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Differential role for CBP and p300 CREB-binding domain in motor skill learning.

Cyclic adenosine monophosphate response element binding protein (CREB) binding protein (CBP) and E1A binding protein (p300) are highly homologous transcriptional coactivators with histone acetyltransferase activity. Although CBP and p300 have unique functions in vivo during embryogenesis and hematopoiesis, their functions within the nervous system remain poorly understood. The authors demonstrate that these coactivators have differential roles in motor skill learning. Mice with a mutation in the CREB-binding (KIX) domain of CBP exhibited motor learning deficits. However, mice with the analogous mutation in the KIX domain of p300 showed normal motor learning. Further, CREB knock-out mice exhibited a motor learning deficit similar to that of CBP-KIX mutant mice. These results suggest that the CREB-CBP interaction is more limiting or critical than the CREB-p300 interaction for motor skill learning. Thus, CBP and p300 are genetically distinct at the behavioral level.

Analysis of Variance↗

Fragmented pictures revisited: long-term changes in repetition priming, relation to skill learning, and the role of cognitive resources.

BACKGROUND: Whereas age-related declines in declarative memory have been demonstrated in multiple cross-sectional and longitudinal studies, the effect of age on non-declarative manifestations of memory, such as repetition priming and perceptual skill learning, are less clear. The common assumption, based on cross-sectional studies, is that these processes are only mildly (if at all) affected by age. OBJECTIVE: To investigate long-term changes in repetition priming and age-related differences in identification of fragmented pictures in a 5-year longitudinal design. METHOD: Healthy adults (age 28-82 years) viewed drawings of objects presented in descending order of fragmentation. The identification threshold (IT) was the highest fragmentation level at which the object was correctly named. After a short interval, old pictures were presented again along with a set of similar but novel pictures. Five years later the participants repeated the experiment. RESULTS: At baseline and 5-year follow-up alike, one repeated exposure improved IT for old (priming) and new (skill acquisition) pictures. However, long-term retention of priming gains was observed only in young adults. Working memory explained a significant proportion of variance in within-occasion priming, long-term priming, and skill learning. CONCLUSION: Contrary to cross-sectional results, this longitudinal study suggests perceptual repetition priming is not an age-invariant phenomenon and advanced age and reduced availability of cognitive resources may contribute to its decline.

Adult↗

Distinguishable brain activation networks for short- and long-term motor skill learning.

The acquisition of a new motor skill is characterized first by a short-term, fast learning stage in which performance improves rapidly, and subsequently by a long-term, slower learning stage in which additional performance gains are incremental. Previous functional imaging studies have suggested that distinct brain networks mediate these two stages of learning, but direct comparisons using the same task have not been performed. Here we used a task in which subjects learn to track a continuous 8-s sequence demanding variable isometric force development between the fingers and thumb of the dominant, right hand. Learning-associated changes in brain activation were characterized using functional MRI (fMRI) during short-term learning of a novel sequence, during short-term learning after prior, brief exposure to the sequence, and over long-term (3 wk) training in the task. Short-term learning was associated with decreases in activity in the dorsolateral prefrontal, anterior cingulate, posterior parietal, primary motor, and cerebellar cortex, and with increased activation in the right cerebellar dentate nucleus, the left putamen, and left thalamus. Prefrontal, parietal, and cerebellar cortical changes were not apparent with short-term learning after prior exposure to the sequence. With long-term learning, increases in activity were found in the left primary somatosensory and motor cortex and in the right putamen. Our observations extend previous work suggesting that distinguishable networks are recruited during the different phases of motor learning. While short-term motor skill learning seems associated primarily with activation in a cortical network specific for the learned movements, long-term learning involves increased activation of a bihemispheric cortical-subcortical network in a pattern suggesting "plastic" development of new representations for both motor output and somatosensory afferent information.

Adult↗

The interaction of observational learning with overt practice: effects on motor skill learning.

This study explored various methods of combining observational learning via demonstration with the effects of overt practice for learning a discrete action pattern. Three groups were compared that varied by the timing of demonstration in relation to practice. An all-pre-practice demonstration group viewed 10 pre-practice videotape demonstrations of an expert performing the skill, and then engaged in practice. An interspersed demonstration group viewed one pre-practice demonstration, then initiated practice on the skill. Every three attempts, practice was halted while participants viewed another demonstration, with this pattern repeated throughout acquisition. A combination demonstration group experienced elements of each schedule by viewing five demonstrations prior to practice, then five more once practice had begun (one every three attempts) so that modeling was completed by mid-acquisition. Ratings of form and accuracy were assessed in an acquisition phase, an immediate retention test, and a 48-h retention test. Group main effects for form scores were detected in acquisition, immediate, and 48-h retention, with the combination group obtaining the highest form scores, followed by the all-pre-practice group, and finally the interspersed group. These findings suggest that several modeling exposures before practice and several more exposures in the early stages of practice were optimal for acquisition and retention of form.

Adult↗

Functional anatomy of visuomotor skill learning in human subjects examined with positron emission tomography.

The present study was designed to examine patterns of regional cerebral blood flow (CBF) associated with the learning of a repeated visuomotor sequence both in the early and late phases of the acquisition process. In addition, changes in blood flow related to the implicit versus explicit aspects of learning such a skill were investigated. Fourteen normal control subjects were scanned while performing the task (i) in both early and advanced learning stages of the visuomotor sequence; (ii) after having acquired explicit knowledge of the sequences; and (iii) in two control conditions (perceptual and random sequence). Subtraction of the random condition from the highly learned condition revealed specific areas of activity in the right ventral striatum and dentate nucleus of the cerebellum. Blood flow changes in the right hemisphere were also seen in the medial posterior parietal and prestriate regions, as well as in the anterior cingulate cortex. Finally, once the subjects had acquired explicit knowledge of the embedded sequence that was presented in the highly learned condition, increased CBF activity was observed only in the mid-ventrolateral frontal area in the right hemisphere. These findings confirm that both the striatum and the cerebellum are involved in the implicit acquisition of a visuomotor skill, especially in the advanced stages of the learning process, and furthermore that the ventrolateral prefrontal cortex contributes preferentially to the declarative aspect of this task.

Adult↗

Skilled-learning-induced potentiation in rat sensorimotor cortex: a transient form of behavioural long-term potentiation.

The relation between the acquisition of a skilled motor task and synaptic plasticity in the sensorimotor cortex of the awake, freely behaving rat was examined. Skilled-motor training was previously found to induce a functional reorganization of the caudal forelimb area, and to induce an increase in synaptic efficacy, measured in vitro, on the side contralateral to the reaching forelimb. Here, we repeatedly measured neocortical evoked potential recordings in awake, freely behaving rats to examine whether skilled training would induce changes in polysynaptic efficacy on the side contralateral to the reaching forelimb. We found that the increase in task proficiency, but not the acquisition of task requirements or the maintenance of task proficiency, induced an increase in synaptic efficacy on the side contralateral to the reaching forelimb. We also tested the hypothesis that skilled learning induced potentiation shares similar mechanisms to long-term potentiation (LTP) and long-term depression by artificially manipulating polysynaptic efficacy in skilled rats with high- and low-frequency stimulation. We observed that, compared with the ipsilateral side, less potentiation but more depression could be induced on the side contralateral to the reaching forelimb. We conclude that a transient, network-based LTP-like mechanism operates during the learning of a skilled motor task.

Animals↗

Skill learning.

This chapter reviews recent experiments that have examined the functional neuroanatomy of motor and visuomotor skill learning using brain imaging techniques such as single photon emission computed tomography, positron emission tomography, and functional magnetic resonance imaging. Special attention has been given to the cerebral blood flow changes in the cerebellum that are associated with the acquisition of these skills, although localizations of other activated regions (cortical and subcortical) are also included. The cognitive processes involved in different skill acquisition paradigms are discussed with particular reference to the learning stages at which subjects were scanned. This approach examines the conditions that are likely to produce cerebellar activation and helps us understand the role of the cerebellum in acquiring skilled behaviors.

Animals↗

Patients with Parkinson's disease learn to control complex systems-an indication for intact implicit cognitive skill learning.

Implicit memory and learning mechanisms are composed of multiple processes and systems. Previous studies demonstrated a basal ganglia involvement in purely cognitive tasks that form stimulus response habits by reinforcement learning such as implicit classification learning. We will test the basal ganglia influence on two cognitive implicit tasks previously described by Berry and Broadbent, the sugar production task and the personal interaction task. Furthermore, we will investigate the relationship between certain aspects of an executive dysfunction and implicit learning. To this end, we have tested 22 Parkinsonian patients and 22 age-matched controls on two implicit cognitive tasks, in which participants learned to control a complex system. They interacted with the system by choosing an input value and obtaining an output that was related in a complex manner to the input. The objective was to reach and maintain a specific target value across trials (dynamic system learning). The two tasks followed the same underlying complex rule but had different surface appearances. Subsequently, participants performed an executive test battery including the Stroop test, verbal fluency and the Wisconsin card sorting test (WCST). The results demonstrate intact implicit learning in patients, despite an executive dysfunction in the Parkinsonian group. They lead to the conclusion that the basal ganglia system affected in Parkinson's disease does not contribute to the implicit acquisition of a new cognitive skill. Furthermore, the Parkinsonian patients were able to reach a specific goal in an implicit learning context despite impaired goal directed behaviour in the WCST, a classic test of executive functions. These results demonstrate a functional independence of implicit cognitive skill learning and certain aspects of executive functions.

Aged↗

Motor-skill learning: changes in synaptic organization of the rat cerebellar cortex.

Rats trained on motor-skill learning tasks for 30 days were previously found to have more synapses in the volume of tissue proportional to a Purkinje cell than rats that exercised or were inactive. In the motor learning tasks, hooded rats were required to traverse an obstacle course requiring balance and coordination. Rats in two exercise groups were required to walk rapidly or allowed to run in activity wheels. Controls were relatively inactive in standard housing and handled once daily. Synapses were classified to determine which synaptic types changed in number across levels of the molecular layer in the paramedian lobule. The motor learning group had significantly more parallel fiber synapses and climbing fiber synapses per unit Purkinje cell reference volume than all other groups. There were also more synapses and more parallel fiber synapses per reference volume in the outermost than in the innermost molecular layer. The plasticity reported here occurs in vivo under normal physiological conditions. Excitatory synapses account for at least 80% of the synapses in the molecular layer. The results support prior predictions that parallel fiber synapses are modifiable during conditions of learning.

Animals↗

Transfer and motor skill learning in association football.

Transfer of learning involves the influence of previous experiences on the performance or learning of new skills. It is defined as a gain (or loss) in the capability for performance on one task as a result of practice on another. The aim of the study was to examine the degree of transfer between various association football skills. Twenty intermediate male players participated in the study. During pre- and post-training tests, participants juggled a football as many times as possible within 30 s using feet or knees. Further tests required participants to control an approaching football inside a restricted area using the preferred and non-preferred kicking leg. Following performance on the pretest, two matched skill groups were obtained. One group participated in a 4-week training period in which feet-only ball juggling was practised for 10 min daily, while the remaining group acted as a control. Trained participants exhibited superior post-test performance on knee juggling and ball control with preferred and non-preferred leg tasks relative to the control group (p < 0.05). Findings indicate positive transfer of learning from juggling practice with the feet to juggling with the knees and a football control task. Implications for theory and practice are highlighted.

Adult↗

Radiographic skills learning: procedure simulation using adaptive hypermedia.

The design and development of a simulation tool supporting learning of radiographic skills is reported. This tool has by textual, graphical and iconic resources, organized according to a building-block, adaptive hypermedia approach, which is described and supported by an image base of radiographs. It offers interactive user-controlled simulation of radiographic imaging procedures. The development is based on a commercially available environment (Toolbook 3.0, Asymetrix Corporation). The core of the system is an attributed precedence (priority) graph, which represents a task outline (concept and resources structure), which is dynamically adjusted to selected procedures. The user interface imitates a conventional radiography system, i.e. operating console, tube, table, patient and cassette. System parameters, such as patient positioning, focus-to-patient distance, magnification, field dimensions, tube voltage and mAs are under user control. Their effects on image quality are presented, by means of an image base acquired under controlled exposure conditions. Innovative use of hypermedia, computer based learning and simulation principles and technology in the development of this tool resulted in an enhanced interactive environment providing radiographic parameter control and visualization of parameter effects on image quality.

Computer Simulation↗

The functional anatomy of sleep-dependent visual skill learning.

Learning of procedural skills develops gradually, with performance improving significantly with practice. But improvement on some tasks, including a visual texture discrimination task, continues in the absence of further practice, expressly during periods of sleep and not across equivalent waking episodes. Here we report that the brain activation revealed significantly different patterns of performance-related functional activity following a night of sleep relative to 1 h post-training without intervening sleep. When task activation patterns after a night of sleep were compared with activation patterns without intervening sleep (1 h post-training), significant regions of increased signal intensity were observed in the primary visual cortex, the occipital temporal junction, the medial temporal lobe and the inferior parietal lobe. In contrast, a region of decreased signal intensity was found in the right temporal pole. Corroborating these condition differences, correlations between behavioural performance and brain activation revealed significantly different patterns of performance-related functional activity following a night of sleep relative to those without intervening sleep. Together, these data provide evidence of overnight bi-directional changes in functional anatomy, differences that may form the neural basis of sleep-dependent learning expressed on this task.

Adult↗

Exercise and the brain: angiogenesis in the adult rat cerebellum after vigorous physical activity and motor skill learning.

This study compared the morphology of cerebellar cortex in adult female rats exposed for 1 month to repetitive exercise, motor learning, or an inactive condition. In the exercise conditions, rats that were run on a treadmill or housed with access to a running wheel had a shorter diffusion distance from blood vessels in the molecular layer of the paramedian lobule when compared to rats housed individually or rats that participated in a motor skill learning task. Rats taught complex motor skills substantially increased the volume of the molecular layer per Purkinje neuron and increased blood vessel number sufficiently to maintain the diffusion distance. These results dissociate angiogenesis associated with increased neuropil volume (as seen in the motor learning group) from angiogenesis associated with increased metabolic demands (as seen in the exercise groups). While the volume fraction of mitochondria did not differ among groups, the mitochondrial volume fraction per Purkinje cell was significantly increased in the motor skill rats. This appears to parallel the previously reported increase in synapses and associated neuropil volume change.

Animals↗

Performance but not acquisition of skill learning is severely impaired in the elderly.

A battery of cognitive tests, specifically designed to assess verbal and skill learning, was administered to healthy volunteer subjects of different ages. Although there were age-related declines in initial and terminal performance in both a pursuit rotor and a mirror reading task, the increase in performance with practice on these tasks was little affected by age. Recall, but not recognition, of verbal material was also impaired in the elderly, as were some measures of frequency estimation. These findings are compatible with the contention that, although acquisition of declarative tasks, which requires conscious processing, is impaired in the elderly, acquisition of nondeclarative tasks, which can be learned without conscious awareness, is not affected by age. However, classical conditioning may be an exception to this generalization for reasons that are at the present time unknown.

Journal Article↗

The neural correlates of consciousness: an analysis of cognitive skill learning.

This paper presents a functional brain-imaging strategy designed to isolate neural correlates of consciousness in humans. This strategy is based on skill learning. In the example presented (rapidly generating verbs for visually presented nouns), a cognitive skill is examined before and after practice. As shown, there are marked qualitative differences in the neural circuitry supporting performance of this task in the naive and practised state that include, importantly, both increases and decreases from the baseline activity of the brain.

Brain↗

Evaluation of consent for peer physical examination: students reflect on their clinical skills learning experience.

INTRODUCTION: Early clinical skills teaching often requires students to learn through examining one another. This model should acknowledge ethical, practical and individual issues, disclosure and identification of abnormalities. Consent to peer physical examination (PPE) is usually expected rather than discussed and sought. OBJECTIVES: We sought to evaluate a formal written consent process for PPE and to explore students' views of this approach. METHOD: A survey tool was designed and distributed to all years 2 and 3 students in the Auckland University medical programme (2004). Results were analysed using univariate statistics and thematic analysis. RESULTS: The response rate was 57% (146/258). Most students had read the participant information sheet prior to signing, with 78% giving consent. They had not felt coerced and the in-course experience matched the 'promise'. Comments included: PPE gave insights into the 'patient's world', encouraged peer learning and raised some professional issues. More than 95% of students took the examination role at least once (less likely if female, P = 0.002). Some European, Maori and Pacific students never took the role; all Asian students did at least once. Students preferred PPE in groups consisting of 'friends'. The task influenced group composition by sex (P < 0.0001) but not ethnicity. DISCUSSION: Students accept and support a formal consent process. PPE participation rates are similar to predictions. The experience must match the promises made. Formal preparation alone might have produced similar student outcomes. Female students are more selective about tasks undertaken. The influence of ethnicity and the effect on future behaviour and attitudes needs further exploration.

Adolescent↗