PERFORMANCE OF TRANSGENIC TgTau-P301L MICE IN A 5-CHOICE SERIAL REACTION TIME TASK (5-CSRTT) AS A MODEL OF ALZHEIMER’S DISEASE

Alzheimer’s disease is increasing to epidemic levels with an estimated 36 million people affected worldwide (Wimo 2010). The aetiology of the disease is not known, which is hindering the progression of the treatment. This study is a longitudinal investigation into the performance of TgTauP301L mice as an animal model of Alzheimer’s disease on the computer automated touchscreen 5- choice serial reaction time task (5-CSRTT). TgTauP301L mice have a single tau mutation in the P301L gene and develop the tau pathology that represents the observed tauopathy in patients with Alzheimer’s disease. The aim of the investigation is to observe if tau pathology in the TgTauP301L mice causes a cognitive impairment in attention and executive function and at what stage this can be identified by the 5-CSRTT task. This will establish if the animals can be used as a therapeutic model for pre-clinical drug trials and help to identify an early indicator and intervention point in patients with Alzheimer’s disease. The animals have previously been studied at 5-months and no differences between performances of the TgTauP301L mice and wild type mice were found (unpublished data). This study measured the performance of the animals at 7- months which is when the tauopathy begins to develop in TgTauP301L mice (Murakami 2005). The results of this study showed that there was no deficit in the performance of the TgTauP301L compared to the wild type mice and there had been no change in the animals’ performance compared to at 5-months. The animals will be retested at 12-months once the pathology has extensively spread to see if the tauopathy causes a deficit in performance

Evolution of GluN2A/B cytoplasmic domains diversified vertebrate synaptic plasticity and behavior

Two genome duplications early in the vertebrate lineage expanded gene families, including GluN2 subunits of the NMDA receptor. Diversification between the four mammalian GluN2 proteins occurred primarily at their intracellular C−terminal domains (CTDs). To identify shared ancestral functions and diversified subunit−specific functions, we exchanged the exons encoding the GluN2A (also known as Grin2a) and GluN2B (also known as Grin2b) CTDs in two knock−in mice and analyzed the mice's biochemistry, synaptic physiology, and multiple learned and innate behaviors. The eight behaviors were genetically separated into four groups, including one group comprising three types of learning linked to conserved GluN2A/B regions. In contrast, the remaining five behaviors exhibited subunit−specific regulation. GluN2A/B CTD diversification conferred differential binding to cytoplasmic MAGUK proteins and differential forms of long−term potentiation. These data indicate that vertebrate behavior and synaptic signaling acquired increased complexity from the duplication and diversification of ancestral GluN2 gene

Typing performance of blind users:an analysis of touch behaviors, learning effect, and in-situ usage

Non-visual text-entry for people with visual impairments has focused mostly on the comparison of input techniques reporting on performance measures, such as accuracy and speed. While researchers have been able to establish that non-visual input is slow and error prone, there is little understanding on how to improve it. To develop a richer characterization of typing performance, we conducted a longitudinal study with five novice blind users. For eight weeks, we collected in-situ usage data and conducted weekly laboratory assessment sessions. This paper presents a thorough analysis of typing performance that goes beyond traditional aggregated measures of text-entry and reports on character-level errors and touch measures. Our findings show that users improve over time, even though it is at a slow rate (0.3 WPM per week). Substitutions are the most common type of error and have a significant impact on entry rates. In addition to text input data, we analyzed touch behaviors, looking at touch contact points, exploration movements, and lift positions. We provide insights on why and how performance improvements and errors occur. Finally, we derive some implications that should inform the design of future virtual keyboards for non-visual input. Categories and Subject Descriptors H.5.2 [Information Interfaces and Presentation]: User Interfaces- Input devices and strategies. K4.2 [Computers an

Impaired object-location learning and recognition memory but enhanced sustained attention in M2 muscarinic receptor-deficient mice

© 2018, The Author(s). Rationale: Muscarinic acetylcholine receptors are known to play key roles in mediating cognitive processes, and impaired muscarinic cholinergic neurotransmission is associated with normal ageing processes and Alzheimer’s disease. However, the specific contributions of the individual muscarinic receptor subtypes (M1–M5) to cognition are presently not well understood. Objectives: The aim of this study was to investigate the contribution of M2-type muscarinic receptor signalling to sustained attention, executive control and learning and memory. Methods: M2 receptor-deficient (M2−/−) mice were tested on a touchscreen-operated task battery testing visual discrimination, behavioural flexibility, object-location associative learning, attention and response control. Spontaneous recognition memory for real-world objects was also assessed. Results: We found that M2−/− mice showed an enhancement of attentional performance, but significant deficits on some tests of learning and memory. Executive control and visual discrimination were unaffected by M2-depletion. Conclusions: These findings suggest that M2 activation has heterogeneous effects across cognitive domains, and provide insights into how acetylcholine may support multiple specific cognitive processes through functionally distinct cholinergic receptor subtypes. They also suggest that therapeutics involving M2 receptor-active compounds should be assessed across a broad range of cognitive domains, as they may enhance some cognitive functions, but impair others

Feasibility of a second iteration wrist and hand supported training system for self-administered training at home in chronic stroke

Telerehabilitation allows continued rehabilitation at home after discharge. The use of rehabilitation technology supporting wrist and hand movements within a motivational gaming environment could enable patients to train independently and ultimately serve as a way to increase the dosage of practice. This has been previously examined in the European SCRIPT project using a first prototype, showing potential feasibility, although several usability issues needed further attention. The current study examined feasibility and clinical changes of a second iteration training system, involving an updated wrist and hand supporting orthosis and larger variety of games with respect to the first iteration. Nine chronic stroke patients with impaired arm and hand function were recruited to use the training system at home for six weeks. Evaluation of feasibility and arm and hand function were assessed before and after training. Median weekly training duration was 113 minutes. Participants accepted the six weeks of training (median Intrinsic Motivation Inventory = 4.4 points and median System Usability Scale = 73%). After training, significant improvements were found for the Fugl Meyer assessment, Action Research Arm Test and self-perceived amount of arm and hand use in daily life. These findings indicate that technology-supported arm and hand training can be a promising tool for self-administered practice at home after stroke.Final Accepted Versio

Human-powered smartphone assistance for blind people

Mobile devices are fundamental tools for inclusion and independence. Yet, there are still many open research issues in smartphone accessibility for blind people (Grussenmeyer and Folmer 2017). Currently, learning how to use a smartphone is non-trivial, especially when we consider that the need to learn new apps and accommodate to updates never ceases. When first transitioning from a basic feature-phone, people have to adapt to new paradigms of interaction. Where feature phones had a finite set of applications and functions, users can extend the possible functions and uses of a smartphone by installing new 3rd party applications. Moreover, the interconnectivity of these applications means that users can explore a seemingly endless set of workflows across applications. To that end, the fragmented nature of development on these devices results in users needing to create different mental models for each application. These characteristics make smartphone adoption a demanding task, as we found from our eight-week longitudinal study on smartphone adoption by blind people. We conducted multiple studies to characterize the smartphone challenges that blind people face, and found people often require synchronous, co-located assistance from family, peers, friends, and even strangers to overcome the different barriers they face. However, help is not always available, especially when we consider the disparity in each barrier, individual support network and current location. In this dissertation we investigated if and how in-context human-powered solutions can be leveraged to improve current smartphone accessibility and ease of use. Building on a comprehensive knowledge of the smartphone challenges faced and coping mechanisms employed by blind people, we explored how human-powered assistive technologies can facilitate use. The thesis of this dissertation is: Human-powered smartphone assistance by non-experts is effective and impacts perceptions of self-efficacy