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Errorless learning and the cognitive rehabilitation of memory-impaired schizophrenic patients.

BACKGROUND: In recent years, evidence has accumulated that a significant proportion of schizophrenic patients have severe memory impairment, which cannot be attributed to the effects of medication, chronicity or institutionalization. Our group has demonstrated that memory impairment is associated with poor psychosocial outcome and treatment resistance. Work on the classical amnesic syndrome has suggested that memory training is facilitated by adopting an 'errorless learning' approach, where subjects do not experience failure during learning. This is based on the theory that the preserved implicit memory of amnesic patients results in implicitly remembered incorrect responses interfering with target items, in the absence of a functioning explicit memory system to allow differentiation. METHOD: We compared three groups of subjects, memory-impaired schizophrenic patients, memory unimpaired schizophrenic patients and healthy controls. RESULTS: An errorless learning approach conferred a significant advantage on the memory-impaired schizophrenic group, bringing their performance up to the level of both control groups. In contrast, adopting a traditional trial and error, or errorful approach resulted in markedly impaired performance in the memory-impaired schizophrenic group only. CONCLUSIONS: We conclude that errorless learning approaches may be worthy of further evaluation in the cognitive rehabilitation of memory-impaired schizophrenic patients.

Adult↗

Lack of generalization of object discrimination between spatial contexts by a bat.

Discrimination and generalization are important elements of cognition in the daily lives of animals. Nectar-feeding bats detect flowers by olfaction and probably vision, but also use echolocation and echo-perception of flowers in immediate target surroundings. The echo received from an interference-rich flower corolla is a function of a bat's own relative position in space. This raises the question how easily a free-flying bat will generalize an echo stimulus from a learning situation to a new spatial context where differences in relative flight approach trajectories may lead to an unfamiliar spectral composition of the self-generated echoes. We trained free-flying Glossophaga soricina in echoacoustic discrimination in a two-alternative forced-choice (2-AFC) paradigm at location A. We then tested at location B for spontaneous transfer of discrimination ability. Bats did not spontaneously transfer the discrimination ability acquired at A to location B. This lack of spontaneous generalization may have been caused by factors of the underlying learning mechanisms. 2-AFC tasks may not be representative of the natural foraging behaviour of flower-visiting bats. In contrast to insect-eating bats that constantly evaluate the environment to detect unpredictable prey, the spatial stability of flowers may allow flower visitors to rely on spatial memory to guide foraging. The 2-AFC task requires the disregard (learned irrelevance) of salient spatial location cues that are different at each new location. In Glossophaga, a conjunction between spatial context and 2-AFC discrimination learning may have inhibited the transfer of learned irrelevance of spatial location in the 2-AFC task to new spatial locations. Alternatively, the bats may have learnt the second discrimination task completely anew, and were faster only because of an acquired learning set. We suggest a dissociation between 2-AFC task acquisition and novel object discrimination learning to resolve the issue.

Animals↗

Spatial learning induces differential changes in calcium/calmodulin-stimulated (ACI) and calcium-insensitive (ACII) adenylyl cyclases in the mouse hippocampus.

Several lines of evidence indicate that Ca2+/calmodulin-stimulated isoforms of adenylyl cyclase (AC) are involved in long-term potentiation and in certain forms of learning. Recently, we found that training in different types of learning task differentially activates Ca2+-sensitive versus Ca2+-insensitive AC activities in certain brain regions, indicating that AC species other than those stimulated by Ca2+/calmodulin may play an important role in learning processes (Guillou, Rose, & Cooper, 1999). Here, we report the effects of spatial reference memory training in a radial arm maze on the levels of AC1 and AC2 mRNA in the dorsal hippocampus of C57BL/6 mice. Acquisition of the task was associated with a learning-specific and time-dependent increase of AC1 mRNA expression selectively in subfields CA1-CA2. In contrast, AC2 mRNA levels were either reduced or not reliably affected depending on the stage of acquisition. Moreover, no significant changes in AC expression were observed either in the dorsal hippocampus of mice trained in a non-spatial (procedural) version of the task or in cortical regions of mice learning the spatial or procedural task. The regional specificity of these effects indicates that the formation of spatial and non-spatial memory requires distinct contributions from Ca2+-sensitive and Ca2+-insensitive AC in the hippocampus. It is suggested that downregulation of AC2 throughout all hippocampal subfields may play a permissive role during the acquisition of spatial learning whereas an upregulation of AC1 specifically in subfield CA1, may be critical to accurately encode, store or use spatial information.

Adenylyl Cyclases↗

Teaching international nursing students: challenges and strategies.

Cross-cultural education presents many challenges and focuses attention on the significant differences in teaching and learning styles around the world. In 1995, the George Mason University College of Nursing and Health Science embarked on the Saudi-US University Project, an effort that brought these theoretical differences to life. The stark contrast between the Saudi Arabian and Western cultures provided administration, faculty, and students the opportunity to develop creative strategies to accommodate learning across cultures.

Acculturation↗

Hippocampal lesions are without effect on olfactory memory formation in the context of pregnancy block.

Female mice which have mated and are subsequently exposed to male urine odours (pheromones), which differ from those of the male that mated (stud male), undergo hormonal changes resulting in a block to pregnancy. Since the stud male's odour blocks the pregnancy of females other than those he mated, this would suggest that a memory specific for this male's odour is established at the time of mating. Hippocampal lesions, when made prior to mating, did not disrupt memory formation to the odour of the stud male. This male's odour did not block pregnancy, while changing odour to that of the strange male did block pregnancy. In order to establish the functional effectiveness of these hippocampal lesions, olfactory discriminations were examined in a modified T-maze. The odour discrimination was urine-soiled bedding taken from a cage of different strain males versus same strain bedding. After 35 trials, neither control nor lesioned females were performing above chance level (50% correct responses), indicating the difficulty in cognitively learning this discrimination. These female mice were therefore trained to distinguish a novel odour (butyl acetate) from familiar strain urine-soiled bedding. Hippocampal-lesioned females were slower to acquire this discrimination and did not perform above chance level after 35 trials, in contrast to the 70% success of sham-lesioned females. Hence, hippocampal lesions, while producing a deficit in olfactory learning in the maze test, are without effect on the formation or retrieval of the specific olfactory memory formed for the stud male at mating, as revealed from pregnancy block tests.

Animals↗

Phosphodiesterase 1B differentially modulates the effects of methamphetamine on locomotor activity and spatial learning through DARPP32-dependent pathways: evidence from PDE1B-DARPP32 double-knockout mice.

Mice lacking phosphodiesterase 1B (PDE1B) exhibit an exaggerated locomotor response to D-methamphetamine and increased in vitro phosphorylation of DARPP32 (dopamine- and cAMP-regulated phosphoprotein, M r 32 kDa) at Thr34 in striatal brain slices treated with the D1 receptor agonist, SKF81297. These results indicated a possible regulatory role for PDE1B in pathways involving DARPP32. Here, we generated PDE1B x DARPP32 double-knockout (double-KO) mice to test the role of PDE1B in DARPP32-dependent pathways in vivo. Analysis of the response to d-methamphetamine on locomotor activity showed that the hyperactivity experienced by PDE1B mutant mice was blocked in PDE1B-/- x DARPP32-/- double-KO mice, consistent with participation of PDE1B and DARPP32 in the same pathway. Further behavioral testing in the elevated zero-maze revealed that DARPP32-/- mice showed a less anxious phenotype that was nullified in double-mutant mice. In contrast, in the Morris water maze, double-KO mice showed deficits in spatial reversal learning not observed in either single mutant compared with wild-type mice. The data suggest a role for PDE1B in locomotor responses to psychostimulants through modulation of DARPP32-dependent pathways; however, this modulation does not necessarily impact other behaviors, such as anxiety or learning. Instead, the phenotype of double-KOs observed in these latter tasks may be mediated through independent pathways.

Analysis of Variance↗

A randomized, controlled comparison of instruction by a diabetes educator versus self-instruction in self-monitoring of blood glucose.

It is not clear whether diabetic patients can learn accurate self-monitoring of blood glucose (SMBG) by use of written package instructions. In addition, it is unclear whether the improvement in accuracy of monitoring that results from professional training is due to the professional intervention or to a personal practice effect. For these reasons, improvement in accuracy of SMBG (using Chemstrip bG, Biodynamics Division, Boehringer-Mannheim, Indianapolis, Indiana) after a 30-min session of professional instruction in one group of diabetic patients was compared with improvement after 30 min of practice and study of package instructions in another group. After initial reading of package instructions in both groups, and after the practice session in the control group, mean percent error was 22-37%. In contrast, mean percent error declined to 9% after a professional training session. We conclude that learning SMBG solely by reading package instructions leads to unacceptable inaccuracy. However, by use of short, intensive instruction sessions, a diabetes educator can reduce such errors and teach highly accurate monitoring to most diabetic patients.

Adult↗

Effects of galanin on passive avoidance response, elevated plus-maze learning, and spontaneous alternation performance in mice.

The present study was done to characterize the effects of intracerebroventricular injection of galanin (GAL) on memory processes by observing passive avoidance response, elevated plus-maze learning, and spontaneous alternation performance in mice. An intermediate dose (3 micrograms) of GAL (3 micrograms) significantly decreased step-down latency of passive avoidance response when given 15 min before training, whereas in particular the middle doses (0.3 and 1 microgram) of GAL significantly decreased it when given 15 min before retention tests. However, GAL (0.3-10 micrograms) was ineffective when given immediately after training. Physostigmine (0.2 mg/kg), a cholinesterase inhibitor, and oxotremorine (0.01 and 0.03 mg/kg), a cholinergic agonist, significantly inhibited the shortening of step-down latency induced by GAL (0.3 microgram) administered 15 min before retention tests, indicating the involvement of cholinergic dysfunction in the GAL (0.3 microgram)-induced shortening of step-down latency. In contrast, GAL (0.3-3 micrograms) failed to influence transfer latency in elevated plus-maze learning or percent alternation in spontaneous alternation performance. These results suggest that the activation of cholinergic neurons improves memory dysfunctions induced by GAL, which primarily impairs retrieval processes of memory. The lack of effects of GAL on the elevated plus-maze learning and spontaneous alternation performance may result from the selective effects of GAL in different learning paradigms.

Amino Acid Sequence↗

Amount of training affects associatively-activated event representation.

The effects of variations in the amount of training on behavioral plasticity were examined in three experiments that used appetitive Pavlovian conditioning procedures with rats. In experiments 1 and 2, an auditory conditioned stimulus (CS) substituted for a food unconditioned stimulus (US) in the acquisition of new learning about the food US after small numbers of CS-US pairings, but not after larger numbers of pairings. After limited exposure to the relation between the auditory CS and food, pairings of the CS with the toxin LiCl, in the absence of food, were sufficient to establish an aversion to the food US that was previously paired with that CS. This CS-mediated learning did not occur after more extensive exposure to the CS-food relation. In contrast, in experiment 3. mediated performance of previously-established conditioned responding was unaffected by the number of CS-US pairings used to establish that performance. Conditioned responding to the auditory CS remained sensitive to post-training devaluation of the food US regardless of the amount of initial CS-US training. Implications of these results for the investigations of cortical and other brain mechanisms of behavioral plasticity are discussed.

Acoustic Stimulation↗

Evidence against hyperspecificity in implicit invariant learning.

Four experiments examined the claim that cross-format transfer in invariant learning is reliant solely on the presence of repetition structure in study and test strings (Stadler, Warren, & Lesch, 2000). Experiments 1, 2, and 3 used strings with no repetitions and found significant cross-format transfer in combination with a non-significant transfer decrement--no significant difference between same- and changed-format conditions. Further investigation of the basis of the role of repetition structure revealed an emphasis on the perceptual salience of test stimuli (Experiment 4). Our results contrast with those of Stadler et al. and suggest that under the conditions we employed invariant learning is not highly sensitive to changes in the perceptual characteristics of stimuli and therefore is inaccurately described as hyperspecific. We suggest that the term hyperspecific be reserved for cases in which minor format changes result in significant performance impairments--for example, typographical effects in implicit memory.

Adult↗

Drosophila mushroom bodies are dispensable for visual, tactile, and motor learning.

A total of 18 associative learning/memory tests have been applied to Drosophila melanogaster flies lacking mushroom bodies. Only in paradigms involving chemosensory cues as conditioned stimuli have flies been found to be compromised by a block in the mushroom body pathway. Among the learning tasks not requiring these structures are a case of motor learning (yaw torque/heat), a test of the fly's spatial orientation in total darkness, conditioned courtship suppression by mated females, and nine different examples of visual learning. The latter used the reinforcers of heat, visual oscillations, mechanical shaking, or sucrose, and as conditioned stimuli, color, intensity contrast, as well as stationary and moving visual patterns. No forms of consolidated memory have been tested in mushroom body-less flies. With respect to short-term memory the mushroom bodies of Drosophila are specially required for chemosensory learning tasks, but not for associative learning and memory in general.

Animals↗

Contextual determinants of auditory learning in bobwhite quail embryos and hatchlings.

This study examined the ability of bobwhite quail embryos and hatchlings to learn an individual bobwhite maternal call. Results revealed that embryos could learn an individual maternal call and remember that call for at least 24 hr following exposure. In contrast, hatchlings reared socially in groups of same-age chicks during postnatal exposure to a maternal call did not demonstrate a preference for that familiar call at 24 hr following exposure. However, individual auditory recognition was exhibited by hatchlings reared in social isolation, suggesting that the perceptual and social complexity of the postnatal situation can disrupt or interfere with early auditory learning. Additional support for this view was the finding that embryos exposed to unusually early visual stimulation during prenatal exposure to a maternal call also failed to prefer that familiar maternal call in subsequent choice tests. The idea that early auditory learning capacity is determined more by context and experience rather than the organism's specific age or stage of development is discussed.

Animal Communication↗

Emotional, developmental, and behavioral health of American children and their families: a report from the 2003 National Survey of Children's Health.

BACKGROUND: Recent children's health surveys have documented a high prevalence of emotional, developmental, and behavioral problems among children. Data from the 2003 National Survey of Children's Health provide new insights into these problems and their association with family function and community participation. These issues have become a current focus of the World Health Organization. METHODS: Answers to questions of interest from the 2003 National Survey of Children's Health were reported using estimates and SEs of rates. Statistical comparisons of rates with chi2 tests at the 0.05 level were made when relevant. RESULTS: The most commonly diagnosed problems among children 6-17 years of age were learning disabilities (11.5%), attention-deficit/hyperactivity disorder (8.8%), and behavioral problems (6.3%); among preschoolers, speech problems (5.8%) and developmental delay (3.2%) were most common. One in 200 children was diagnosed with autism. In contrast, rates of parental concerns about emotional, developmental, or behavioral problems were much higher; for example, 41% of parents had concerns about learning difficulties and 36% about depression or anxiety. Children with developmental problems had lower self-esteem, more depression and anxiety, more problems with learning, missed more school, and were less involved in sports and other community activities. Their families experienced more difficulty in the areas of childcare, employment, parent-child relationships, and caregiver burden. CONCLUSIONS: The most recent National Survey of Children's Health mirrored results of previous surveys regarding rates of diagnosed emotional, developmental, and behavioral problems, including an escalating diagnosis of autism among children. Reported rates of parental concerns about these problems were much higher, suggesting possible underdiagnosis of children's problems. Children with chronic problems had diminished family functioning, more school absences, and less participation in community activities compared with other children. Their parents experienced more difficulty with childcare, employment, and parenting skills. A change in treatment emphasis is needed, away from an exclusive focus on a child's developmental and behavioral problems to one that addresses the impacts of these problems on the family and community participation. A new approach to the way these issues are addressed and managed has the potential to enhance the quality of life for a child, as well as the parents, and to produce more meaningful and tangible solutions to these complex and increasingly evident problems.

Adolescent↗

Long-term effects of status epilepticus in the immature brain are specific for age and model.

PURPOSE: Status epilepticus (SE) is more common in children than adults and has a high mortality and morbidity rate. SE in adult rats results in long-term disturbances in learning and memory, as well as an enhanced seizure susceptibility to further seizures. In contrast, a number of studies suggest that the immature brain is less vulnerable to the morphologic and physiologic alterations after SE. The goal of this study was to determine whether the long-term consequences of SE during development on hippocampal plasticity and cognitive function are age and model specific. METHODS: We used lithium-pilocarpine (Li-PC) to induce SE at different age points during development (P12, P16, P20) and evaluated the effects of this abnormal neural activity on spatial memory performance and seizure susceptibility in the animals beginning at P55, corresponding to young adulthood. RESULTS: We demonstrated that SE at P12 did not result in any structural or functional changes detectable in adulthood, whereas SE at both P16 and P20 induced cell loss and mossy fiber sprouting within the hippocampus and cognitive impairment when the animals were tested as adults. CONCLUSIONS: Whereas the seizure threshold to generalized seizures was not altered, animals with SE at P20 showed an increased susceptibility to kindling in adulthood.

Age Factors↗

Pattern discrimination in a hawkmoth: innate preferences, learning performance and ecology.

Spatial patterns are important cues for flower detection and recognition by nectar-feeding insects. Pattern vision has been studied in much detail in bees and flies but rarely in butterflies and moths. In this paper, I present a first proof of pattern-learning abilities in a moth, and discuss reasons for the limitations to their pattern learning. The diurnal hawkmoth Macroglossum stellatarum spontaneously prefers patterned to uniformly coloured stimuli but can be trained to choose the uniform stimulus. By contrast, experience does not override the innate preferences for radial over tangential patterns, and for tangential over striped patterns. These results do not reflect bad visual discrimination but rather a lack of learning ability and motivation to abolish innate preferences. I propose that radial and tangential flower patterns are good predictors of nectar reward, a condition under which learning is unlikely to evolve. These patterns serve not only as cues for flower detection but also as guides to the reward. Hovering pollinators strongly depend on these guides and should therefore: (i). have rigid pattern preferences; and (ii). not be motivated to abolish these preferences as easily as their innate preferences for colours.

Animals↗

Role of the hippocampal system in associative learning beyond the spatial domain.

Expert opinion remains divided on the issue of whether the hippocampal system functions exclusively in spatial information processing, e.g. in navigation or in understanding spatial relations, or whether it plays a more general role in higher brain function. Previous work on monkeys and rats has tended to support the former view, whereas observations in the clinic point to the latter, including functions as diverse as declarative knowledge, episodic memory, word learning, and understanding relations among objects. One influential theory posits a general role for the hippocampal system in associative learning, with emphasis on associations learned rapidly and recently. The results presented here are consistent with this theory, along with previous clinical and theoretical studies indicating that the hippocampal system is necessary for associative learning even if no component of the association relies on spatial information. In the study reported here, rhesus monkeys learned a series of conditional stimulus-response associations involving complex visual stimuli presented on a video monitor. Each stimulus instructed one of three responses: tapping the stimulus with the hand, steady hand contact with the stimulus for a brief period of time, or steady contact for a longer time. Fornix transection impaired the learning of these associations, even though both the stimuli and the responses were nonspatially differentiated, and this deficit persisted for at least 2 years. This finding indicates that the hippocampal system plays an important role in associative learning regardless of the relevance of spatial information to any aspect of the association. Fornix-transected monkeys were impaired in learning new stimulus-response associations even when the stimuli were highly familiar. Thus, the deficit was one of associating each stimulus with a response, as opposed to problems in distinguishing the stimuli from each other. In contrast to these effects, fornix transection did not impair performance when familiar stimuli instructed a response according to an already-learned association, which shows that the deficit was one of learning new associations rather than one of retention or retrieval of previously learned ones. Taken together, these results show that fornix transection causes a long-lasting impairment in associative learning outside of the spatial domain, in a manner consistent with theories of hippocampal-system function that stress a general role in the rapid acquisition of associative knowledge.

Animals↗

Learned food aversions: heterogeneity of animal models of tumor-induced anorexia.

Learned food aversions have been implicated in the anorexia which develops in rats with transplantable PW-739 tumors. There appear to be striking differences in growth characteristics and physiological effects of different experimental tumors. The present studies examined the issue of heterogeneity of tumor models, while assessing the generality of the finding that learned food aversions arise in anorexic, tumor-bearing animals. This was done by comparing effects on food intake and diet preferences of two transplantable tumors, the Leydig cell tumor, LTW(m), and the Walker-256 carcinosarcoma. We found that animals with Leydig tumors, like those with PW-739 tumors, developed strong aversions to the specific diet they had eaten after tumor implant. In contrast, animals with Walker-256 tumors did not develop diet aversions. These results support the idea that learned food aversions contribute to anorexia in animals with Leydig but not Walker tumors. They further suggest that learned food aversions in tumor-bearing animals are not a response to illness, in general, but rather that the unconditioned stimulus responsible for these aversions is quite specific, and may ultimately prove identifiable.

Animals↗

Virtual reality simulation training can improve technical skills during laparoscopic salpingectomy for ectopic pregnancy.

OBJECTIVES: To assess the first commercially available virtual reality (VR) simulator to incorporate procedural modules for training of inexperienced gynaecological surgeons to perform laparoscopic salpingectomy for ectopic pregnancy. DESIGN: Prospective cohort study. SETTING: Departments of surgery and gynaecology in central London teaching hospitals. SAMPLE: Thirty gynaecological surgeons were recruited to the study, and were divided into novice (<10 laparoscopic procedures), intermediate (20-50) and experienced (>100) groups. METHODS: All subjects were orientated to the VR simulator with a basic skills task, followed by performing ten repetitions of the virtual ectopic pregnancy module, in a distributed manner. MAIN OUTCOME MEASURES: Operative performance was assessed by the time taken to perform surgery, blood loss and total instrument path length. RESULTS: There were significant differences between the groups at the second repetition of the ectopic module for time taken (median 551.1 versus 401.2 versus 249.2 seconds, P = 0.001), total blood loss (median 304.2 versus 187.4 versus 123.3 ml, P = 0.031) and total instrument path length (median 17.8 versus 8.3 versus 6.8 m, P = 0.023). The learning curves of the experienced operators plateaued at the second session, although greater numbers of sessions were necessary for intermediate (seven) and novice (nine) surgeons to achieve similar levels of skill. CONCLUSIONS: Gynaecological surgeons with minimal laparoscopic experience can improve their skills during short-phase training on a VR procedural module. In contrast, experienced operators showed nonsignificant improvements. Thus, VR simulation may be useful for the early part of the learning curve for surgeons who wish to learn to perform laparoscopic salpingectomy for ectopic pregnancy.

Clinical Competence↗