Long-term Effects of Cholestatic Liver Disease in Childhood on Neuropsychological Outcomes and Neurochemistry.

OBJECTIVES: Children with liver disease have increased risk of long-term cognitive deficits. We differentiated between the effects of chronic liver disease from that associated with transplantation by recruiting children with cholestatic liver disease (CLD) with and without transplantation. METHODS: Psychometric measures and magnetic resonance spectroscopy were obtained for 3 groups of children: stable liver disease without transplantation; CLD from birth with transplantation; and individuals healthy to 18 months of age, before transplantation for acute liver failure. RESULTS: Cognitive outcomes between children with different disease histories were significantly associated with the duration of liver disease but not the effects of transplantation, including that of immunosuppression. Lower intellectual ability was most frequently observed in the CLD group, whereas all of the acute liver failure group scored within the normal range. Myoinositol and glutamate/glutamine concentrations in cortex were significantly associated with disease duration across the cohort. Neurometabolite profiles in stable liver disease were consistent with subclinical encephalopathy. Impaired growth in early childhood was associated with later cognitive performance. CONCLUSION: Children with prolonged liver disease had the poorest cognitive outcomes despite successful transplantation, suggesting that prolonged cholestasis before transplantation adversely affects neurodevelopment, and reinforces the need for timely interventions.

Developing a User-Centred Planning Tool for Young Adults with Development Disorders: A Research-Based Teaching Project.

People with development disorders, for instance autism, need structured plans to help create predictability in their daily lives. Digital plans can facilitate enhanced independency, learning, and quality of life, but existing apps are largely general purpose and lack the flexibility required by this specific but heterogeneous user group. Universal design is both a goal and a process and should be based on a holistic approach and user-centered design, interacting with the users in all stages of the development process. At Oslo and Akershus University College (HiOA) we conducted a research-based teaching project in co-operation with the Department of Neuro-habilitation at Oslo University Hospital (OUS) with two employees acting as project managers and students as developers. Three groups of Computer Science bachelor students developed digital prototypes for a planning tool for young adults with pervasive development disorders, who live either with their families or in supervised residences, and do not receive extensive public services. The students conducted the initial planning phase of the software development process, focusing on prototyping the system requirements, whilst a professional software company programmed the end solution. The goal of the project was to develop flexible and adaptive user-oriented and user-specific app solutions for tablets that can aid this diverse user group in structuring daily life, whereby, for example, photos of objects and places known to the individual user replace general pictures or drawings, and checklists can be elaborate or sparse as necessary. The three student groups worked independently of each other and created interactive working prototypes based on tests, observations and short interviews with end users (both administrators and residents) and regular user feedback from the project managers. Three very different solutions were developed that were of high enough quality that an external software company were able to continue the work and create a beta version of the app. The first phase in software development process is always challenging and time consuming. Using a research-based teaching approach allowed us to not only save time and expense in the development phase, but, importantly, allowed us to thoroughly investigate a variety of aspects of the problem to create an accessible solution, whilst leveraging our students' knowledge, competencies and creativity. The next stage will be to evaluate the beta version of the app and study its impact on the user's quality of life. Although the end solution is designed for a specific user group, the built-in flexibility of its structure and function means there is the inherent potential to open it up to all users. The universal benefit lies in the flexibility of the solution.

Moderate relationships between NAA and cognitive ability in healthy adults: implications for cognitive spectroscopy.

BACKGROUND: Proton Magnetic Resonance Spectroscopy ((1)H-MRS) is a non-invasive imaging technique that enables quantification of neurochemistry in vivo and thereby facilitates investigation of the biochemical underpinnings of human cognitive variability. Studies in the field of cognitive spectroscopy have commonly focused on relationships between measures of N-acetyl aspartate (NAA), a surrogate marker of neuronal health and function, and broad measures of cognitive performance, such as IQ. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used (1)H-MRS to interrogate single-voxels in occipitoparietal and frontal cortex, in parallel with assessments of psychometric intelligence, in a sample of 40 healthy adult participants. We found correlations between NAA and IQ that were within the range reported in previous studies. However, the magnitude of these effects was significantly modulated by the stringency of data screening and the extent to which outlying values contributed to statistical analyses. CONCLUSIONS/SIGNIFICANCE: (1)H-MRS offers a sensitive tool for assessing neurochemistry non-invasively, yet the relationships between brain metabolites and broad aspects of human behavior such as IQ are subtle. We highlight the need to develop an increasingly rigorous analytical and interpretive framework for collecting and reporting data obtained from cognitive spectroscopy studies of this kind.