: the major form of AChE present in these conditions is monomeric. Moreover, AChE has been shown to lose its typical characteristic of substrate inhibition in both development and degeneration. This study characterizes a form of AChE truncated after amino acid 548 (T548-AChE), whose truncation site is homologue to that of a physiological form of T-AChE detected in fetal bovine serum that has lost its C-terminal moiety supposedly due to proteolytic cleavage. Peptide sequences covered by this C-terminal sequence have been shown to be crucially involved in both developmental and degenerative mechanisms in vitro. Numerous studies have addressed the structure-function relationship of the AChE C-terminus with T548-AChE representing one of the most frequently studied forms of truncated AChE. In this study, we provide new insight into the understanding of the functional characteristics that T548-AChE acquires in solution: T548-AChE is incubated with agents of varying net charge and molecular weight. Together with kinetic studies and an analysis of different molecular forms and aggregation states of T548-AChE, we show that the enzymatic activity of T548-AChE, an enzyme verging at its catalytic limit is, nonetheless, apparently enhanced by up to 800%. We demonstrate, first, how the activity of T548-AChE can be enhanced through agents that contain highly positive charged moieties. Moreover, the un-competitive mechanism of activity enhancement most likely involves the peripheral anionic site of AChE that is reflected in delayed substrate inhibition being observed for activity enhanced T548-AChE. The data provides evidence towards a mechanistic and functional link between the form of AChE unique to both development and degeneration and a C-terminal peptide of T-AChE acting under those conditions.

A multifaceted approach to neuroscience outreach: meeting the challenges.

UK government targets aim for 50% of 18- to 30-year-olds entering higher education; however, with the vast choice of subjects to study available at this level, it is important to help pupils make informed decisions. As part of this process, awareness of newer fields such as neuroscience, which is not on the syllabus for science at school, needs to be promoted. Various challenges face neuroscientists working with visiting school pupils, including the lack of appropriate teaching resources, the culture and language barrier, and the risk of misinterpretation through oversimplification. The authors have designed a workshop to promote neuroscience and related scientific issues with school pupils aged 16 to 18 years. Pupil feedback showed that awareness of options within science increased after the workshop. The workshop also used resources taken from an undergraduate course successfully, demonstrating that appropriate resources are already available. A practical session using human brains was most popular, with all pupils believing it to be thought provoking and interesting. The final session aimed to challenge stereotypes within science, and despite the lowest pupil ratings overall, the majority agreed this aim was met. Pupils reported that the workshop was interesting and that the information about options within science useful. The most impressive outcome was that, although no pupil recorded less inclination to continue in science following the workshop, 46% said that they were more likely to do so. These data confirm the importance of outreach work for pupils' interest and career choice.