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PubMed1999

Actions of CRF and its analogs.

Corticotropin-releasing factor (CRF), urocortin, sauvagine and urotensin I form the CRF family. These peptides bind with different affinities to two subtypes of CRF receptor (CRFR), CRFR1 and CRFR2. The latter exists as two splice variants, the neuronal CRFR2a and the peripheral CRFR2b. CRFR is a G protein-dependent receptor which acts mainly through Gs enhancing cAMP production. However, CRFR1 expressed in neutrophils of the spleen in response to immunologic stimulation and psychological stress does not seem to function through Gs, as indicated by the inability of CRF to stimulate the cAMP production of CRFR1+ neutrophils. Besides the two receptors, a 37 kD CRF binding protein (CRF-BP) binds several CRF peptides with high affinity. CRFR and CRF-BP do not share a common amino acid sequence representing the ligand binding site. In view of the unusually slow offrate of CRF-BP, it is proposed that CRF-BP provides an efficient uptake of free extracellular CRF. Thus, the time of exposure of CRFR to CRF or urocortin can be limited. At this time, the fate of the ligand CRF-BP complex is unclear. CRFR1 is not only involved in the hypophyseal stimulation of corticotropin release, but hippocampal CRFR1 mediates enhancement of stress-induced learning. CRFR1 may also be involved in basic anxiety. In contrast, at least in the mouse, CRFR2 of the lateral intermediate septum mediates tonic impairment of learning. In response to stressful stimuli or after local injection of high CRF doses, CRFR2 mediates anxiety. Effects requiring CRFR2 can be blocked specifically by the recently developed peptidic antagonist antisauvagine-30.

Amino Acid Sequence↗

PubMed2003

Reverse engineering of genetic networks with Bayesian networks.

This paper provides a brief introduction to learning Bayesian networks from gene-expression data. The method is contrasted with other approaches to the reverse engineering of biochemical networks, and the Bayesian learning paradigm is briefly described. The article demonstrates an application to a simple synthetic toy problem and evaluates the inference performance in terms of ROC (receiver operator characteristic) curves.

Bayes Theorem↗

PubMed2007

Circadian-dependent learning and memory enhancement in nociceptin receptor-deficient mice with a novel KUROBOX apparatus using stress-free positive cue task.

Using the novel apparatus KUROBOX, learning and memory behaviors, as well as various parameters of movement activity, were reevaluated in mice deficient for nociceptin/orphanin FQ receptor (NOP-/- mice) or mu-opioid receptor (MOP-/- mice). This method has the advantages that no handling procedures are required throughout the experiments performed over 3 days, positive cue paradigms are used without water or shock stress, and the method does not disturb the nocturnal habit of mice. NOP-/- mice displayed a significant enhancement of learning and memory under stress-free conditions, but there were no changes in the various physical and psychological parameters of movement activity (nest stay ratio, distance moved, speed and angle in the movement) and biological rhythm that were measured. Enhancement of nocturnal learning was observed during the first 12-h dark cycle, and enhancement of memory was observed at the beginning of the second dark cycle in NOP-/- mice. In contrast, MOP-/- mice showed no significant change in learning and memory behaviors or in physical and psychological parameters of movement activity, except for speed, MOP-/- mice showed a significant decrease in speed of movement. Thus, the KUROBOX apparatus provides a useful alternative method to evaluate learning and memory activity under the more physiological conditions. In addition, this apparatus has an advantage that various physical and psychological parameters of movement activity affecting learning and memory behavior are also evaluated at the same time.

Animals↗

PubMed2001

Enhanced or impaired cognitive function in Parkinson's disease as a function of dopaminergic medication and task demands.

We investigated how dopamine (DA) systems contribute to cognitive performance in the domain of learning and attentional flexibility by examining effects of withdrawing DA-ergic medication in patients with Parkinson's disease (PD). Medication remediated impairments in switching between two tasks, thought to depend on circuitry connecting the dorsolateral prefrontal cortex and the posterior parietal cortex to the dorsal caudate nucleus, which is profoundly DA-depleted in PD. By contrast, the same medication impaired probabilistic reversal learning that implicates orbitofrontal cortex- ventral striatal circuitry, which is relatively spared of DA loss in PD. Hence, DA-ergic medication improves or impairs cognitive performance depending on the nature of the task and the basal level of DA function in underlying cortico-striatal circuitry.

Attention↗

PubMed1999

Learning the parts of objects by non-negative matrix factorization.

Is perception of the whole based on perception of its parts? There is psychological and physiological evidence for parts-based representations in the brain, and certain computational theories of object recognition rely on such representations. But little is known about how brains or computers might learn the parts of objects. Here we demonstrate an algorithm for non-negative matrix factorization that is able to learn parts of faces and semantic features of text. This is in contrast to other methods, such as principal components analysis and vector quantization, that learn holistic, not parts-based, representations. Non-negative matrix factorization is distinguished from the other methods by its use of non-negativity constraints. These constraints lead to a parts-based representation because they allow only additive, not subtractive, combinations. When non-negative matrix factorization is implemented as a neural network, parts-based representations emerge by virtue of two properties: the firing rates of neurons are never negative and synaptic strengths do not change sign.

Algorithms↗

PubMed2006

Different signal transduction cascades are activated simultaneously in the rat insular cortex and hippocampus following novel taste learning.

Novel taste learning is a robust one-trial incidental learning process, dependent on functional activity of the insular (taste) cortex. In contrast to that of the cortex, the role of the hippocampus in taste learning is controversial. We set out to identify the time courses of the activation of mitogen-associated protein kinase (MAPK), transcription factor cAMP-response element-binding protein (CREB) and Akt/PKB (protein kinase B) in the insular cortex and hippocampus of rats subsequent to novel taste learning. Following taste learning, an early response (20 min) occurred at the same time in the insular cortex and the hippocampus. However, whereas MAPK was activated specifically in the insular cortex, CREB and Akt were phosphorylated in the hippocampus but not in the cortex. In addition, the immediate early gene, CCAAT/enhancer binding protein (C/EBPbeta) was induced in both the hippocampus and the insular cortex 18 h following taste learning. The results demonstrate, for the first time, correlative activation and gene expression in the hippocampus following novel taste learning. Moreover, the results suggest that different signal transduction cascades necessary for taste learning are activated in concert in different brain structures, to enable taste learning and consolidation.

Animals↗

PubMed1985

Auditory-successive selective attention for learning disabled and normal boys.

Improvement in auditory-successive selective attention was noted across the age range of 9 through 16 yr. In contrast to comparable paradigms with visual-simultaneous materials, 30 learning disabled and 30 normal boys did not differ. Results of research on selective attention may be affected by task materials and encoding requirements.

Adolescent↗

PubMed1988

Influence of hippocampal kindling on avoidance learning in cats.

The formation of avoidance response and differentiation was studied in 13 control and 7 kindled cats with developed hippocampal epileptic focus and complex partial or secondary generalized tonic-clonic seizures. Conditioning sessions lasted from 15 to 20 min in a period following afterdischarges and seizures resulting from electrical stimulation of the hippocampal formation. In two out of seven kindled cats the conditioned reflex was established within time limits (9 and 20 days) comparable to the control cats. These two animals had relatively short-lasting afterdischarges (mean values: 17 and 19 s). In cats with longer-lasting afterdischarges and complex partial seizures (mean duration: 32 to 65 s, in different animals) criterion was not reached during parallel kindling-conditioning stage of 10 to 30 days. The level of correct responses was low and variable (0-70 percent), despite typical reactions to the unconditioned stimuli and clear orienting responses to the conditioning stimuli on more advanced stages of training. Four kindled animals entered the stage of secondary generalization of seizures after hippocampal stimulation. Reflex performance after tonic-clonic seizures was practically abolished. The termination of kindling resulted in acquisition of the conditioned reflex in all the animals. The results indicate, that in animals with long-lasting complex partial seizures the learning of the avoidance response is impaired. In contrast to the effects exerted by afterdischarges and complex partial seizures, intensive interictal hippocampal spiking did not seem to have a direct negative influence on, this particular type of learning.

Animals↗

PubMed2006

Cognitive sequence learning in Parkinson's disease and amnestic mild cognitive impairment: Dissociation between sequential and non-sequential learning of associations.

Evidence suggests that dopaminergic mechanisms in the basal ganglia (BG) are important in the learning of sequential associations. To test the specificity of this hypothesis, we assessed never-medicated patients with Parkinson's disease (PD) and amnestic mild cognitive impairment (aMCI) using a chaining task. In the training phase of the chaining task, each link in a sequence of stimuli leading to reward is trained step-by-step using feedback after each decision, until the complete sequence is learned. In the probe phase of the chaining task, the context of stimulus-response associations must be used (the position of the associations in the sequence). Results revealed that patients with PD showed impaired learning during the training phase of the chaining task, but their performance was spared in the probe phase. In contrast, patients with aMCI with prominent medial temporal lobe (MTL) dysfunctions showed intact learning during the training phase of the chaining task, but their performance was impaired in the probe phase of the chaining task. These results indicate that when dopaminergic mechanisms in the BG are dysfunctional, series of stimulus-response associations are less efficiently acquired, but their sequential manner is maintained. In contrast, MTL dysfunctions may result in a non-sequential learning of associations, which may indicate a loss of contextual information.

Aged↗

PubMed1998

Conspecific and heterospecific song discrimination in male zebra finches with lesions in the anterior forebrain pathway.

Adult zebra finches can produce normal song in the absence of Area X, IMAN, or DLM, nuclei that constitute the anterior forebrain pathway of songbirds. Here, we address whether lesions involving Area X and IMAN affect adult male zebra finches' ability to discriminate between conspecific or heterospecific songs. Intact birds and lesioned birds were trained on an operant GO/NOGO conditioning paradigm to discriminate between hetero- or conspecific songs. Both lesioned and intact birds were able to learn all discriminations. Lesioned and intact birds performed equivalently on canary song discriminations. In contrast, discriminations involving bird's own song took significantly more trails to learn for lesioned birds than for intact birds. Discrimination between conspecific songs in general also took longer in the lesioned birds, but missed significance level. Birds with control lesions medial to Area X did not show any differences from intact animals. Our results suggest that an intact anterior forebrain pathway is not required to discriminate between heterospecific songs. In contrast, Area X and IMAN contribute to a male zebra finch's ability to discriminate between its own song and that of other zebra finches.

Animals↗

PubMed2002

Orthographic learning during reading: examining the role of self-teaching.

Thirty-four second grade children read target homophonic pseudowords (e.g., slurst/slirst) in the context of real stories in a test of the self-teaching theory of early reading acquisition. The degree of orthographic learning was assessed with three converging tasks: homophonic choice, spelling, and target naming. Each of the tasks indicated that orthographic learning had taken place because processing of target homophones (e.g., yait) was superior to that of their homophonic controls (e.g., yate). Consistent with the self-teaching hypothesis, we obtained a substantial correlation (r=.52) between orthographic learning and the number of target homophones correctly decoded during story reading. Hierarchical multiple regression analyses indicated that neither RAN tasks nor general cognitive ability predicted variance in orthographic learning once the number of target homophones correctly decoded during story reading had been partialed out. In contrast, a measure of orthographic knowledge predicted variance in orthographic learning once the number of targets correctly decoded had been partialed. The development of orthographic knowledge appears to be not entirely parasitic on decoding ability. (c) 2002 Elsevier Science (USA).

Child↗

PubMed2002

Kinematics and dynamics are not represented independently in motor working memory: evidence from an interference study.

Our capacity to learn multiple dynamic and visuomotor tasks is limited by the time between the presentations of the tasks. When subjects are required to adapt to equal and opposite position-dependent visuomotor rotations (Krakauer et al., 1999) or velocity-dependent force fields (Brashers-Krug et al., 1996) in quick succession, interference occurs that prevents the first task from being consolidated in memory. In contrast, such interference is not observed between learning a position-dependent visuomotor rotation and an acceleration-dependent force field. On the basis of this finding, it has been argued that internal models of kinematic and dynamic sensorimotor transformations are learned independently (Krakauer et al., 1999). However, these findings are also consistent with the perturbations interfering only if they depend on the same kinematic variable. We evaluated this hypothesis using kinematic and dynamic transformations matched in terms of the kinematic variable on which they depend. Subjects adapted to a position-dependent visuomotor rotation followed 5 min later by a position-dependent rotary force field either with or without visual feedback of arm position. The force field tended to rotate the hand in the direction opposite to the visuomotor rotation. To assess learning, all subjects were retested 24 hr later on the visuomotor rotation, and their performance was compared with a control group exposed only to the visuomotor rotation on both days. Adapting to the position-dependent force field, both with and without visual feedback, impaired learning of the visuomotor rotation. Thus, interference between our kinematic and dynamic transformations was observed, suggesting that the key determinant of interference is the kinematic variable on which the transformation depends.

Adolescent↗

PubMed1999

Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour.

RATIONALE: Altered serotonergic and dopaminergic function have been widely implicated in behavioural disorders associated with impulsivity and risk-taking. However, little research has addressed the specific cognitive consequences of changed monoaminergic function that might contribute to the production of impulsive behaviour. OBJECTIVES AND METHODS: We compared the effects of rapid plasma tryptophan depletion, acute doses of the mixed indirect catecholamine agonist, methylphenidate (40 mg), and acute doses of the alpha(1)/alpha(2 )agonist, clonidine (1.5 microg/kg), on aspects of visual discrimination learning involving either acquisition of altered stimulus-reward associations (i.e. updating the affective valence of exteroceptive stimuli) or the control of attention towards relevant as opposed to irrelevant stimulus dimensions. RESULTS: Relative to subjects who received placebo, subjects with reduced tryptophan exhibited a deficit in the ability to learn changed stimulus-reward associations, but were still able to shift an acquired attentional set away from a now-irrelevant stimulus dimension towards a newly relevant dimension. By contrast, subjects who received methylphenidate were able to learn effectively about changing stimulus-reward associations, but showed an enhanced ability to shift an attentional bias, in combination with slowed response times. Subjects who received clonidine showed neither of these changes. CONCLUSIONS: These results suggest that reduction in central serotonin leads to altered neuromodulation of the cortical and subcortical regions (e.g. orbitofrontal cortex, striatum and anterior temporal structures) that mediate important aspects of associative learning whereby exteroceptive stimuli acquire altered incentive motivational value. On the other hand, facilitation of catecholamine neurotransmitters may disrupt the allocation of attention between relevant and irrelevant features of the environment, perhaps through altered modulation of the dorsolateral prefrontal cortex. The implications of these results for understanding the differential neuromodulation of cognitive functions are discussed.

Adolescent↗

PubMed1994

[Problem-based learning--a cautious approach].

Most medical schools in Canada have, over the last few years, introduced Problem Based Learning (PBL) into their undergraduate curricula. In contrast to some other schools which have radically transformed their entire curricula, the University of Western Ontario approach has been more cautious, setting aside 20 per cent of the time during the first two years of the curriculum to PBL, more traditional, didactic methods being used otherwise. The main challenges have been to integrate the underlying values of the two different approaches to teaching and learning to develop valid and reliable examination and evaluation procedures, and to sustain the enthusiasm and interest of a large, mostly voluntary, group of faculty members, continually improving their skills as tutors. The most beneficial results of this curricular change have been an increased interest in medical education reform in general, and an increased recognition of the importance of teaching in relation to appointments and promotions. Students have appreciated the break from a never ending stream of lectures, and many have welcomed the challenged to explore in depth areas of special interest.

Curriculum↗

PubMed1993

Altered synaptic plasticity and memory formation in nitric oxide synthase inhibitor-treated rats.

Nitric oxide (NO) is a messenger molecule that is produced in the brain from the metabolism of L-arginine to L-citrulline. Growing evidence suggests a physiological role for NO in long-term potentiation (LTP). Since LTP is a form of synaptic plasticity thought to be involved in learning and memory, we have tested whether inhibition of endogenous NO production affects memory capacities of rats. We found that the NO synthase [L-arginine, NADPH:oxygen oxidoreductase (nitric oxide-forming), EC 1.14.13.39] inhibitor N omega-nitro-L-arginine, at doses blocking LTP in hippocampal slices, impairs spatial learning in a radial arm maze and olfactory memory in a social recognition test. In contrast, N omega-nitro-L-arginine left shock-avoidance learning unaffected. These results indicate that NO is involved in some but not all forms of memory and further support the existence of a causal link between LTP and spatial learning.

Amino Acid Oxidoreductases↗

PubMed2000

Enhancing Science Literacy for All Students With Embedded Reading Instruction and Writing-to-Learn Activities.

Reading and writing in science have been frequently maligned but infrequently studied since the 1960s move toward hands-on science. Current interest in the printed-based language arts in science is supported by contemporary educational reforms and the realization that simply doing more hands-on activities may not improve meaningful learning. Students need opportunities to consolidate their science experiences and to contrast their understandings with the interpretations of the science establishment. Science literacy means that students learn about the "big" ideas of science and how to inform and persuade others about these ideas. This article attempts to sketch a substantive framework for using science reading and science writing with deaf students based on research and informed practice with hearing students.

Journal Article↗

PubMed1999

Learning-related effects and functional neuroimaging.

A fundamental problem in the study of learning is that learning-related changes may be confounded by nonspecific time effects. There are several strategies for handling this problem. This problem may be of greater significance in functional magnetic resonance imaging (fMRI) compared to positron emission tomography (PET). Using the general linear model, we describe, compare, and discuss two approaches for separating learning-related from nonspecific time effects. The first approach makes assumptions on the general behavior of nonspecific effects and explicitly models these effects, i.e., nonspecific time effects are incorporated as a linear or nonlinear confounding covariate in the statistical model. The second strategy makes no a priori assumption concerning the form of nonspecific time effects, but implicitly controls for nonspecific effects using an interaction approach, i.e., learning effects are assessed with an interaction contrast. The two approaches depend on specific assumptions and have specific limitations. With certain experimental designs, both approaches may be used and the results compared, lending particular support to effects that are independent of the method used. A third and perhaps better approach that sometimes may be practically unfeasible is to use a completely temporally balanced experimental design. The choice of approach may be of particular importance when learning-related effects are studied with fMRI.

Adult↗

PubMed2002

Success and failure in teaching the [r]-[l] contrast to Japanese adults: tests of a Hebbian model of plasticity and stabilization in spoken language perception.

A Hebbian model of learning predicts that adults may be able to acquire a nonnative speech contrast if they are trained with stimuli that are exaggerated to make them perceptually distinct. To test these ideas, we asked Japanese adults to identify contrasting [r]-[l] stimuli (e.g., rock-lock) in two training conditions. In the adaptive condition, the [r]-[l] contrast was exaggerated at first and then adjusted to maintain accurate identification. In the fixed condition, a fixed pair of stimuli were used that were distinguishable by native English speakers but difficult for the Japanese learners to discriminate. To examine whether feedback contributes to learning, we ran separate groups with and without feedback in the fixed and the adaptive conditions. Without feedback, 3 days of adaptive training produced substantial improvements, but 3 days of fixed training produced no benefit relative to control, consistent with the Hebbian account. With feedback, both fixed and adaptive training led to robust improvements, and the benefit of training transferred to a second continuum (e.g., road-load). The results are consistent with Hebbian models that are augmented to be sensitive to feedback.

Adult↗