Use of nonintrusive sensor-based information and communication technology for real-world evidence for clinical trials in dementia

Cognitive function is an important end point of treatments in dementia clinical trials. Measuring cognitive function by standardized tests, however, is biased toward highly constrained environments (such as hospitals) in selected samples. Patient-powered real-world evidence using information and communication technology devices, including environmental and wearable sensors, may help to overcome these limitations. This position paper describes current and novel information and communication technology devices and algorithms to monitor behavior and function in people with prodromal and manifest stages of dementia continuously, and discusses clinical, technological, ethical, regulatory, and user-centered requirements for collecting real-world evidence in future randomized controlled trials. Challenges of data safety, quality, and privacy and regulatory requirements need to be addressed by future smart sensor technologies. When these requirements are satisfied, these technologies will provide access to truly user relevant outcomes and broader cohorts of participants than currently sampled in clinical trials

Information and communication technology solutions for outdoor navigation in dementia

INTRODUCTION: Information and communication technology (ICT) is potentially mature enough to empower outdoor and social activities in dementia. However, actual ICT-based devices have limited functionality and impact, mainly limited to safety. What is an ideal operational framework to enhance this field to support outdoor and social activities? METHODS: Review of literature and cross-disciplinary expert discussion. RESULTS: A situation-aware ICT requires a flexible fine-tuning by stakeholders of system usability and complexity of function, and of user safety and autonomy. It should operate by artificial intelligence/machine learning and should reflect harmonized stakeholder values, social context, and user residual cognitive functions. ICT services should be proposed at the prodromal stage of dementia and should be carefully validated within the life space of users in terms of quality of life, social activities, and costs. DISCUSSION: The operational framework has the potential to produce ICT and services with high clinical impact but requires substantial investment

The Neuroscience of Moral Judgment: Empirical and Philosophical Developments

We chart how neuroscience and philosophy have together advanced our understanding of moral judgment with implications for when it goes well or poorly. The field initially focused on brain areas associated with reason versus emotion in the moral evaluations of sacrificial dilemmas. But new threads of research have studied a wider range of moral evaluations and how they relate to models of brain development and learning. By weaving these threads together, we are developing a better understanding of the neurobiology of moral judgment in adulthood and to some extent in childhood and adolescence. Combined with rigorous evidence from psychology and careful philosophical analysis, neuroscientific evidence can even help shed light on the extent of moral knowledge and on ways to promote healthy moral development

Are developmental disorders like cases of adult brain damage? Implications from connectionist modelling

It is often assumed that similar domain-specific behavioural impairments found in cases of adult brain damage and developmental disorders correspond to similar underlying causes, and can serve as convergent evidence for the modular structure of the normal adult cognitive system. We argue that this correspondence is contingent on an unsupported assumption that atypical development can produce selective deficits while the rest of the system develops normally (Residual Normality), and that this assumption tends to bias data collection in the field. Based on a review of connectionist models of acquired and developmental disorders in the domains of reading and past tense, as well as on new simulations, we explore the computational viability of Residual Normality and the potential role of development in producing behavioural deficits. Simulations demonstrate that damage to a developmental model can produce very different effects depending on whether it occurs prior to or following the training process. Because developmental disorders typically involve damage prior to learning, we conclude that the developmental process is a key component of the explanation of endstate impairments in such disorders. Further simulations demonstrate that in simple connectionist learning systems, the assumption of Residual Normality is undermined by processes of compensation or alteration elsewhere in the system. We outline the precise computational conditions required for Residual Normality to hold in development, and suggest that in many cases it is an unlikely hypothesis. We conclude that in developmental disorders, inferences from behavioural deficits to underlying structure crucially depend on developmental conditions, and that the process of ontogenetic development cannot be ignored in constructing models of developmental disorders

What can developmental disorders tell us about the neurocomputational constraints that shape development? the case of Williams syndrome

The uneven cognitive phenotype in the adult outcome of Williams syndrome has led some researchers to make strong claims about the modularity of the brain and the purported genetically determined, innate specification of cognitive modules. Such arguments have particularly been marshaled with respect to language. We challenge this direct generalization from adult phenotypic outcomes to genetic specification and consider instead how genetic disorders provide clues to the constraints on plasticity that shape the outcome of development. We specifically examine behavioral studies, brain imaging, and computational modeling of language in Williams syndrome but contend that our theoretical arguments apply equally to other cognitive domains and other developmental disorders. While acknowledging that selective deficits in normal adult patients might justify claims about cognitive modularity, we question whether similar, seemingly selective deficits found in genetic disorders can be used to argue that such cognitive modules are prespecified in infant brains. Cognitive modules are, in our view, the outcome of development, not its starting point. We note that most work on genetic disorders ignores one vital factor, the actual process of ontogenetic development, and argue that it is vital to view genetic disorders as proceeding under different neurocomputational constraints, not as demonstrations of static modularity

Digital Oculomotor Biomarkers in Dementia

Dementia is an umbrella term that covers a number of neurodegenerative syndromes featuring gradual disturbance of various cognitive functions that are severe enough to interfere with tasks of daily life. The diagnosis of dementia occurs frequently when pathological changes have been developing for years, symptoms of cognitive impairment are evident and the quality of life of the patients has already been deteriorated significantly. Although brain imaging and fluid biomarkers allow the monitoring of disease progression in vivo, they are expensive, invasive and not necessarily diagnostic in isolation. Recent studies suggest that eye-tracking technology is an innovative tool that holds promise for accelerating early detection of the disease, as well as, supporting the development of strategies that minimise impairment during every day activities. However, the optimal methods for quantitative evaluation of oculomotor behaviour during complex and naturalistic tasks in dementia have yet to be determined. This thesis investigates the development of computational tools and techniques to analyse eye movements of dementia patients and healthy controls under naturalistic and less constrained scenarios to identify novel digital oculomotor biomarkers. Three key contributions are made. First, the evaluation of the role of environment during navigation in patients with typical Alzheimer disease and Posterior Cortical Atrophy compared to a control group using a combination of eye movement and egocentric video analysis. Secondly, the development of a novel method of extracting salient features directly from the raw eye-tracking data of a mixed sample of dementia patients during a novel instruction-less cognitive test to detect oculomotor biomarkers of dementia-related cognitive dysfunction. Third, the application of unsupervised anomaly detection techniques for visualisation of oculomotor anomalies during various cognitive tasks. The work presented in this thesis furthers our understanding of dementia-related oculomotor dysfunction and gives future research direction for the development of computerised cognitive tests and ecological interventions

Co-designing smart home technology with people with dementia or Parkinson's disease

Involving users is crucial to designing technology successfully, especially for vulnerable users in health and social care, yet detailed descriptions and critical reflections on the co-design process, techniques and methods are rare. This paper introduces the PERCEPT (PERrsona-CEntred Participatory Technology) approach for the co-design process and we analyse and discuss the lessons learned for each step in this process. We applied PERCEPT in a project to develop a smart home toolset that will allow a person living with early stage dementia or Parkinson's to plan, monitor and self-manage his or her life and well-being more effectively. We present a set of personas which were co-created with people and applied throughout the project in the co-design process. The approach presented in this paper will enable researchers and designers to better engage with target user groups in co-design and point to considerations to be made at each step for vulnerable users

Models of atypical development must also be models of normal development

Functional magnetic resonance imaging studies of developmental disorders and normal cognition that include children are becoming increasingly common and represent part of a newly expanding field of developmental cognitive neuroscience. These studies have illustrated the importance of the process of development in understanding brain mechanisms underlying cognition and including children ill the study of the etiology of developmental disorders

Opportunities for multiscale computational modelling of serotonergic drug effects in Alzheimer’s disease

Alzheimer's disease (AD) is an age-specific neurodegenerative disease that compromises cognitive functioning and impacts the quality of life of an individual. Pathologically, AD is characterised by abnormal accumulation of beta-amyloid (A$\beta$) and hyperphosphorylated tau protein. Despite research advances over the last few decades, there is currently still no cure for AD. Although, medications are available to control some behavioural symptoms and slow the disease's progression, most prescribed medications are based on cholinesterase inhibitors. Over the last decade, there has been increased attention towards novel drugs, targeting alternative neurotransmitter pathways, particularly those targeting serotonergic (5-HT) system. In this review, we focused on 5-HT receptor (5-HTR) mediated signalling and drugs that target these receptors. These pathways regulate key proteins and kinases such as GSK-3 that are associated with abnormal levels of A$\beta$ and tau in AD. We then review computational studies related to 5-HT signalling pathways with the potential for providing deeper understanding of AD pathologies. In particular, we suggest that multiscale and multilevel modelling approaches could potentially provide new insights into AD mechanisms, and towards discovering novel 5-HTR based therapeutic targets.Comment: Accepted manuscript in Neuropharmacolog