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PubMed2004

Examination of potential overlap in autism and language loci on chromosomes 2, 7, and 13 in two independent samples ascertained for specific language impairment.

Specific language impairment is a neurodevelopmental disorder characterized by impairments essentially restricted to the domain of language and language learning skills. This contrasts with autism, which is a pervasive developmental disorder defined by multiple impairments in language, social reciprocity, narrow interests and/or repetitive behaviors. Genetic linkage studies and family data suggest that the two disorders may have genetic components in common. Two samples, from Canada and the US, selected for specific language impairment were genotyped at loci where such common genes are likely to reside. Significant evidence for linkage was previously observed at chromosome 13q21 in our Canadian sample (HLOD 3.56) and was confirmed in our US sample (HLOD 2.61). Using the posterior probability of linkage (PPL) to combine evidence for linkage across the two samples yielded a PPL over 92%. Two additional loci on chromosome 2 and 7 showed weak evidence for linkage. However, a marker in the cystic fibrosis transmembrane conductance regulator (7q31) showed evidence for association to SLI, confirming results from another group (O'Brien et al. 2003). Our results indicate that using samples selected for components of the autism phenotype may be a useful adjunct to autism genetics.

Autistic Disorder↗
PubMedDate not supplied

Calculation of the circular dichroism of Chironomus hemoglobin in the light of the quality of its X-ray structure.

For the larval hemoglobin III of the insect Chironomus thummi thummi, the rotational strength of the B (Soret) and Q band is calculated with a monopole/monopole and a dipole/dipole approximation applied to the atomic co-ordinates of the X-ray structures at 2.5 and 1.4 A resolution. In previous calculations using the 2.5 A co-ordinates and with perturbing groups being restricted to aromatic side-chains, the dipole/dipole approximation clearly confirmed the negative sign observed by experiment. The predominant interactions were those of phenylalanine residues. Recalculation with X-ray data refined to the present limits of performance corroborates the negativity of the rotational strength, but now the most important contributions are due to the peptide bonds formerly neglected. Also for the 2.5 A coordinates it is learned that in contrast to earlier expectation the influence of the backbone in this hemoglobin is rather strong. A substantial contribution is further obtained for the perturbation by one of the propionic acid carboxylate groups of the heme. Perspectives and problems of the approach are outlined.

Amino Acids↗
PubMed1998

Teachers' experiential learning about learning.

OBJECTIVE: An experiential model of learning suggests that changing a learner's understanding will lead to the learner choosing to change behavior. A workshop was designed for medical educators to examine their understanding of learning in order to change their behavior as teachers. This article describes that workshop which was presented as part of a conference on successful techniques for education of primary care practitioners. METHOD: Eighteen medical educators participated in the workshop. The educators were instructed to reflect on a recent personal learning experience. Group discussion led to production of a list of components of effective learning. These learning components were then applied in small groups to three hypothetical tasks related to mental health education. RESULTS: Essential characteristics of three generic features of learning were identified: characteristics of the teacher, learner, and learning experience. When these characteristics were then applied to the hypothetical tasks, a major theme that emerged was a focus on the importance of learner motivation. CONCLUSIONS: The essential components of learning and their application demonstrate the importance of adult learning theory in which it is more important for the learner than for the teacher to determine what, when, and how to learn. This is in contrast to traditional medical education in which the teacher decides what to learn and if it has been learned. To improve education for practicing primary care providers, a shift from a teaching paradigm to a learning paradigm is indicated.

Adult↗
PubMedDate not supplied

Is attention deficit hyperactivity disorder familial?

Using two sources of data, we review methodologic issues pertinent to family studies of attention deficit hyperactivity disorder to evaluate whether such studies define attention deficit hyperactivity disorder as a familial disorder. We systematically evaluate the relevant literature and provide a detailed overview of the Massachusetts General Hospital family-genetic studies of attention deficit disorder as defined in DSM-III and attention deficit hyperactivity disorder as defined in DSM-III-R. The available literature, and our double-blind, controlled studies indicate that attention deficit disorder and attention deficit hyperactivity disorder are familial. Moreover, the pattern of transmission of comorbid disorders suggests that attention deficit hyperactivity disorder is, from a familial perspective, distinct from anxiety disorders and learning disabilities. In contrast, attention deficit hyperactivity disorder with conduct disorder appears to be a familial subtype, and major depression appears to be a variable expression of the familial predisposition to attention deficit hyperactivity disorder. Although the available literature provides strong evidence for the familial transmission of attention deficit hyperactivity disorder, the mode of transmission requires further clarification. In addition, attention deficit hyperactivity disorder appears to be genetically heterogeneous, indicating that more work is needed to delineate genetically homogeneous subtypes and to describe the range of expression of their underlying genotypes. Family-genetic studies will continue to clarify the etiology and nosology of attention deficit hyperactivity disorder.

Adult↗
PubMed2001

[Effect of the configuration of a route on distance perception].

Numerous studies have been carried out to investigate the knowledge of route distance in environmental space. Evidence suggests that the knowledge of distance is influenced by the environmental features and structures of the route. The purpose of this study was to investigate the factors that affect this knowledge. In particular, the aim was to determine the role of the structure versus that of characteristic environmental features along the route. In two experiments, it was found that the knowledge of distance was not affected by the structure alone. Rather it was determined by the environmental features along the route. Participants seem to infer the environmental distance between two locations indirectly using successively perceived and stored retrievable features. It could be shown in a third experiment that in an intentional learning condition--in contrast to an incidental condition--, the number of environmental features does not seem to influence distance knowledge. In this condition, a direct retrieval of information appears to be possible. The experiments took place in a virtual environment.

Adult↗
PubMed2001

Cognitive and psychomotor effects of paroxetine and sertraline on healthy elderly volunteers.

The authors evaluated the cognitive and psychomotor effects of serotonin reuptake inhibitors in healthy elderly volunteers. Paroxetine, sertraline, and placebo were compared for 3 weeks of testing in a double-blind study with behavioral testing at baseline and at the end of each week. MANOVA models demonstrated no between-group differences; however, mixed-model random regression analyses revealed that Day 14 plasma paroxetine levels correlated negatively with delayed verbal recall and paired-associate learning scores. In contrast, plasma sertraline levels correlated positively with Day 7 immediate verbal recall, Day 14 tapping, and Day 21 delayed verbal recall scores, and negatively with divided-attention task scores on Day 21. Plasma paroxetine levels were associated with mild behavioral impairment at Day 14, with no other significant adverse effects. Plasma sertraline levels were associated with mild and transient behavioral changes, as well as early termination in several subjects.

Aged↗
PubMed2001

Restoration of vision IV: role of compensatory soma swelling of surviving retinal ganglion cells in recovery of vision after optic nerve crush.

PURPOSE: Diffuse axonal injury following partial optic nerve crush (ONC) leads to severe visual deficits from which rats can partially recover within 2-3 weeks. To evaluate tbc role of surviving retinal ganglion cells (RGCS) in recovery, we have observed their morphology repeatedly in vivo with ICON-microscopy and correlated cell size changes with recovery of vision which we observed in parallel in the same animals. METHODS: After rats had learned a visual contrast discrimination task using an automated, computer-based test, RGCs were labeled retrogradely with fluorescent beads. Animals then received either no lesion, a complete axotomy or bilateral mild, moderate or severe ONC. Before surgery and for 40 days post-operatively, ROC number and soma size was repeatedly quantified every five days with tbc in vivo confocal neuroimaging method (Sabel et al., Nature med. 3, 1997, p. 244). In parallel, visual function was quantified with the contrast-discrimination task. RESULTS: After ONC about 70 % of the ROCs died after having undergone a fast and massive soma swelling. The extent of cell death was independent of crush severity. RGCs surviving the injury did not change their body size over time in the severe group and these animals also did not recover their vision. In contrast, after a mild or moderate crush, about half of the surviving RGCs experienced a slow and moderate, "compensatory" cell soma swelling and the rats showed partial recovery of vision. Both the number of RGCs showing such compensatory soma swelling and the extent of the swelling correlated highly (r = 0.96) with recovery of contrast discrimination performance at post-operative days 23 and 38. CONCLUSIONS: Depending en the time course and extent, soma swelling after neurotrauma may be associated either with cell death or recovery of function. Because of the very high correlation between extent of recovery and amount of soma swelling, moderate soma swelling contributes in a prominent way to recovery of vision. We believe that these cells provide an important structural substrate for neuronal tissue repair and therefore term these cells "compensatory neurons".

Adaptation, Physiological↗
PubMed1989

Information systems to support medical practice and scientific discovery.

In many educational applications of the computer, systems are designed to contain information or knowledge that is to be conveyed to the student or user via an interactive learning scheme. In contrast, most NLM systems strive merely to increase the user's access to the broad range of published scientific literature, or to link the user to appropriate factual databases. Providing or enhancing access is, of course, made more difficult than in didactic systems because of the relatively large size of the files that make up the bibliographic and factual databases. For example, the MEDLARS files contain over 12 million records, made up of roughly thirty billion online characters. Users send electronic queries to these files on-line via commercial value-added networks (24 hrs/day, 365 days/year), in total about 4 million queries per year. Of the 4 million, approximately half of the queries were (in the opinion of the users polled) prompted by questions that arose in caring for a particular patient. The remaining 2 million queries concerned research, teaching, and public policy.

Biotechnology↗
PubMed1988

Inferotemporal-frontal disconnection and fornix transection in visuomotor conditional learning by monkeys.

The first 2 experiments examined the ability of monkeys (Macaca fascicularis) to learn a series of visuomotor conditional discrimination problems for food reward. In each discrimination problem there were 2 visual stimuli, which were different from those in any previous discrimination problem. Each trial within a problem presented either one visual stimulus or the other, and the stimulus indicated which of 2 motor responses, tap or hold, was correct; the motor responses were defined in such a way as to be mutually exclusive. Successive problems were each trained to a criterion of correct performance. In the first experiment, it was found that fornix transection did not impair monkey's learning rate in this task. This result contrasts with previous results showing an impairment of learning rate following fornix transection in visuo-motor conditional discriminations in which the 2 motor responses were differentiated from each other by their spatial position or direction. The present result shows that the earlier demonstrated impairments are specific to spatial responses. In the second experiment, learning rate in the present task was found to be impaired by the combination of a unilateral inferotemporal ablation, contralateral to the hand used in the task by the animal, with a transection of the anterior corpus callosum. This result suggests that cortico-cortical interaction between the inferotemporal area and the frontal lobe contralateral to the hand in use is necessary for efficient learning in this task. The third experiment examined simultaneous 2-choice visual discrimination learning in the animals which had participated in experiment 2. In contrast to the results of Expt. 2, learning rate in this task was unimpaired. Experiment 3 shows that the impairment observed in Expt. 2 is not a general impairment of visual learning.

Animals↗
PubMed1990

[Objective determination of refraction].

Objective determination of refraction is basically necessary for the subjective adjustment of refraction aimed at prescribing glasses. At least as important is the use of objective determination of refraction as a basis of ophthalmological diagnosis because the best-corrected visual acuity forms basic diagnostic information. Three methods of objective determination of refraction are available. Photorefraction has only been used for screening preschool children, as it has no value for the above-mentioned purpose. Refractometry is widely being used for objective determination of refraction, and during the last few years automated refractometry has also become more and more common. This trend is supported by the possibility of delegating automated refractometry to assistant medical personnel. Retinoscopy and automated refractometry yield comparable results. Retinoscopy has some advantages: great flexibility and the fact that retinoscopy forms an image of optical aberrations of the eye, giving the ophthalmologist an idea of the optical quality of the patient's eye. Due to its flexibility retinoscopy can be used for refractioning babies and infants without any problem. The disadvantage of retinoscopy is the impossibility of delegating it to assistant medical personnel and the fact that this method must be learned by the ophthalmologist. In contrast to retinoscopy, automated refractometry can easily be learned and can be delegated to assistant medical personnel. Its drawback is that it is inflexible, making it inconvenient for refractioning babies and infants. If automated refractometry and retinoscopy are used with cycloplegia, precautions are essential to avoid errors caused by optical aberrations of the eye. The measurement must be done in the center of the pupil.(ABSTRACT TRUNCATED AT 250 WORDS)

Eyeglasses↗
PubMed1991

Rhesus monkey (Macaca mulatta) complex learning skills reassessed.

Results from three experiments on basic learning and transfer in rhesus monkeys (Macaca mulatta) are reported in which fully automated testing paradigms, afforded by the Language Research Center's Computerized Test System (LRC-CTS), were employed. Performance levels for discrimination learning set, transfer index, and mediational-learning testing were uniformly higher than was predicted from the literature, in contrast to previous reports of compromised learning under similar conditions (automated apparatus, planimetric stimuli, spatial discontiguity between stimuli and response loci). Analyses reveal relatively advanced learning set performance, transfer-index ratios, and positive transfer of learning even at stringent criterion levels. Moreover, the data suggest that rhesus monkeys tested in these experiments exhibit mediational instead of associative learning strategies, as do great apes and in contrast to previous reports of rhesus learning. We argue that the LRC-CTS enhances learning by nonhuman primate subjects, obviating those factors, reported in the literature from experiments in which manual or other automated systems were employed, that compromise learning.

Animals↗
PubMed2003

Functional imaging of perceptual learning in human primary and secondary somatosensory cortex.

Cellular mechanisms underlying synaptic plasticity are in line with the Hebbian concept. In contrast, data linking Hebbian learning to altered perception are rare. Combining functional magnetic resonance imaging with psychophysical tests, we studied cortical reorganization in primary and secondary somatosensory cortex (SI and SII) and the resulting changes of tactile perception before and after tactile coactivation, a simple type of Hebbian learning. Coactivation on the right index finger (IF) for 3 hr lowered its spatial discrimination threshold. In parallel, blood-oxygen level-dependent (BOLD) signals from the right IF representation in SI and SII enlarged. The individual threshold reduction was linearly correlated with the enlargement in SI, implying a close relation between altered discrimination and cortical reorganization. Controls consisting of a single-site stimulation did not affect thresholds and cortical maps. Accordingly, changes within distributed cortical networks based on Hebbian mechanisms alter the individual percept.

Adult↗
PubMed2003

Cognitive experience and its effect on age-dependent cognitive decline in beagle dogs.

Test-sophisticated beagle dogs show marked age sensitivity in a size discrimination learning task, with old and senior dogs performing significantly more poorly than young dogs. By contrast, age differences in learning were not seen in dogs naive with respect to neuropsychological test experience. These results indicate that old animals benefit less from prior cognitive experience than young animals, which is an example of an age-dependent loss in plasticity. This finding also suggests that behaviorally experienced animals are a more useful model of human cognitive aging than behaviorally naïve animals. We also looked at the effect of a program of behavioral enrichment in aged dogs. One year of enrichment did not lead to significant differences, but after 2 years the behaviorally enriched group performed significantly better than the control group. The effect after 2 years indicates that a prolonged program of cognitive enrichment can serve as an effective intervention in aged dogs. These findings demonstrate that cognitive abilities in aged animals can be modified by providing behavioral experience, indicating that cognitive abilities remain moderately plastic, even in very old animals.

Age Factors↗
PubMed2002

Effect of sound source position on learning and performance of auditory delayed matching-to-sample task in dogs.

Spatial adjacency of stimulus source and response site has been proven important for learning of simple behavioural tasks, including auditory quality and location discrimination. We investigated effect of sound source position (adjacent or not adjacent to manipulanda) on learning and performance of a complex auditory recognition memory task. Spatial adjacency of stimuli and manipulanda improved learning of a simple auditory directional task, which was an intermediate stage of training. In contrast, no improvement of learning and performance of the recognition task was found.

Acoustic Stimulation↗
PubMed2005

Using errorless learning to treat letter-by-letter reading: contrasting word versus letter-based therapy.

Some pure alexic readers have been shown to activate lexical and semantic knowledge under brief presentation conditions. This ability is not seen when letter-by-letter reading accuracy is high or the reading impairment is very severe. It is also unlikely to occur under normal untimed presentation because the pure alexic will make deliberate use of their letter-by-letter strategy. This paper presents data from a moderately severe letter-by-letter reader, FD, who had visual processing problems affecting reading. He also had other mild aphasic characteristics. FD showed implicit reading abilities under brief presentation conditions, being able to make lexical decisions and semantic categorisations well above chance. FD was given two therapy programmes, the first, whole word therapy to exploit this implicit ability and the second to improve letter-by-letter accuracy and speed. FD showed some improvement in reading ability after both therapy programmes, particularly for words of personal interest to him. His letter naming accuracy and reading of visually similar words were the most resistant to change. A striking effect of therapy was the cessation of FD's letter-by-letter reading and the emergence of some of the characteristics of deep dyslexia. Even when therapy concentrated on letter accuracy, FD did not revert back to his original letter-by-letter reading strategy. The results are discussed with reference to the two theories of pure alexia. Some conclusions are drawn about the need for therapists to examine and exploit all residual reading skills when devising therapeutic programmes.

Acoustic Stimulation↗
PubMed2006

Visuomotor learning in immersive 3D virtual reality in Parkinson's disease and in aging.

Successful adaptation to novel sensorimotor contexts critically depends on efficient sensory processing and integration mechanisms, particularly those required to combine visual and proprioceptive inputs. If the basal ganglia are a critical part of specialized circuits that adapt motor behavior to new sensorimotor contexts, then patients who are suffering from basal ganglia dysfunction, as in Parkinson's disease should show sensorimotor learning impairments. However, this issue has been under-explored. We tested the ability of 8 patients with Parkinson's disease (PD), off medication, ten healthy elderly subjects and ten healthy young adults to reach to a remembered 3D location presented in an immersive virtual environment. A multi-phase learning paradigm was used having four conditions: baseline, initial learning, reversal learning and aftereffect. In initial learning, the computer altered the position of a simulated arm endpoint used for movement feedback by shifting its apparent location diagonally, requiring thereby both horizontal and vertical compensations. This visual distortion forced subjects to learn new coordinations between what they saw in the virtual environment and the actual position of their limbs, which they had to derive from proprioceptive information (or efference copy). In reversal learning, the sign of the distortion was reversed. Both elderly subjects and PD patients showed learning phase-dependent difficulties. First, elderly controls were slower than young subjects when learning both dimensions of the initial biaxial discordance. However, their performance improved during reversal learning and as a result elderly and young controls showed similar adaptation rates during reversal learning. Second, in striking contrast to healthy elderly subjects, PD patients were more profoundly impaired during the reversal phase of learning. PD patients were able to learn the initial biaxial discordance but were on average slower than age-matched controls in adapting to the horizontal component of the biaxial discordance. More importantly, when the biaxial discordance was reversed, PD patients were unable to make appropriate movement corrections. Therefore, they showed significantly degraded learning indices relative to age-matched controls for both dimensions of the biaxial discordance. Together, these results suggest that the ability to adapt to a sudden biaxial visuomotor discordance applied in three-dimensional space declines in normal aging and Parkinson disease. Furthermore, the presence of learning rate differences in the PD patients relative to age-matched controls supports an important contribution of basal ganglia-related circuits in learning novel visuomotor coordinations, particularly those in which subjects must learn to adapt to sensorimotor contingencies that were reversed from those just learned.

Adaptation, Physiological↗
PubMed1975

Stimulus generalization following extra-dimensional training in educationally subnormal (severely) children.

The use of discrimination learning paradigms in the study of attentional transfer is discussed. The technique of go/no-go discrimination learning followed by stimulus generalization testing is contrasted with the more familiar simultaneous learning paradigm followed by a shift in the relevant cues. In the former paradigm the effect of training a discrimination on one dimension on the slope of the stimulus generalization gradient on an independent gradient dimension (extra-dimensional training) is assessed. A steepening of the gradient relative to appropriate control procedures is taken as evidence of positive attentional transfer. The relevance of the technique to the detailed study of attentional transfer in educationally subnormal (severely) (ESN(S)) children is considered. In Expt. I nine ESN(S) children were trained in a go/no-go discrimination involving stimuli differing in orientation, and were generalization tested on a dimension that was orthogonal, namely hue. Of the six subjects who learnt the discrimination five showed clear decremental gradients on the hue dimension. In contrast a Pseudo-Discrimination group (PD) of eight subjects matched to those in the TD group showed no gradients. These subjects were not trained in the orientation discrimination, but were reinforced for responding on 50 per cent of each of the S+ and S- stimulus presentations. They thus received equal exposure to, but no differential training on, the orientation dimension. An S+ only group of four subjects who received no exposure to the orientation stimuli showed no gradients when stimulus generalization testing on the hue continuum was carried out. The result is discussed in terms of transfer deriving from stimulus control by relational aspects of the stimuli; in terms of control by constant irrelevant stimuli; and in terms of the study of stimulus control in ESN(S) children. In Expt. II the influence of the codability of the colours on the location of the peak of the stimulus generalization gradients in the TD group is investigated.

Adolescent↗