Towards a cognitive neurobiology of brain-gut axis disorders

The past two decades have seen substantial gains in our understanding of the complex processes underlying disturbed brain-gut communication in disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Despite a growing understanding of the neurobiology of brain-gut axis dysfunction, there is a relative paucity of investigations into how the various factors involved in dysregulating the brain-gut axis, including stress, immune activation and pain, could impact on fundamental brain processes such as cognitive performance. To this end, we proposed a cognitive neurobiology of brain-gut axis dysfunction and took a novel approach to examine how disturbed brain-gut interactions may manifest as altered cognitive performance in IBS and IBD, both cross-sectionally and prospectively. We have demonstrated that, disorders of the brain-gut axis are characterised by stable deficits in specific cognitive domains. Specifically, patients with IBS exhibit a consistent hippocampal mediated visuospatial memory impairment. In addition we have found evidence to suggest a similar visuospatial impairment in IBD. However, our most consistent finding within this population was that patients with Crohn’s disease exhibit impaired selective attention/ response inhibition on the classic Stroop interference test. These cognitive deficits may serve to perpetuate and sustain brain-gut axis dysfunction. Furthermore, this research has shed light on some of the underlying neurobiological mechanisms that may be mediating cognitive dysfunction in IBS. Our findings may have significant implications for the individual who suffers from a brain-gut axis disorder and may also inform future treatment strategies. Taken together, these findings can be incorporated into existing neurobiological models of brain-gut axis dysfunction, to develop a more comprehensive model accounting for the cognitive-neurobiology of brain-gut axis disorders. This has furthered our understanding of disease pathophysiology and may ultimately aid in both the diagnosis and treatment of these highly prevalent, but poorly understood disorders.

MyRoom: A user-centred model of affective responsive architecture

Can my immediate physical environment affect how I feel? The instinctive answer to this question must be a resounding “yes”. What might seem a throwaway remark is increasingly borne out by research in environmental and behavioural psychology, and in the more recent discipline of Evidence-Based Design. Research outcomes are beginning to converge with findings in neuroscience and neurophysiology, as we discover more about how the human brain and body functions, and reacts to environmental stimuli. What we see, hear, touch, and sense affects each of us psychologically and, by extension, physically, on a continual basis. The physical characteristics of our daily environment thus have the capacity to profoundly affect all aspects of our functioning, from biological systems to cognitive ability. This has long been understood on an intuitive basis, and utilised on a more conscious basis by architects and other designers. Recent research in evidence-based design, coupled with advances in neurophysiology, confirm what have been previously held as commonalities, but also illuminate an almost frightening potential to do enormous good, or alternatively, terrible harm, by virtue of how we make our everyday surroundings. The thesis adopts a design methodology in its approach to exploring the potential use of wireless sensor networks in environments for elderly people. Vitruvian principles of “commodity, firmness and delight” inform the research process and become embedded in the final design proposals and research conclusions. The issue of person-environment fit becomes a key principle in describing a model of continuously-evolving responsive architecture which makes the individual user its focus, with the intention of promoting wellbeing. The key research questions are: What are the key system characteristics of an adaptive therapeutic single-room environment? How can embedded technologies be utilised to maximise the adaptive and therapeutic aspects of the personal life-space of an elderly person with dementia?.

Towards a model for exploring the relationship between managerial decision problems and decision support opportunities

The organisational decision making environment is complex, and decision makers must deal with uncertainty and ambiguity on a continuous basis. Managing and handling decision problems and implementing a solution, requires an understanding of the complexity of the decision domain to the point where the problem and its complexity, as well as the requirements for supporting decision makers, can be described. Research in the Decision Support Systems domain has been extensive over the last thirty years with an emphasis on the development of further technology and better applications on the one hand, and on the other hand, a social approach focusing on understanding what decision making is about and how developers and users should interact. This research project considers a combined approach that endeavours to understand the thinking behind managers’ decision making, as well as their informational and decisional guidance and decision support requirements. This research utilises a cognitive framework, developed in 1985 by Humphreys and Berkeley that juxtaposes the mental processes and ideas of decision problem definition and problem solution that are developed in tandem through cognitive refinement of the problem, based on the analysis and judgement of the decision maker. The framework facilitates the separation of what is essentially a continuous process, into five distinct levels of abstraction of manager’s thinking, and suggests a structure for the underlying cognitive activities. Alter (2004) argues that decision support provides a richer basis than decision support systems, in both practice and research. The constituent literature on decision support, especially in regard to modern high profile systems, including Business Intelligence and Business analytics, can give the impression that all ‘smart’ organisations utilise decision support and data analytics capabilities for all of their key decision making activities. However this empirical investigation indicates a very different reality.

Cognitive dysfunction in Duchenne muscular dystrophy: a possible role for neuromodulatory immune molecules

Duchenne muscular dystrophy (DMD) is an X chromosome-linked disease characterized by progressive physical disability, immobility, and premature death in affected boys. Underlying the devastating symptoms of DMD is the loss of dystrophin, a structural protein that connects the extracellular matrix to the cell cytoskeleton and provides protection against contraction-induced damage in muscle cells, leading to chronic peripheral inflammation. However, dystrophin is also expressed in neurons within specific brain regions, including the hippocampus, a structure associated with learning and memory formation. Linked to this, a subset of boys with DMD exhibit nonprogressing cognitive dysfunction, with deficits in verbal, short-term, and working memory. Furthermore, in the genetically comparable dystrophin-deficient mdx mouse model of DMD, some, but not all, types of learning and memory are deficient, and specific deficits in synaptogenesis and channel clustering at synapses has been noted. Little consideration has been devoted to the cognitive deficits associated with DMD compared with the research conducted into the peripheral effects of dystrophin deficiency. Therefore, this review focuses on what is known about the role of full-length dystrophin (Dp427) in hippocampal neurons. The importance of dystrophin in learning and memory is assessed, and the potential importance that inflammatory mediators, which are chronically elevated in dystrophinopathies, may have on hippocampal function is also evaluated.