A predictive in vitro model of the impact of drugs with anticholinergic properties on human neuronal and astrocytic systems

The link between off-target anticholinergic effects of medications and acute cognitive impairment in older adults requires urgent investigation. We aimed to determine whether a relevant in vitro model may aid the identification of anticholinergic responses to drugs and the prediction of anticholinergic risk during polypharmacy. In this preliminary study we employed a co-culture of human-derived neurons and astrocytes (NT2.N/A) derived from the NT2 cell line. NT2.N/A cells possess much of the functionality of mature neurons and astrocytes, key cholinergic phenotypic markers and muscarinic acetylcholine receptors (mAChRs). The cholinergic response of NT2 astrocytes to the mAChR agonist oxotremorine was examined using the fluorescent dye fluo-4 to quantitate increases in intracellular calcium [Ca2+]i. Inhibition of this response by drugs classified as severe (dicycloverine, amitriptyline), moderate (cyclobenzaprine) and possible (cimetidine) on the Anticholinergic Cognitive Burden (ACB) scale, was examined after exposure to individual and pairs of compounds. Individually, dicycloverine had the most significant effect regarding inhibition of the astrocytic cholinergic response to oxotremorine, followed by amitriptyline then cyclobenzaprine and cimetidine, in agreement with the ACB scale. In combination, dicycloverine with cyclobenzaprine had the most significant effect, followed by dicycloverine with amitriptyline. The order of potency of the drugs in combination frequently disagreed with predicted ACB scores derived from summation of the individual drug scores, suggesting current scales may underestimate the effect of polypharmacy. Overall, this NT2.N/A model may be appropriate for further investigation of adverse anticholinergic effects of multiple medications, in order to inform clinical choices of suitable drug use in the elderly.

Leaders' sensemaking under crises:emerging cognitive consensus over time within management teams

When facing a crisis, leaders' sensemaking can take a considerable amount of time due to the need to develop consensus in how to deal with it so that vision formation and sensegiving can take place. However, research into emerging cognitive consensus when leaders deal with a crisis over time is lacking. This is limiting a detailed understanding of how organizations respond to crises. The findings, based on a longitudinal analysis of cognitive maps within three management teams at a single organization, highlight considerable individual differences in cognitive content when starting to make sense of a crisis. Evidence for an emerging viable prescriptive mental model for the future was found, but not so much in the management as a whole. Instead, the findings highlight increasing cognitive consensus based on similarities in objectives and cause-effect beliefs within well-defined management teams over time.

Body iron is associated with cognitive executive planning function in college women

Evidence of the relationship between altered cognitive function and depleted Fe status is accumulating in women of reproductive age but the degree of Fe deficiency associated with negative neuropsychological outcomes needs to be delineated. Data are limited regarding this relationship in university women in whom optimal cognitive function is critical to academic success. The aim of the present study was to examine the relationship between body Fe, in the absence of Fe-deficiency anaemia, and neuropsychological function in young college women. Healthy, non-Anaemic undergraduate women (n 42) provided a blood sample and completed a standardised cognitive test battery consisting of one manual (Tower of London (TOL), a measure of central executive function) and five computerised (Bakan vigilance task, mental rotation, simple reaction time, immediate word recall and two-finger tapping) tasks. Women's body Fe ranged from - 4·2 to 8·1 mg/kg. General linear model ANOVA revealed a significant effect of body Fe on TOL planning time (P= 0.002). Spearman's correlation coefficients showed a significant inverse relationship between body Fe and TOL planning time for move categories 4 (r - 0.39, P= 0.01) and 5 (r - 0.47, P= 0.002). Performance on the computerised cognitive tasks was not affected by body Fe level. These findings suggest that Fe status in the absence of anaemia is positively associated with central executive function in otherwise healthy college women. Copyright © The Authors 2012.

An empirical examination of emotional and cognitive responses to threat appeals

Advertising and other forms of communications are often used by government bodies, non-government organisations, and other institutions to try to influence the population to either a) reduce some form of harmful behaviour (e.g. smoking, drunk- driving) or b) increase some more healthy behaviour (e.g. eating healthily). It is common for these messages to be predicated on the chances of some negative event occurring if the individual does not either a) stop the harmful behaviour, or b) start / increase the healthy behaviour. This design of communication is referred to by many names in the relevant literature, but for the purposes of this thesis, will be termed a ‘threat appeal’. Despite their widespread use in the public sphere, and concerted academic interest since the 1950s, the effectiveness of threat appeals in delivering their objective remains unclear in many ways. In a detailed, chronological and thematic examination of the literature, two assumptions are uncovered that have either been upheld despite little evidence to support them, or received limited attention at all, in the literature. Specifically, a) that threat appeal characteristics can be conflated with their intended responses, and b) that a threat appeal always and necessarily evokes a fear response in the subject. A detailed examination of these assumptions underpins this thesis. The intention is to take as a point of departure the equivocality of empirical results, and deliver a novel approach with the objective of reducing the confusion that is evident in existing work. More specifically, the present thesis frames cognitive and emotional responses to threat appeals as part of a decision about future behaviour. To further develop theory, a conceptual framework is presented that outlines the role of anticipated and anticipatory emotions, alongside subjective probabilities, elaboration and immediate visceral emotions, resultant from manipulation of the intrinsic message characteristics of a threat appeal (namely, message direction, message frame and graphic image). In doing so, the spectrum of relevant literature is surveyed, and used to develop a theoretical model which serves to integrate key strands of theory into a coherent model. In particular, the emotional and cognitive responses to the threat appeal manipulations are hypothesised to influence behaviour intentions and expectations pertaining to future behaviour. Using data from a randomised experiment with a sample of 681 participants, the conceptual model was tested using analysis of covariance. The results for the conceptual framework were encouraging overall, and also with regard to the individual hypotheses. In particular, empirical results showed clearly that emotional responses to the intrinsic message characteristics are not restricted to fear, and that different responses to threat appeals were clearly attributed to specific intrinsic message characteristics. In addition, the inclusion of anticipated emotions alongside cognitive appraisals in the framework generated interesting results. Specifically, immediate emotions did not influence key response variables related to future behaviour, in support of questioning the assumption of the prominent role of fear in the response process that is so prevalent in existing literature. The findings, theoretical and practical implications, limitations and directions for future research are discussed.

Psychotherapy and social change:utilizing principles of cognitive-behavioral therapy to help develop new prejudice-reduction interventions

We propose that key concepts from clinical psychotherapy can inform science-based initiatives aimed at building tolerance and community cohesion. Commonalities in social and clinical psychology are identified regarding (1) distorted thinking (intergroup bias and cognitive bias), (2) stress and coping (at intergroup level and intrapersonal level), and (3) anxiety (intergroup anxiety and pathological anxiety). On this basis we introduce a new cognitive-behavioral model of social change. Mental imagery is the conceptual point of synthesis, and anxiety is at the core, through which new treatment-based approaches to reducing prejudice can be developed. More generally, we argue that this integration is illustrative of broader potential for cross-disciplinary integration in the social and clinical sciences, and has the potential to open up new possibilities and opportunities for both disciplines.

Performance analysis of IEEE 802.11 cognitive radio ad hoc networks

IEEE 802.11 standard is the dominant technology for wireless local area networks (WLANs). In the last two decades, the Distributed coordination function (DCF) of IEEE 802.11 standard has become the one of the most important media access control (MAC) protocols for mobile ad hoc networks (MANETs). The DCF protocol can also be combined with cognitive radio, thus the IEEE 802.11 cognitive radio ad hoc networks (CRAHNs) come into being. There were several literatures which focus on the modeling of IEEE 802.11 CRAHNs, however, there is still no thorough and scalable analytical models for IEEE 802.11 CRAHNs whose cognitive node (i.e., secondary user, SU) has spectrum sensing and possible channel silence process before the MAC contention process. This paper develops a unified analytical model for IEEE 802.11 CRAHNs for comprehensive MAC layer queuing analysis. In the proposed model, the SUs are modeled by a hyper generalized 2D Markov chain model with an M/G/1/K model while the primary users (PUs) are modeled by a generalized 2D Markov chain and an M/G/1/K model. The performance evaluation results show that the quality-of-service (QoS) of both the PUs and SUs can be statistically guaranteed with the suitable settings of duration of channel sensing and silence phase in the case of under loading.

Mobility changes in older age: neuropsychological, neurophysiological and cognitive predictors of successful adaptation in a real world scenario

The aims of this thesis were to investigate the neuropsychological, neurophysiological, and cognitive contributors to mobility changes with increasing age. In a series of studies with adults aged 45-88 years, unsafe pedestrian behaviour and falls were investigated in relation to i) cognitive functions (including response time variability, executive function, and visual attention tests), ii) mobility assessments (including gait and balance and using motion capture cameras), iii) motor initiation and pedestrian road crossing behavior (using a simulated pedestrian road scene), iv) neuronal and functional brain changes (using a computer based crossing task with magnetoencephalography), and v) quality of life questionnaires (including fear of falling and restricted range of travel). Older adults are more likely to be fatally injured at the far-side of the road compared to the near-side of the road, however, the underlying mobility and cognitive processes related to lane-specific (i.e. near-side or far-side) pedestrian crossing errors in older adults is currently unknown. The first study explored cognitive, motor initiation, and mobility predictors of unsafe pedestrian crossing behaviours. The purpose of the first study (Chapter 2) was to determine whether collisions at the near-side and far-side would be differentially predicted by mobility indices (such as walking speed and postural sway), motor initiation, and cognitive function (including spatial planning, visual attention, and within participant variability) with increasing age. The results suggest that near-side unsafe pedestrian crossing errors are related to processing speed, whereas far-side errors are related to spatial planning difficulties. Both near-side and far-side crossing errors were related to walking speed and motor initiation measures (specifically motor initiation variability). The salient mobility predictors of unsafe pedestrian crossings determined in the above study were examined in Chapter 3 in conjunction with the presence of a history of falls. The purpose of this study was to determine the extent to which walking speed (indicated as a salient predictor of unsafe crossings and start-up delay in Chapter 2), and previous falls can be predicted and explained by age-related changes in mobility and cognitive function changes (specifically within participant variability and spatial ability). 53.2% of walking speed variance was found to be predicted by self-rated mobility score, sit-to-stand time, motor initiation, and within participant variability. Although a significant model was not found to predict fall history variance, postural sway and attentional set shifting ability was found to be strongly related to the occurrence of falls within the last year. Next in Chapter 4, unsafe pedestrian crossing behaviour and pedestrian predictors (both mobility and cognitive measures) from Chapter 2 were explored in terms of increasing hemispheric laterality of attentional functions and inter-hemispheric oscillatory beta power changes associated with increasing age. Elevated beta (15-35 Hz) power in the motor cortex prior to movement, and reduced beta power post-movement has been linked to age-related changes in mobility. In addition, increasing recruitment of both hemispheres has been shown to occur and be beneficial to perform similarly to younger adults in cognitive tasks (Cabeza, Anderson, Locantore, & McIntosh, 2002). It has been hypothesised that changes in hemispheric neural beta power may explain the presence of more pedestrian errors at the farside of the road in older adults. The purpose of the study was to determine whether changes in age-related cortical oscillatory beta power and hemispheric laterality are linked to unsafe pedestrian behaviour in older adults. Results indicated that pedestrian errors at the near-side are linked to hemispheric bilateralisation, and neural overcompensation post-movement, 4 whereas far-side unsafe errors are linked to not employing neural compensation methods (hemispheric bilateralisation). Finally, in Chapter 5, fear of falling, life space mobility, and quality of life in old age were examined to determine their relationships with cognition, mobility (including fall history and pedestrian behaviour), and motor initiation. In addition to death and injury, mobility decline (such as pedestrian errors in Chapter 2, and falls in Chapter 3) and cognition can negatively affect quality of life and result in activity avoidance. Further, number of falls in Chapter 3 was not significantly linked to mobility and cognition alone, and may be further explained by a fear of falling. The objective of the above study (Study 2, Chapter 3) was to determine the role of mobility and cognition on fear of falling and life space mobility, and the impact on quality of life measures. Results indicated that missing safe pedestrian crossing gaps (potentially indicating crossing anxiety) and mobility decline were consistent predictors of fear of falling, reduced life space mobility, and quality of life variance. Social community (total number of close family and friends) was also linked to life space mobility and quality of life. Lower cognitive functions (particularly processing speed and reaction time) were found to predict variance in fear of falling and quality of life in old age. Overall, the findings indicated that mobility decline (particularly walking speed or walking difficulty), processing speed, and intra-individual variability in attention (including motor initiation variability) are salient predictors of participant safety (mainly pedestrian crossing errors) and wellbeing with increasing age. More research is required to produce a significant model to explain the number of falls.

The development of a semantic model for the interpretation of mathematics including the use of technology

The semantic model developed in this research was in response to the difficulty a group of mathematics learners had with conventional mathematical language and their interpretation of mathematical constructs. In order to develop the model ideas from linguistics, psycholinguistics, cognitive psychology, formal languages and natural language processing were investigated. This investigation led to the identification of four main processes: the parsing process, syntactic processing, semantic processing and conceptual processing. The model showed the complex interdependency between these four processes and provided a theoretical framework in which the behaviour of the mathematics learner could be analysed. The model was then extended to include the use of technological artefacts into the learning process. To facilitate this aspect of the research, the theory of instrumentation was incorporated into the semantic model. The conclusion of this research was that although the cognitive processes were interdependent, they could develop at different rates until mastery of a topic was achieved. It also found that the introduction of a technological artefact into the learning environment introduced another layer of complexity, both in terms of the learning process and the underlying relationship between the four cognitive processes.