Nucleotide supplementation: a randomised double-blind placebo controlled trial of IntestAidIB in people with Irritable Bowel Syndrome [ISRCTN67764449].

BACKGROUND: Dietary nucleotide supplementation has been shown to have important effects on the growth and development of cells which have a rapid turnover such as those in the immune system and the gastrointestinal tract. Work with infants has shown that the incidence and duration of diarrhoea is lower when nucleotide supplementation is given, and animal work shows that villi height and crypt depth in the intestine is increased as a result of dietary nucleotides. Dietary nucleotides may be semi-essential under conditions of ill-health, poor diet or stress. Since people with Irritable Bowel Syndrome tend to fulfil these conditions, we tested the hypothesis that symptoms would be improved with dietary nucleotide supplementation. METHODS: Thirty-seven people with a diagnosis of Irritable Bowel gave daily symptom severity ratings for abdominal pain, diarrhoea, urgency to have a bowel movement, incomplete feeling of evacuation after a bowel movement, bloating, flatulence and constipation for 28 days (baseline). They were then assigned to either placebo (56 days) followed by experimental (56 days) or the reverse. There was a four week washout period before crossover. During the placebo and experimental conditions participants took one 500 mg capsule three times a day; in the experimental condition the capsule contained the nutroceutical substances. Symptom severity ratings and psychological measures (anxiety, depression, illness intrusiveness and general health) were obtained and analysed by repeated measures ANOVAs. RESULTS: Symptom severity for all symptoms (except constipation) were in the expected direction of baseline>placebo>experimental condition. Symptom improvement was in the range 4 - 6%. A feeling of incomplete evacuation and abdominal pain showed the most improvement. The differences between conditions for diarrhoea, bloating and flatulence were not significant at the p < .05 level. There were no significant differences between the conditions for any of the psychological measures. CONCLUSION: Dietary nucleotide supplementation improves some of the symptoms of irritable bowel above baseline and placebo level. As expected, placebo effects were high. Apart from abdominal pain and urgency to have a bowel movement, the improvements, while consistent, are modest, and were not accompanied by improvements in any of the psychological measures. We suggest that the percentage improvement over and above the placebo effect is a physiological effect of the nucleotide supplement on the gut. The mechanisms by which these effects might improve symptoms are discussed.

Is there a link between Irritable Bowel Syndrome and left-handedness?: An exploratory study.

Recent research has found that people with Irritable Bowel Syndrome (IBS) and those with Inflammatory Bowel Disease (IBD) show a relative deficit in verbal IQ, compared to their own performance IQ, and the IQ of a healthy comparison group. It has been suggested that the elevated prevalence of left-handedness shown in previous studies investigating people with IBD is due to compromised left-hemisphere development. This may be associated with a decrement in certain cognitive functions such as verbal IQ. A shift in brain dominance from left to right has been found in many atopic and immunological diseases as well as in autonomic dysfunctions. It was uncertain whether this would apply to people with IBS, a functional disorder in which the cause or causes remain unclear. Therefore, the aim of this preliminary study was to investigate whether people with IBS have an increased prevalence of left-handedness. It was found that there was an association between IBS and left-handedness, showing that further research on this association both in IBS and other functional disorders (as well as on the similarities between IBS and IBD) is warranted.

The role of virtual reality technology in the assessment and training of inexperienced powered wheelchair users.

PURPOSE: The current paper provides quantitative and qualitative data concerning the application of two virtual environments to the assessment and training of inexperienced powered wheelchair users, both in terms of the ability to control the chair accurately without hitting objects in the environment (manoeuvrability) and in terms of being able to find ones way around a complex environment without becoming lost (route-finding). METHOD: Six novice powered wheelchair users participated in the project, completing either the manoeuvrability or route finding components of the study. Performance measures were taken in real life pre and post training and throughout virtual reality sessions. Participants also completed a questionnaire regarding the aesthetics of the virtual environments and aspects of the powered wheelchair simulation. RESULTS: The participants rated the aesthetics of the virtual environments positively and engaged well with the virtual system. However, they found the manoeuvrability tasks considerably more difficult in virtual reality (VR) than in real life. Some difficulties with controlling the simulated wheelchair were apparent. Some improvements on virtual and real life manoeuvrability tasks and route finding were noted following conventional and virtual training. CONCLUSIONS: The study indicated that the two virtual environments represent a potentially useful means of assessing and training novice powered wheelchair users. The virtual environments however must become less challenging if they are to represent a motivating and effective means of improving performance. Further development of the way in which wheelchair movement is controlled and simulated represents a key element in this multi stage project.

An evaluation of the efficacy of training people with learning disabilities in a virtual environment.

PURPOSE: To evaluate the efficacy of using a virtual kitchen for vocational training of people with learning disabilities. METHOD: Twenty four catering students with learning disabilities participated in the study. Half the students were currently being trained in the kitchen on which the virtual kitchen was modelled but the remaining students were unfamiliar with this kitchen. Students were first pre-tested on four food preparation tasks and identification of 12 hazards in their own training kitchens. They were subsequently trained on one food preparation task and three hazards in their own training kitchens, one food preparation task and three hazards in the virtual kitchen, and one food preparation task and three hazards in specially designed workbooks. They were then retested in their own training kitchens on all the food preparation tasks and all the hazards. RESULTS: Virtual training was found to be as beneficial as real training and more beneficial than workbook and no training in the food preparation tasks. However, virtual, real and workbook training were found to be equally beneficial in the hazard identification task. Students who were unfamiliar with the kitchen on which the virtual kitchen was modelled benefited from virtual training to the same extent as students who were familiar with the kitchen. CONCLUSIONS: Vocational students with learning disabilities were able to use the virtual environment and were motivated to learn using this training method. Depending on the task being trained, virtual training had a more beneficial effect on real task performance than workbook training, even when the virtual kitchen was not modelled on the real training kitchen.

An exploratory investigation into the usability and usefulness of training people with learning disabilities in a virtual environment.

PURPOSE: Two studies sought to answer the following questions. Are people with learning disabilities capable of using a virtual environment? Are they motivated to learn using this training method? Do they show any benefit from using a virtual environment? Does any benefit transfer to improved real world performance? METHOD: In the first study, 30 students with learning disabilities were sequentially allocated to an active or a passive experimental group. Active participants explored a virtual bungalow searching for a toy car. Passive participants watched the exploration undertaken by the preceding active participant and searched for the toy car. All participants then performed spatial and object recognition tests of their knowledge of the virtual environment. In the second study, the errors of 45 participants on a real steadiness tester task were noted before they were randomly allocated to three groups-a real training group, a virtual training group and a no training group. After training, the participants performed a second test trial on the real steadiness tester. RESULTS: The students were capable of using a virtual environment and were motivated to use this training method. Active exploration of a virtual environment was found to enhance their memory of the spatial layout of the bungalow but not their memory of the virtual objects. In the second study, virtual training was found to transfer to real task performance. CONCLUSIONS: These two laboratory-based studies provide answers to four important questions concerning virtual training of people with learning disabilities. Hopefully, the findings will encourage this training aid to be used more widely.

Training in virtual environments: transfer to real world tasks and equivalence to real task training.

Virtual environments (VEs) are extensively used in training but there have been few rigorous scientific investigations of whether and how skills learned in a VE are transferred to the real world. This research aimed to measure and evaluate what is transferring from training a simple sensorimotor task in a VE to real world performance. In experiment 1, real world performances after virtual training, real training and no training were compared. Virtual and real training resulted in equivalent levels of post-training performance, both of which significantly exceeded task performance without training. Experiments 2 and 3 investigated whether virtual and real trained real world performances differed in their susceptibility to cognitive and motor interfering tasks (experiment 2) and in terms of spare attentional capacity to respond to stimuli and instructions which were not directly related to the task (experiment 3). The only significant difference found was that real task performance after training in a VE was less affected by concurrently performed interference tasks than was real task performance after training on the real task. This finding is discussed in terms of the cognitive load characteristics of virtual training. Virtual training therefore resulted in equivalent or even better real world performance than real training in this simple sensorimotor task, but this finding may not apply to other training tasks. Future research should be directed towards establishing a comprehensive knowledge of what is being transferred to real world performance in other tasks currently being trained in VEs and investigating the equivalence of virtual and real trained performances in these situations.

A preliminary investigation into the use of virtual environments in memory retraining after vascular brain injury: indications for future strategy?

PURPOSE: In a preliminary investigation of the use of Virtual Environments (VEs) in neurorehabilitation, this study compares the effects of active and passive experience of a VE on two types of memory in vascular brain injury patients and controls. METHOD: Forty-eight patients with vascular brain injury and 48 non-impaired control participants were randomly assigned to active and passive VE conditions. The active participants explored a virtual bungalow seeking a particular object; the passive participants observed, but did not control movement through the VE, also seeking the object. Afterwards, both active and passive participants completed spatial recognition and object recognition tests. RESULTS: Expectedly, the patients were impaired relative to the controls but were able to perform the virtual tasks. Active participation in the VE enhanced memory for its spatial layout in both patients and controls. On object recognition, active and passive patients performed similarly, but passive controls performed better than active controls. CONCLUSIONS: The findings are discussed in relation to their implications for memory rehabilitation strategies.

The specificity of memory enhancement during interaction with a virtual environment.

Two experiments investigated differences between active and passive participation in a computer-generated virtual environment in terms of spatial memory, object memory, and object location memory. It was found that active participants, who controlled their movements in the virtual environment using a joystick, recalled the spatial layout of the virtual environment better than passive participants, who merely watched the active participants' progress. Conversely, there were no significant differences between the active and passive participants' recall or recognition of the virtual objects, nor in their recall of the correct locations of objects in the virtual environment. These findings are discussed in terms of subject-performed task research and the specificity of memory enhancement in virtual environments.

Virtual environments in the diagnosis, prevention, and intervention of age-related diseases: a review of VR scenarios proposed in the EC VETERAN Project.

A group of worldwide virtual reality and health-care researchers have decided to combine their efforts in a multidisciplinary project titled VETERAN-virtual environments in the diagnosis, prevention and intervention of age-related diseases. The main goal of the VETERAN project is the tuning and testing of different virtual environments, designed to address the cognitive/functional impairments that may occur due to the aging process and age-related disorders. In particular the developed modules will address the problems commonly found in the following pathologies that have a strong impact on the elderly health care policy: Alzheimer's disease and other senile dementias; stroke and unilateral spatial neglect; mobility-related accidents within specific environments (e.g., falls, shocks). The project will focus on research into clinical aspects of age-related diseases and disorders of high morbidity and specifically target goals of prevention, treatment, or delay in onset. Another goal of the VETERAN project is to define and develop new protocols and tools to be used for general rehabilitation purposes. These tools will aim to provide systematic restorative training within the context of functionally relevant, ecologically valid simulated environments. This approach is hoped to optimise the degree of transfer of training and/or generalisation of learning to the person's real world environment.

Virtual reality: a new prosthesis for brain injury rehabilitation.

Virtual Reality (VR) technology is a relatively new application to rehabilitation medicine, yet it offers considerable potential to achieve significant successes in assessment, treatment and improved outcome, thereby increasing our knowledge of neuroplasticity. The capabilities of VR are especially evident in neurological rehabilitation, where cognitive and behavioural problems often interact with physical impairments to reduce the overall level of functioning and interaction. The need for effective interventions in neurological rehabilitation demands communication and collaboration between disciplines. This paper presents some of the current areas of the clinical applications of VR, emphasising the link between experimental evidence on recovery after brain damage and the clinical problems encountered in a ward setting.

Virtual environments in brain damage rehabilitation: a rationale from basic neuroscience.

The potential of virtual environments in assessment and training of cognitive function is a more than adequate reason for their application to neurorehabilitation. However, there is a more fundamental justification, and one which is firmly rooted in the neuroscience literature. Over the last half century there has been a wealth of published evidence that enriching the environments of laboratory rats stimulates neuroplastic change in the cerebral cortex, enhances learning and problem solving in normal rats and reduces cognitive impairment in brain damaged rats. Central to all three effects of enrichment are the increased levels of interaction with the physical environment engendered by enrichment. Placing humans who have damaged brains in virtual environments is one way of enhancing their levels of environmental interaction which, because of cognitive impairments and sensory and motor disabilities, is otherwise difficult to achieve. In this chapter we explore the potential of virtual environments as enriched environments within the rehabilitation regime. The underlying assumption, that interaction with a virtual environment is functionally equivalent to interaction with a real environment, is examined. Three lines of relevant evidence are reviewed, neuroimaging studies and psychophysiological studies of people in virtual environments and studies of transfer of training from virtual to real tasks. An agenda for future research in this are is proposed.

Rehabilitation of the head-injured child: basic research and new technology.

The view that brain damage in children is less impairing than equivalent damage in adults is no longer acceptable. However, it is acknowledged that recovery following brain damage, when it does occur, owes much to the plasticity of the brain and that the young brain displays greater plasticity than the mature brain. To maximize brain damage recovery in children we need to focus both on what is known about brain plasticity and how to influence it. Research on environmental enrichment in rats has told us that enforced interaction with a complex environment can both stimulate anatomical and biochemical plasticity and ameliorate some of the behavioural consequences of brain damage. The view that environmental interaction has rehabilitative value also accords with clinical experience. However, the sensory, motor and cognitive consequences of brain damage often conspire to make environmental interaction difficult. One potential solution lies in using computers to generate virtual environments tailored to the precise sensory and motor capacities of the brain-injured child. In this way children may be enabled to benefit from environmental interaction whatever their level of disability. The use of Virtual Reality (VR) in the context of rehabilitation is discussed and relevant work reviewed.

Virtual environments in neuropsychological assessment and rehabilitation.

Brain damage constitutes a major problem for those affected, for their families and friends and for society as a whole. The need for effective rehabilitation strategies is clear. Yet, until the early 1960s, the brain was generally considered to be a somewhat fixed and inflexible organ. In consequence the impairments associated with brain damage were generally regarded as "incurable". Since that time neuroscientists have had reason to change their views dramatically. However, much remains to be done. Progress depends upon a co-ordinated multidisciplinary approach within which assistive technology will be a key player. Within the area of assistive technology, one of the developments which holds particular promise for the field of neurological rehabilitation is the computer technology underlying virtual environments (commonly known as virtual reality). In this chapter we describe the new opportunities offered by virtual reality to pursue several aspects of the rehabilitation process. The value of the technology of virtual environments in this context is that it allows us to immerse people with brain damage in relatively realistic interactive environments which, because of their patterns of impairment, would otherwise be unavailable to them.

Virtual reality: an assistive technology in neurological rehabilitation.

The need for improved neurological rehabilitation strategies is self-evident. Recent developments in the computer technology of virtual reality hold the promise of exciting progress in this area. In this paper four areas of potential application of virtual reality to neurological rehabilitation are reviewed.

Age and recovery from brain injury: clinical opinions and experimental evidence.

For many years the notion that brain damage causes less impairment in children than in adults (sometimes known as the 'Kennard Principle') has enjoyed widespread support among scientists and clinicians. More recently neuroscientists have questioned the Principle, most now taking an opposing view that damage to the rapidly developing brain can be more harmful than equivalent damage in adulthood. Many clinicians, however, appear reluctant to reject the Kennard Principle. This study investigates the extent to which the Kennard Principle still guides the judgement of different groups of health-care professionals (neurosurgeons, neurologists, neuropsychologists, general practitioners, nurses, physiotherapists, occupational therapists, and speech therapists). Subjects were asked to estimate the extent of recovery in clinically based but fictitious case studies which differed only in the reported age of the patient. The professions differed in their levels of optimism regarding the extent of recovery to be expected, but all predicted better recovery in younger patients (under 10) than in adults with otherwise similar brain injuries. The results are discussed in terms of their implications for the treatment of brain injuries in the young.

Environmental enrichment following brain damage: an aid to recovery or compensation?

Postoperative environmental enrichment (EC) in rats with brain lesions has been hailed as a potential agent of recovery of function following brain damage. However, most such claims are based on examining the effects of EC on acquisition of a new task following brain injury. Elsewhere we have argued that since this paradigm fails to establish a preoperative behavioural baseline against which to compare subsequent performance it may demonstrate compensation but cannot provide evidence of recovery. The present study directly addresses this issue by examining the effects of postoperative EC both on performance of a preoperatively acquired water maze escape response as well as on de novo acquisition of such a response in rats with bilateral occipital and sham lesions. In terms of swim times postoperative EC was found to significantly improve the performance of subjects which had not been preoperatively trained but not the performance of those subjects which had. However, in terms of a trials to criterion measure postoperative EC benefitted animals in both the preoperative and postoperative training conditions. The results, therefore, support the view that what has been observed in most previous studies is EC-induced compensation rather than recovery and also help to define the conditions under which this occurs. However, they also argue for further investigation of the hypothesis that postoperative EC may enhance recovery of lesion-impaired performance consistency.

How does environmental enrichment aid performance following cortical injury in the rat?

Understanding how postoperative environmental brain damage in animals may help in devising treatment regimes for brain injured humans. This study tests Finger's hypothesis that EC increases the animal's ability to switch to alternative cues when brain damage renders the cues normally used in performing the task less salient or unavailable. Following preoperative water maze training to visual cues, rats were given either bilateral occipital lesions or sham operations, housed in either EC or standard conditions and then tested in the water maze in alternating visual and non-visual cue conditions. We found no evidence that postoperative EC helped lesioned rats to switch to non-visual cues when visual cues were unavailable.

Maternal hypothyroxinemia and brain development: II. Biochemical, metabolic and behavioural correlates.

Using a rat model, we have investigated the influence of maternal hypothyroxinemia throughout pregnancy on brain development in young and adult progeny. Although no consistent change was observed in whole brain total protein concentration, the subcellular distribution of protein was adversely affected. Isolation of glycoprotein from developing brain by concanavalin A-affinity chromatography and subsequent resolution by gel electrophoresis revealed the selective compromise of particular glycoprotein species. Furthermore, both control and experimental progeny expressed unique glycoprotein species which either persisted over the period studied or were transient. Calcineurin, a regulator of neurite elongation, was compromised in young progeny, as were a number of lysosomal enzymes (beta-D-glucosidase and aryl sulphatase). In adult progeny, the content of cerebroside sulphate (a major myelin galactolipid) was reduced in midbrain and paleocortex, and brain region-specific compromise was observed for acetylcholine metabolic enzymes. These changes were associated with alterations in behavioural output. We conclude that the availability of maternal thyroxine to the fetus may be a critical determinant for normal brain development and function.

The relationship between laterality and numerical and spatial ability.

Hypotheses derived from right shift theory concerning the relationship between laterality and mathematical ability were investigated. This was done by dividing a group of 129 subjects into subgroups with presumably different distributions of the rs+ +, rs+ - and rs- - genotypes on the basis of their manual skills and then assessing their numerical and spatial abilities. No relationship was found between laterality and ability when the group as a whole were considered, but some marginal effects were found for numerical ability when data for a subgroup of 96 young female subjects were analysed separately. The results did not, however, conform to the predictions of right shift theory.