Biochemical correlates of cognition: exploring the relationships between blood, brain and behaviour

This multi-modal investigation aimed to refine analytic tools including proton magnetic resonance spectroscopy (1H-MRS) and fatty acid gas chromatography-mass spectrometry (GC-MS) analysis, for use with adult and paediatric populations, to investigate potential biochemical underpinnings of cognition (Chapter 1). Essential fatty acids (EFAs) are vital for the normal development and function of neural cells. There is increasing evidence of behavioural impairments arising from dietary deprivation of EFAs and their long-chain fatty acid metabolites (Chapter 2). Paediatric liver disease was used as a deficiency model to examine the relationships between EFA status and cognitive outcomes. Age-appropriate Wechsler assessments measured Full-scale IQ (FSIQ) and Information Processing Speed (IPS) in clinical and healthy cohorts; GC-MS quantified surrogate markers of EFA status in erythrocyte membranes; and 1H-MRS quantified neurometabolite markers of neuronal viability and function in cortical tissue (Chapter 3). Post-transplant children with early-onset liver disease demonstrated specific deficits in IPS compared to age-matched acute liver failure transplant patients and sibling controls, suggesting that the time-course of the illness is a key factor (Chapter 4). No signs of EFA deficiency were observed in the clinical cohort, suggesting that EFA metabolism was not significantly impacted by liver disease. A strong, negative correlation was observed between omega-6 fatty acids and FSIQ, independent of disease diagnosis (Chapter 5). In a study of healthy adults, effect sizes for the relationship between 1H-MRS- detectable neurometabolites and cognition fell within the range of previous work, but were not statistically significant. Based on these findings, recommendations are made emphasising the need for hypothesis-driven enquiry and greater subtlety of data analysis (Chapter 6). Consistency of metabolite values between paediatric clinical cohorts and controls indicate normal neurodevelopment, but the lack of normative, age-matched data makes it difficult to assess the true strength of liver disease-associated metabolite changes (Chapter 7). Converging methods offer a challenging but promising and novel approach to exploring brain-behaviour relationships from micro- to macroscopic levels of analysis (Chapter 8).

The brain in business:the case for organizational cognitive neuroscience?

The application of cognitive neuroscientific techniques to understanding social behaviour has resulted in many discoveries. Yet advocates of the ‘social cognitive neuroscience’ approach maintain that it suffers from a number of limitations. The most notable of these is its distance from any form of real-world applicabity. One solution to this limitation is ‘Organisational Cognitive Neuroscience’ – the study of the cognitive neuroscience of human behaviour in, and in response to, organizations. Given that all of us will spend most of our lives in some sort of work related organisation, organisational cognitive neuroscience allows us to examine the cognitive underpinnings of social behaviour that occurs in what may be our most natural ecology. Here we provide a brief overview of this approach, a definition and also some possible questions that the new approach would be best suited to address.

A randomized controlled trial of the effect of thyroxine replacement on cognitive function in community-living elderly subjects with subclinical hypothyroidism: the Birmingham elderly thyroid study

Context: Subclinical hypothyroidism (SCH) and cognitive dysfunction are both common in the elderly and have been linked. It is important to determine whether T4 replacement therapy in SCH confers cognitive benefit. Objective: Our objective was to determine whether administration of T4 replacement to achieve biochemical euthyroidism in subjects with SCH improves cognitive function. Design and Setting: We conducted a double-blind placebo-controlled randomized controlled trial in the context of United Kingdom primary care. Patients: Ninety-four subjects aged 65 yr and over (57 females, 37 males) with SCH were recruited from a population of 147 identified by screening. Intervention: T4 or placebo was given at an initial dosage of one tablet of either placebo or 25 µg T4 per day for 12 months. Thyroid function tests were performed at 8-weekly intervals with dosage adjusted in one-tablet increments to achieve TSH within the reference range for subjects in treatment arm. Fifty-two subjects received T4 (31 females, 21 males; mean age 73.5 yr, range 65–94 yr); 42 subjects received placebo (26 females, 16 males; mean age 74.2 yr, 66–84 yr). Main Outcome Measures: Mini-Mental State Examination, Middlesex Elderly Assessment of Mental State (covering orientation, learning, memory, numeracy, perception, attention, and language skills), and Trail-Making A and B were administered. Results: Eighty-two percent and 84% in the T4 group achieved euthyroidism at 6- and 12-month intervals, respectively. Cognitive function scores at baseline and 6 and 12 months were as follows: Mini-Mental State Examination T4 group, 28.26, 28.9, and 28.28, and placebo group, 28.17, 27.82, and 28.25 [not significant (NS)]; Middlesex Elderly Assessment of Mental State T4 group, 11.72, 11.67, and 11.78, and placebo group, 11.21, 11.47, and 11.44 (NS); Trail-Making A T4 group, 45.72, 47.65, and 44.52, and placebo group, 50.29, 49.00, and 46.97 (NS); and Trail-Making B T4 group, 110.57, 106.61, and 96.67, and placebo group, 131.46, 119.13, and 108.38 (NS). Linear mixed-model analysis demonstrated no significant changes in any of the measures of cognitive function over time and no between-group difference in cognitive scores at 6 and 12 months. Conclusions: This RCT provides no evidence for treating elderly subjects with SCH with T4 replacement therapy to improve cognitive function.

TRial of an Educational intervention on patients' knowledge of Atrial fibrillation and anticoagulant therapy, INR control, and outcome of Treatment with warfarin (TREAT)

Background Atrial fibrillation (AF) patients with a high risk of stroke are recommended anticoagulation with warfarin. However, the benefit of warfarin is dependent upon time spent within the target therapeutic range (TTR) of their international normalised ratio (INR) (2.0 to 3.0). AF patients possess limited knowledge of their disease and warfarin treatment and this can impact on INR control. Education can improve patients' understanding of warfarin therapy and factors which affect INR control. Methods/Design Randomised controlled trial of an intensive educational intervention will consist of group sessions (between 2-8 patients) containing standardised information about the risks and benefits associated with OAC therapy, lifestyle interactions and the importance of monitoring and control of their International Normalised Ratio (INR). Information will be presented within an 'expert-patient' focussed DVD, revised educational booklet and patient worksheets. 200 warfarin-naïve patients who are eligible for warfarin will be randomised to either the intervention or usual care groups. All patients must have ECG-documented AF and be eligible for warfarin (according to the NICE AF guidelines). Exclusion criteria include: aged < 18 years old, contraindication(s) to warfarin, history of warfarin USE, valvular heart disease, cognitive impairment, are unable to speak/read English and disease likely to cause death within 12 months. Primary endpoint is time spent in TTR. Secondary endpoints include measures of quality of life (AF-QoL-18), anxiety and depression (HADS), knowledge of AF and anticoagulation, beliefs about medication (BMQ) and illness representations (IPQ-R). Clinical outcomes, including bleeding, stroke and interruption to anticoagulation will be recorded. All outcome measures will be assessed at baseline and 1, 2, 6 and 12 months post-intervention. Discussion More data is needed on the clinical benefit of educational intervention with AF patients receiving warfarin. Trial registration ISRCTN93952605

Experiments and observations on the behaviour and brain of the aging female mouse with special reference to dementia of the Alzheimer type

The objective of this research was to investigate the effects of normal aging and the additional effects of chronic exposure to two experimental diets, one enriched in aluminium, the other enriched in lecithin, on aspects of the behaviour and brain histology of the female mouse. The aluminium diet was administered in an attempt to develop a rodent model of Dementia of the Alzheimer Type (DAT). With normal aging, almost all assessed aspects of behaviour were found to be impaired. As regards cognition, selective impairments of single-trial passive avoidance and Morris place learning were observed. While all aspects of open-field behaviour were impaired, the degree of impairment was directly related to the degree of motoric complexity. Deficits were also observed on non-visual sensorimotor coordination tasks and in olfactory discrimination. Histologically, neuron loss, gliosis, vacuolation and congophilic angiopathy were observed in several of the brain regions/fibre tracts believed to contribute to the control of some of the assessed behaviours. The aluminium treatment had very selective effects on both behaviour and brain histology, inducing several features observed in DAT. Behaviourally, the treatment induced impaired spatial reference memory; reduced ambulation; disturbed olfactory function and induced the premature development of the senile pattern of swimming. Histologically, significant neuron loss and gliosis were observed in the hippocampus, entorhinal cortex, amygdala, medial septum, pyriform and pr-frontal cortex. In addition, the brain distribution of congophilic angiopathy was significantly increased by the treatment. The lecithin treatment had effects on both non-cognitive and cognitive aspects of behaviour. The effects of aging on open-field ambulation and rearing were partially ameliorated by the treatment. A similar effect was observed for single-trial passive avoidance performance. Age-dependent improvements in acquisition/retention were observed in 17-23 month mice and Morris place task performance was improved in 11 and 17 month mice. Histologically, a partial sparing of neurons in the cerebellum, hippocampus, entorhinal cortex and subiculum was observed.

The brain in business:neuromarketing and organisational cognitive neuroscience

The application of cognitive neuroscientific techniques to understanding social behaviour has resulted in many discoveries. Yet advocates of the ‘social cognitive neuroscience’ approach maintain that it suffers from a number of limitations. The most notable of these is its distance from any form of real-world applicabity. One solution to this limitation is ‘Organisational Cognitive Neuroscience’— the study of the cognitive neuroscience of human behaviour in, and in response to, organizations, which are arguably our most natural contemporary ecology. Here we provide a brief overview of this approach, a definition and also some examples of questions that the approach would be best suited to address. Furthemore, we consider neuromarketing as a subfield of organizational cognitive neuroscience, arguing that such a relationship clarifies the role of scholarly marketing research in the area, and provides a welcome emphasis on theoretical rigour.

How checking breeds doubt:reduced performance in a simple working memory task

A paradox of memory research is that repeated checking results in a decrease in memory certainty, memory vividness and confidence [van den Hout, M. A., & Kindt, M. (2003a). Phenomenological validity of an OCD-memory model and the remember/know distinction. Behaviour Research and Therapy, 41, 369–378; van den Hout, M. A., & Kindt, M. (2003b). Repeated checking causes memory distrust. Behaviour Research and Therapy, 41, 301–316]. Although these findings have been mainly attributed to changes in episodic long-term memory, it has been suggested [Shimamura, A. P. (2000). Toward a cognitive neuroscience of metacognition. Consciousness and Cognition, 9, 313–323] that representations in working memory could already suffer from detrimental checking. In two experiments we set out to test this hypothesis by employing a delayed-match-to-sample working memory task. Letters had to be remembered in their correct locations, a task that was designed to engage the episodic short-term buffer of working memory [Baddeley, A. D. (2000). The episodic buffer: a new component in working memory? Trends in Cognitive Sciences, 4, 417–423]. Of most importance, we introduced an intermediate distractor question that was prone to induce frustrating and unnecessary checking on trials where no correct answer was possible. Reaction times and confidence ratings on the actual memory test of these trials confirmed the success of this manipulation. Most importantly, high checkers [cf. VOCI; Thordarson, D. S., Radomsky, A. S., Rachman, S., Shafran, R, Sawchuk, C. N., & Hakstian, A. R. (2004). The Vancouver obsessional compulsive inventory (VOCI). Behaviour Research and Therapy, 42(11), 1289–1314] were less accurate than low checkers when frustrating checking was induced, especially if the experimental context actually emphasized the irrelevance of the misleading question. The clinical relevance of this result was substantiated by means of an extreme groups comparison across the two studies. The findings are discussed in the context of detrimental checking and lack of distractor inhibition as a way of weakening fragile bindings within the episodic short-term buffer of Baddeley's (2000) model. Clinical implications, limitations and future research are considered.