DOPAMINE D2 RECEPTOR MECHANISMS CONTRIBUTE TO AGE-RELATED COGNITIVE DECLINE - THE EFFECTS OF QUINPIROLE ON MEMORY AND MOTOR-PERFORMANCE IN MONKEYS

The D2 dopamine (DA) receptor agonist, quinpirole, was characterized in young adult monkeys, young reserpine-treated monkeys and aged monkeys to assess the contribution of DA to age-related loss of prefrontal cortical (PFC) cognitive function, Monkeys were tested on a delayed response memory task that depends on the PFC, and a fine motor task that taps the functions of the motor cortex, In young adult monkeys, low quinpirole doses impaired performance of the PFC and fine motor tasks, while higher doses improved memory performance and induced dyskinesias and ''hallucinatory-like'' behaviors. The pattern of the quinpirole response in reserpine-treated monkeys suggested that the impairments in delayed response and fine motor performance resulted from drug actions at D2 autoreceptors, while the improvement in delayed response performance, dyskinesias and ''hallucinatory-like'' behaviors resulted from actions at postsynaptic receptors. In aged monkeys, low doses of quinpirole continued to impair fine motor performance, but lost their ability to impair delayed response performance. The magnitude of cognitive improvement and the incidence of ''hallucinatory-like'' behaviors were also reduced in the aged animals, suggesting some loss of postsynaptic D2 receptor function, The pattern of results is consistent with the greater loss of DA from the PFC than from motor areas in aged monkey brain (Goldman-Rakic and Brown, 1981; Wenk et al., 1989), and indicates that DA depletion contributes significantly to age-related cognitive decline.

Improving effects of huperzine A on spatial working memory in aged monkeys and young adult monkeys with experimental cognitive impairment

Our previous studies demonstrated that huperzine A, a reversible and selective acetylcholinesterase inhibitor, exerts beneficial effects on memory deficits in various rodent models of amnesia. To extend the antiamnesic action of huperzine A to nonhuman primates, huperzine A was evaluated for its ability to reverse the deficits in spatial memory produced by scopolamine in young adult monkeys or those that are naturally occurring in aged monkeys using a delayed-response task. Scopolamine, a muscarinic receptor antagonist, dose dependently impaired performance with the highest dose (0.03 mg/kg, i.m.) producing a significant reduction in choice accuracy in young adult monkeys. The delayed performance changed from an average of 26.8/30 trials correct on saline control to an average of 20.2/30 trials correct after scopolamine administration. Huperzine A (0.01-0.1 mg/kg, i.m.) significantly reversed deficits induced by scopolamine in young adult monkeys on a delayed-response task; performance after an optimal dose (0.1 mg/kg) averaged 25.0/30 correct. In four aged monkeys, huperzine A (0.001-0.01 mg/kg, i.m.) significantly increased choice accuracy from 20.5/30 on saline control to 25.2/30 at the optimal dose (0.001 mg/kg for two monkeys and 0.01 mg/kg for the other two monkeys). The beneficial effects of huperzine A on delayed-response performance were long lasting; monkeys remained improved for about 24 h after a single injection of huperzine A. This study extended the findings that huperzine A improves the mnemonic performance requiring working memory in monkeys, and suggests that huperzine A may be a promising agent for clinical therapy of cognitive impairments in patients with Alzheimer's disease.

Inventors and entrepreneurs in academia: What types of skills and experience matter?

This paper aims to improve our understanding of the attributes of academic researchers that influence the capacity to contribute to technical advance, by adding to the pool of technological opportunities available to industry or engaging in the exploitation of entrepreneurial opportunities. We investigate a number of factors associated with the skills developed by academic researchers. We find that contributions to the pool of technological opportunities and exploitation of entrepreneurial opportunities involve different sets of skills and expertise of scientists. Our results show that the former is driven by academic scientists research excellence and discovery of earlier technological opportunities and the latter is driven by previous collaboration with industry partners, scientific breadth and experience of technological discovery. © 2011 Elsevier Ltd. All rights reserved.

A framework for studying cognitive impairment to inform inclusive design

Chapter 12 A Framework for Studying Cognitive Impairment to Inform Inclusive Design E. Jokisuu, PM Langdon and PJ Clarkson 12.1 Introduction Cognitive impairment is an exceptionally complicated phenomenon, for which no simple solutions ...

Modulation of pain processing in hyperalgesia by cognitive demand.

The relationship between pain and cognitive function is of theoretical and clinical interest, exemplified by observations that attention-demanding activities reduce pain in chronically afflicted patients. Previous studies have concentrated on phasic pain, which bears little correspondence to clinical pain conditions. Indeed, phasic pain is often associated with differential or opposing effects to tonic pain in behavioral, lesion, and pharmacological studies. To address how cognitive engagement interacts with tonic pain, we assessed the influence of an attention-demanding cognitive task on pain-evoked neural responses in an experimental model of chronic pain, the capsaicin-induced heat hyperalgesia model. Using functional magnetic resonance imaging (fMRI), we show that activity in the orbitofrontal and medial prefrontal cortices, insula, and cerebellum correlates with the intensity of tonic pain. This pain-related activity in medial prefrontal cortex and cerebellum was modulated by the demand level of the cognitive task. Our findings highlight a role for these structures in the integration of motivational and cognitive functions associated with a physiological state of injury. Within the limitations of an experimental model of pain, we suggest that the findings are relevant to understanding both the neurobiology and pathophysiology of chronic pain and its amelioration by cognitive strategies.

Cognitive Tomography Reveals Complex, Task-Independent Mental Representations

Humans develop rich mental representations that guide their behavior in a variety of everyday tasks. However, it is unknown whether these representations, often formalized as priors in Bayesian inference, are specific for each task or subserve multiple tasks. Current approaches cannot distinguish between these two possibilities because they cannot extract comparable representations across different tasks [1-10]. Here, we develop a novel method, termed cognitive tomography, that can extract complex, multidimensional priors across tasks. We apply this method to human judgments in two qualitatively different tasks, "familiarity" and "odd one out," involving an ecologically relevant set of stimuli, human faces. We show that priors over faces are structurally complex and vary dramatically across subjects, but are invariant across the tasks within each subject. The priors we extract from each task allow us to predict with high precision the behavior of subjects for novel stimuli both in the same task as well as in the other task. Our results provide the first evidence for a single high-dimensional structured representation of a naturalistic stimulus set that guides behavior in multiple tasks. Moreover, the representations estimated by cognitive tomography can provide independent, behavior-based regressors for elucidating the neural correlates of complex naturalistic priors. © 2013 The Authors.

Cognitive models in biomimetic pattern cognition

We describe a new model which is based on the concept of cognizing theory. The method identifies subsets of the data which are embedded in arbitrary oriented lower dimensional space. We definite k-mean covering, and study its property. Covering subsets of points are repeatedly sampled to construct trial geometry space of various dimensions. The sampling corresponding to the feature space having the best cognition ability between a mode near zero and the rest is selected and the data points are partitioned on the basis of the best cognition ability. The repeated sampling then continues recursively on each block of the data. We propose this algorithm based on cognition models. The experimental results for face recognition demonstrate that the correct rejection rate of the test samples excluded in the classes of training samples is very high and effective.

Effects of Naotan Pill on repair of neural cells and cognitive disorders in juvenile rats following hypoxia and ischemia

BACKGROUND: Hypoxia and ischemia induce neuronal damage, decreased neuronal numbers and synaptophysin levels, and deficits in learning and memory functions. Previous studies have shown that lycium barbarum polysaccharide, the most effective component of barbary wolfberry fruit, has protective effects on neural cells in hypoxia-ischemia. OBJECTIVE: To investigate the effects of Naotan Pill on glutamate-treated neural cells and on cognitive function in juvenile rats following hypoxia-ischemia. DESIGN, TIME AND SETTING: The randomized, controlled, in vivo study was performed at the Cell Laboratory of Lanzhou University, Lanzhou Institute of Modern Physics of Chinese Academy of Sciences, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from December 2005 to August 2006. The cellular neurobiology, in vitro experiment was conducted at the Institute of Human Anatomy, Histology, Embryology and Neuroscience, School of Basic Medical Sciences, Lanzhou University, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from March 2007 to January 2008. MATERIALS: Naotan Pill, composed of barbary wolfberry fruit, danshen root, grassleaf sweetflag rhizome, and glossy privet fruit, was prepared by Gansu Provincial Rehabilitation Center, China. Rabbit anti-synaptophysin, choline acetyl transferase polyclonal antibody, streptavidin-biotin complex kit and diaminobenzidine kit (Boster, Wuhan, China), as well as glutamate (Hualian, Shanghai, China) were used in this study. METHODS: Cortical neural cells were isolated from neonatal Wistar rats. Neural cell damage models were induced using glutamate, and administered Naotan Pill prior to and following damage. A total of 54 juvenile Wistar rats were equally and randomly assigned into model, Naotan Pill, and sham operation groups. The left common carotid artery was ligated, and then rat models of hypoxic-ischemic injury were assigned to the model and Naotan Pill groups. At 2 days following model induction, rats in the Naotan Pill group were administered Naotan Pill suspension for 21 days. In the model and sham operation groups, rats received an equal volume of saline. MAIN OUTCOME MEASURES: Neural cell morphology was observed using an inverted phase contrast microscope. Survival rate of neural cells was measured by MTT assay. Synaptophysin and choline acetyl transferase expression was observed in the hippocampal CA1 region of juvenile rats using immunohistochemistry. Cognitive function was tested by the Morris water maze. RESULTS: Pathological changes were detected in glutamate-treated neural cells. Neural cell morphology remained normal after Naotan Pill intervention. Absorbance and survival rate of neural cells were significantly greater following Naotan Pill intervention, compared to glutamate-treated neural cells (P < 0.05). Synaptophysin and choline acetyl transferase expression was lowest in the hippocampal CA1 region in the model group and highest in the sham operation group. Significant differences among groups were observed (P < 0.05). Escape latency and swimming distance were significantly longer in the model group compared to the Naotan Pill group (P < 0.05). CONCLUSION: Naotan Pill exhibited protective and repair effects on glutamate-treated neural cells. Naotan Pill upregulated synaptophysin and choline acetyl transferase expression in the hippocampus and improved cognitive function in rats following hypoxia-ischemia.

听力障碍与听力正常群体视觉注意发展及其机制的比较

One of the most important functions in the individual development is the interaction and integration of each sensory input. There exist two competing theories, i.e. the deficiency theory and the compensatory theory, regarding the origin and nature of changes in visual functions observed after auditory deprivation. The deficiency theory proposed that integrative processes are essential for normal development. In contrast, the compensatory theory stated that the loss of one sense may be met by a greater reliance upon, therefore an enhancement of the remaining senses. Given that hearing impaired children’s learning depends primarily on visual information, it is important to recognize the differences of visual attention between them and their hearing age-mates. Differences among age groups could exist in either selectivity or sustained attention. Study 1 and study 2 explored the selective and sustained attention development of hearing impaired and hearing students with average cognitive ability, aged from 7 years to college students. The analysis and discussion of the results are based on the visual attention development as well as deficiency theory and compensatory theory. According to the results of the study 1 and study 2, the spatial distribution and controlling of the visual attention between hearing impaired and hearing students were also investigated in the study 3 and study 4. The present work showed that: Firstly, both hearing impaired and hearing participants had the similar developmental trajectory of the sustained attention. The ability of children’s sustained attention appeared to improve with age, and in adolescence it reached the peak. The hearing impaired participants had the comparable sustained attention skills to the matched hearing ones. Besides, the results of the hearing impaired participants showed that they could maintain their attention and vigilance on the current task over the observation period. Secondly, group differences of visual attention development were found between hearing impaired and hearing participants. In the childhood, the visual attention developmental speed of the hearing impaired children was slower than that of the hearing ones. The selective attention skill of the hearing impaired were not comparable to the hearing ones, however, their selective skill improved with age, so in the adulthood, hearing impaired students showed the slight advantage in the selective attention skill over the hearing ones. Thirdly, hearing impaired and hearing participants showed the similar spatial distribution in the attention resources. In the low perceptual load condition, both participants were suffered great interference of the distrator at the fixation. In contrast, in the high perceptual load condition, hearing impaired adults were suffered more interference of the peripheral distractor, which suggested that they distributed more attention resources to the peripheral field when faced difficult tasks. Fourthly, both groups showed similar processing in the visual attention tasks. That is, they both searched the target with only the color feature in a parallel way, but in a serial way while processing orientation feature and the features with the combination of the color and orientation. Furthermore, the results indicated that two groups show similar ways in the attention controlling. In summary, the present study showed that visual attention development was dependent upon the integration of multimodal sensory information. Because of the interaction and integration of the input from various sensory, it has a negative impact on the intact sensory at the early stage of one sensory loss, however, it can better the functions of other intact sensory gradually with development and practice.

Tense, Aspect and the Cognitive Representation of Time

This paper explores the relationships between a computation theory of temporal representation (as developed by James Allen) and a formal linguistic theory of tense (as developed by Norbert Hornstein) and aspect. It aims to provide explicit answers to four fundamental questions: (1) what is the computational justification for the primitive of a linguistic theory; (2) what is the computational explanation of the formal grammatical constraints; (3) what are the processing constraints imposed on the learnability and markedness of these theoretical constructs; and (4) what are the constraints that a linguistic theory imposes on representations. We show that one can effectively exploit the interface between the language faculty and the cognitive faculties by using linguistic constraints to determine restrictions on the cognitive representation and vice versa. Three main results are obtained: (1) We derive an explanation of an observed grammatical constraint on tense?? Linear Order Constraint??m the information monotonicity property of the constraint propagation algorithm of Allen's temporal system: (2) We formulate a principle of markedness for the basic tense structures based on the computational efficiency of the temporal representations; and (3) We show Allen's interval-based temporal system is not arbitrary, but it can be used to explain independently motivated linguistic constraints on tense and aspect interpretations. We also claim that the methodology of research developed in this study??oss-level" investigation of independently motivated formal grammatical theory and computational models??a powerful paradigm with which to attack representational problems in basic cognitive domains, e.g., space, time, causality, etc.

Aphasia rehabilitation and the strange neglect of speed.

Timing data is infrequently reported in aphasiological literature and time taken is only a minor factor, where it is considered at all, in existing aphasia assessments. This is not surprising because reaction times are difficult to obtain manually, but it is a pity, because speed data should be indispensable in assessing the severity of language processing disorders and in evaluating the effects of treatment. This paper argues that reporting accuracy data without discussing speed of performance gives an incomplete and potentially misleading picture of any cognitive function. Moreover, in deciding how to treat, when to continue treatment and when to cease therapy, clinicians should have regard to both parameters: Speed and accuracy of performance. Crerar, Ellis and Dean (1996) reported a study in which the written sentence comprehension of 14 long-term agrammatic subjects was assessed and treated using a computer-based microworld. Some statistically significant and durable treatment effects were obtained after a short amount of focused therapy. Only accuracy data were reported in that (already long) paper, and interestingly, although it has been a widely read study, neither referees nor subsequent readers seemed to miss "the other side of the coin": How these participants compared with controls for their speed of processing and what effect treatment had on speed. This paper considers both aspects of the data and presents a tentative way of combining treatment effects on both accuracy and speed of performance in a single indicator. Looking at rehabilitation this way gives us a rather different perspective on which individuals benefited most from the intervention. It also demonstrates that while some subjects are capable of utilising metalinguistic skills to achieve normal accuracy scores even many years post-stroke, there is little prospect of reducing the time taken to within the normal range. Without considering speed of processing, the extent of this residual functional impairment can be overlooked.

Choking RECtified: embodied expertise beyond Dreyfus

On a Dreyfusian account performers choke when they reflect upon and interfere with established routines of purely embodied expertise. This basic explanation of choking remains popular even today and apparently enjoys empirical support. Its driving insight can be understood through the lens of diverse philosophical visions of the embodied basis of expertise. These range from accounts of embodied cognition that are ultra conservative with respect to representational theories of cognition to those that are more radically embodied. This paper provides an account of the acquisition of embodied expertise, and explanation of the choking effect, from the most radically enactive, embodied perspective, spelling out some of its practical implications and addressing some possible philosophical challenges. Specifically, we propose: (i) an explanation of how skills can be acquired on the basis of ecological dynamics; and (ii) a non-linear pedagogy that takes into account how contentful representations might scaffold skill acquisition from a radically enactive perspective.

Lessons learned in an information skills training programme for a mental health Trust

Parker, R. & Urquhart, C. (2007). Lessons learned in an information skills training programme for a mental health Trust. Health Information and Libraries Journal, 24(1), 58-61.

Learning from triads: training undergraduates in counselling skills

Background: Research has shown that counselling skills training in undergraduate programmes is effective. However, there is potential that premature intimacy and disclosures during triad work may impact on relationships which must be maintained out-with the counselling component of the course. Little research has examined individual pedagogical practices within training. Aim: The aim of this research was to explore the experience of the practical skills training component of a counselling course for a cohort of undergraduate students, and the impact of this learning experience. The objective being an evaluation of the use of this approach for this group and of the impact of personal sharing within cohorts of undergraduates. Method: Semi-structured interviews focusing on the experience of skills training and self-disclosure during training were carried out on 12 undergraduates taking counselling skills modules as part of their BSc Psychology and Counselling degree. Thematic analysis was carried out on the interview transcripts. Results: As a result of engagement in skills training and acting as ‘clients’ for one another, individuals perceived the formation of a positive group identity with implicit ‘rules’, but also an impact of training on relationships within the group which relied on the ability to maintain boundaries and personal identities with peers, and this influenced the learning experience. The ability to manage their engagement on the programme was dependent on ongoing support and guidance from tutors. Discussion: While this pedagogical approach appears appropriate for facilitating learning and potentially provides a rich learning journey for undergraduate students, tutors must act proactively to ensure a safe learning environment.